US20030129601A1 - Comparative mycobacterial genomics as a tool for identifying targets for the diagnosis, prophylaxis or treatment of mycobacterioses - Google Patents
Comparative mycobacterial genomics as a tool for identifying targets for the diagnosis, prophylaxis or treatment of mycobacterioses Download PDFInfo
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- US20030129601A1 US20030129601A1 US10/080,170 US8017002A US2003129601A1 US 20030129601 A1 US20030129601 A1 US 20030129601A1 US 8017002 A US8017002 A US 8017002A US 2003129601 A1 US2003129601 A1 US 2003129601A1
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
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- A61P31/04—Antibacterial agents
- A61P31/08—Antibacterial agents for leprosy
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/345—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Brevibacterium (G)
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/35—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Mycobacteriaceae (F)
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6888—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms
- C12Q1/689—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for bacteria
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Definitions
- the present invention is directed to a method of selection of purified nucleotidic sequences or polynucleotides encoding proteins or part of proteins carrying at least an essential function for the survival or the virulence of mycobacterium species by a comparative genomic analysis of the sequence of the genome of M. tuberculosis aligned on the genome sequence of M. leprae .
- the selection by the method of the invention of these nucleotidic or peptidic sequences of interest which are encoding said essential functions of mycobacterium leads to identify and characterize specific antigens or regulator sequences, said antigens being chosen as potential candidates for an immunogenic or vaccine composition, but also useful to determine novel potential drug targets for the pharmaceutical industry.
- the molecules having essential functions encoded by these genes or corresponding to regulatory elements represent also new highly specific targets for chemotherapy.
- the sequence of the polynucleotides according to the invention have the particularity to be maintained during the evolution of the mycobacterium and therefore have been highly conserved in pathogenic mycobacterium species.
- the invention is directed to purified nucleic acid selected by the method of the invention as well as the purified polypeptides with essential functions for the survival or the virulence of mycobacterium species encoded by these sequences.
- the invention is directed to genes that code for essential proteins for which the functions have been attributed.
- the invention is also directed to a process for the production of recombinant polypeptides and chimeric polypeptides comprising them, antibodies generated against these polypeptides, immunogenic or vaccine compositions comprising at least one polypeptide useful as protective antigens or capable to induce a protective response in vivo or in vitro against mycobacterium infections, immunotherapeutic compositions comprising at least such a polypeptide according to the invention, and the use of such nucleic acids and polypeptides in diagnostic methods, vaccines, kits, or antimicrobial therapy.
- a comparative genomic analysis which permitted the inventors to select the sequences encoding essential molecules as regulatory nucleotidic sequences and proteins for the survival or the virulence of mycobacterium species, has been made by analysis of the complete genome sequence of both Mycobacterium tuberculosis and Mycobacterium leprae . The whole genome comparisons led also to the identification of genes that are present in both M. tuberculosis and M. leprae but have no counterparts elsewhere.
- polypeptides having essential functions for the survival or the virulence mycobacterium species are characterized by at least 40% identity at the protein level and at least 70% identity at the gene level between both genomic sequences.
- the amino acid sequences have been compared using the program GAP, “GCG” (Genetic Computer Group) from Program Manual (UNIX), Wisconsin Sequence Analysis PackageTM, Algorithm of Needleman and Wunsch. (J.Mol.Biol.48:443, 1970) The parameters are chosen as follows:
- Length the sequence to be compared are the following XXX SED ID NO:XXX and having XXX amino acids.
- Leprosy one of the oldest recorded diseases, remains a major public health problem. Although prevalence has been reduced extensively by WHO multidrug therapy and vaccination with BCG1,2, the incidence of the disease remains worrying with more than 690,000 new cases annually3 in the world. Leprosy was common in Europe in the middle ages but gradually disappeared.
- the invention aids in fulfilling these needs in the art.
- the method according to the invention has the advantage to reduce drastically the number of potential new targets and protective antigens by giving for the first time an exhaustive description of conserved proteins in the tuberculosis and leprae bacilli .
- the isolated polynucleotides and proteins described in the present invention which are highly conserved in both genomic sequences of M. tuberculosis and M. leprae, are by this characteristic essential for the survival or the virulence of these mycobacteria in the host.
- the identification of antigens and potentially therapeutic targets has been made on an evolutionary basis by a method of comparative genomic analysis.
- This invention provides a method for the identification and the selection of essential genes for the survival or the virulence of mycobacterium species which comprises:
- step c testing the polypolynucleotide selected in step b) for its capacity of virulence or involved in the survival of a mycobacterium species, said testing being based on the activation or inactivation of said polyucleotide in a bacterial host or said testing being based on the activity of the product of expression of said polynucleotide in vivo or in vitro.
- This invention provides also a method for the identification and the selection in silico of essential genes for the survival or the virulence of mycobacterium species which comprises the following steps:
- testing the polypolynucleotide selected in step b) for its capacity of virulence or involved in the survival of a mycobacterium species can be carried out, said testing being based on the activation or inactivation of said polynucleotide in a bacterial host or said testing being based on the activity of the product of expression of said polynucleotide in vivo or in vitro.
- the method according to the invention permits also to determine the polynucleotidic sequences, which encode for polypeptides and regulatory sequences essential for the virulence and/or the survival of mycobacterium which are, in one hand, specific to Mycobacterium tuberculosis and, in the other hand, specific to Mycobacterium leprae, that is to say, said polynucleotidic sequences are not found in publicly accessible banks of non- Mycobacterium tuberculosis and non- Mycobacterium leprae genome.
- a gene according to the invention is a defined nucleotidic sequence, which contains an open reading frame with base composition, codon usage, GC skew and other features typical of a microorganism, preferably a mycobacterium.
- the definition of gene according to the invention comprises nucleotidic sequences, which encode an antigen or a fragment thereof, or nucleotidic sequences, which encode for essential polypeptide with essential function in the host, or nucleotidic sequence, which encodes polypeptide with regulation function in the bacteria, by example, in the DNA expression or in the transcription.
- An essential function for a polypeptide in bacteria according to the invention comprises functions implicated in the survival or in the virulence of the bacteria.
- the first genomic sequence of mycobacterium belongs to Mycobacterium tuberculosis .
- the Mycobacterium microti is a Mycobacterium which infect the vole. It has a genome sequence close to the sequence of Mycobacterium tuberculosis (Cole et al. (1998, Nature, 393, 537-544)) and therefore in a second preferred embodiment, the first genomic sequence of Mycobacterium microti belongs to Mycobacterium genus.
- the second genomic sequence of mycobacterium belongs to Mycobacterium leprae.
- the method according to the invention comprises the complete genomic sequence of said mycobacterium species which is analysed.
- This invention provides purified polypolynucleotide molecule obtained by the method according to the invention.
- this invention provides a purified polynucleotide molecule according to the invention which encodes essential proteins or fragments of proteins of Mycobacterium species.
- the invention also encompasses a purified polynucleotide molecule of a formula selected from the group consisting of polynucleotidic sequences, which encode for polypeptides and regulatory sequences essential for the virulence and/or the survival of mycobacterium which are, in one hand, specific to Mycobacterium tuberculosis and, in the other hand, specific to Mycobacterium leprae, that is to say, said polynucleotidic sequences are not found in publicly accessible banks of non- Mycobacterium tuberculosis and non- Mycobacterium leprae genome.
- this purified polynucleotide is obtained by the method according to the invention.
- the invention emcompasses a purified polypolynucleotide molecule that hybridizes to either stand of a denatured, double-stranded DNA comprising the purified polynucleotide sequence according to the invention under conditions of moderate stringency in 50% formamide and 6 ⁇ SSC at 42° C. with washing conditions of 60° C., 0.5 ⁇ SSC, 0.1% SDS.
- This invention provides a purified polypeptide of a formula selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 644.
- This invention also provides a purified nucleic acid molecule encoding a polypeptide of a formula selected from the group consisting of SEQ ID NO:1 to SEQ ID NO:644.
- the nucleic acid molecules of the invention which include DNA and RNA, are referred to herein as “ M. tuberculosis and M. leprae marker nucleic acids” or “ M. tuberculosis and M. leprae marker DNA”.
- the polypeptides encoded by these molecules which are referred to herein as “ M. tuberculosis and M. Ieprae marker polypeptides,” have formulas selected from the group consisting of SEQ ID NO:1 to SEQ ID NO:644.
- this invention provides a purified nucleic acid molecule that hybridizes to either strand of a denatured, double-stranded DNA comprising the nucleic acid molecule encoding the polypeptide of a formula selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO:644 under conditions of moderate stringency in 50% formamide and 6 ⁇ SSC, at 42° C. with washing conditions of 60° C., 0.5 ⁇ SSC, 0.1% SDS.
- This nucleic acid molecule that hybridizes under the stated conditions can be derived by in vitro mutagenesis of a M. tuberculosis and M. leprae marker nucleic acid of the invention.
- the invention also encompasses purified nucleic acid molecules degenerate from M. tuberculosis and M. leprae marker nucleic acids as a result of the genetic code, purified nucleic acid molecules that are allelic variants of M. tuberculosis and M. leprae marker nucleic acids, and a species homolog of M. tuberculosis and M. leprae marker nucleic acids.
- the invention also encompasses recombinant vectors that direct the expression of these nucleic acid molecules and host cells transformed or transfected with these vectors.
- the invention further encompasses methods for the production of M. tuberculosis and M. leprae marker polypeptides, including culturing a host cell under conditions promoting expression, and recovering the polypeptide from the culture medium.
- methods for the production of M. tuberculosis and M. leprae marker polypeptides including culturing a host cell under conditions promoting expression, and recovering the polypeptide from the culture medium.
- the expression of M. tuberculosis and M. leprae marker polypeptides in bacteria, yeast, plant, and animal cells is encompassed by the invention.
- This invention also provides labeled M. tuberculosis and M. leprae marker polypeptides.
- the labeled polypeptides are in purified form. It is also preferred that the unlabeled or labeled polypeptide is capable of being immunologically recognized by human body fluid containing antibodies to a mycobacterium.
- the polypeptides can be labeled, for example, with an immunoassay label selected from the group consisting of radioactive, enzymatic, fluorescent, chemiluminescent labels, and chromophores.
- Immunological complexes between the M. tuberculosis and M. leprae marker polypeptides of the invention and antibodies recognizing the polypeptides are also provided.
- the immunological complexes can be labeled with an immunoassay label selected from the group consisting of radioactive, enzymatic, fluorescent, chemiluminescent labels, and chromophores.
- this invention provides a method for detecting infection by mycobacteria.
- the method comprises providing a composition comprising a biological material suspected of being infected with a mycobacteria, and assaying for the presence of M. tuberculosis and M. leprae marker polypeptide of the mycobacteria.
- the polypeptides are typically assayed by electrophoresis or by immunoassay with antibodies that are immunologically reactive with M. tuberculosis and M. leprae marker polypeptides of the invention.
- This invention also provides an in vitro diagnostic method for the detection of the presence or absence of antibodies, which bind to an antigen comprising a M. tuberculosis and M. leprae marker polypeptide of the invention or mixtures of the polypeptides.
- the method comprises contacting the antigen with a biological fluid for a time and under conditions sufficient for the antigen and antibodies in the biological fluid to form an antigen-antibody complex, and then detecting the formation of the complex.
- the detection step can further comprise measuring the formation of the antigen-antibody complex.
- the formation of the antigen-antibody complex is preferably measured by immunoassay based on Western blot technique, ELISA (enzyme linked immunosorbent assay), indirect immunofluorescent assay, or immunoprecipitation assay.
- polypeptides of this invention are thus useful as a portion of a diagnostic composition for detecting the presence of antibodies to antigenic proteins associated with mycobacteria.
- a diagnostic kit for the detection of the presence or absence of antibodies, which bind to the M. tuberculosis and M. leprae marker polypeptide of the invention or mixtures of the polypeptides contains antigen comprising the M. tuberculosis and M. leprae marker polypeptide, or mixtures thereof, and means for detecting the formation of immune complex between the antigen and antibodies.
- the antigens and the means are present in an amount sufficient to perform the detection.
- This invention also provides an immunogenic composition
- an immunogenic composition comprising a M. tuberculosis and M. leprae marker polypeptide of the invention or a mixture thereof in an amount sufficient to induce an immunogenic or protective response in vivo, in association with a pharmaceutically acceptable carrier therefor.
- a vaccine composition of the invention comprises a neutralizing amount of the M. tuberculosis and M. leprae marker polypeptide and a pharmaceutically acceptable carrier therefor.
- M. tuberculosis and M. leprae marker polypeptides can be used to raise antibodies for detecting the presence of antigenic proteins associated with a mycobacterium.
- Purified polyclonal or monoclonal antibodies that bind to M. tuberculosis and M. leprae marker polypeptides are encompassed by the invention.
- the polypeptides of the invention can be also employed to raise neutralizing antibodies that either inactivate the mycobacteria, reduce the viability of a mycobacterium in vivo, or inhibit or prevent bacterial replication.
- the ability to elicit mycobacteria-neutralizing antibodies is especially important when the proteins and polypeptides of the invention are used in immunizing or vaccinating compositions to activate the B-cell arm of the immune response or induce a cytotoxic T lymphocyte response (CTL) in the recipient host, or other T cell mediated response.
- CTL cytotoxic T lymphocyte response
- this invention provides a method for detecting the presence or absence of a mycobacterium comprising:
- nucleotide probe is complementary to the full-length sequence of a purified M. tuberculosis and M. leprae marker nucleic acid of the invention.
- this invention provides a method of comparing genetic complements of different types of organisms, wherein the method comprises:
- the method can be carried out using a computer system comprising a database including sequence libraries for a plurality of types of organisms, wherein the libraries have multiple genomic sequences, and providing a database including the one or more probe sequences encoding a polypeptide of a formula selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO:644.
- the computer system includes a user interface capable of receiving sequence information from the sequence libraries and the probe sequence information for comparison and displaying the results of the comparison.
- FIG. 1 is a circular genome map. From the outside, circles 1 , 2 , clockwise and anticlockwise, genes on the ⁇ and + strands, respectively; circles 3 and 4 , pseudogenes; 5 and 6 , M. leprae specific genes; 7 , repeat sequences; 8 , G+C content; 9 , G/C bias (G+C)/(G ⁇ C). See legend to FIG. 2 for colour code.
- FIG. 2 is a comparison of the pros loci of M. leprae and M. tuberculosis .
- FIG. 3 shows distribution of genes by functional category. The number of complete (blue) and pseudogenes (red) within each category for M. leprae is shown. Data for M. tuberculosis (green) were taken from the published genome sequence 8 .
- FIG. 4 Polynucleotidic sequence of the Mycobacterium tuberculosis H37Rv BAC clone, BAC-Rv221, deposited at the C.N.C.M. under the accession number I-2625, which corresponds to pBelo BACII with HindIII partial digest fragment from the genome of M. tuberculosis H37 Rv that starts at position 2,115,612 and extends to position 2,198,604 according to Cole et al. (1998, Nature, 393, 537-544). All of the M. tuberculosis genes contained herein are of interest.
- FIG. 5 Polynucleotidic sequence of the Mycobacterium tuberculosis H37Rv BAC clone, BAC-Rv230, deposited at the C.N.C.M. under the accession number I-2626, which corresponds to pBelo BACII with HindIII partial digest fragment from the genome of M. tuberculosis H37 Rv that starts at position 1,336,764 and extends to position 1,411,979 according to Cole et al. (1998, Nature, 393, 537-544). All of the M. tuberculosis genes contained herein are of interest.
- FIG. 6 Polynucleotidic sequence of the Mycobacterium tuberculosis H37Rv BAC clone, BAC-Rv234, deposited at the C.N.C.M. under the accession number I-2627, which corresponds to pBelo BACII with HindIII partial digest fragment from the genome of M. tuberculosis H37 Rv that starts at position 2,847,864 and extends to position 2,928,420 according to Cole et al. (1998, Nature, 393, 537-544). All of the M. tuberculosis genes contained herein are of interest.
- FIG. 7 Polynucleotidic sequence of the Mycobacterium tuberculosis H37Rv BAC clone, BAC-Rv265, deposited at the C.N.C.M. under the accession number I-2628, which corresponds to pBelo BACII with Hindlul partial digest fragment from the genome of M. tuberculosis H37 Rv that starts at position 514,402 and extends to position 599,515 according to Cole et al. (1998, Nature, 393, 537-544). All of the M. tuberculosis genes contained herein are of interest.
- FIG. 8 Polynucleotidic sequence of the Mycobacterium tuberculosis H37Rv BAC clone, BAC-Rv267, deposited at the C.N.C.M. under the accession number I-2629, which corresponds to pBelo BACII with HindIII partial digest fragment from the genome of M. tuberculosis H37 Rv that starts at position 1,124,621 and extends to position 1,169,811 according to Cole et al. (1998, Nature, 393, 537-544). All of the M. tuberculosis genes contained herein are of interest.
- FIG. 9 Polynucleotidic sequence of the Mycobacterium leprae cosmid which corresponds to pYUB18 with Sau3A partial digest fragment from the genome of M. leprae that starts at position 1,373,705 and extends to position 1,403,746.
- This sequence comprises the sequence of the Mycobacterium leprae cosmid MLCY 811 which corresponds to pYUB18 with Sau3A partial digest fragment of the genome of M. leprae deposited at the C.N.C.M. under the accession number I-2633 that starts at position 1,363,759 and extends to position 1,403,737 according to Cole et al. (2001, Nature, 409, 1007-1011).
- FIG. 10 Polynucleotidic sequence of the Mycobacterium leprae cosmid which corresponds to pYUB18 with Sau3A partial digest fragment of the genome of M. leprae that starts at position 3,160,443 and extends to position 3,194,161.
- This sequence comprises the sequence of the Mycobacterium leprae cosmid MLCY 047 which corresponds to pYUB18 with Sau3A partial digest fragment of the genome of M. leprae deposited at the C.N.C.M. under the accession number I-2632 that starts at position 3,160,458 and extends to position 3,194,087 according to Cole et al. (2001, Nature, 409, 1007-1011).
- FIG. 4 to 10 can be found in the APPENDIX hereto.
- M. leprae contains 3,268,203 bp, and has an average G+C content of 57.8%. These values are much lower than those reported for the M. tuberculosis genome, comprising ⁇ 4,000 genes, 4,411,529 bp and 65.6% G+C 8 .
- proteome sequences 8, 9 it was immediately apparent that only 49.5% of the genome was occupied by protein-coding genes, while 27% contained recognisable pseudogenes, inactive reading frames with functional counterparts in the tubercle bacillus. The remaining 23.5% of the genome did not appear to be coding, and probably contains gene remnants mutated beyond recognition.
- the G+C content of M. leprae genes (60.1%) is higher than that of the pseudogenes (56.5%), and the remainder of the genome (54.5%).
- the high G+C content of M. leprae, and other mycobacteria is apparently driven by the codon preference of active genes, while random mutation within non-coding regions results in drift towards a more neutral G+C content, closer to that of the host.
- M. tuberculosis H37Rv which contains at least two prophages and 56 intact or truncated IS elements 8, 18
- M. leprae has only three phage-like genes, all with M. tuberculosis orthologs, and 26 transposase gene fragments.
- some signs of horizontal transfer of genetic material were detected when the aminoacyl-tRNA synthetase genes were examined. With one exception, all of these are more closely related to M. tuberculosis enzymes than to those of any other organism.
- prolyl-tRNA synthetase encoded by proS
- proS is more similar to the enzymes of Borrelia burgdorfieri and eukaryotes such as Drosophila, humans and yeast. It has been proposed that horizontal transfer of tRNA synthetase genes occurs frequently, and that the pathogen B. burgdorferi may have acquired proS from its host 19 . Comparison of the genetic context provides further support for this hypothesis as the M. leprae proS is both displaced and inverted with respect to the M. tuberculosis genome (FIG. 4), consistent with recent acquisition.
- leprae M leprae Function Pathway Gene Gene Pseudogene gitA1, gltA2, gltA2 citA Citrate synthase Krebs cycle cit, 4 icd1, icd2 icd2 icd1 Isocitrate Krebs cycle dehydrogenase ic1, aceA aceA ic1 Isocitrate lyase Glyoxy- latecycle gnd1, gnd2 gnd1 qnd2 6- Pentose phosphogluconated phosphate ehydrogenase pathway pfkA, pjkB pfkA pfkB Phospho- Glycolysis fructokinase aceE, lpdA, aceE, lpd lpdA, pdhA, Pyruvate, Energy pdhA, pdhB, (Rv0462) pdhB, pdhC dehydrogenase metabolism pdhC,
- Mycolic acids structural components of all mycobacteria, include the alpha mycolates, lacking oxygen functions, and the oxygenated keto- and methoxy- forms. Reappraisal of mycolic acid modification is now possible in the light of the reduced cmaA, mmaA and umaA gene-sets encoding the effector methyltransferases.
- M. Ieprae contains no methoxy-mycolates 23 , probably due to the loss of the MmaA2 and MmaA3 enzymes that attach the methoxy group in M. tuberculosis 10, 24 .
- the mycolic acids do contain cyclopropane functions 25 that in M. tuberculosis are introduced by MmaA2 and CmaAI.
- PGL1 phenolic glycolipid 1
- PGL1 is derived from phthiocerol-dimycocerosate (PDIM), an esterified compound lipid generated by mycocerosic acid synthase and a type I polyketide synthase (PKS), by addition of three o-methylated deoxy sugars 23 .
- PDIM phthiocerol-dimycocerosate
- PKS type I polyketide synthase
- tuberculosis requires the RND protein, MmpL7, for its transport across the cytoplasmic membrane 9,28,29 .
- MmpL7 the RND protein
- MmpL7 the RND protein
- PKS systems identifiable in M. tuberculosis 8 only six were predicted in M. leprae and the number of mmpL genes (often linked to PKS genes) has decreased from 16 to five, presumably because they are no longer required for polyketide or lipid export. Deletion of such systems may be reflected in the lack of mycolipenic and hydroxylipenic acids, polyketides esterified to trehalose in M. tuberculosis. Further PKS missing from M. leprae include the mbt operon required for production of the salicylate-based mycobactin siderophores.
- Lipids, polyketides and aromatic compounds are often substrates, for cytochrome-P450 monooxygenases 30 , enzymes that are exceptionally abundant in M. tuberculosis 8 . Astonishingly, none of these is functional in M. leprae although a novel enzyme is predicted.
- Intracellular mycobacteria probably derive much of their energy from degradation of host-derived lipids 31 , a process initiated by lipases.
- M. tuberculosis M. Ieprae has only two lipase genes, of which, lipG, clusters with mmaA genes and could, therefore, effect fatty acid remodelling. This appears to leave just one lipase for scavenging fatty acids.
- the enzyme LipE (ML1190) or its counterpart in M. tuberculosis (Rv3775) could represent an attractive drug target.
- FadA and FadB enzymes which catalyse ⁇ -oxidation, M.
- tuberculosis has numerous alternative systems for fatty acid degradation 8 .
- M. leprae has roughly one third as many potential enzymes; however, there are three-times more FadD acyl-CoA synthases than FadE acyl-CoA dehydrogenases, whereas these are expected in equal amounts in M. tuberculosis . This may be explained by the dual role of FadD in ⁇ -oxidative and anabolic processes while FadE only participates catabolically.
- M. leprae is limited to growth on very few carbon sources, or even a limited and rather specialised combination, on which it can maintain a balanced carbon metabolism. Though a similar range of potential substrates is available to both M. leprae and M.
- the leprosy bacillus has lost anaerobic and microacrophilic electron transfer systems, such as formate dehydrogenase, nitrate, and fumarate reductase together with the biosynthetic and transport systems required to produce the cognate prosthetic groups.
- the aerobic respiratory chain of M. leprae is truncated as only the 3′-end of the NADH oxidase operon, nuoA-N, remains.
- the consequences of this event are far-reaching, for not only has the potential to produce ATP from the oxidation of NADH been lost, but also regeneration of NAD + may be limited, relying heavily on ndh, which is involved only in recycling NAD + .
- M. leprae may regenerate NAD + from NADH by (1) diverting pyruvate to acetate and CO 2 using lactate dehydrogenase and lactate oxidase; (2) diverting PEP to malate or fumarate via oxaloacetate, using its PEP carboxylase (an enzyme not found in the tubercle bacillus) that only catalyses the reaction in this direction. Given the loss of genes reviewed above, the acids produced by (1) and (2) cannot be recycled and must be excreted.
- tuberculosis met genes are all intact. This requirement for methionine may be dictated by the inactivation of the sulphate transport operon, cysYWA, and in turn this implies that M. leprae depends upon an organic source of sulphur.
- a second auxotrophy that is predicted is for cobinamide, as examination of the cob genes shows selective deletion of those to make cobinamide, while the genes needed to produce vitamin B12 from cobinamide are retained.
- M. leprae Central to a successful pathogenic lifestyle is the ability to obtain iron.
- M. leprae has many genes for haem and iron-based proteins and employs the iron regulatory systems, ideR and furB, yet may be severely handicapped compared to M. tuberculosis as it appears to have lost the mbt operon, encoding the non-ribosomal peptide synthase required for production of the iron-scavenging siderophores, mycobactin/exochelin 8, 36, 37 .
- part of the iron uptake system is functional in M. leprae, as it transports exochelinMN, from M. neoaurum but not those of M. smegmatis or M. tuberculosis 38 .
- the genes for exochelinMN are unknown and seem unlikely to occur in M. leprae.
- M. leprae contains several enzymes that have no counterparts in the tubercle bacillus, including a eukaryotic-like uridine phosphorylase and adenylate cyclase.
- a eukaryotic-like uridine phosphorylase and adenylate cyclase there are two transport systems that may play significant physiological roles: an ABC-transporter for sugars, and a second member of the Nrampl family, involved in divalent metal ion uptake.
- M. leprae may have acquired another Nrampl gene 39 to ensure adequate intracellular iron concentrations resulting from its lack of mycobactin siderophores.
- M. leprae shows a marked tropism for myelin-producing Schwann cells, and a surface-exposed 21 kDa laminin-binding protein (LBP) may be an important virulence factor 40-42 . Inspection of the genome sequence revealed a single LBP gene and this also occurs in M. tuberculosis . No further candidates for virulence genes were detected, and many of those present in M. tuberculosis have been inactivated or lost, including three of the Mce operons encoding putative invasins 9, 43 . Although the leprosy and tubercle bacilli both survive within macrophages, M. leprae has no catalase-peroxidase 44 , and fewer peroxidoxins and epoxide hydrolases to combat reactive oxygen species. It has retained both superoxide dismutases suggesting that these may contribute to its survival.
- LBP laminin-binding protein
- Comparative genomics is a powerful new tool for exploring micobial evolution and identifying those genes that might encode new drug targets or protective antigens. Coupled with knowledge derived from bioinformatic analysis of the proteome, and understanding of the underlying microbiology, it is possible to reduce the number of potential new targets within a pathogen to a more tangible level.
- This invention includes discoveries resulting from the findings of a comparative analysis in which gene and protein sets of the leprosy and tubercle bacilli have been compared pairwise, and against the completed genome sequences of various prokaryotes and eukaryotes.
- the genome of M. leprae is substantially smaller than that of M. tuberculosis and contains numerous pseudogenes. While the genome of M. tuberculosis comprises 4.41 Mb and contains around 4,000 genes, the genome of M. leprae is only 3.27 Mb and a mere 49.5% is occupied by protein-coding genes. About 27% of the M. leprae genome contains recognizable pseudogenes, inactive reading frames with functional counterparts in the tubercle bacillus. The remaining 23.5% of the genome does not appear to be coding, and probably contains gene remnants mutated beyond recognition. The distribution of the 1,114 pseudogenes was essentially random throughout the chromosome.
- Proteins that are secreted via the general secretory pathway 52 are readily identifiable by their characteristic signal peptides, whereas those metallo-enzymes that are secreted by the twin arginine transporter system, Tat, can be recognized by the presence at the N-terminus of the cognate motif, S/TRRXFLK preceeding the signal peptide 53 , 5 . This will be discussed further below.
- ESAT-6 is a potent T-cell antigen that induces strong Th1-type responses 55 and has been extensively studied as a potential diagnostic reagent for infection 56 , since its gene is missing from BCG 57 , 58 , 59 , and as a component of a subunit vaccine 60 .
- the comparative genomic analysis identified several ESAT-6 proteins, and their potential secretion machinery, that were common to both M. tuberculosis and M. leprae (Table 2).
- ML0048 Name of an identified ORF in the genome of M. leprae.
- Rv3876 Name of Equivalent ORF in the genome of M. tuberculosis published in 1998.
- BLASTP score which indicates how similar the protein sequences are.
- the analyses of the results are described in Cole et al. for the comparisons between the genome of M. tuberculosis and the genome of BCG (Analysis of the proteome of Mycobacterium tuberculosis in silico, tuber Lung. Dis. 1999; 79(6):329-42).
- Sc3C3.03C Nomenclature of the streptomyces protein.
- EMB AL031231: Accession number in EMBL databank for the sequence of the Streptomyces protein found to be most similar to ML0048.
- FASTA score Different method, like BLAST, for comparing sequences for their similarity.
- Score denotes the degree of similarity.
- 31.6% Percentage of identity between C terminal part of the Streptomyces protein and the amino acid sequence of ML0048. This 31.6% identity is found in an overlapping region of 580 amino acids between the two sequences. The other examples should be read similarly. TABLE 2 Proteins of limited distribution with potential as drug targets, diagnostic antigens or subunit vaccine components M. Group leprae M. tub.
- EMBL:AB003693 hypothetical 38 protein
- F:O24754 EMBL:AB003693
- Fasta score E( ) 2.1e-15, 34.5% identity in 148 aa overlap.
- coelicolor putative lipoprotein SCE33.13C TR:CAB90922 (EMBL:AL355774) fasta scores: E( ): 0.00039, 24.4% id in 624 aa A whiB1 Rv3219 6,00E- Transcription factor 31 A ML0814 Rv3208c 3,00E- S.
- coelicolor hypothetical protein 32 gp
- coelicolor putative integral membrane protein 40 SC5F7.32 TR:Q9S2R7 (EMBL:AL096872) A ML0876 Rv2199c 2,00E- S.
- coelicolor hypothetical proteins e.g. putative 43 integral membrane protein SC6G10.27C TR:Q9X812 (EMBL:AL049497) (132 aa) fasta scores: E( ) : 6.2e-15, 38.8% id in 139 aa
- coelicolor TR:Q53873 (EMBL:AL031317) (411 aa); Fasta score E( ) 1.1e-12, 28.3% identity in 410 aa overlap A ML1439 Rv2050 4,00E- emb
- S. coelicolor 101 4e-21 A ML1485 Rv2466c 2,00E- S. coelicolor TR:CAB71809 (EMBL:AL138662) (216 aa); 66 Fasta score E( ): 0, 52.3% identity in 214 aa overlap A ML1508 Rv1155 2,00E- S.
- coelicolor TR:Q9S3Y6 (EMBL:AF170560) (597 aa); Fasta score E( ): 0, 55.5% identity in 566 aa overlap
- (AL132644) putative membrane protein [Streptomyc . . . 109 4e-23 A ML1649 Rv2239c 3,00E- emb
- coelicolor TR:Q9Z586 (EMBL:AL035569) (331 aa); 91 Fasta score E( ): 0, 38.6% identity in 337 aa overlap, A ML1781 Rv2256c 4,00E- 4pir
- coelicolor hypothetical protein TR:CAE88434 14 (EMBL:AL353815) fasta scores: E( ): 0.0092, 39.3% in 61 aa; truncated at C-terminus; may represent a pseudogene A ML2063 Rv1846c 3,00E- possible regulator, pir
- coelicolor putative integral membrane protein 82 SC10A7.04 TR:Q9XAS1 (EMBL:AL078618) fasta scores: E( ): 1.8e-19, 32.6% in 328 aa A ML2073 Rv1830 2,00E- S.
- coelicolor hypothetical 19.1 kda protein 74 TR:CAB88877 (ENBL:AL353861) fasta scores: E( ): 3.7e- 30, 64.8% in 145 aa A ML2075 Rv1828 7,00E- S.
- coelicolor putative membrane protein TR:Q9XAE8 (EMBL:AL079356) fasta scores: E( ) : 1.5e-13, 27.1% in 255 aa A ML2137 Rv0883c 1,00E- S. coelicolor hypothetical 39.0 kda protein TR:O50529 76 (EMBL:AL009204) fasta scores: E( ): 2.2e-19, 36.0% in 247 aa A ML2142 Rv0877 8,00E- S. coelicolor hypothetical 32.2 kda protein 91 TR:CAB93404 (EMBL:AL357524) fasta scores: E( ): 2.5e- 19, 43.3% in 270 aa.
- coelicolor putative integral membrane 43 transport protein SCH5.28 TR:Q9X930 (EMBL:AL035636) (162 aa) fasta scores: E( ): 3.3e-10, 37.3% id A ML2306 Rv3680 e-110 S.
- coelicolor putative ion-transporting ATPase TR:Q9XA35 (EMBL:AL079353) (481 aa) fasta scores: E( ): 0, 48.6% id in 432 aa A ML2307 Rv3681c 4,00E- whiB4 28 A ML2330 Rv3716c 6,00E- pir
- coelicolor hypothetical protein TR:Q9X8H2 94 (EMBL:AL049819) (271 aa) fasta scores: E( ): 0, 48.4% id in 250 aa
- S. coelicolor putative lipoprotein TR:CAB76012 (EMBL:AL157916) fasta scores: E( ): 2.5e-24, 28.6% id in 405 aa.
- coelicolor putative dehydratase TR:CAB77291 (EMBL:AL160312) A ML2630 Rv0007 4,00E- emb
- N. tuberculosis protein M ML1993 Rv0098 3,00E- — 50 M ML1995 Rv0100 1,00E- — 18 M ML2010 Rv1906c 4,00E- putative lipoprotein (secreted in Mt) 31 M ML2022 Rv1893 2,00E- — 13 M ML2023 Rv1891 2.00E- Contains probable N-terminal signal sequence.
- Pseudomonas putida SW:CLCD_PSEPU (P11453) (236 aa) X ML1494 Rv1171 8,00E- conserved membrane protein, pir
- M. tuberculosis and M. leprae marker polypeptides are disclosed in SEQ ID NO: 1 to SEQ ID NO:644.
- the discovery of the M. tuberculosis and M. Ieprae marker polypeptides and DNA encoding the polypeptides enables construction of expression vectors comprising nucleic acid sequences encoding M. tuberculosis and M. leprae marker polypeptides; host cells transfected or transformed with the expression vectors; biologically active M. tuberculosis and M. leprae marker polypeptides and M. tuberculosis and M.
- leprae marker polypeptides as isolated or purified peptides; and antibodies immunoreactive with M. tuberculosis and M. leprae marker polypeptides.
- understanding of the mechanism by which M. tuberculosis and M. leprae marker polypeptides function enables the design of assays to detect inhibitors of M. tuberculosis and M. leprae marker polypeptide activity.
- M. tuberculosis and M. leprae marker polypeptides refers to a genus of polypeptides that encompasses polypeptides of a formula selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO:644, as well as those polypeptides having a high degree of similarity (at least 90% homology) with such amino acid sequences and which polypeptides are immunoreactive or biologically active.
- the term “purified” as used herein, means that the M. tuberculosis and M. leprae marker polypeptides are essentially free of association with other proteins or polypeptides, for example, as a purification product of recombinant host cell culture or as a purified product from a non-recombinant source.
- substantially purified refers to a mixture that contains M. tuberculosis and M. leprae marker polypeptides and is essentially free of association with other proteins or polypeptides, but for the presence of known proteins that can be removed using a specific antibody, and which substantially purified M. tuberculosis and M. leprae marker polypeptides can be used as antigens.
- a M. tuberculosis and M. leprae marker polypeptide “variant” as referred to herein means a polypeptide substantially homologous to native M. tuberculosis and M. leprae marker polypeptides, but which has an amino acid sequence different from that of native M. tuberculosis and M. leprae marker polypeptides because of one or more deletions, insertions, or substitutions.
- the variant amino acid sequence preferably is at least 80% identical to a native M. tuberculosis and M. leprae marker polypeptide amino acid sequence, most preferably at least 90% identical.
- the percent identity can be determined, for example by comparing sequence information using the GAP computer program, version 6.0 described by Devereux et al. ( Nucl. Acids Res. 12:387, 1984) and available from the University of Wisconsin Genetics Computer Group (UWGCG).
- the GAP program utilizes the alignment method of Needleman and Wunsch ( J. Mol. Biol. 48:443, 1970), as revised by Smith and Waterman ( Adv. Appl. Math 2:482, 1981).
- the preferred default parameters for the GAP program include: (1) a unary comparison matrix (containing a value of 1 for identities and 0 for non-identities) for nucleotides, and the weighted comparison matrix of Gribskov and Burgess, Nucl. Acids Res.
- Variants can comprise conservatively substituted sequences, meaning that a given amino acid residue is replaced by a residue having similar physicochemical characteristics.
- conservative substitutions include substitution of one aliphatic residue for another, such as Ile, Val, Leu, or Ala for one another, or substitutions of one polar residue for another, such as between Lys and Arg; Glu and Asp; or Gln and Asn.
- Other such conservative substitutions for example, substitutions of entire regions having similar hydrophobicity characteristics, are well known.
- Naturally occurring M. tuberculosis and M. leprae marker polypeptide variants are also encompassed by the invention.
- variants are proteins that result from alternate mRNA splicing events or from proteolytic cleavage of the M. tuberculosis and M. leprae marker polypeptides.
- Variations attributable to proteolysis include, for example, differences in the termini upon expression in different types of host cells, due to proteolytic removal of one or more terminal amino acids from the M. tuberculosis and M. leprae marker polypeptides.
- variantations attributable to frameshifting include, for example, differences in the termini upon expression in different types of host cells due to different amino acids.
- the invention provides isolated and purified, or homogeneous, M. tuberculosis and M. leprae marker polypeptides, both recombinant and non-recombinant.
- Variants and derivatives of native M. tuberculosis and M. leprae marker polypeptides that can be used as antigens can be obtained by mutations of nucleotide sequences coding for native M. tuberculosis and M. leprae marker polypeptides. Alterations of the native amino acid sequence can be accomplished by any of a number of conventional methods.
- Mutations can be introduced at particular loci by synthesizing oligonucleotides containing a mutant sequence, flanked by restriction sites enabling ligation to fragments of the native sequence. Following ligation, the resulting reconstructed sequence encodes an analog having the desired amino acid insertion, substitution, or deletion.
- oligonucleotide directed, site specific mutagenesis procedures can be employed to provide an altered gene wherein predetermined codons can be altered by substitution, deletion, or insertion.
- Exemplary methods of making the alterations set forth above are disclosed by Walder et al. ( Gene 42:133, 1986); Bauer et al. ( Gene 37:73, 1985); Craik ( BioTechniques, January 1985, 12-19); Smith et al. ( Genetic Engineering: Principles and Methods , Plenum Press, 1981); Kunkel ( Proc. Natl. Acad. Sci. USA 82:488, 1985); Kunkel et al. ( Methods in Enzymol. 154:367, 1987); and U.S. Pat. Nos. 4,518,584 and 4,737,462, all of which are incorporated by reference.
- M. tuberculosis and M. leprae marker polypeptides can be utilized to prepare antibodies that specifically bind to M. tuberculosis and M. leprae marker polypeptides.
- the term “antibodies” is meant to include polyclonal antibodies, monoclonal antibodies, fragments thereof such as F(ab′)2 and Fab fragments, as well as any recombinantly produced binding partners. Antibodies are defined to be specifically binding if they bind M. tuberculosis and M. leprae marker polypeptides with a K a of greater than or equal to about 10 7 M ⁇ 1 .
- binding partners or antibodies can be readily determined using conventional techniques, for example, those described by Scatchard et al., Ann. N. Y Acad. Sci., 51:660 (1949).
- Polyclonal antibodies can be readily generated from a variety of sources, for example, horses, cows, goats, sheep, dogs, chickens, rabbits, mice, or rats, using procedures that are well known in the art.
- the invention further encompasses isolated fragments and oligonucleotides derived from the nucleotide sequences of the invention.
- the invention also encompasses polypeptides encoded by these fragments and oligonucleotides.
- Nucleic acid sequences within the scope of the invention include isolated DNA and RNA sequences that hybridize to the native M. tuberculosis and M. leprae marker nucleic acids disclosed herein under conditions of moderate or severe stringency, and which encode M. tuberculosis and M. leprae marker polypeptides.
- conditions of moderate stringency as known to those having ordinary skill in the art, and as defined by Sambrook et al. Molecular Cloning: A Laboratory Manual, 2 ed. Vol. 1, pp.
- a DNA sequence can vary and still encode a M. tuberculosis and M. leprae marker polypeptide of a formula selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO:644.
- Such variant DNA sequences can result from silent mutations (e.g., occurring during PCR amplification), or can be the product of deliberate mutagenesis of a native sequence.
- the invention thus provides equivalent isolated DNA sequences, encoding M. tuberculosis and M. leprae marker polypeptides, selected from: (a) DNA derived from the coding region of a native M. tuberculosis and M. leprae marker nucleic acid; (b) cDNA comprising the nucleotide sequence of the invention; (c) DNA capable of hybridization to a DNA of (a) under conditions of moderate stringency and which encode M. tuberculosis and M. leprae marker polypeptides; and (d) DNA which is degenerate as a result of the genetic code to a DNA defined in (a), (b) or (c) and which encodes M. tuberculosis and M. leprae marker polypeptides. M. tuberculosis and M. leprae marker polypeptides encoded by such DNA equivalent sequences are encompassed by the invention.
- DNA that is equivalent to the DNA sequence of the invention will hybridize under moderately stringent conditions to the double-stranded native DNA sequence that encodes polypeptides of a formula selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO:644.
- M. tuberculosis and M. leprae marker polypeptides encoded by such DNA include, but are not limited to, M. tuberculosis and M. leprae marker polypeptide fragments and M. tuberculosis and M. leprae marker polypeptides comprising inactivated N-glycosylation site(s), inactivated protease processing site(s), or conservative amino acid substitution(s), as described above.
- M. tuberculosis and M. leprae marker polypeptides encoded by DNA derived from other species, wherein the DNA will hybridize to the complement of the DNA of the invention are also encompassed.
- Recombinant expression vectors containing a nucleic acid sequence encoding M. tuberculosis and M. leprae marker polypeptides can be prepared using well known methods.
- the expression vectors include a M. tuberculosis and M. leprae marker DNA sequence operably linked to suitable transcriptional or translational regulatory nucleotide sequences, such as those derived from a mammalian, microbial, viral, or insect gene.
- suitable transcriptional or translational regulatory nucleotide sequences such as those derived from a mammalian, microbial, viral, or insect gene.
- regulatory sequences include transcriptional promoters, operators, or enhancers, an mRNA ribosomal binding site, and appropriate sequences which control transcription and translation initiation and termination.
- Nucleotide sequences are “operably linked” when the regulatory sequence functionally relates to the M.
- a promoter nucleotide sequence is operably linked to a M. tuberculosis and M. leprae marker DNA sequence if the promoter nucleotide sequence controls the transcription of the M. tuberculosis and M. leprae marker DNA sequence.
- the ability to replicate in the desired host cells, usually conferred by an origin of replication, and a selection gene by which transformants are identified can additionally be incorporated into the expression vector.
- sequences encoding appropriate signal peptides that are not naturally associated with M. tuberculosis and M. leprae marker polypeptides can be incorporated into expression vectors.
- a DNA sequence for a signal peptide secretory leader
- M. tuberculosis and M. leprae marker nucleotide sequence so that the M. tuberculosis and M. leprae marker polypeptide is initially translated as a fusion protein comprising the signal peptide.
- a signal peptide that is functional in the intended host cells enhances extracellular secretion of the M. tuberculosis and M. leprae marker polypeptide.
- the signal peptide can be cleaved from the M. tuberculosis and M. leprae marker polypeptide upon secretion of the marker polypeptide from the cell.
- Expression vectors fdr use in prokaryotic host cells generally comprise one or more phenotypic selectable marker genes.
- a phenotypic selectable marker gene is, for example, a gene encoding a protein that confers antibiotic resistance or that supplies an autotrophic requirement.
- useful expression vectors for prokaryotic host cells include those derived from commercially available plasmids.
- Commercially available vectors include those that are specifically designed for the expression of proteins. These include pMAL-p2 and pMAL-c2 vectors, which are used for the expression of proteins fused to maltose binding protein (New England Biolabs, Beverly, Mass., USA).
- Promoter sequences commonly used for recombinant prokaryotic host cell expression vectors include ⁇ -lactamase (penicillinase), lactose promoter system (Chang et al., Nature 275:615, 1978; and Goeddel et al., Nature 281:544, 1979), tryptophan (trp) promoter system (Goeddel et al., Nucl. Acids Res. 8:4057, 1980; and EP-A-36776), and tac promoter (Maniatis, Molecular Cloning: A Laboratory Manual , Cold Spring Harbor Laboratory, p. 412, 1982).
- ⁇ -lactamase penicillinase
- lactose promoter system Chang et al., Nature 275:615, 1978; and Goeddel et al., Nature 281:544, 1979
- tryptophan (trp) promoter system Goeddel et al., Nucl. Acids Res. 8:
- Suitable host cells for expression of M. tuberculosis and M. leprae marker polypeptides include prokaryotes, yeast or higher eukaryotic cells.
- Appropriate cloning and expression vectors for use with bacterial, fungal, yeast, and mammalian cellular hosts are described, for example, in Pouwels et al. Cloning Vectors: A Laboratory Manual , Elsevier, N.Y., (1985). Cell-free translation systems could also be employed to produce M. tuberculosis and M. leprae marker polypeptides using RNAs derived from DNA constructs disclosed herein.
- the present invention is intended to encompass the previously described proteins in isolated or purified form, whether obtained using the techniques described herein or other methods.
- the M. tuberculosis and M. leprae marker polypeptides are substantially free of human tissue and human tissue components, nucleic acids, extraneous proteins and lipids, and adventitious microorganisms, such as bacteria and a mycoplasma.
- the invention encompasses equivalent proteins having substantially the same biological and immunogenic properties. Thus, this invention is intended to cover serotypic variants of the proteins of the invention.
- M. tuberculosis and M. leprae marker polypeptides of the invention it may be desirable to label them.
- suitable labels are radioactive labels, enzymatic labels, fluorescent labels, chemiluminescent labels, and chromophores.
- the methods for labeling proteins and glycoproteins of the invention do not differ in essence from those widely used for labeling immunoglobulin.
- the need to label may be avoided by using labeled antibody to the antigen of the invention or anti- immunoglobulin to the antibodies to the antigen as an indirect marker.
- M. tuberculosis and M. leprae marker polypeptides of the invention can be used to produce polyctonal and monoclonal antibodies reactive therewith.
- a polypeptide of the invention can be used to immunize an animal host by techniques known in the art. Such techniques usually involve inoculation, but they may involve other modes of administration. A sufficient amount of the polypeptide is administered to create an immunogenic response in the animal host. Any host that produces antibodies to the antigen of the invention can be used. Once the animal has been immunized and sufficient time has passed for it to begin producing antibodies to the antigen, polyclonal antibodies can be recovered.
- the general method comprises removing blood from the animal and separating the serum from the blood.
- the serum which contains antibodies to the antigen, can be used as an antiserum to the antigen.
- the antibodies can be recovered from the serum.
- Affinity purification is a preferred technique for recovering purified polyclonal antibodies to the antigen from the serum.
- Monoclonal antibodies to the antigens of the invention can also be prepared.
- One method for producing monoclonal antibodies reactive with the antigens comprises the steps of immunizing a host with the antigen; recovering antibody producing cells from the spleen of the host; fusing the antibody producing cells with myeloma cells deficient in the enzyme hypoxanthine-guanine phosphoribosyl transferase to form hybridomas; select at least one of the hybridomas by growth in a medium comprising hypoxanthine, aminopterin, and thymidine; identifying at least one of the hybridomas that produces an antibody to the antigen, culturing the identified hybridoma to produce antibody in a recoverable quantity; and recovering the antibodies produced by the cultured hybridoma.
- polyclonal or monoclonal antibodies can be used in a variety of applications. Among these is the neutralization of corresponding proteins. They can also be used to detect viral antigens in biological preparations or in purifying corresponding proteins, glycoproteins, or mixtures thereof, for example, when used in a affinity chromatographic columns.
- the M. tuberculosis and M. leprae marker polypeptides can be used as antigens to identify antibodies to a mycobacteria in materials and to determine the concentration of the antibodies in those materials.
- the antigens can be used for qualitative or quantitative determination of a mycobacteria in a material.
- materials include human tissue and human cells, as well as biological fluids, such as human body fluids, including human sera.
- the antigens of the present invention provide an assay that is convenient, rapid, sensitive, and specific.
- the antigens of the invention can be employed for the detection of a mycobacterium by means of immunoassays that are well known for use in detecting or quantifying humoral components in fluids.
- immunoassays that are well known for use in detecting or quantifying humoral components in fluids.
- antigen-antibody interactions can be directly observed or determined by secondary reactions, such as precipitation or agglutination.
- immunoelectrophoresis techniques can also be employed. For example, the classic combination of electrophoresis in agar followed by reaction with anti-serum can be utilized, as well as two-dimensional electrophoresis, rocket electrophoresis, and immunolabeling of polyacrylamide gel patterns (Western Blot or immunoblot).
- immunoassays in which the antigens of the present invention can be employed include, but are not limited to, radioimmunoassay, competitive immunoprecipitation assay, enzyme immunoassay, and immunofluorescence assay. It will be understood that turbidimetric, calorimetric, and nephelometric techniques can be employed. An immunoassay based on Western Blot technique is preferred.
- Immunoassays can be carried out by immobilizing one of the immunoreagents, either an antigen of the invention or an antibody of the invention to the antigen, on a carrier surface while retaining immunoreactivity of the reagent.
- the reciprocal immunoreagent can be unlabeled or labeled in such a manner that immunoreactivity is also retained.
- enzyme immunoassays such as enzyme linked immunosorbent assay (ELISA) and competitive inhibition enzyme immunoassay (CIEIA).
- the support is usually a glass or plastic material.
- Plastic materials molded in the form of plates, tubes, beads, or disks are preferred. Examples of suitable plastic materials are polystyrene and polyvinyl chloride.
- a carrier material can be interposed between the reagent and the support. Examples of suitable carrier materials are proteins, such as bovine serum albumin, or chemical reagents, such as gluteraldehyde or urea. Coating of the solid phase can be carried out using conventional techniques.
- the invention provides immunogenic M. tuberculosis and M. leprae marker polypeptides, and more particularly, protective polypeptides for use in the preparation of vaccine compositions against a mycobacterium.
- These polypeptides can thus be employed as viral vaccines by administering the polypeptides to a mammal susceptible to a mycobacteria infection.
- Conventional modes of administration can be employed. For example, administration can be carried out by oral, respiratory, or parenteral routes. Intradermal, subcutaneous, and intramuscular routes of administration are preferred when the vaccine is administered parenterally.
- the major purpose of the immune response in a mycobacteria-infected mammal is to inactivate the free mycobacteria and to eliminate mycobacteria infected cells that have the potential to release infectious mycobacteria.
- the B-cell arm of the immune response has some responsibility for inactivating free mycobacteria. The principal manner in which this is achieved is by neutralization of infectivity.
- Another major mechanism for destruction of the a mycobacteria-infected cells is provided by cytotoxic T lymphocytes (CTL) that recognize M. tuberculosis and M. leprae marker antigens expressed in combination with class I histocompatibility antigens at the cell surface.
- CTLs recognize M. tuberculosis and M.
- this invention can be employed to stimulate a B-cell response to M. tuberculosis and M. leprae marker polypeptides, as well as immunity mediated by a CTL response following infection.
- the CTL response can play an important role in mediating recovery from primary mycobacterial infection and in accelerating recovery during subsequent infections.
- the ability of the M. tuberculosis and M. leprae marker polypeptides and vaccines of the invention to induce protective levels of neutralizing antibody in a host can be enhanced by emulsification with an adjuvant, incorporating in a liposome, coupling to a suitable carrier, or by combinations of these techniques.
- the M. tuberculosis and M. leprae marker polypeptides of the invention can be administered with a conventional adjuvant, such as aluminum phosphate and aluminum hydroxide gel, in an amount sufficient to potentiate humoral or cell-mediated immune responses in the host.
- the M. tuberculosis and M. leprae marker polypeptides can be bound to lipid membranes or incorporated in lipid membranes to form liposomes. The use of nonpyrogenic lipids free of nucleic acids and other extraneous matter can be employed for this purpose.
- the immunization schedule will depend upon several factors, such as the susceptibility of the host to infection and the age of the host.
- a single dose of the vaccine of the invention can be administered to the host or a primary course of immunization can be followed in which several doses at intervals of time are administered. Subsequent doses used as boosters can be administered as needed following the primary course.
- the M. tuberculosis and M. leprae marker polypeptides and vaccines of the invention can be administered to the host in an amount sufficient to prevent or inhibit a mycobacteria infection or replication in vivo. In any event, the amount administered should be at least sufficient to protect the host against substantial immunosuppression, even though a mycobacterial infection may not be entirely prevented.
- An immunogenic response can be obtained by administering the polypeptides of the invention to the host in an amount of about 10 to about 500 micrograms antigen per kilogram of body weight, preferably about 50 to about 100 micrograms antigen per kilogram of body weight.
- the polypeptides and vaccines of the invention can be administered together with a physiologically acceptable carrier. For example, a diluent, such as water or a saline solution, can be employed.
- Another aspect of the invention provides a method of DNA vaccination.
- the method also includes administering any combination of the nucleic acids encoding M. tuberculosis and M. leprae marker polypeptides, with or without carrier molecules, to an individual.
- the individual is an animal, and is preferably a mammal. More preferably, the mammal is selected from the group consisting of a human, a dog, a cat, a bovine, a pig, and a horse. In an especially preferred embodiment, the mammal is a human.
- the methods of treating include administering immunogenic compositions comprising M. tuberculosis and M. leprae marker polypeptides, but compositions comprising nucleic acids encoding M. tuberculosis and M. leprae marker polypeptides as well.
- nucleic acid vaccines e.g., DNA vaccines
- nucleic acid vaccine technology as well as protein and polypeptide based technologies.
- the nucleic acid based technology allows the administration of nucleic acids encoding M. tuberculosis and M. leprae marker polypeptides, naked or encapsulated, directly to tissues and cells without the need for production of encoded proteins prior to administration.
- nucleic acid vaccine technology includes, but is not limited to, delivery of naked DNA and RNA and delivery of expression vectors encoding M. tuberculosis and M. leprae marker polypeptides.
- vaccine it is equally applicable to immunogenic compositions that do not result in a protective response. Such non-protection inducing compositions and methods are encompassed within the present invention.
- nucleic acids encoding M. tuberculosis and M. leprae marker polypeptides and carrier molecules are included within the scope of the invention.
- kits capable of diagnosing mycobacteria infection contains the DNA sequences of this invention, which are capable of hybridizing to RNA or analogous DNA sequences to indicate the presence of a mycobacteria infection.
- Different diagnostic techniques can be used which include, but are not limited to: (I) Southern blot procedures to identify cellular DNA which may or may not be digested with restriction enzymes; (2) Northern blot techniques to identify RNA extracted from cells; and (3) dot blot techniques, i.e., direct filtration of the sample through an ad hoc membrane, such as nitrocellulose or nylon, without previous separation on agarose gel.
- Suitable material for dot blot technique could be obtained from body fluids including, but not limited to, serum and plasma, supernatants from culture cells, or cytoplasmic extracts obtained after cell lysis and removal of membranes and nuclei of the cells by centrifugation.
- the invention also provides screening assays for identifying agents that modulate (e.g. augment or inhibit) the activity of M. tuberculosis and M. leprae marker polypeptides.
- agents that modulate e.g. augment or inhibit
- Assays for detecting the ability of agents to inhibit or augment the activity of M. tuberculosis and M. leprae marker polypeptides provide for facile high-throughput screening of agent banks (e.g., compound libraries, peptide libraries, and the like) to identify antagonists or agonists of these marker polypeptides.
- agent banks e.g., compound libraries, peptide libraries, and the like
- Such M. tuberculosis and M. leprae marker polypeptide antagonists and agonists may modulate marker polypeptide activity and thereby modulate, inhibit, or even prevent infection of a host by M. tuberculosis and M. leprae
- yeast comprising (1) an expression cassette encoding a GAL4 DNA binding domain (or GAL4 activator domain) fused to a binding fragment of M. tuberculosis or M. leprae marker polypeptide, (2) an expression cassette encoding a GAL4 DNA activator domain (or GAL4 binding domain, respectively) fused to a binding fragment of a test polypeptide, and (3) a reporter gene (e.g., ⁇ -galactosidase) comprising a cis-linked GAL4 transcriptional response element can be used for agent screening.
- a reporter gene e.g., ⁇ -galactosidase
- Such yeast are incubated, and expression of the reporter gene (e.g., ⁇ -galactosidase) is determined by the capacity of the agent to affect expression of the reporter gene and thereby identify the test polypeptide as a candidate modulatory agent for M. tuberculosis or M. leprae marker polypeptides.
- the reporter gene e.g., ⁇ -galactosidase
- Yeast two-hybrid systems can be used to screen a mammalian (typically human) cDNA expression library, wherein cDNA is fused to a GAL4 DNA binding domain or activator domain, and either a M. tuberculosis or M. leprae marker polypeptide sequence is fused to a GAL4 activator domain or DNA binding domain, respectively.
- a yeast two-hybrid system can screen for cDNAs that encode proteins that interact with M. tuberculosis or M. leprae marker polypeptides.
- Polypeptides that interact with M. tuberculosis or M. leprae marker polypeptides can also be identified by immunoprecipitation of M. tuberculosis or M. leprae marker polypeptides with antibody, and identification of co-precipitating species. Further, polypeptides that interact with M. tuberculosis or M. leprae marker polypeptides can be identified by screening a peptide library (e.g., a bacteriophage peptide display library) with a M. tuberculosis or M. leprae marker polypeptide.
- a peptide library e.g., a bacteriophage peptide display library
- Additional embodiments of the invention are directed to methods that employ specific antisense polynucleotides complementary to all or part of M. tuberculosis or M. leprae marker nucleic acids.
- Such complementary antisense polynucleotides may include nucleotide substitutions, additions, deletions, or transpositions, so long as specific hybridization to the relevant target sequence corresponding to M. tuberculosis or M. leprae marker nucleic acids is retained as a functional property of the polynucleotide.
- Complementary antisense polynucleotides include soluble antisense RNA or DNA oligonucleotides that can hybridize specifically to M. tuberculosis and M.
- leprae marker nucleic acid species and prevent transcription of the mRNA species and/or translation of the encoded polypeptide. See (Ching et al. (1989) Proc. Natl. Acad. Sci. U.S.A. 86:10006; Broder et al. (1990) Ann. Int. Med. 113:604; Loreau et al. (1990) FEBS Letters 274:53; Holcenberg et al., WO91/11535; U.S. Ser. No. 07/530,165; WO91/09865; WO91/04753; WO90/13641; and EP 386563).
- the antisense polynucleotides therefore, inhibit production of M.
- Antisense polynucleotides that prevent transcription and/or translation of mRNA corresponding to M. tuberculosis or M. leprae marker polypeptides may inhibit or prevent infection by M. tuberculosis or M. leprae .
- Antisense polynucleotides of various lengths may be produced, although such antisense polynucleotides typically comprise a sequence of about at least 25 consecutive nucleotides, which are substantially identical to a naturally-occurring M. tuberculosis or M. leprae marker nucleic acids, and typically are identical to a M. tuberculosis or M. leprae marker nucleic acid.
- Antisense RNA and DNA (1988) D.A. Melton, Ed., Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.).
- Polypeptides with similar sequence should have similar function.
- the functions of M. tuberculosis and M. leprne marker polypeptides can be assessed by a database search.
- One method by which structural and functional domains can be identified is by comparison of the nucleotide and/or amino acid sequence data for M. tuberculosis and M. lepree marker polypeptides, or M. tuberculosis or M. leprae marker nucleic acids, to public or proprietary sequence databases.
- computerized comparison methods are used to identify sequence motifs or predict polypeptide conformation domains that occur in other polypeptides of known structure and/or function. For example, methods to identify protein sequences that fold into a known three-dimensional structure are known (Bowie et al. (1991) Science 253:164).
- the programs GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package can be used to identify sequences in databases, such as GenBank/EMBL, that have regions of homology with M. tuberculosis or M. leprae marker polypeptides or M. tuberculosis or M. leprae marker nucleic acids. Such homologous regions are candidate structural or functional domains. Alternatively, other algorithms are provided for identifying such domains from sequence data. Further, network methods, whether implemented in hardware or software, can be used to: (1) identify related protein sequences and nucleotide sequences, and (2) define structural or functional domains in M. tuberculosis and M. leprae marker polypeptides.
- Proteins can contain signals within their sequence which assist in their processing within the cell, for example leader sequences or signals which target proteins to specific compartments within cells. Web resources are available to help predict both these types of sites. Different regions of a polypeptide evolve at different rates; some parts of a polypeptide must retain a certain pattern of residues for the polypeptide to function. By identifying such conserved regions, it is possible to make predictions about the polypeptide function. Examples of conserved sequences can be found around the active sites of enzymes, sites of post-translational modification, binding sites for co-factors, protein sorting signals, etc. A number of bioinformatics resources have been developed both to build databases of conserved patterns and to search for instances of such patterns in sequences. One of the best known motif databases is PROSITE, which can be employed in this invention.
- the whole genome sequence was obtained from a combination of sequenced cosmids 45 and 54,000 end sequences (giving 7.1 ⁇ coverage) from a pUC18 genomic shotgun library using dye terminator chemistry on ABI373 or 377 automated sequencers
- the sequences of 42 cosmids previously generated by multiplex sequencing46 were used for scaffolding purposes only.
- the sequence was assembled using Phrap (P. Green, unpublished), finished using GAP4 47 then compared with sequences present in public databases using FASTA, BLASTN and BLASTX 48 .
- Potential CDS were predicted, and gene and protein sequences analysed as described previously 8, 49 , using Artemis 50 to collate data and facilitate annotation.
- tuberculosis H37Rv were compared pairwise to identify conserved genes using the Artemis Comparison Tool (ACT) (K. Rutherford; unpublished; http://www.sanger.ac.uk/Software/ACT/). Pseudogenes had one or more mutations that would ablate expression and were pinpointed by direct comparison with M. tuberculosis
- Preproteins transported by the TAT pathway generally bind redox cofactors and fold or oligomerize before crossing the membrane 54, 62 . After removal of the signal peptide, these proteins usually function in extracytoplasmic electron transfer chains.
- the specialized machinery that recognizes the twin-arginine motif, and translocates the preprotein across the membrane, is composed of several different Tat proteins. In Escherichia coli, TatA and TatE are 50% identical and share weak similarity with TatB.
- TatC protein is predicted to be an integral membrane protein with six transmembrane segments. M. tuberculosis and M. leprae both contain clearly identifiable tatA, tatB, tatC, and tatD genes and must, therefore, produce a functional Tat system.
- leprae in the face of massive gene loss, is a strong indication that it must play an important biological role. Given the many parallels with Tat systems elsewhere, it is likely to be in electron transport. These indirect arguments suggest on the one hand that, if this function were essential, the ML1190/Rv2525c gene product might represent a novel drug target or, on the other, since it is likely to be located extracellularly it may, therefore, be an important sentinel protein antigen.
- the Mycobacterium tuberculosis strain HRV37 genomic library has been deposited at the Collection Nationale de Cultures de Microorganismes (C.N.C.M.), of Institut Pasteur, 28, rue du Dondel Roux, F-75724 Paris, Cedex 15, France, on Nov. 19, 1997, under the Accession Number I-1945.
- This genomic DNA library is disclosed in International patent application No. WO 9954487 (Institut Pasteur).
- Leprosy a chronic human neurological disease, results from infection with the obligate intracellular pathogen Mycobacterium leprae , a close relative of the tubercle bacillus.
- M. leprae has the longest doubling time of all known bacteria and has thwarted every effort at axenic culture.
- Comparison of the 3.27 Mb genome sequence of an armadillo-derived Indian isolate of the leprosy bacillus with that of Mycobacterium tuberculosis (4.41 Mb) provides clear explanations for these properties and reveals an extreme case of reductive evolution. Less than half of the genome contains functional genes while pseudogenes, with intact counterparts in M. tuberculosis, abound.
- Genome downsizing and the current mosaic arrangement appear to have resulted from extensive recombination events between dispersed repetitive sequences.
- Gene deletion and decay have eliminated many important metabolic activities including siderophore production, part of the oxidative, and all of the microaerophilic and anaerobic respiratory chains, together with numerous catabolic systems and their regulatory circuits.
- tuberculosis proteins that are potential targets for the diagnosis, prophylaxis or treatment of mycobacterioses.
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Abstract
The present invention is directed to a method of selection of purified nucleotidic sequences or polynucleotides encoding proteins or part of proteins carrying at least an essential function for the survival or the virulence of mycobacterium species by a comparative genomic analysis of the sequence of the genome of M. tuberculosis aligned on the genome sequence of M. leprae and M. tuberculosis and M. leprae marker polypeptides of nucleotides encoding the polypeptides, and methods for using the nucleotides and the encoded polypeptides are disclosed.
Description
- This application is based on and claims the benefit of U.S. Provisional application Ser. No. 60/270,123, filed Feb. 22, 2001 (attorney docket no. 03495.6061) The entire disclosure of this application is relied upon and incorporated by reference herein.
- The present invention is directed to a method of selection of purified nucleotidic sequences or polynucleotides encoding proteins or part of proteins carrying at least an essential function for the survival or the virulence of mycobacterium species by a comparative genomic analysis of the sequence of the genome ofM. tuberculosis aligned on the genome sequence of M. leprae. The selection by the method of the invention of these nucleotidic or peptidic sequences of interest which are encoding said essential functions of mycobacterium leads to identify and characterize specific antigens or regulator sequences, said antigens being chosen as potential candidates for an immunogenic or vaccine composition, but also useful to determine novel potential drug targets for the pharmaceutical industry. The molecules having essential functions encoded by these genes or corresponding to regulatory elements represent also new highly specific targets for chemotherapy. The sequence of the polynucleotides according to the invention have the particularity to be maintained during the evolution of the mycobacterium and therefore have been highly conserved in pathogenic mycobacterium species. The invention is directed to purified nucleic acid selected by the method of the invention as well as the purified polypeptides with essential functions for the survival or the virulence of mycobacterium species encoded by these sequences. In a preferred embodiment, the invention is directed to genes that code for essential proteins for which the functions have been attributed. The invention is also directed to a process for the production of recombinant polypeptides and chimeric polypeptides comprising them, antibodies generated against these polypeptides, immunogenic or vaccine compositions comprising at least one polypeptide useful as protective antigens or capable to induce a protective response in vivo or in vitro against mycobacterium infections, immunotherapeutic compositions comprising at least such a polypeptide according to the invention, and the use of such nucleic acids and polypeptides in diagnostic methods, vaccines, kits, or antimicrobial therapy.
- To illustrate the new approach of comparative mycobacterial genomics for identifying essential molecules as regulator nucleotidic sequences and proteins for the survival or the virulence of mycobacterium species, the inventors made several examples which will not limit the scope of the present invention. A comparative genomic analysis, which permitted the inventors to select the sequences encoding essential molecules as regulatory nucleotidic sequences and proteins for the survival or the virulence of mycobacterium species, has been made by analysis of the complete genome sequence of bothMycobacterium tuberculosis and Mycobacterium leprae. The whole genome comparisons led also to the identification of genes that are present in both M. tuberculosis and M. leprae but have no counterparts elsewhere. The polypeptides having essential functions for the survival or the virulence mycobacterium species are characterized by at least 40% identity at the protein level and at least 70% identity at the gene level between both genomic sequences. The amino acid sequences have been compared using the program GAP, “GCG” (Genetic Computer Group) from Program Manual (UNIX), Wisconsin Sequence Analysis Package™, Algorithm of Needleman and Wunsch. (J.Mol.Biol.48:443, 1970) The parameters are chosen as follows:
- For amino acid comparisons:
- Gap penalty: 5
- Gap extension penalty: 0.30
- Length: the sequence to be compared are the following XXX SED ID NO:XXX and having XXX amino acids.
- For nucleotide comparisons:
- Gap penalty: 50
- Gap extension penalty: 3
- Also the parameters could be adapted case by case.
- Other techniques are known by the man of the art for the comparison of sequences. We can refer to the algorithm of Smith and Wateman (Ad. App. Math. 2: 482, 1982), the method of search of similarities of Pearson and Lipman (Proc. NatI. Acad. Sci. USA 85: 2444, 1988), Zhang et al. “a greedy algorithm for aligning DNA sequences” (J. Comp. Biol. 2000, Feb-Apr. 7 (1-2) p203-214), these algorithms are used by the way of informatic tools (GAP, BLASTP, BLASTN, BLASTX, BESTFIT, FASTA and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Sciences Dr., Madison Wis.).
- The recombinant clones carrying DNA fromMycobacterium tuberculosis and Mycobacterium leprae strains containing genomic sequences of said bacteria, have been deposited at the Collection Nationale de Cultures de Microoganismes (C.N.C.M.), of Institut Pasteur, 28, rue du Docteur Roux, F-75724 Paris cedex 15, France, and are designated as following.
- HRV37 genomic library, deposited on Nov. 19, 1997 . . . under the accession number I-1945;
- A recombinant BAC containing a fragment ofM. tuberculosis genome deposited at the C.N.C.M. under the accession number I-2625.
- A recombinant BAC containing a fragment ofM. tuberculosis genome deposited on Feb. 20, 2001, at the C.N.C.M. under the accession number I-2626.
- A recombinant BAC containing a fragment ofM. tuberculosis genome deposited on Feb. 20, 2001, at the C.N.C.M. under the accession number I-2627.
- A recombinant BAC containing a fragment ofM. tuberculosis genome deposited on Feb. 20, 2001, at the C.N.C.M. under the accession number I-2628.
- A recombinant BAC containing a fragment ofM. tuberculosis genome deposited on Feb. 20, 2001, at the C.N.C.M. under the accession number I-2629.
- A recombinant cosmid containing a fragment ofM. leprae genome deposited on Feb. 21, 2001, at the C.N.C.M. under the accession number I-2632.
- A recombinant cosmid containing a fragment ofM. leprae genome deposited on Feb. 21, 2001, at the C.N.C.M. under the accession number I-2633.
- Leprosy, one of the oldest recorded diseases, remains a major public health problem. Although prevalence has been reduced extensively by WHO multidrug therapy and vaccination with BCG1,2, the incidence of the disease remains worrying with more than 690,000 new cases annually3 in the world. Leprosy was common in Europe in the middle ages but gradually disappeared.
- In 1873, in the first convincing association of a microorganism with a human disease, Armauer Hansen4 discovered the leprosy bacillus in skin biopsies but failed to cultureMycobacterium leprae. A century later, the nine-banded armadillo5 was used as a surrogate host, enabling large quantities of the bacillus to be isolated for biochemical and physiological studies. Subsequent efforts to demonstrate multiplication in synthetic media have been equally fruitless altough metabolic activity can be detected6. The exceptionally slow growth of the bacillus, which has a doubling time of ˜14
days 7, may contribute to these failures. - The means of transmission of leprosy is uncertain but, like tuberculosis, it is believed to be spread by the respiratory route since lepromatous patients harbour bacilli in their nasal passages. The bacterium accumulates principally in the extremities of the body where it resides with macrophages and infects the Schwann cells of the peripheral nervous system. Lack of myelin production by infected Schwann cells, and their desctruction by host-mediated immune reactions, leads to nerve damage, sensory loss and the disfiguration that, sadly, are hallmarks of leprosy.
- There is no data or technical information in the prior art which permit to select specifically potential new targets and protective antigens for new drugs and vaccine compositions to treat and prevent mycobacterial diseases, particularly tuberculosis and leprosy. Furthermore, there is a need for the development of new tools for the selection of genes which are encoding for essential proteins or regulatory nucleotidic sequences in the survival or infection of mycobacterium species and useful for the design of antituberculosis drugs and vaccines based on the knowledge of comparative mycobactertial genomics.
- The invention aids in fulfilling these needs in the art. The method according to the invention has the advantage to reduce drastically the number of potential new targets and protective antigens by giving for the first time an exhaustive description of conserved proteins in thetuberculosis and leprae bacilli. The isolated polynucleotides and proteins described in the present invention, which are highly conserved in both genomic sequences of M. tuberculosis and M. leprae, are by this characteristic essential for the survival or the virulence of these mycobacteria in the host. The identification of antigens and potentially therapeutic targets has been made on an evolutionary basis by a method of comparative genomic analysis.
- This invention provides a method for the identification and the selection of essential genes for the survival or the virulence of mycobacterium species which comprises:
- a. Aligning the genomic sequence of a first mycobacterium species on a genomic sequence of the genomic sequence of a second mycobacterium species,
- b. Selecting a polypolynucleotide sequence highly conserved in both genomes with no counterparts in other bacterial genomic sequences and which corresponds to an essential gene for the survival or the virulence of mycobacterium species, and
- c. Optionaly, testing the polypolynucleotide selected in step b) for its capacity of virulence or involved in the survival of a mycobacterium species, said testing being based on the activation or inactivation of said polyucleotide in a bacterial host or said testing being based on the activity of the product of expression of said polynucleotide in vivo or in vitro.
- This invention provides also a method for the identification and the selection in silico of essential genes for the survival or the virulence of mycobacterium species which comprises the following steps:
- a. Aligning the genomic sequence of a first mycobacterium specie on a genomic sequence of the genomic sequence of a second mycobacterium specie, and
- b. Selecting a polynucleotide sequence highly conserved in both genomes with no counterparts in other bacterial genomic sequences and which corresponds to an essential gene for the survival or the virulence of mycobacterium species.
- Optionally, testing the polypolynucleotide selected in step b) for its capacity of virulence or involved in the survival of a mycobacterium species can be carried out, said testing being based on the activation or inactivation of said polynucleotide in a bacterial host or said testing being based on the activity of the product of expression of said polynucleotide in vivo or in vitro.
- The method according to the invention permits also to determine the polynucleotidic sequences, which encode for polypeptides and regulatory sequences essential for the virulence and/or the survival of mycobacterium which are, in one hand, specific toMycobacterium tuberculosis and, in the other hand, specific to Mycobacterium leprae, that is to say, said polynucleotidic sequences are not found in publicly accessible banks of non-Mycobacterium tuberculosis and non-Mycobacterium leprae genome.
- A gene according to the invention is a defined nucleotidic sequence, which contains an open reading frame with base composition, codon usage, GC skew and other features typical of a microorganism, preferably a mycobacterium. The definition of gene according to the invention comprises nucleotidic sequences, which encode an antigen or a fragment thereof, or nucleotidic sequences, which encode for essential polypeptide with essential function in the host, or nucleotidic sequence, which encodes polypeptide with regulation function in the bacteria, by example, in the DNA expression or in the transcription. An essential function for a polypeptide in bacteria according to the invention comprises functions implicated in the survival or in the virulence of the bacteria.
- In a preferred embodiment the first genomic sequence of mycobacterium belongs toMycobacterium tuberculosis. The Mycobacterium microti is a Mycobacterium which infect the vole. It has a genome sequence close to the sequence of Mycobacterium tuberculosis (Cole et al. (1998, Nature, 393, 537-544)) and therefore in a second preferred embodiment, the first genomic sequence of Mycobacterium microti belongs to Mycobacterium genus.
- In another preferred embodiment the second genomic sequence of mycobacterium belongs toMycobacterium leprae.
- In a preferred embodiment, the method according to the invention comprises the complete genomic sequence of said mycobacterium species which is analysed. This invention provides purified polypolynucleotide molecule obtained by the method according to the invention.
- Further, this invention provides a purified polynucleotide molecule according to the invention which encodes essential proteins or fragments of proteins of Mycobacterium species.
- The invention also encompasses a purified polynucleotide molecule of a formula selected from the group consisting of polynucleotidic sequences, which encode for polypeptides and regulatory sequences essential for the virulence and/or the survival of mycobacterium which are, in one hand, specific toMycobacterium tuberculosis and, in the other hand, specific to Mycobacterium leprae, that is to say, said polynucleotidic sequences are not found in publicly accessible banks of non-Mycobacterium tuberculosis and non-Mycobacterium leprae genome. In a preferred embodiment, this purified polynucleotide is obtained by the method according to the invention.
- The invention emcompasses a purified polypolynucleotide molecule that hybridizes to either stand of a denatured, double-stranded DNA comprising the purified polynucleotide sequence according to the invention under conditions of moderate stringency in 50% formamide and 6× SSC at 42° C. with washing conditions of 60° C., 0.5×SSC, 0.1% SDS.
- This invention provides a purified polypeptide of a formula selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 644.
- This invention also provides a purified nucleic acid molecule encoding a polypeptide of a formula selected from the group consisting of SEQ ID NO:1 to SEQ ID NO:644.
- The nucleic acid molecules of the invention, which include DNA and RNA, are referred to herein as “M. tuberculosis and M. leprae marker nucleic acids” or “M. tuberculosis and M. leprae marker DNA”. The polypeptides encoded by these molecules, which are referred to herein as “M. tuberculosis and M. Ieprae marker polypeptides,” have formulas selected from the group consisting of SEQ ID NO:1 to SEQ ID NO:644.
- Further, this invention provides a purified nucleic acid molecule that hybridizes to either strand of a denatured, double-stranded DNA comprising the nucleic acid molecule encoding the polypeptide of a formula selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO:644 under conditions of moderate stringency in 50% formamide and 6× SSC, at 42° C. with washing conditions of 60° C., 0.5×SSC, 0.1% SDS. This nucleic acid molecule that hybridizes under the stated conditions can be derived by in vitro mutagenesis of aM. tuberculosis and M. leprae marker nucleic acid of the invention.
- The invention also encompasses purified nucleic acid molecules degenerate fromM. tuberculosis and M. leprae marker nucleic acids as a result of the genetic code, purified nucleic acid molecules that are allelic variants of M. tuberculosis and M. leprae marker nucleic acids, and a species homolog of M. tuberculosis and M. leprae marker nucleic acids. The invention also encompasses recombinant vectors that direct the expression of these nucleic acid molecules and host cells transformed or transfected with these vectors.
- The invention further encompasses methods for the production ofM. tuberculosis and M. leprae marker polypeptides, including culturing a host cell under conditions promoting expression, and recovering the polypeptide from the culture medium. Especially, the expression of M. tuberculosis and M. leprae marker polypeptides in bacteria, yeast, plant, and animal cells is encompassed by the invention.
- This invention also provides labeledM. tuberculosis and M. leprae marker polypeptides. Preferably, the labeled polypeptides are in purified form. It is also preferred that the unlabeled or labeled polypeptide is capable of being immunologically recognized by human body fluid containing antibodies to a mycobacterium. The polypeptides can be labeled, for example, with an immunoassay label selected from the group consisting of radioactive, enzymatic, fluorescent, chemiluminescent labels, and chromophores.
- Immunological complexes between theM. tuberculosis and M. leprae marker polypeptides of the invention and antibodies recognizing the polypeptides are also provided. The immunological complexes can be labeled with an immunoassay label selected from the group consisting of radioactive, enzymatic, fluorescent, chemiluminescent labels, and chromophores.
- Furthermore, this invention provides a method for detecting infection by mycobacteria. The method comprises providing a composition comprising a biological material suspected of being infected with a mycobacteria, and assaying for the presence ofM. tuberculosis and M. leprae marker polypeptide of the mycobacteria. The polypeptides are typically assayed by electrophoresis or by immunoassay with antibodies that are immunologically reactive with M. tuberculosis and M. leprae marker polypeptides of the invention.
- This invention also provides an in vitro diagnostic method for the detection of the presence or absence of antibodies, which bind to an antigen comprising aM. tuberculosis and M. leprae marker polypeptide of the invention or mixtures of the polypeptides. The method comprises contacting the antigen with a biological fluid for a time and under conditions sufficient for the antigen and antibodies in the biological fluid to form an antigen-antibody complex, and then detecting the formation of the complex. The detection step can further comprise measuring the formation of the antigen-antibody complex. The formation of the antigen-antibody complex is preferably measured by immunoassay based on Western blot technique, ELISA (enzyme linked immunosorbent assay), indirect immunofluorescent assay, or immunoprecipitation assay.
- The polypeptides of this invention are thus useful as a portion of a diagnostic composition for detecting the presence of antibodies to antigenic proteins associated with mycobacteria. Thus, a diagnostic kit for the detection of the presence or absence of antibodies, which bind to theM. tuberculosis and M. leprae marker polypeptide of the invention or mixtures of the polypeptides, contains antigen comprising the M. tuberculosis and M. leprae marker polypeptide, or mixtures thereof, and means for detecting the formation of immune complex between the antigen and antibodies. The antigens and the means are present in an amount sufficient to perform the detection.
- This invention also provides an immunogenic composition comprising aM. tuberculosis and M. leprae marker polypeptide of the invention or a mixture thereof in an amount sufficient to induce an immunogenic or protective response in vivo, in association with a pharmaceutically acceptable carrier therefor. A vaccine composition of the invention comprises a neutralizing amount of the M. tuberculosis and M. leprae marker polypeptide and a pharmaceutically acceptable carrier therefor.
- In addition, theM. tuberculosis and M. leprae marker polypeptides can be used to raise antibodies for detecting the presence of antigenic proteins associated with a mycobacterium. Purified polyclonal or monoclonal antibodies that bind to M. tuberculosis and M. leprae marker polypeptides are encompassed by the invention.
- The polypeptides of the invention can be also employed to raise neutralizing antibodies that either inactivate the mycobacteria, reduce the viability of a mycobacterium in vivo, or inhibit or prevent bacterial replication. The ability to elicit mycobacteria-neutralizing antibodies is especially important when the proteins and polypeptides of the invention are used in immunizing or vaccinating compositions to activate the B-cell arm of the immune response or induce a cytotoxic T lymphocyte response (CTL) in the recipient host, or other T cell mediated response.
- Further, this invention provides a method for detecting the presence or absence of a mycobacterium comprising:
- (1) contacting a sample suspected of containing bacterial genetic material of a mycobacterium with at least one nucleotide probe, and
- (2) detecting hybridization between the nucleotide probe and the bacterial genetic material in the sample,
- wherein said nucleotide probe is complementary to the full-length sequence of a purifiedM. tuberculosis and M. leprae marker nucleic acid of the invention.
- Also, this invention provides a method of comparing genetic complements of different types of organisms, wherein the method comprises:
- (a) providing a database including sequence libraries for a plurality of types of organisms, said libraries having multiple genomic sequences;
- (b) providing one or more probe sequences encoding a polypeptide of a formula selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO:644;
- (c) determining homologous matches between one or more of said probe sequences and one or more sequences of said sequences in said genomic libraries; and
- (d) displaying the results of said determination.
- The method can be carried out using a computer system comprising a database including sequence libraries for a plurality of types of organisms, wherein the libraries have multiple genomic sequences, and providing a database including the one or more probe sequences encoding a polypeptide of a formula selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO:644. The computer system includes a user interface capable of receiving sequence information from the sequence libraries and the probe sequence information for comparison and displaying the results of the comparison.
- The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawings will be provided by the Office upon request and payment of the necessary fee. This invention will be described with reference to the drawings in which:
- FIG. 1 is a circular genome map. From the outside, circles1, 2, clockwise and anticlockwise, genes on the − and + strands, respectively; circles 3 and 4, pseudogenes; 5 and 6, M. leprae specific genes; 7, repeat sequences; 8, G+C content; 9, G/C bias (G+C)/(G−C). See legend to FIG. 2 for colour code.
- FIG. 2 is a comparison of the pros loci ofM. leprae and M. tuberculosis . A. The M. Ieprae pros region is shown above that of M. tuberculosis. Genes or operons are depicted by arrows while crosses denote pseudogenes. Note the absence of ugpAEBC and dinF from M. leprae and the presence of pros at this site. B. Domain structures of prolyl-tRNA synthetases of bacterial (M. tuberculosis ) or eukaryotic (M. leprae ) types after19.
- FIG. 3 shows distribution of genes by functional category. The number of complete (blue) and pseudogenes (red) within each category forM. leprae is shown. Data for M. tuberculosis (green) were taken from the published genome sequence8. Functional categories: 1. Small-molecule catabolism, 2. Energy Metabolism, 3. Central intermediary metabolism, 4. Amino acid biosynthesis, 5. Nucleosides and nucleotide biosynthesis and metabolism, 6. Biosynthesis of cofactors, prosthetic groups and carriers, 7. Lipid biosynthesis, 8. Polyketide and nonribosomal peptide synthesis, 9. Proteins performing regulatory functions, 10. Synthesis and modification of macromolecules, 11. Degradation of macromolecules, 12. Cell envelope constituents, 13. Transport/binding proteins, 14. Chaperones/Heat shock proteins, 15. Cell division proteins, 16. Protein and peptide secretion, 17. Adaptations and atypical conditions, 18. Detoxification, 19. Virulence determinants, 20. IS elements and phage derived proteins, 21. PE and PPE families, 22. Antibiotic production and resistance, 23. Cytochrome P450 enzymes, 24. Coenzyme F420-dependent enzymes, 25. Miscellaneous transferases, 26. Miscellaneous phosphatases, lyases and hydrolases, 27. Cyclases, and 28. Chelatases. Inset graph: The Y axis shows the number of genes within each functional category. The X axis shows the functional categories: 29. Conserved hypothetical proteins, 30. Hypothetical proteins which share no significant similarity with any protein currently in the databases.
- FIG. 4: Polynucleotidic sequence of theMycobacterium tuberculosis H37Rv BAC clone, BAC-Rv221, deposited at the C.N.C.M. under the accession number I-2625, which corresponds to pBelo BACII with HindIII partial digest fragment from the genome of M. tuberculosis H37 Rv that starts at position 2,115,612 and extends to position 2,198,604 according to Cole et al. (1998, Nature, 393, 537-544). All of the M. tuberculosis genes contained herein are of interest.
- FIG. 5: Polynucleotidic sequence of theMycobacterium tuberculosis H37Rv BAC clone, BAC-Rv230, deposited at the C.N.C.M. under the accession number I-2626, which corresponds to pBelo BACII with HindIII partial digest fragment from the genome of M. tuberculosis H37 Rv that starts at position 1,336,764 and extends to position 1,411,979 according to Cole et al. (1998, Nature, 393, 537-544). All of the M. tuberculosis genes contained herein are of interest.
- FIG. 6: Polynucleotidic sequence of theMycobacterium tuberculosis H37Rv BAC clone, BAC-Rv234, deposited at the C.N.C.M. under the accession number I-2627, which corresponds to pBelo BACII with HindIII partial digest fragment from the genome of M. tuberculosis H37 Rv that starts at position 2,847,864 and extends to position 2,928,420 according to Cole et al. (1998, Nature, 393, 537-544). All of the M. tuberculosis genes contained herein are of interest.
- FIG. 7: Polynucleotidic sequence of theMycobacterium tuberculosis H37Rv BAC clone, BAC-Rv265, deposited at the C.N.C.M. under the accession number I-2628, which corresponds to pBelo BACII with Hindlul partial digest fragment from the genome of M. tuberculosis H37 Rv that starts at position 514,402 and extends to position 599,515 according to Cole et al. (1998, Nature, 393, 537-544). All of the M. tuberculosis genes contained herein are of interest.
- FIG. 8: Polynucleotidic sequence of theMycobacterium tuberculosis H37Rv BAC clone, BAC-Rv267, deposited at the C.N.C.M. under the accession number I-2629, which corresponds to pBelo BACII with HindIII partial digest fragment from the genome of M. tuberculosis H37 Rv that starts at position 1,124,621 and extends to position 1,169,811 according to Cole et al. (1998, Nature, 393, 537-544). All of the M. tuberculosis genes contained herein are of interest.
- FIG. 9: Polynucleotidic sequence of theMycobacterium leprae cosmid which corresponds to pYUB18 with Sau3A partial digest fragment from the genome of M. leprae that starts at position 1,373,705 and extends to position 1,403,746. This sequence comprises the sequence of the Mycobacterium leprae cosmid MLCY 811 which corresponds to pYUB18 with Sau3A partial digest fragment of the genome of M. leprae deposited at the C.N.C.M. under the accession number I-2633 that starts at position 1,363,759 and extends to position 1,403,737 according to Cole et al. (2001, Nature, 409, 1007-1011).
- FIG. 10: Polynucleotidic sequence of theMycobacterium leprae cosmid which corresponds to pYUB18 with Sau3A partial digest fragment of the genome of M. leprae that starts at position 3,160,443 and extends to position 3,194,161. This sequence comprises the sequence of the Mycobacterium leprae cosmid MLCY 047 which corresponds to pYUB18 with Sau3A partial digest fragment of the genome of M. leprae deposited at the C.N.C.M. under the accession number I-2632 that starts at position 3,160,458 and extends to position 3,194,087 according to Cole et al. (2001, Nature, 409, 1007-1011).
- FIG. 4 to10 can be found in the APPENDIX hereto.
- The complete genome sequence ofM. leprae contains 3,268,203 bp, and has an average G+C content of 57.8%. These values are much lower than those reported for the M. tuberculosis genome, comprising ˜4,000 genes, 4,411,529 bp and 65.6% G+C8. On detailed pairwise comparisons of both genome and proteome sequences8, 9, it was immediately apparent that only 49.5% of the genome was occupied by protein-coding genes, while 27% contained recognisable pseudogenes, inactive reading frames with functional counterparts in the tubercle bacillus. The remaining 23.5% of the genome did not appear to be coding, and probably contains gene remnants mutated beyond recognition. The distribution of the 1,114 pseudogenes was essentially random (FIG. 1) and, after their exclusion, 1604 potentially active genes remained, of which 1,439 were common to both pathogens. Among the remaining 165 genes, with no ortholog in M. tuberculosis , were 29 for which functions could be attributed. Many of the 136 residual CDS in M. leprae , showing no similarity to known genes, may also represent pseudogenes as they are shorter than average and occur in regions of low gene density (FIGS. 1).
- Assuming that the genome ofM. leprae was once topologically equivalent and similar in size to those of all other mycobacteria (˜4.4 Mb)10-12, then extensive downsizing and rearrangement must have occurred during evolution. Loss of 1.1 Mb would eliminate ˜1100 CDS, and M. leprae would, therefore, be expected to produce 3000 proteins compared to the 4000 predicted in M. tuberculosis. On analysis of the proteome only 391 soluble protein species were detected13, compared to nearly 1800 in M. tuberculosis 4, consistent with there being many pseudogenes. In conclusion, since diverging from the last common mycobacterial ancestor, the leprosy bacillus may have lost >2000 genes.
- Reductive evolution is documented in obligate intracellular parasites, such as Rickettsia and Chlamydia spp., and in some endosymbionts15, as genes become inactivated once their functions are no longer required in highly specialised niches. This process may have naturally defined the minimal gene set for a pathogenic mycobacterium. The most extensive genome degradation reported previously was in Rickettsia prowazekii, the typhus agent, where only 76% of the potential coding capacity was used and 12 pseudogenes identified16. In comparison with M. leprae, the level of gene loss detected was modest, and it is striking that elimination of pseudogenes by deletion lags far behind gene inactivation in both pathogens. Intriguingly, the G+C content of M. leprae genes (60.1%) is higher than that of the pseudogenes (56.5%), and the remainder of the genome (54.5%). The high G+C content of M. leprae, and other mycobacteria, is apparently driven by the codon preference of active genes, while random mutation within non-coding regions results in drift towards a more neutral G+C content, closer to that of the host.
- While the precise mechanism behind pseudogene formation inM. leprae is unclear, loss of dnaQ-mediated proof-reading activities of DNA polymerase III17 may have contributed. By contrast, there is extensive evidence for large scale rearrangements and deletions arising from homologous recombination events. Comparison with M. tuberculosis delineated ˜65 segments that show synteny but differ in their relative order and distribution in the M. leprae genome. Breaks in synteny generally correspond to dispersed repeats, tRNA genes or gene-poor regions. Copies of all three repeats, RLEP, REPLEP, and LEPREP, occur at the junctions of discontinuity suggesting that the mosaic arrangement of the M. leprae genome reflects multiple recombination events between related repetitive sequences. In some cases, aberrant recombination may have occurred as truncated repeats exist.
- While there is little sequence similarity indicating that they are insertion sequences, RLEP is clearly capable of transposition since it exists within sequences corresponding to known genes. UnlikeM. tuberculosis H37Rv, which contains at least two prophages and 56 intact or truncated IS elements8, 18, M. leprae has only three phage-like genes, all with M. tuberculosis orthologs, and 26 transposase gene fragments. However, some signs of horizontal transfer of genetic material were detected when the aminoacyl-tRNA synthetase genes were examined. With one exception, all of these are more closely related to M. tuberculosis enzymes than to those of any other organism. Surprisingly, prolyl-tRNA synthetase, encoded by proS, is more similar to the enzymes of Borrelia burgdorfieri and eukaryotes such as Drosophila, humans and yeast. It has been proposed that horizontal transfer of tRNA synthetase genes occurs frequently, and that the pathogen B. burgdorferi may have acquired proS from its host19. Comparison of the genetic context provides further support for this hypothesis as the M. leprae proS is both displaced and inverted with respect to the M. tuberculosis genome (FIG. 4), consistent with recent acquisition.
- Half of the genes (52%) present inM. tuberculosis arose from gene duplication events leading to extensive functional redundancy9. Many of these are involved in lipid metabolism or belong to the novel PE and PPE families, encoding unusual glycine-rich proteins of repetitive structure and unknown function. The latter are confined to certain mycobacterial species20, and represent sources of genetic and, possibly antigenic, variation8. The corresponding 167 genes are exceptionally GC-rich and occupy >8% of the M. tuberculosis genome21. By contrast, only 9 intact PE and PPE genes were found in M. leprae although 30 pseudogenes were present. No intact members of the PE-PGRS subfamily were found. This reduction partly contributes to the smaller genome size and the lower GC content of M. leprae . Recently, some PE-PGRS proteins were shown to be upregulated in Mycobacterium marinum during granuloma formation in frogs22. However, this effect is probably not mediated directly by the PE-PGRS, as granulomas are a prominent cytological feature of all forms of leprosy. Essentially all of the gene families9 have undergone extensive retraction in M. leprae and now encode “just-enough” activity to permit intracellular growth. Selected examples of this are given in Table 1, whereas the comprehensive comparison presented in FIG. 3 shows that all functional categories have shrunk.
TABLE 1 Selected examples of metabolic streamlining. M. tuberculosis M. leprae M. leprae Function Pathway Gene Gene Pseudogene gitA1, gltA2, gltA2 citA Citrate synthase Krebs cycle cit, 4 icd1, icd2 icd2 icd1 Isocitrate Krebs cycle dehydrogenase ic1, aceA aceA ic1 Isocitrate lyase Glyoxy- latecycle gnd1, gnd2 gnd1 qnd2 6- Pentose phosphogluconated phosphate ehydrogenase pathway pfkA, pjkB pfkA pfkB Phospho- Glycolysis fructokinase aceE, lpdA, aceE, lpd lpdA, pdhA, Pyruvate, Energy pdhA, pdhB, (Rv0462) pdhB, pdhC dehydrogenase metabolism pdhC, lpd complex (Rv0462) lldD1, lldD2 lldD2 lldD1 L-lactate Respiration dehydrogenase mmaA1, mmaA2, mmaA1, mmaA2, Methyltransferase Mycolic acid mmaA3, mmaA4, mmaA4, nmaA3, modification cmaA1, cmaA2, cmaA2, umaA2 cmaA1, umaA1 umaAl, umaA2 glnA1, glnA2, glnA1, glnA2 glnA3, glnA4 Glutamine Glutamine glnA3, glnA4 synthase biosynthesis metA, metB, met4, metB, metC Various Methionine metC, metE, metE, biosynthesis metH, metK, metZ metH, metK, metZ bfrA, bfrB bfrA bfrB Bacterioferritin Iron storage ligA, 11gB, ligC ligA 1igB DNA ligase DNA metabolism - Successive generations of microbiologists have failed to growM. leprae in axenic culture leading to the notion that the bacterium lacks certain biosynthetic pathways. Complete genome comparisons shed new light on this. Lipid metabolism is prominent in the biochemical repertoire of M. leprae but to a lesser extent than in the tubercle bacillus whose cell envelope has a greater diversity of lipids, glycolipids and carbohydrates23.
- Mycolic acids, structural components of all mycobacteria, include the alpha mycolates, lacking oxygen functions, and the oxygenated keto- and methoxy- forms. Reappraisal of mycolic acid modification is now possible in the light of the reduced cmaA, mmaA and umaA gene-sets encoding the effector methyltransferases.M. Ieprae contains no methoxy-mycolates23, probably due to the loss of the MmaA2 and MmaA3 enzymes that attach the methoxy group in M. tuberculosis 10, 24. However, the mycolic acids do contain cyclopropane functions25 that in M. tuberculosis are introduced by MmaA2 and CmaAI. Since both the mmaA2 and cmaA1 genes have decayed in M. leprae , cyclopropanation must be encoded by one of the related umaA genes. Recently, both umaA2 and cmaA2 were shown to be essential for the cyclopropanation function in M. tuberculosis 26, The same enzymes also catalyse cyclopropanation in M. leprae as their duplicate copies are both inactive (Table 1).
- Foremost among the outer lipids of the leprosy bacillus is phenolic glycolipid 1 (PGL1), an envelope component not found inM. tuberculosis 27. PGL1 is derived from phthiocerol-dimycocerosate (PDIM), an esterified compound lipid generated by mycocerosic acid synthase and a type I polyketide synthase (PKS), by addition of three o-methylated deoxy sugars23. However, the genes for the glycosyltransferases, that modify PDIM to produce PGLI, could not be detected despite extensive comparisons. PDIM, a virulence factor in M. tuberculosis, requires the RND protein, MmpL7, for its transport across the cytoplasmic membrane9,28,29. Of the 18 PKS systems identifiable in M. tuberculosis 8, only six were predicted in M. leprae and the number of mmpL genes (often linked to PKS genes) has decreased from 16 to five, presumably because they are no longer required for polyketide or lipid export. Deletion of such systems may be reflected in the lack of mycolipenic and hydroxylipenic acids, polyketides esterified to trehalose in M. tuberculosis. Further PKS missing from M. leprae include the mbt operon required for production of the salicylate-based mycobactin siderophores. Lipids, polyketides and aromatic compounds are often substrates, for cytochrome-P450 monooxygenases30, enzymes that are exceptionally abundant in M. tuberculosis 8. Astonishingly, none of these is functional in M. leprae although a novel enzyme is predicted.
- Intracellular mycobacteria probably derive much of their energy from degradation of host-derived lipids31, a process initiated by lipases. In remarkable contrast to the 22 lip genes of M. tuberculosis, M. Ieprae has only two lipase genes, of which, lipG, clusters with mmaA genes and could, therefore, effect fatty acid remodelling. This appears to leave just one lipase for scavenging fatty acids. The enzyme LipE (ML1190) or its counterpart in M. tuberculosis (Rv3775) could represent an attractive drug target. In addition to the multifunctional FadA and FadB enzymes, which catalyse β-oxidation, M. tuberculosis has numerous alternative systems for fatty acid degradation8. Once again, M. leprae has roughly one third as many potential enzymes; however, there are three-times more FadD acyl-CoA synthases than FadE acyl-CoA dehydrogenases, whereas these are expected in equal amounts in M. tuberculosis. This may be explained by the dual role of FadD in β-oxidative and anabolic processes while FadE only participates catabolically.
- The acetyl-CoA produced by β-oxidation, or glycolysis, flows into the central pathways of carbon metabolism inM. leprae . However, the pattern of “just enough” genes for each step is firmly established, so that the redundancy seen in M. tuberculosis almost never occurs. For instance, there is only one isocitrate lyase (with low predicted activity) capable of participating in the glyoxylate shunt (Table 1)32, 33, and one enzyme complex that oxidatively decarboxylates pyruvate to acetyl-CoA, compared to two such systems in M. tuberculosis. In the Krebs cycle, as in glycolysis, replicate genes for the same activity are deleted although differences in expression levels might compensate for some missing copies. Thus, while lack of pdh genes is reflected in a low rate of oxidative decarboxylation of pyruvate, isocitrate dehydrogenase activity is comparable in host-grown leprosy and tubercle bacilli34 even though a duplicate icd gene is inactivated in M. leprae.
- Despite an active glyoxylate cycle, there appear to be fundamental differences elsewhere in anaplerotic pathways betweenM. leprae and M. tuberculosis. Here, phospho-enol-pyruvate (PEP) carboxylase replaces the pyruvate carboxylase of M. tuberculosis, and the malic enzyme, associated with fast growth in mycobacteria35, is missing. The metabolic implications are that flux between C3 and C4 compounds and the balance between glycolysis and gluconeogenesis will be very different. Another missing link between by-products of lipid metabolism and the Krebs cycle is the production of succinyl-CoA by catabolic Acc carboxylases predicted for M. tuberculosis 8. Other carbon sources lost to M. leprae are acetate, as ackA, pta and acs are all inactive, and galactose, so the cell wall galactan can only be produced from glucose since the galK, T genes are missing. This might imply that M. leprae is limited to growth on very few carbon sources, or even a limited and rather specialised combination, on which it can maintain a balanced carbon metabolism. Though a similar range of potential substrates is available to both M. leprae and M. tuberculosis in the host, marked differences in their ability to exploit them are apparent on examination of the systems involved in carbon and nitrogen compound degradation: there are fewer oxidoreductases, oxygenases and short-chain alcohol dehydrogenases, and their probable regulatory genes, (FIG. 3). The inescapable conclusion is that catabolism in M. leprae is severely limited.
- In the same vein, the leprosy bacillus has lost anaerobic and microacrophilic electron transfer systems, such as formate dehydrogenase, nitrate, and fumarate reductase together with the biosynthetic and transport systems required to produce the cognate prosthetic groups. Likewise, the aerobic respiratory chain ofM. leprae is truncated as only the 3′-end of the NADH oxidase operon, nuoA-N, remains. The consequences of this event are far-reaching, for not only has the potential to produce ATP from the oxidation of NADH been lost, but also regeneration of NAD+ may be limited, relying heavily on ndh, which is involved only in recycling NAD+. Alternatively, M. leprae may regenerate NAD+ from NADH by (1) diverting pyruvate to acetate and CO2 using lactate dehydrogenase and lactate oxidase; (2) diverting PEP to malate or fumarate via oxaloacetate, using its PEP carboxylase (an enzyme not found in the tubercle bacillus) that only catalyses the reaction in this direction. Given the loss of genes reviewed above, the acids produced by (1) and (2) cannot be recycled and must be excreted.
- In surprising contrast, all the anabolic pathways seem to be relatively intact. With few exceptions, complete enzyme systems are predicted for synthesis of amino acids, purines, pyrimidines, nucleosides, nucleotides, most vitamins and cofactors. This suggests that the availability of these metabolites in phagosomes is either highly limited or thatM. leprae cannot transport them efficiently. It also sets the biology of the leprosy bacillus apart from that of the other obligate parasites for which genomes have been sequenced15, 16. M., leprae may, however, be auxotrophic for methionine as metC, encoding cystathionine β-lyase, is a pseudogene, whereas the other counterparts of M. tuberculosis met genes are all intact. This requirement for methionine may be dictated by the inactivation of the sulphate transport operon, cysYWA, and in turn this implies that M. leprae depends upon an organic source of sulphur. A second auxotrophy that is predicted is for cobinamide, as examination of the cob genes shows selective deletion of those to make cobinamide, while the genes needed to produce vitamin B12 from cobinamide are retained.
- Central to a successful pathogenic lifestyle is the ability to obtain iron.M. leprae has many genes for haem and iron-based proteins and employs the iron regulatory systems, ideR and furB, yet may be severely handicapped compared to M. tuberculosis as it appears to have lost the mbt operon, encoding the non-ribosomal peptide synthase required for production of the iron-scavenging siderophores, mycobactin/exochelin8, 36, 37. However, part of the iron uptake system is functional in M. leprae, as it transports exochelinMN, from M. neoaurum but not those of M. smegmatis or M. tuberculosis 38. The genes for exochelinMN are unknown and seem unlikely to occur in M. leprae.
- As might be expected given the differences in their respective pathologies,M. leprae contains several enzymes that have no counterparts in the tubercle bacillus, including a eukaryotic-like uridine phosphorylase and adenylate cyclase. In addition, there are two transport systems that may play significant physiological roles: an ABC-transporter for sugars, and a second member of the Nrampl family, involved in divalent metal ion uptake. M. leprae may have acquired another Nrampl gene39 to ensure adequate intracellular iron concentrations resulting from its lack of mycobactin siderophores.
-
- Comparative genomics is a powerful new tool for exploring micobial evolution and identifying those genes that might encode new drug targets or protective antigens. Coupled with knowledge derived from bioinformatic analysis of the proteome, and understanding of the underlying microbiology, it is possible to reduce the number of potential new targets within a pathogen to a more tangible level.
- This invention includes discoveries resulting from the findings of a comparative analysis in which gene and protein sets of the leprosy and tubercle bacilli have been compared pairwise, and against the completed genome sequences of various prokaryotes and eukaryotes.
- The genome ofM. leprae , an exceptionally slow growing bacterium, is substantially smaller than that of M. tuberculosis and contains numerous pseudogenes. While the genome of M. tuberculosis comprises 4.41 Mb and contains around 4,000 genes, the genome of M. leprae is only 3.27 Mb and a mere 49.5% is occupied by protein-coding genes. About 27% of the M. leprae genome contains recognizable pseudogenes, inactive reading frames with functional counterparts in the tubercle bacillus. The remaining 23.5% of the genome does not appear to be coding, and probably contains gene remnants mutated beyond recognition. The distribution of the 1,114 pseudogenes was essentially random throughout the chromosome. 1,604 potentially active genes were identified, of which 1,439 were common to both pathogens. Among the remaining 165 genes, with no ortholog in M. tuberculosis, were 29 for which functions could be attributed. Many of the 136 residual CDS in M. leprae, showing no similarity to known genes, may also represent pseudogenes as they are shorter than average and occur in regions of low gene density. In summary, assuming that all mycobacteria are descendants of a common ancestor, M. leprae has probably lost around 2,000 genes during evolution and the minimal gene set required by a pathogenic mycobacterium has been naturally defined.
- Whole genome comparisons led to the identification of genes that are present in bothM. tuberculosis and M. leprae but have no counterparts elsewhere. Since these pathogenic mycobacteria occupy similar niches in the human body where they encounter the same physiological stresses and immune responses, it is conceivable that the products of some of these genes may conduct highly specialized functions that could be essential for intracellular growth of mycobacteria. If this were the case, the corresponding proteins or enzymes might represent novel drug targets. In addition to those proteins that are confined to the species or the genus, there is a second group of polypeptides that also occur in Streptomyces spp., related members of the Actinomycetales kingdom, but not in other prokaryotes. It is reasonable to assume that such proteins confer specific properties on actinomycetes.
- Knowledge of the subcellular location of proteins is particularly valuable for the design of new tuberculosis vaccines since it is widely believed that surface-exposed or secreted proteins correspond to those antigenic components that are first encountered by the immune system during infection51. Bioinformatics has also been used to identify proteins that localize to the cell envelope and these include transmembrane proteins with hydrophobic domains, and lipoproteins with N-terminal cysteine residues that are modified by addition of lipid groups. Proteins that are secreted via the general secretory pathway52 are readily identifiable by their characteristic signal peptides, whereas those metallo-enzymes that are secreted by the twin arginine transporter system, Tat, can be recognized by the presence at the N-terminus of the cognate motif, S/TRRXFLK preceeding the signal peptide53, 5. This will be discussed further below.
- Other proteins that lack signal peptides and are secreted from mycobacteria in a Sec-independent manner, include those belonging to the ESAT-6 family61. ESAT-6 is a potent T-cell antigen that induces strong Th1-type responses55 and has been extensively studied as a potential diagnostic reagent for infection56, since its gene is missing from BCG57, 58, 59, and as a component of a subunit vaccine60. The comparative genomic analysis identified several ESAT-6 proteins, and their potential secretion machinery, that were common to both M. tuberculosis and M. leprae (Table 2).
- Several examples are given in Table 2 of proteins of limited distribution with potential drug targets, diagnostic antigens or subunit vaccine components.
- Legend of Table 2:
- The reading of the first example, by instance,
-
- ML0048: Name of an identified ORF in the genome ofM. leprae.
-
- Rv3876: Name of Equivalent ORF in the genome ofM. tuberculosis published in 1998.
- BLASTP:
- Method of comparing protein sequences for establishing their degree of similarity or identity.
- 1,00E−79:
- BLASTP score, which indicates how similar the protein sequences are. The analyses of the results are described in Cole et al. for the comparisons between the genome ofM. tuberculosis and the genome of BCG (Analysis of the proteome of Mycobacterium tuberculosis in silico, tuber Lung. Dis. 1999; 79(6):329-42).
- Description:
- Description of the protein, identified from all publically accessible databases, with highest similarity for theM. leprae protein ML0048.
- Sc3C3.03C: Nomenclature of the streptomyces protein.
- EMB : AL031231: Accession number in EMBL databank for the sequence of the Streptomyces protein found to be most similar to ML0048.
- 1083: length of the sequence in the EMBL databank.
- FASTA score: Different method, like BLAST, for comparing sequences for their similarity.
- Score denotes the degree of similarity.
- 31.6%: Percentage of identity between C terminal part of the Streptomyces protein and the amino acid sequence of ML0048. This 31.6% identity is found in an overlapping region of 580 amino acids between the two sequences. The other examples should be read similarly.
TABLE 2 Proteins of limited distribution with potential as drug targets, diagnostic antigens or subunit vaccine components M. Group leprae M. tub. BLASTP Description A ML0048 Rv3876 1,00E- C-terminal half of Streptomyces coelicolor SC3C3.03C, 79 hypothetical protein, TR:O86637 (EMBL:AL031231) (1083 aa); Fasta score E( ): 5.9e-27, 31.6% identity in 580 aa overlap, which contains Pro-Gln repeats A ML0115 Rv3780 2,00E- S. coelicolor SCGD3.23C, hypothetical protein, 44 TR:Q9XA56 (EMBL:AL096822) A ML0124 Rv0164 2,00E- S. coelicolor SC6CG0.02C, hypothetical protein, 40 TR:Q9X7Y8 (EMBL:AL049497) (144 aa); Fasta score E( ): 7e-05, 21.9% identity in 137 aa overlap. A ML0151 Rv0948c 2,00E- S. coelicolor SC063.16C, hypothetical protein, 25 TR:CAB82023 (EMBL:AL161755) A ML0169 Rv0966c 7,00E- S. coelicolor SCE6.30C, hypothetical protein, 66 TR:CAB88834 (EMBL:AL353832) (277 aa); Fasta score E( ): 3.3e-20, 41.0% identity in 205 aa overlap. A ML0229 Rv3603c 2,00E- N-terminal half of S. coelicolor SCE126.02C, 60 hypothetical protein, TR:Q9X845 (ENBL:AL049630) (420 aa); Fasta score E( ): 4.1e-24, 36.7% identity in 294 aa overlap A lsr2 Rv3597c 1,00E- S. coelicolor SCE94.26C, putative lsr2-like protein, 27 TR:g9X8N1 (EMBL:AL049628) (111 aa); Fasta score E( ): 7.3e-18, 56.3% identity in 112 aa overlap A ML0284 Rv0360c 3,00E- S. coelicolor SCH10.25C, hypothetical protein, 23 TR:Q9X8R4 (EMBL:AL049754) A whiB3 Rv3416 6,00E- Transcriptional regulator 38 A lppS Rv2518c e-135 many predicted lipoproteins from S. coelicolor. A ML0451 Rv2609c 2,00E- S. coelicolor e.g. SC2E1.17, hypothetical protein, 85 TR:O69888 (EMBL:AL023797) (172 aa); Fasta score E( ): 2e-13, 43.3% identity in 150 aa overlap. A ML0486 Rv2588c 2,00E- S. coelicolor SCL2.07C, putative secreted protein, 19 TR:CAB70919 (EMBL:AL137778) (169 aa); Fasta score E( ) 7.3e-08, 35.8% identity in 120 aa overlap A ML0542 Rv1390 6,00E- S. coelicolor 5C9C5.02C, hypothetical protein, 51 TR:CAB93358 (EMBL:AL357523) (90 aa); Fasta score E( ): 2e-18, 71.3% identity in 80 aa overlap. A ML0561 Rv1417 3,00E- Corynebacterium ammoniagenes ribX, hypothetical 38 protein, TR:O24754 (EMBL:AB003693) (184 aa); Fasta score E( ): 2.1e-15, 34.5% identity in 148 aa overlap. Contains hydrophobic, possible membrane-spanning regions A ML0580 Rv1446c 2,00E- hypothetical proteins from S. coelicolor e.g. 64 SCC22.20, hypothetical protein, TR:Q9XAB8 (EMBL:AL096839) (351 aa); Fasta score E( ): 7.1e-21, 36.0% identity in 203 aa overlap, although these have a short N-terminal extension relative to this homologue. A ML0603 Rv2413c 3,00E- S. coelicolor SCC123.02C, putative DNA-binding 77 protein, TR:Q9RDM2 (EMBL:AL136518) (336 aa); Fasta score E( ): 0, 39.3% identity in 326 aa overlap. A ML0630 Rv2365c 2,00E- S. coelicolor SCC77.05, hypothetical protein, 15 TR:Q9RDF3 (Er4BL:AL136503) (132 aa); Fasta score E( ): 3.3e-06, 39.4% identity in 99 aa overlap. A ML0642 Rv3195 e-143 S. coelicolor SCE9.14C, hypothetical protein, TR:Q9X8I7 (EMBL:AL049841) (375 aa) ; Fasta score E( ) 4.9e-12, 24.9% identity in 305 aa overlap. A whiB2 Rv3260c 9,00E- Transcription factor 31 A ML0762 Rv3258c 4,00E- S. coelicolor hypothetical 15.0 kDa protein 5CE34.11C 41 TR:CAB88914 (EMBL:AL353862) fasta scores: E( ): 4.8e- 16, 47.0% id in 151 aa. A lpqB Rv3244c 0.0 S. coelicolor putative lipoprotein SCE33.13C TR:CAB90922 (EMBL:AL355774) fasta scores: E( ): 0.00039, 24.4% id in 624 aa A whiB1 Rv3219 6,00E- Transcription factor 31 A ML0814 Rv3208c 3,00E- S. coelicolor hypothetical protein 32 gp|AL390975|AL390975_32 (94 aa) E( ): 2.5e-09; 47.945% identity A ML0816 Rv3207c e-101 S. coelicolor putative membrane protein SC2H12.28c (314 aa) TR:CAB94652 (EMBL:AL359215) fasta scores: E( ): 1e-13, 30.2% id in 331 aa A ML0857 Rv2219 2,00E- S. coelicolor putative integral membrane protein 59 SC3H12.04 TR:CAB90843 (EMBL:AL355740) (234 aa) fasta scores: E( ): 1.2e-26, 39.6% id in 230 aa A ML0869 Rv2206 4,00E- S. coelicolor putative integral membrane protein 40 SC5F7.32 TR:Q9S2R7 (EMBL:AL096872) A ML0876 Rv2199c 2,00E- S. coelicolor hypothetical proteins e.g. putative 43 integral membrane protein SC6G10.27C TR:Q9X812 (EMBL:AL049497) (132 aa) fasta scores: E( ) : 6.2e-15, 38.8% id in 139 aa A ML0920 Rv2147c 3,00E- pir||T34949 hypothetical protein SC4A10.12c - 89 Streptomyces coelicolor A ML0921 Rv2146c 5,00E- S. coelicolor TR:Q9S2X3 (EMBL:AL109663) (94 aa); Fasta 32 score E( ): 2.9e-12, 40.7% identity in 86 aa overlap. Contains possible membrane spanning hydrophobic domains. A ML0986 Rv2738c 3,00E- S. coelicolor TR:O50484 (EMBL:AL020958) (64 aa); Fasta 21 score E( ) : 2.5e-08, 44.4% identity in 63 aa overlap A ML0994 Rv2728c 1,00E- S. coelicolor TR:O69964 (EMBL:AL022268) (237 aa); 56 Fasta score E( ): 1.3e-13, 32.9% identity in 243 aa overlap A ML1009 Rv2714 e-106 pir||T35742 hypothetical protein SC7H2.11c S. coelicolor A ML1016 Rv2708c 1,00E- emb|CAB72193.1| (AL138851) hypothetical protein 25 SCE59.06c [S. coelicolor A3(2)] Length = 97 A ML1026 Rv2699c 2,00E- T34816 hypothetical protein SC2E9.05 SC2E9.05 - S. 32 coelicolor 144 2e-34 A ML1027 Rv2698 1,00E- membrane protein, S. coelicolor TR:O54132 33 (EMBL:AL021530) (154 aa); Fasta score E( ) : 1.1e-08, 33.6% identity in 149 aa overlap. A ML1029 Rv2696c 7,00E- pir||T34821 hypothetical protein SC2E9.10 SC2E9.10 - 69 S. coelicolor 86 4e-16 A ML1041 Rv2680 2,00E- pir||T34710 hypothetical protein SC1C3.18c SC1C3.18c - 62 S. coelicolor 158 5e-38 A ML1067 Rv1211 9,00E- emb|CAC01346.1| (AL390975) conserved hypothetical 23 protein S. coelicolor 101 1e-21 A ML1093 Rv1244 5,00E- lipoprotein, pir||T35857 probable secreted substrate- 78 binding protein - S. coelicolor 67 3e-10 A ML1105 Rv1259 e-115 S. coelicolor TR:Q9S2L3 (EMBL:AL109732) (237 aa); Fasta score E( ): 0, 54.5% identity in 231 aa overlap. A ML1117 Rv1276c 3,00E- pir||T36773 hypothetical protein SC128.03c - S. 53 coelicolor 115 4e-25 A ML1147 Rv1312 3,00E- possible secreted protein, emb|CAB94546.1| (AL359152) 42 putative secreted/membrane protein S. coelicolor 66 2e-10 A ML1166 Rv1332 7,00E- S. coelicolor TR:Q9S2G6 (EMBL:AL096852) (202 aa); 54 Fasta score E( ) 1.5e-05, 34.6% identity in 188 aa overlap. A ML1230 Rv1182 e-149 papA3, emb|CAC08383.1|(AL392176) hypothetical protein S.coelicolor 132 8e-30 A ML1306 Rv2125 5,00E- S. coelicolor TR:Q9S2K6 (EMBL:AL109732) (312 aa); 87 Fasta score E( ) 1.6e-07, 23.4% identity in 278 aa overlap A ML1321 Rv2111c 3,00E- upstream of bacterial proteasome beta subunits 07 including: Mycobacterium smegmatis TR:O30517 (EMBL:AF009645) (64 aa); Fasta score E( ): 6.2e-18, 82.8% identity in 64 aa overlap, Rhodococcus A ML1338 Rv2673 e-150 conserved integral membrane protein, S. coelicolor TR:Q53873 (EMBL:AL031317) (411 aa); Fasta score E( ) 1.1e-12, 28.3% identity in 410 aa overlap A ML1439 Rv2050 4,00E- emb|CAB61670.1| (AL133213) hypothetical protein 31 SC6D7.18c. S. coelicolor 101 4e-21 A ML1485 Rv2466c 2,00E- S. coelicolor TR:CAB71809 (EMBL:AL138662) (216 aa); 66 Fasta score E( ): 0, 52.3% identity in 214 aa overlap A ML1508 Rv1155 2,00E- S. coelicolor TR:Q9XAG1 (EMBL:AL079356) (144 aa); 48 Fasta score E( ): 5.6e-25, 54.3% identity in 140 aa overlap. A ML1525 Rv2771c 8,00E- S. coelicolor TR:Q9RD46 (EMBL:AL133424) (151 aa); 27 Fasta score E( ): 1.3e-28, 56.1% identity in 148 aa overlap A ML1548 Rv2795c e-132 S. coelicolor TR:O88028 (EMBL:AL031107) (295 aa); Fasta score E( ): 0, 54.4% identity in 285 aa overlap A ML1557 Rv2840c 2,00E- emb|CAB91141.1| (AL355913) hypothetical protein S. 27 coelicolor 46 7e-05 A ML1561 Rv2844 1,00E- S. coelicolor TR:CAB91137 (ENBL:AL355913) (167 aa); 39 Fasta score E( ): 1.4e-07, 35.8% identity in 137 aa A ML1624 Rv2917 0.0 S. coelicolor TR:Q9S3Y6 (EMBL:AF170560) (597 aa); Fasta score E( ): 0, 55.5% identity in 566 aa overlap A ML1644 Rv2235 e-113 N-terminal signal sequence plus membrane spanning hydrophobic domain; emb|CAB59445.1| (AL132644) putative membrane protein [Streptomyc . . . 109 4e-23 A ML1649 Rv2239c 3,00E- emb|CAB92846.1| (AL356892) hypothetical protein 36 [Streptomyces Co . . . 137 6e-32 A ML1652 Rv2242 0.0 S. coelicolor TR:Q9RDP8 (EMBL:AL133423) (401 aa); Fasta score E( ) : 4.3e-26, 42.0% identity A ML1666 Rv2968c 9,00E- S. coelicolor putative integral membrane protein 59 TR:CAB93387 (EMBL:AL357523) (240 aa); Fasta score E( ): 3.6e-25, 36.1% identity in 191 aa overlap A ML1698 Rv3005c 4,00E- conserved membrane protein, emb|CAB61735.1| (AL133220) 54 putative membrane protein. S. coelicolor 99 5e-20 A ML1706 Rv3015c 1,00E- S. coelicolor TR:Q9Z586 (EMBL:AL035569) (331 aa); 91 Fasta score E( ): 0, 38.6% identity in 337 aa overlap, A ML1781 Rv2256c 4,00E- 4pir||T11215 hypothetical protein 5 - Streptomyces 62 glaucescens >g . . . 153 1e-36 A ML1782 Rv2257c e-121 S. coelicolor SC4A7.08 TR:Q9RDQ4 (EMBL:AL133423) (273 aa); Fasta score E( ): 0, 53.2% identity in 269 aa overlap A ML1791 Rv1976c 8,00E- S. coelicolor hypothetical protein SC1C3.03C TR:O69845 25 (EMBL:AL023702) (125 aa); Fasta score E( ): 4.3e-06, 36.6% identity in 112 aa overlap. A ML1908 Rv0637 3,00E- S. coelicolor SCD82.07 TR:CAB77410 (EMBL:AL160431) 62 (150 aa); Fasta score E( ): 4.7e-11, 29.3% identity in 150 aa overlap. A ML1910 Rv0635 9,00E- emb|CAB77410.1| (AL160431) hypothetical protein 49 SCD82.07 S. coelicolor 83 1e-15 A ML1926 Rv0431 6,00E- S. coelicolor hypothetical protein SCD95A.20 24 TR:CAB93047 (EMBL:AL357432) (84 aa); Fasta score E( ): 4.1e-11 A ML1927 Rv0430 2,00E- S. coelicolor hypothetical protein SCD95A.20 25 TR:CAB93047 (EMBL:AL357432) (84 aa) ; Fasta score E( ) 4.1e-11, 52.8% identity in 72 aa overlap. A ML1997 Rv0970 7,00E- S. coelicolor putative integral membrane protein 39 SCM2.15C A ML2030 Rv1884c 1,00E- Rpf, emb|CAC09538.1| (AL442120) putative secreted 34 protein S. coelicolor 108 5e-23 A ML2031 Rv1883c 1,00E- Streptomyces actuosus NSH-OrfB TR:P72384 (EMBL:U75434) 44 fasta scores: E( ): 2.5e-08, 34.4% in 125 aa A ML2048 Rv1871c 2,00E- S. coelicolor hypothetical protein TR:CAE88434 14 (EMBL:AL353815) fasta scores: E( ): 0.0092, 39.3% in 61 aa; truncated at C-terminus; may represent a pseudogene A ML2063 Rv1846c 3,00E- possible regulator, pir||T36388 hypothetical protein 35 SCE94.28c - S. coelicolor 64 6e-10 A ML2064 Rv1845c 3,00E- S. coelicolor putative integral membrane protein 82 SC10A7.04 TR:Q9XAS1 (EMBL:AL078618) fasta scores: E( ): 1.8e-19, 32.6% in 328 aa A ML2073 Rv1830 2,00E- S. coelicolor hypothetical 19.1 kda protein 74 TR:CAB88877 (ENBL:AL353861) fasta scores: E( ): 3.7e- 30, 64.8% in 145 aa A ML2075 Rv1828 7,00E- S. coelicolor hypothetical 26.5 kda protein 71 TR:CAB88879 (EMBL:AL353861) fasta scores: E( ): 1.1e- 14, 41.4% in 237 aa. A ML2114 Rv0909 7,00E- S. coelicolor hypothetical 9.9 kda protein TR:O69965 07 (EMBL:AL022268) fasta scores: E( ): 0.038, 41.3% in 46 aa A ML2135 Rv0885 e-123 S. coelicolor putative membrane protein TR:Q9XAE8 (EMBL:AL079356) fasta scores: E( ) : 1.5e-13, 27.1% in 255 aa A ML2137 Rv0883c 1,00E- S. coelicolor hypothetical 39.0 kda protein TR:O50529 76 (EMBL:AL009204) fasta scores: E( ): 2.2e-19, 36.0% in 247 aa A ML2142 Rv0877 8,00E- S. coelicolor hypothetical 32.2 kda protein 91 TR:CAB93404 (EMBL:AL357524) fasta scores: E( ): 2.5e- 19, 43.3% in 270 aa. A ML2143 Rv0876c e-172 S. coelicolor putative integral membrane protein TR:CAB93403 (EMBL:AL357524) fasta scores: E( ): 5.3e- 16, 38.8% in 448 aa. A ML2151 Rv0867c 1,00E- Probable resusicitation-promoting factors, exported 35 protein A ML2156 Rv0862c 0.0 S. coelicolor hypothetical 90.4 kda protein TR:CAB93395 (EMBL:AL357524) fasta scores: E( ): 3.9e- 27, 34.6% in 856 aa A ML2193 Rv0819 2,00E- Acetyltransferase (GNAT) family, emb|CAB88484.1| 87 (AL353816) putative acetyltransferase S. coelicolor 216 3e-55 A ML2199 Rv3118 1,00E- Saccharopolyspora erythraea hypothetical 10.2 kda 28 protein TR:Q54084 (EMBL:M29612) fasta scores: E( ): 2.7e-16, 53.0% in 100 aa A ML2200 Rv0813c 3,00E- S. coelicolor hypothetical 21.7 kda protein 59 TR:CAB94083 (EMBL:AL358692) fasta scores: E( ): 4.4e- 11, 30.5% in 167 aa A ML2204 Rv0810c 2,00E- S. coelicolor hypothetical 9.3 kda protein SCD25.24C 13 TR:Q9RKJ8 (EMBL:AL118514) fasta scores: E( ): 1.3e-06, 46.8% id in 62 aa. A ML2207 Rv0807 8,00E- S. coelicolor hypothetical protein SCD25.20 TR:Q9RKK0 36 (EMBL:AL118514) (202 aa) fasta scores: E( ): 6.6e-16, 52.5% id in 101 aa. A ML2219 ARv0787A 1,00E- S. coelicolor hypothetical protein SCD25.13 (AL118514) 33 A ML2253 Rv2145c 1,00E- antigen 84 homolog, also in S. coelicolor, etc. 06 A ML2261 Rv0546c 1,00E- emb|CAB95979.1| (AL360034) conserved hypothetical 43 protein S. coelicolor 119 1e-26 A ML2289 Rv3662c 7,00E- S. coelicolor putative oxidoreductase SCH5.22C 64 TR:Q9X924 (EMBL:AL035636) (274 aa) fasta scores: E( ) 1e-11, 40.9% id in 269 aa A ML2295 Rv3668c 7,00E- emb″CAB61552.1| (AL133171) protease precursor S. 67 coelicolor 53 2e-06 A ML2296 Rv3669 2,00E- Similar_to S. coelicolor putative integral membrane 43 transport protein SCH5.28 TR:Q9X930 (EMBL:AL035636) (162 aa) fasta scores: E( ): 3.3e-10, 37.3% id A ML2306 Rv3680 e-110 S. coelicolor putative ion-transporting ATPase TR:Q9XA35 (EMBL:AL079353) (481 aa) fasta scores: E( ): 0, 48.6% id in 432 aa A ML2307 Rv3681c 4,00E- whiB4 28 A ML2330 Rv3716c 6,00E- pir||T35387 hypothetical protein SC66T3.30c - S. 10 coelicolor 47 6e-05 A ML2332 Rv3718c 1,00E- S. coelicolor conserved hypothetical protein TR:Q9ZBJ2 39 (EMBL:AL035161) (147 aa) fasta scores: E( ) : 1.4e-22, 47.6% id in 147 aa. A ML2410 Rv0528 e-160 conserved membrane protein, emb|CAC08381.1| (AL392176) putative integral membrane protein S. coelicolor 221 2e-56 A ML2425 Rv0504c 7,00E- emb|CAB77410.1| (AL160431) hypothetical protein 52 SCD82.07 [Strept . . . 73 2e-12 A ML2428 ARv0500B 6,00E- Small, strongly basic, S. coelicolor SCE68.25c, 17 gp|AL079345|AL079345_25 S. coelicolor (32 aa) E( ): 1.7e-07; 93.103% A ML2432 Rv0498 e-101 S. coelicolor hypothetical protein TR:Q9X8H0 (EMBL:AL049819) (285 aa) fasta scores: E( ): 3.2e-30, 51.6% id in 273 aa A ML2435 Rv0495c 7,00E- S. coelicolor hypothetical protein TR:Q9X8H2 94 (EMBL:AL049819) (271 aa) fasta scores: E( ): 0, 48.4% id in 250 aa A ML2442 Rv0487 1,00E- emb|CAC04041.1| (AL391406) conserved hypothetical 47 protein S. coelicolor 142 2e-33 A ML2446 Rv0483 e-137 possible lipoprotein, S. coelicolor putative lipoprotein TR:CAB76012 (EMBL:AL157916) fasta scores: E( ): 2.5e-24, 28.6% id in 405 aa. A ML2453 Rv0476 9,00E- conserved membrane protein, emb|CAC04036.1| (AL391406) 22 putative membrane protein S. coelicolor 57 3e-08 A ML2522 Rv0309 5,00E- S. coelicolor putative secreted protein SCL24.08 65 TR:CAB76092 (EMBL:AL157956) A ML2529 Rv0290 e-116 S. coelicolor putative integral membrane protein SC3C3.21 TR:O86654 (EMBL:AL031231) fasta scores: E( ): 1.9e-05, 23.8% id in 483 aa A ML2566 Rv0241c e-125 S. coelicolor putative dehydratase TR:CAB77291 (EMBL:AL160312) A ML2630 Rv0007 4,00E- emb|CAB92992.1| (AL357152) putative integral membrane 06 protein S. coelicolor 69 5e-11 A ML2640 Rv0146 3,00E- pir||T35930 hypothetical protein 5C9E5.10 - S. 93 coelicolor 141 1e-32 A ML2664 Rv0116c 1,00E- possible secreted protein, pir||T35535 probable 72 secreted protein - S. coelicolor 154 7e-37 A ML2687 Rv0051 e-150 conserved membrane protein, pir||T36589 probable transmembrane protein - S. coelicolor 185 1e-45 A ML2699 Rv3909 0.0 putative secreted protein, pir||T36582 hypothetical protein SCH24.17c - S. coelicolor 90 8e-17 M ML0007 Rv0007 6,00E- Putative membrane protein 51 M ML0012 Rv0010c 4,00E- Contains hydrophobic, possible membrane-spanning 30 regions. M ML0013 Rv0011c 3,00E- Contains hydrophobic, possible membrane-spanning 36 regions. M ML0022 Rv0020c e-114 — M ML0030 Rv0039c 9,00E- putative membrane protein 06 M ML0031 Rv0040c 3,00E- Contains a probable N-terminal signal sequence 48 M ML0042 Rv3882c e-138 putative membrane protein M ML0044 Rv3880c 2,00E- — 19 M ML0047 Rv3877 e-146 putative membrane protein M ML0049 Rv3875 5,00E- possible secreted protein, ESAT-6 14 M ML0050 Rv3874 4,00E- possible secreted protein, ESAT-6 12 M ML0051 Rv3873 1,00E- PPE-family protein 30 M ML0054 Rv3869 e-151 putative membrane protein M ML0056 Rv3867 2,00E- — 13 M ML0068 Rv3850 8,00E- — 71 M ML0069 Rv3849 4,00E- — 41 M ML0071 Rv3847 2,00E- — 65 M ML0073 Rv3843c 3,00E- putative membrane protein 51 M ML0081 Rv3835 e-107 putative membrane protein, possible membrane-spanning region near the N-terminus. M ML0091 Rv3810 1,00E- erp, pirG, exported repetitive protein precursor 39 M ML0093 Rv3808c 0.0 — M ML0094 Rv3807c 6,00E- putative membrane protein 30 M ML0096 Rv3805c 0.0 putative membrane protein M ML0099 Rv3802c 8,00E- — 96 M embB Rv3795 0.0 arabinosyl transferase M embA Rv3794 0.0 arabinosyl transferase M embC Rv3793 0.0 arabinosyl transferase M ML0107 Rv3792 0.0 Nycobacterium smegmatis ORF3, hypothetical membrane protein M ML0116 Rv3779 e-179 putative membrane protein M ML0133 Rv2949c 3,00E- Pfam match to entry PF01947 DUF98, Protein of unknown 64 function M lppX Rv2945c 6,00E- putative lipoprotein 60 M ML0158 Rv0954 4,00E- 34 kDa antigen, membrane protein 20 M ML0159 Rv0955 2,00E- putative membrane protein 74 M ML0185 Rv0996 2,00E- possible membrane-spanning regions 74 M ML0187 Rv0998 e-124 Cyclic nucleotide-binding domain. M ML0199 Rv3647c 2,00E- — 52 M ML0208 Rv3632 2,00E- putative membrane protein 38 M ML0227 Rv3605c 3,00E- putative membrane protein 36 M MML0228 Rv3604c 2,00E- putative membrane protein 51 M lpqT Rv1016c 1,00E- putative lipoprotein 52 M ML0256 Rv1024 2,00E- Contains hydrophobic, possible membrane-spanning 42 region M ML0271 Rv0401 1,00E- putative membrane protein 23 M ML0279 Rv0356c 9,00E- — 63 M ML0281 Rv0358 2,00E- — 36 M ML0285 Rv0361 1,00E- putative membrane protein 50 M ML0298 Rv0416 5,00E- possibly thiamine_biosynthesis 10 M lpqE Rv3584 3,00E- putative lipoprotein 40 M ML0370 Rv3438 2,00E- Contains PS00107 Protein kinases ATP-binding region 78 signature M NL0383 Rv3415c 5,00E- — 59 M ML0386 Rv3412 4,00E- — 45 M ML0405 Rv3616c 1,00E- — 71 M ML0406 Rv3615c 2,00E- — 14 M ML0407 Rv3614c 2,00E- — 45 M ML0410 Rv2107 8,00E- PE-family protein 08 M ML0411 Rv2108 1,00E- PPE-family protein, serine-rich antigen 22 M ML0425 Rv2520c 2,00E- putative membrane protein 10 M ML0431 Rv2507 1,00E- putative membrane protein 41 M ML0520 Rv2536 1,00E- putative membrane protein 40 M PE Rv1386 1,00E- PE protein family 21 M PPE.0 Rv1387 3,00E- PPE protein family 99 M mihF Rv1388 4,00E- integration host factor 24 M lprG Rv1411c 1,00E- putative lipoprotein 50 M mtb12 Rv2376c 2,00E- putative secreted protein 28 M ML0676 Rv3354 2,00E- — 15 M ML0703 Rv3311 e-125 — M ML0730 Rv3281 1,00E- Contains Ffam match to entry PF01039 Carboxyl_trans, 20 Carboxyl transferase domain M ML0733 Rv3278c 4,00E- putative membrane protein 53 M ML0734 Rv3277 2,00E- putative membrane protein 64 M ML0748 Rv3269 1,00E- irpA 15 M ML0761 Rv3259 2,00E- Mycobacterium smegmatis hypothetical 6.0 kDa protein 48 (partial CDS) TR:Q9S425 (EMBL:AE164439) fasta scores: E( ): 1e-10, 75.5% id in 53 aa M ML0764 Rv3256c 1,00E- — 79 M ML0806 Rv3217c 5,00E- putative membrane protein 25 M ML0810 Rv3212 e-104 putative membrane protein M ML0813 Rv3209 2,00E- putative membrane protein 24 M ML0818 Rv3205c e-102 — M ML0834 Rv2342 1,00E- — 21 M ML0872 Rv2203 9,00E- putative membrane protein 43 M mmpS3 Rv219Bc 3,00E- putative membrane protein 49 M ML0878 Rv2197c 1,00E- putative membrane protein 55 M ML0888 Rv2186c 8,00E- — 41 M ML0889 Rv2185c 8,00E- — 41 M ML0891 Rv2183c 2,00E- — 27 M ML0895 Rv2179c 1,00E- — 60 M ML0898 Rv2175c 1,00E- putative DNA-binding protein 41 M MML0901 Rv2172c e-102 — M ML0902 Rv2171 3,00E- probable lipoprotein 57 M ML0903 Rv2170 9,00E- — 55 M ML0904 Rv2169c 7,00E- putative membrane protein 32 M ML0907 Rv2164c 2,00E- putative conserved membrane protein 50 M ML0923 Rv2144c 3,00E- possible membrane protein 07 M ML0984 Rv2740 3,00E- — 31 M ML0990 Rv2732c 9,00E- possible conserved membrane protein 46 M ML1001 Rv2722 7,00E- — 06 M ML1004 Rv2719c 1,00E- possible conserved membrane protein 17 M ML1015 Rv2709 7,00E- possible conserved membrane protein 26 M ML1025 Rv2700 1,00E- possible secreted protein 62 M ML1030 Rv2695 1,00E- — 47 M ML1053 Rv2107 8,00E- PE protein 11 M ML1055 Rv2347c 1,00E- —, family 19 M ML1056 Rv3619c 6,00E- —, family 18 M ML1065 Rv1209 6,00E- membrane protein 21 M ML1077 Rv1222 3,00E- Mycobacterium avium TR:O05736 (EMBL:U87308) (133 aa); 34 Fasta score E( ): 0, 71.7% identity in 138 aa overlap M ML1079 Rv1224 2,00E- possible secreted protein 29 M ML1096 Rv1249c 2,00E- putative membrane protein 48 M ML1098 Rv1251c 0.0 some_similarity_to_GTP-binding_proteins M ML1099 Rv1252c 5,00E- putative lipoprotein 41 M ML1115 Rv1274 3,00E- lipoprotein, lprB 58 M ML1116 Rv1275 8,00E- lipoprotein, lprC 54 M ML1120 Rv1278 0.0 Contains multiple possible coiled-coils. Contains PS00017 ATP/GTP-binding site motif A (P-loop) M ML1138 Rv1303 3,00E- integral membrane protein 20 M ML1176 Rv1342c 3,00E- possible conserved membrane protein 34 M ML1177 Rv1343c 5,00E- possible lipoprotein, membrane protein 43 M ML1180 Rv3619c 6,00E- ESAT-6 family 18 M ML1181 Rv2347c 1,00E- QILSS family 19 M ML1182 Rv1361c 2,00E- PPE family 47 M ML1183 Rv2107 8,00E- PE family 11 M ML1190 Rv2525c 3,00E- —, twin-Arginine secreted protein 70 M ML1221 Rv1590 2,00E- — 18 M ML1222 Rv1591 1,00E- membrane protein 29 M ML1232 Rv1184c 2,00E- Possibly secreted PE protein, Contains PS00017 77 ATP/GTP-binding site motif A (P-loop) M ML1233 Rv3821 9,00E- conserved membrane protein 33 M ML1244 Rv2484c e-130 conserved membrane protein M ML1255 Rv2468c 1,00E- — 41 M ML1270 Rv1610 8,00E- conserved membrane protein, Contains Pfam match to 36 entry PF00218 IGPS, M ML1296 Rv2137c 1,00E- — 25 M ML1299 Rv2134c 9,00E- — 60 M ML1300 Rv2133c 4,00E- — 90 M ML1315 Rv2116 1,00E- lipoprotein, LppK 35 M ML1334 Rv2091c 6,00E- conserved membrane protein, calcium-binding 28 M ML1357 Rv1693 7,00E- — 09 M ML1361 Rv1697 e-114 conserved membrane protein M ML1362 Rv1698 6,00E- conserved secreted protein 58 M ML1389 Rv1635c e-144 conserved membrane protein M ML1446 Rv2061c 5,00E- — 35 M ML1470 Rv2446c 2,00E- conserved membrane protein 16 M ML1505 Rv1158c 7,00E- conserved hypothetical Proline rich protein, possibly 17 secreted M ML1506 Rv1157c 4,00E- — 62 M ML1526 Rv2772c 2,00E- conserved membrane protein 43 M ML1537 Rv1797 1,00E- possible secreted protein 98 M ML1540 Rv1794 e-101 — M ML1544 Rv1782 e-155 conserved membrane protein M ML1560 Rv2843 8,00E- — 24 M ML1584 Rv2876 3,00E- conserved membrane protein 25 M ML1607 Rv2898c 2,00E- Contains Pfam match to entry PF02021 UPF0102, 17 Uncharacterised protein family UPF0102, sp|O83883|Y913_TREPA HYPOTHETICAL PROTEIN TP0913 >gi|7514634|pir. M ML1610 Rv2901c 2,00E- — 39 M ML1638 Rv2229c 2,00E- — 63 M ML1677 Rv2980 3,00E- possible secreted protein 33 M ML1704 Rv3013 6,00E- — 71 M ML1720 Rv3035 e-107 — M ML1813 Rv1476 3,00E- — 39 M PPE.1 Rv0256c 3,00E- PPE-family protein 93 M ML1828A Rv0257 1,00E- Probably pseudogene as Rv0257 is longer 15 M ML1911A Rv0634A —, May be pseudogene as Rv0634A is predicted to be 13 aa longer M ML1918 Rv3587c 5,00E- conserved hypothetical membrane protein 69 M ML1937 Rv1111c 9,00E- probable integral membrane protein 39 M MML1939 Rv1109c 9,00E- — 49 M ML1945 Rv1100 6,00E- possible membrane protein 57 M ML1991 Rv0096 4,00E- PPE 90 M ML1988 Rv0093c 1,00E- Contains possible membrane spanning hydrophobic 52 domains. Note lacks the N-terminal 46 aa of the N. tuberculosis protein M ML1993 Rv0098 3,00E- — 50 M ML1995 Rv0100 1,00E- — 18 M ML2010 Rv1906c 4,00E- putative lipoprotein (secreted in Mt) 31 M ML2022 Rv1893 2,00E- — 13 M ML2023 Rv1891 2.00E- Contains probable N-terminal signal sequence. 46 M ML2054 Rv1861 1,00E- integral membrane protein 07 M ML2070 Rv1836c e-171 — M ML2111 Rv0912 1,00E- membrane protein 35 M ML2113 Rv0910 6,00E- — 49 M ML2141 Rv0879c 9,00E- — 22 M ML2144 Rv0875c 2,00E- possible exported protein 45 M ML2155 Rv0863 2,00E- — 18 M ML2195 Rv0817c 4,00E- probable exported protein 68 M ML2228 Rv0779c 3,00E- probable membrane protein 50 M ML2258 Rv0543c 2,00E- — 28 M ML2259 Rv0544c 2,00E- possible membrane protein 16 M ML2271 Rv0556 6,00E- putative membrane protein 46 M ML2274 Rv0559c 9,00E- putative secreted protein 23 M ML2320 Rv3705c 8,00E- — 64 M ML2337 Rv3723 4,00E- possible membrane spanning hydrophobic domains 57 M ML2377 Rv0451c 1,00E- mmpS4, Mycobacterium avium TmtpA TR:Q9XCF4 35 (ENBL:AF143772) (221 aa) fasta scores: E( ): 0, 58.9% id in 146 aa M ML2380 Rv0455c 2,00E- possible secreted protein 37 M ML2388 Rv0463 9,00E- possible membrane protein 18 M ML2390 Rv1083 1,00E- possible secreted/membrane protein 10 M ML2392 Rv1081c 6,00E- conserved membrane protein, 34 hydrophobic_stretch_from_aa_26-48 M ML2407 Rv0531 5,00E- putative membrane protein 06 M ML2433 Rv0497 5,00E- conserved membrane protein 39 M ML2450 Rv0479c 7,00E- possible secreted protein, >gb|AAF74996.1|AF143402_1 57 (AF143402) putative multicopper oxidase [Mycobacterium avium] M ML2452 Rv0477 2,00E- — 23 M ML2454 Rv0475 6,00E- possible hemagglutinin 40 M ML2465 Rv0464c 7,00E- — 53 M ML2473 Rv3753c 2,00E- — 53 M ML2489 Rv0383c 5,00E- possible secreted protein, hydrophobic N-terminus and 91 Pro-rich C-terminus M ML2491 Rv1754c e-109 — M ML2518 Rv0313 1,00E- — 39 M ML2527 Rv0292 2,00E- conserved membrane protein, 69 M ML2530 Rv0289 2,00E- — 92 M ML2531 Rv0288 5,00E- ESAT-6 family, possible cell surface protein 27 M ML2532 Rv3020c 9,00E- PE-family protein 10 M ML2534 Rv0285 9,00E- PE-family protein 13 M ML2536 Rv0283 e-156 conserved membrane protein M ML2557 Rv0250c 2,00E- — 26 M mce Rv0169 e-107 Mce protein M ML2569A Rv0236A 2,00E- Small secreted protein with typical N-terminal signal 24 peptide M ML2570 Rv0236c 0.0 possible integral membrane protein M ML2581 Rv0227c e-116 putative integral membrane protein M ML2582 Rv0226c e-132 conserved membrane protein M ML2595 Rv0175 2,00E- possible membrane protein 41 M ML2596 Rv0176 1,00E- conserved membrane protein 73 M ML2597 Rv0177 1,00E- conserved membrane protein 42 M ML2598 Rv0178 2,00E- conserved membrane protein 43 M ML2604 Rv0184 8,00E- — 64 M ML2605 Rv0185 3,00E- — 47 M ML2614 Rv0199 3,00E- conserved membrane protein 47 M ML2615 Rv0200 5,00E- probable membrane protein 55 M ML2616 Rv0201c 5,00E- — 36 M ML2621 Rv0207c 2,00E- — 43 M ML2627 Rv0216 e-103 — M ML2629 Rv0164 6,00E- — 44 M ML2689 Rv0049 1,00E- — 45 X ML0190 Rv1000 7,00E- gp|AL357613|AL357613_12 S. coelicolor cosmid (210 aa) 53 E( ): 2.4e-44; 55.122% identity in 205 aa overlap; AE003963|AE003963_5 Xylella fastidiosa, E( ) 9.7e- 14; 3 9.894% identity in 188 aa overlap. Weak similarity to proteins involved in DNA repair X ML0257 Rv1025 4,00E- Also hypothetical proteins from Thermotoga maritima 72 e.g. TN1078, hypothetical protein, TR:Q9X0G7 (EMBL:AE001768) (170 aa) X ML0418 Rv3368c 2,00E- weak similarity Thermus aquaticus nox, NADH 76 dehydrogenase, SW:NOX_THETH (X60110) (205 aa); Fasta score E( ) 0.00023, 28.8% identity in 212 aa overlap. X ML0577 Rv1440 9,00E- putative protein-export membrane protein, secG 12 X ML0776 Rv3242c 3,00E- probable competence protein ComF - Deinococcus 11 radio . . . 77 2e-13 X ML1037 Rv2683 2,00E- Contains 2 Pfam matches to entry PF00571 CBS, CBS 42 domain. X ML1119 Rv1277 e-105 possibly phosphoesterase X ML1159 Rv1324 e-116 probable thioredoxin X ML1249 Rv2476c 0.0 Rickettsia prowazekii TR:Q9ZCI2 (ENBL:AJ235273) (1581 aa); Fasta score E( ): 0, 32.9% identity in 1494 aa overlap X ML1399 Rv1647 1,00E- weakly adenylate cyclases 76 X ML1444 Rv2054 3,00E- Weakly several carboxymethylenebutenolidases (EC 94 3.1.1.45) involved in 3-chlorocatechol degradation e.g. Pseudomonas putida SW:CLCD_PSEPU (P11453) (236 aa) X ML1494 Rv1171 8,00E- conserved membrane protein, pir||PH0210 hypothetical 19 protein 133 ( fdxA 5′ region) - Saccharo . . . 74 5e-13 X ML1503A Rv1159A 9,00E- S. coelicolor (SC5C7.25) gp|AL03151 33 5AL031515|AL031515_25 (101 aa) E( ): 1.9e-06; 34.831% identity in 89 aa overlap; and archaebacteria. X ML1660 Rv2926c 2,00E- —, pir||E72412 conserved hypothetical protein - 69 Thermotoga manitima . . . 66 4e-10 X ML1723 Rv3038c e-152 —, gb|AAC01738.1| (AF040571) methyltransferase [Amycolatopsis medit . . . 59 1e-07 X ML1909 Rv0636 9,00E- Contains Pfam match to entry PF01575 MaoC_dehydratas, 72 MaoC like domain. ML2566 X desA2 Rv1094 7,00E- Gossypium hirsutum (Upland cotton) acyl-[acyl-carrier 85 protein) desaturase precursor SW:STAD_GOSHI (X95988) (397 aa); Fasta score E( ): 5.6e-05, 23.9% identity in 293 aa overlap. X ML1983 Rv1919c 8,00E- weakly similar pollen allergen 45 X ML2366 Rv3760 1,00E- Deinococcus radiodurans conserved hypothetical 12 protein TR:Q9RU17 X ML2463 Rv0466 e-102 weakly similar acyl-ACP thioesterase -
TABLE 3 Possible twin arginine secreted proteins M. tuberculosis M. leprae Gene Predicted function Rv0203 del — unknown Rv0265c NF fecB2 iron_transport_protein_FeIII_dicitrate_transporter Rv0846c ML2171 pa — similar_to_several_L-ascorbate_oxidases Rv1755c del plcD phospholipase_C_precursor Rv2349c NF plcC phospholipase_C_precursor Rv2350c del plcB phospholipase_C_precursor Rv2351c NF plcA phospholipase_C_precursor Rv2525c ML1190 — unknown Rv2577 ML0497 ps — similarity_to_G755244_acid_phosphatase Rv2833c del uqpB sn-glycerol-3-phosphate transport Rv3353c del — unknown NF ML2649 — unknown - The implications for this invention are widespread.M. tuberculosis and M. leprae marker polypeptides are disclosed in SEQ ID NO: 1 to SEQ ID NO:644. The discovery of the M. tuberculosis and M. Ieprae marker polypeptides and DNA encoding the polypeptides enables construction of expression vectors comprising nucleic acid sequences encoding M. tuberculosis and M. leprae marker polypeptides; host cells transfected or transformed with the expression vectors; biologically active M. tuberculosis and M. leprae marker polypeptides and M. tuberculosis and M. leprae marker polypeptides as isolated or purified peptides; and antibodies immunoreactive with M. tuberculosis and M. leprae marker polypeptides. In addition, understanding of the mechanism by which M. tuberculosis and M. leprae marker polypeptides function enables the design of assays to detect inhibitors of M. tuberculosis and M. leprae marker polypeptide activity.
- As used herein, the term “M. tuberculosis and M. leprae marker polypeptides” refers to a genus of polypeptides that encompasses polypeptides of a formula selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO:644, as well as those polypeptides having a high degree of similarity (at least 90% homology) with such amino acid sequences and which polypeptides are immunoreactive or biologically active.
- The term “purified” as used herein, means that theM. tuberculosis and M. leprae marker polypeptides are essentially free of association with other proteins or polypeptides, for example, as a purification product of recombinant host cell culture or as a purified product from a non-recombinant source. The term “substantially purified” as used herein, refers to a mixture that contains M. tuberculosis and M. leprae marker polypeptides and is essentially free of association with other proteins or polypeptides, but for the presence of known proteins that can be removed using a specific antibody, and which substantially purified M. tuberculosis and M. leprae marker polypeptides can be used as antigens.
- AM. tuberculosis and M. leprae marker polypeptide “variant” as referred to herein means a polypeptide substantially homologous to native M. tuberculosis and M. leprae marker polypeptides, but which has an amino acid sequence different from that of native M. tuberculosis and M. leprae marker polypeptides because of one or more deletions, insertions, or substitutions. The variant amino acid sequence preferably is at least 80% identical to a native M. tuberculosis and M. leprae marker polypeptide amino acid sequence, most preferably at least 90% identical. The percent identity can be determined, for example by comparing sequence information using the GAP computer program, version 6.0 described by Devereux et al. (Nucl. Acids Res. 12:387, 1984) and available from the University of Wisconsin Genetics Computer Group (UWGCG). The GAP program utilizes the alignment method of Needleman and Wunsch (J. Mol. Biol. 48:443, 1970), as revised by Smith and Waterman (Adv. Appl. Math 2:482, 1981). The preferred default parameters for the GAP program include: (1) a unary comparison matrix (containing a value of 1 for identities and 0 for non-identities) for nucleotides, and the weighted comparison matrix of Gribskov and Burgess, Nucl. Acids Res. 14:6745, 1986, as described by Schwartz and Dayhoff, eds., Atlas of Protein Sequence and Structure, National Biomedical Research Foundation, pp. 353-358, 1979; (2) a penalty of 3.0 for each gap and an additional 0.10 penalty for each symbol in each gap; and (3) no penalty for end gaps.
- Variants can comprise conservatively substituted sequences, meaning that a given amino acid residue is replaced by a residue having similar physicochemical characteristics. Examples of conservative substitutions include substitution of one aliphatic residue for another, such as Ile, Val, Leu, or Ala for one another, or substitutions of one polar residue for another, such as between Lys and Arg; Glu and Asp; or Gln and Asn. Other such conservative substitutions, for example, substitutions of entire regions having similar hydrophobicity characteristics, are well known. Naturally occurringM. tuberculosis and M. leprae marker polypeptide variants are also encompassed by the invention. Examples of such variants are proteins that result from alternate mRNA splicing events or from proteolytic cleavage of the M. tuberculosis and M. leprae marker polypeptides. Variations attributable to proteolysis include, for example, differences in the termini upon expression in different types of host cells, due to proteolytic removal of one or more terminal amino acids from the M. tuberculosis and M. leprae marker polypeptides. Variations attributable to frameshifting include, for example, differences in the termini upon expression in different types of host cells due to different amino acids.
- As stated above, the invention provides isolated and purified, or homogeneous,M. tuberculosis and M. leprae marker polypeptides, both recombinant and non-recombinant. Variants and derivatives of native M. tuberculosis and M. leprae marker polypeptides that can be used as antigens can be obtained by mutations of nucleotide sequences coding for native M. tuberculosis and M. leprae marker polypeptides. Alterations of the native amino acid sequence can be accomplished by any of a number of conventional methods. Mutations can be introduced at particular loci by synthesizing oligonucleotides containing a mutant sequence, flanked by restriction sites enabling ligation to fragments of the native sequence. Following ligation, the resulting reconstructed sequence encodes an analog having the desired amino acid insertion, substitution, or deletion.
- Alternatively, oligonucleotide directed, site specific mutagenesis procedures can be employed to provide an altered gene wherein predetermined codons can be altered by substitution, deletion, or insertion. Exemplary methods of making the alterations set forth above are disclosed by Walder et al. (Gene 42:133, 1986); Bauer et al. (Gene 37:73, 1985); Craik (BioTechniques, January 1985, 12-19); Smith et al. (Genetic Engineering: Principles and Methods, Plenum Press, 1981); Kunkel (Proc. Natl. Acad. Sci. USA 82:488, 1985); Kunkel et al. (Methods in Enzymol. 154:367, 1987); and U.S. Pat. Nos. 4,518,584 and 4,737,462, all of which are incorporated by reference.
- Within an aspect of the invention,M. tuberculosis and M. leprae marker polypeptides can be utilized to prepare antibodies that specifically bind to M. tuberculosis and M. leprae marker polypeptides. The term “antibodies” is meant to include polyclonal antibodies, monoclonal antibodies, fragments thereof such as F(ab′)2 and Fab fragments, as well as any recombinantly produced binding partners. Antibodies are defined to be specifically binding if they bind M. tuberculosis and M. leprae marker polypeptides with a Ka of greater than or equal to about 107 M−1. Affinities of binding partners or antibodies can be readily determined using conventional techniques, for example, those described by Scatchard et al., Ann. N. Y Acad. Sci., 51:660 (1949). Polyclonal antibodies can be readily generated from a variety of sources, for example, horses, cows, goats, sheep, dogs, chickens, rabbits, mice, or rats, using procedures that are well known in the art.
- The invention further encompasses isolated fragments and oligonucleotides derived from the nucleotide sequences of the invention. The invention also encompasses polypeptides encoded by these fragments and oligonucleotides.
- Nucleic acid sequences within the scope of the invention include isolated DNA and RNA sequences that hybridize to the nativeM. tuberculosis and M. leprae marker nucleic acids disclosed herein under conditions of moderate or severe stringency, and which encode M. tuberculosis and M. leprae marker polypeptides. As used herein, conditions of moderate stringency, as known to those having ordinary skill in the art, and as defined by Sambrook et al. Molecular Cloning: A Laboratory Manual, 2 ed. Vol. 1, pp. 1.101-104, Cold Spring Harbor Laboratory Press, (1989), include use of a prewashing solution for the
nitrocellulose filters 5× SSC, 0.5% SDS, 1.0 mM EDTA (pH 8.0), hybridization conditions of 50% formamide, 6× SSC at 42° C. (or other similar hybridization solution, such as Stark's solution, in 50% formamide at 42° C.), and washing conditions of about 60° C., 0.5× SSC, 0.1% SDS. Conditions of high stringency are defined as hybridization conditions as above, and with washing at 68° C., 0.2× SSC, 0.1% SDS. The skilled artisan will recognize that the temperature and wash solution salt concentration can be adjusted as necessary according to factors such as the length of the probe. - Due to the known degeneracy of the genetic code, wherein more than one codon can encode the same amino acid, a DNA sequence can vary and still encode aM. tuberculosis and M. leprae marker polypeptide of a formula selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO:644. Such variant DNA sequences can result from silent mutations (e.g., occurring during PCR amplification), or can be the product of deliberate mutagenesis of a native sequence.
- The invention thus provides equivalent isolated DNA sequences, encodingM. tuberculosis and M. leprae marker polypeptides, selected from: (a) DNA derived from the coding region of a native M. tuberculosis and M. leprae marker nucleic acid; (b) cDNA comprising the nucleotide sequence of the invention; (c) DNA capable of hybridization to a DNA of (a) under conditions of moderate stringency and which encode M. tuberculosis and M. leprae marker polypeptides; and (d) DNA which is degenerate as a result of the genetic code to a DNA defined in (a), (b) or (c) and which encodes M. tuberculosis and M. leprae marker polypeptides. M. tuberculosis and M. leprae marker polypeptides encoded by such DNA equivalent sequences are encompassed by the invention.
- DNA that is equivalent to the DNA sequence of the invention will hybridize under moderately stringent conditions to the double-stranded native DNA sequence that encodes polypeptides of a formula selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO:644. Examples ofM. tuberculosis and M. leprae marker polypeptides encoded by such DNA, include, but are not limited to, M. tuberculosis and M. leprae marker polypeptide fragments and M. tuberculosis and M. leprae marker polypeptides comprising inactivated N-glycosylation site(s), inactivated protease processing site(s), or conservative amino acid substitution(s), as described above. M. tuberculosis and M. leprae marker polypeptides encoded by DNA derived from other species, wherein the DNA will hybridize to the complement of the DNA of the invention are also encompassed.
- Recombinant expression vectors containing a nucleic acid sequence encodingM. tuberculosis and M. leprae marker polypeptides can be prepared using well known methods. The expression vectors include a M. tuberculosis and M. leprae marker DNA sequence operably linked to suitable transcriptional or translational regulatory nucleotide sequences, such as those derived from a mammalian, microbial, viral, or insect gene. Examples of regulatory sequences include transcriptional promoters, operators, or enhancers, an mRNA ribosomal binding site, and appropriate sequences which control transcription and translation initiation and termination. Nucleotide sequences are “operably linked” when the regulatory sequence functionally relates to the M. tuberculosis and M. leprae marker DNA sequence. Thus, a promoter nucleotide sequence is operably linked to a M. tuberculosis and M. leprae marker DNA sequence if the promoter nucleotide sequence controls the transcription of the M. tuberculosis and M. leprae marker DNA sequence. The ability to replicate in the desired host cells, usually conferred by an origin of replication, and a selection gene by which transformants are identified can additionally be incorporated into the expression vector.
- In addition, sequences encoding appropriate signal peptides that are not naturally associated withM. tuberculosis and M. leprae marker polypeptides can be incorporated into expression vectors. For example, a DNA sequence for a signal peptide (secretory leader) can be fused in-frame to the M. tuberculosis and M. leprae marker nucleotide sequence so that the M. tuberculosis and M. leprae marker polypeptide is initially translated as a fusion protein comprising the signal peptide. A signal peptide that is functional in the intended host cells enhances extracellular secretion of the M. tuberculosis and M. leprae marker polypeptide. The signal peptide can be cleaved from the M. tuberculosis and M. leprae marker polypeptide upon secretion of the marker polypeptide from the cell.
- Expression vectors fdr use in prokaryotic host cells generally comprise one or more phenotypic selectable marker genes. A phenotypic selectable marker gene is, for example, a gene encoding a protein that confers antibiotic resistance or that supplies an autotrophic requirement. Examples of useful expression vectors for prokaryotic host cells include those derived from commercially available plasmids. Commercially available vectors include those that are specifically designed for the expression of proteins. These include pMAL-p2 and pMAL-c2 vectors, which are used for the expression of proteins fused to maltose binding protein (New England Biolabs, Beverly, Mass., USA).
- Promoter sequences commonly used for recombinant prokaryotic host cell expression vectors include β-lactamase (penicillinase), lactose promoter system (Chang et al.,Nature 275:615, 1978; and Goeddel et al., Nature 281:544, 1979), tryptophan (trp) promoter system (Goeddel et al., Nucl. Acids Res. 8:4057, 1980; and EP-A-36776), and tac promoter (Maniatis, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, p. 412, 1982).
- Suitable host cells for expression ofM. tuberculosis and M. leprae marker polypeptides include prokaryotes, yeast or higher eukaryotic cells. Appropriate cloning and expression vectors for use with bacterial, fungal, yeast, and mammalian cellular hosts are described, for example, in Pouwels et al. Cloning Vectors: A Laboratory Manual, Elsevier, N.Y., (1985). Cell-free translation systems could also be employed to produce M. tuberculosis and M. leprae marker polypeptides using RNAs derived from DNA constructs disclosed herein.
- It will be understood that the present invention is intended to encompass the previously described proteins in isolated or purified form, whether obtained using the techniques described herein or other methods. In a preferred embodiment of this invention, theM. tuberculosis and M. leprae marker polypeptides are substantially free of human tissue and human tissue components, nucleic acids, extraneous proteins and lipids, and adventitious microorganisms, such as bacteria and a mycoplasma. It will also be understood that the invention encompasses equivalent proteins having substantially the same biological and immunogenic properties. Thus, this invention is intended to cover serotypic variants of the proteins of the invention.
- Depending on the use to be made of theM. tuberculosis and M. leprae marker polypeptides of the invention, it may be desirable to label them. Examples of suitable labels are radioactive labels, enzymatic labels, fluorescent labels, chemiluminescent labels, and chromophores. The methods for labeling proteins and glycoproteins of the invention do not differ in essence from those widely used for labeling immunoglobulin. The need to label may be avoided by using labeled antibody to the antigen of the invention or anti- immunoglobulin to the antibodies to the antigen as an indirect marker.
- Once theM. tuberculosis and M. leprae marker polypeptides of the invention have been obtained, they can be used to produce polyctonal and monoclonal antibodies reactive therewith. Thus, a polypeptide of the invention can be used to immunize an animal host by techniques known in the art. Such techniques usually involve inoculation, but they may involve other modes of administration. A sufficient amount of the polypeptide is administered to create an immunogenic response in the animal host. Any host that produces antibodies to the antigen of the invention can be used. Once the animal has been immunized and sufficient time has passed for it to begin producing antibodies to the antigen, polyclonal antibodies can be recovered. The general method comprises removing blood from the animal and separating the serum from the blood. The serum, which contains antibodies to the antigen, can be used as an antiserum to the antigen. Alternatively, the antibodies can be recovered from the serum. Affinity purification is a preferred technique for recovering purified polyclonal antibodies to the antigen from the serum.
- Monoclonal antibodies to the antigens of the invention can also be prepared. One method for producing monoclonal antibodies reactive with the antigens comprises the steps of immunizing a host with the antigen; recovering antibody producing cells from the spleen of the host; fusing the antibody producing cells with myeloma cells deficient in the enzyme hypoxanthine-guanine phosphoribosyl transferase to form hybridomas; select at least one of the hybridomas by growth in a medium comprising hypoxanthine, aminopterin, and thymidine; identifying at least one of the hybridomas that produces an antibody to the antigen, culturing the identified hybridoma to produce antibody in a recoverable quantity; and recovering the antibodies produced by the cultured hybridoma.
- These polyclonal or monoclonal antibodies can be used in a variety of applications. Among these is the neutralization of corresponding proteins. They can also be used to detect viral antigens in biological preparations or in purifying corresponding proteins, glycoproteins, or mixtures thereof, for example, when used in a affinity chromatographic columns.
- TheM. tuberculosis and M. leprae marker polypeptides can be used as antigens to identify antibodies to a mycobacteria in materials and to determine the concentration of the antibodies in those materials. Thus, the antigens can be used for qualitative or quantitative determination of a mycobacteria in a material. Such materials of course include human tissue and human cells, as well as biological fluids, such as human body fluids, including human sera. When used as a reagent in an immunoassay for determining the presence or concentration of the antibodies to a mycobacteria, the antigens of the present invention provide an assay that is convenient, rapid, sensitive, and specific.
- More particularly, the antigens of the invention can be employed for the detection of a mycobacterium by means of immunoassays that are well known for use in detecting or quantifying humoral components in fluids. Thus, antigen-antibody interactions can be directly observed or determined by secondary reactions, such as precipitation or agglutination. In addition, immunoelectrophoresis techniques can also be employed. For example, the classic combination of electrophoresis in agar followed by reaction with anti-serum can be utilized, as well as two-dimensional electrophoresis, rocket electrophoresis, and immunolabeling of polyacrylamide gel patterns (Western Blot or immunoblot). Other immunoassays in which the antigens of the present invention can be employed include, but are not limited to, radioimmunoassay, competitive immunoprecipitation assay, enzyme immunoassay, and immunofluorescence assay. It will be understood that turbidimetric, calorimetric, and nephelometric techniques can be employed. An immunoassay based on Western Blot technique is preferred.
- Immunoassays can be carried out by immobilizing one of the immunoreagents, either an antigen of the invention or an antibody of the invention to the antigen, on a carrier surface while retaining immunoreactivity of the reagent. The reciprocal immunoreagent can be unlabeled or labeled in such a manner that immunoreactivity is also retained. These techniques are especially suitable for use in enzyme immunoassays, such as enzyme linked immunosorbent assay (ELISA) and competitive inhibition enzyme immunoassay (CIEIA).
- When either the antigen of the invention or antibody to the antigen is attached to a solid support, the support is usually a glass or plastic material. Plastic materials molded in the form of plates, tubes, beads, or disks are preferred. Examples of suitable plastic materials are polystyrene and polyvinyl chloride. If the immunoreagent does not readily bind to the solid support, a carrier material can be interposed between the reagent and the support. Examples of suitable carrier materials are proteins, such as bovine serum albumin, or chemical reagents, such as gluteraldehyde or urea. Coating of the solid phase can be carried out using conventional techniques.
- The invention provides immunogenicM. tuberculosis and M. leprae marker polypeptides, and more particularly, protective polypeptides for use in the preparation of vaccine compositions against a mycobacterium. These polypeptides can thus be employed as viral vaccines by administering the polypeptides to a mammal susceptible to a mycobacteria infection. Conventional modes of administration can be employed. For example, administration can be carried out by oral, respiratory, or parenteral routes. Intradermal, subcutaneous, and intramuscular routes of administration are preferred when the vaccine is administered parenterally.
- The major purpose of the immune response in a mycobacteria-infected mammal is to inactivate the free mycobacteria and to eliminate mycobacteria infected cells that have the potential to release infectious mycobacteria. The B-cell arm of the immune response has some responsibility for inactivating free mycobacteria. The principal manner in which this is achieved is by neutralization of infectivity. Another major mechanism for destruction of the a mycobacteria-infected cells is provided by cytotoxic T lymphocytes (CTL) that recognizeM. tuberculosis and M. leprae marker antigens expressed in combination with class I histocompatibility antigens at the cell surface. The CTLs recognize M. tuberculosis and M. leprae marker polypeptides processed within cells from a M. tuberculosis and M. leprae marker polypeptide that is produced, for example, by the infected cell or that is internalized by a phagocytic cell. Thus, this invention can be employed to stimulate a B-cell response to M. tuberculosis and M. leprae marker polypeptides, as well as immunity mediated by a CTL response following infection. The CTL response can play an important role in mediating recovery from primary mycobacterial infection and in accelerating recovery during subsequent infections.
- The ability of theM. tuberculosis and M. leprae marker polypeptides and vaccines of the invention to induce protective levels of neutralizing antibody in a host can be enhanced by emulsification with an adjuvant, incorporating in a liposome, coupling to a suitable carrier, or by combinations of these techniques. For example, the M. tuberculosis and M. leprae marker polypeptides of the invention can be administered with a conventional adjuvant, such as aluminum phosphate and aluminum hydroxide gel, in an amount sufficient to potentiate humoral or cell-mediated immune responses in the host. Similarly, the M. tuberculosis and M. leprae marker polypeptides can be bound to lipid membranes or incorporated in lipid membranes to form liposomes. The use of nonpyrogenic lipids free of nucleic acids and other extraneous matter can be employed for this purpose.
- The immunization schedule will depend upon several factors, such as the susceptibility of the host to infection and the age of the host. A single dose of the vaccine of the invention can be administered to the host or a primary course of immunization can be followed in which several doses at intervals of time are administered. Subsequent doses used as boosters can be administered as needed following the primary course.
- TheM. tuberculosis and M. leprae marker polypeptides and vaccines of the invention can be administered to the host in an amount sufficient to prevent or inhibit a mycobacteria infection or replication in vivo. In any event, the amount administered should be at least sufficient to protect the host against substantial immunosuppression, even though a mycobacterial infection may not be entirely prevented. An immunogenic response can be obtained by administering the polypeptides of the invention to the host in an amount of about 10 to about 500 micrograms antigen per kilogram of body weight, preferably about 50 to about 100 micrograms antigen per kilogram of body weight. The polypeptides and vaccines of the invention can be administered together with a physiologically acceptable carrier. For example, a diluent, such as water or a saline solution, can be employed.
- Another aspect of the invention provides a method of DNA vaccination. The method also includes administering any combination of the nucleic acids encodingM. tuberculosis and M. leprae marker polypeptides, with or without carrier molecules, to an individual. In embodiments, the individual is an animal, and is preferably a mammal. More preferably, the mammal is selected from the group consisting of a human, a dog, a cat, a bovine, a pig, and a horse. In an especially preferred embodiment, the mammal is a human.
- The methods of treating include administering immunogenic compositions comprisingM. tuberculosis and M. leprae marker polypeptides, but compositions comprising nucleic acids encoding M. tuberculosis and M. leprae marker polypeptides as well. Those of skill in the art are cognizant of the concept, application, and effectiveness of nucleic acid vaccines (e.g., DNA vaccines) and nucleic acid vaccine technology as well as protein and polypeptide based technologies. The nucleic acid based technology allows the administration of nucleic acids encoding M. tuberculosis and M. leprae marker polypeptides, naked or encapsulated, directly to tissues and cells without the need for production of encoded proteins prior to administration. The technology is based on the ability of these nucleic acids to be taken up by cells of the recipient organism and expressed to produce an immunogenic determinant to which the recipient's immune system responds. Typically, the expressed antigens are displayed on the surface of cells that have taken up and expressed the nucleic acids, but expression and export of the encoded antigens into the circulatory system of the recipient individual is also within the scope of the present invention. Such nucleic acid vaccine technology includes, but is not limited to, delivery of naked DNA and RNA and delivery of expression vectors encoding M. tuberculosis and M. leprae marker polypeptides. Although the technology is termed “vaccine”, it is equally applicable to immunogenic compositions that do not result in a protective response. Such non-protection inducing compositions and methods are encompassed within the present invention.
- Although it is within the present invention to deliver nucleic acids encodingM. tuberculosis and M. leprae marker polypeptides and carrier molecules as naked nucleic acid, the present invention also encompasses delivery of nucleic acids as part of larger or more complex compositions. Included among these delivery systems are mycobacterium, mycobacteria-like particles, or bacteria containing the nucleic acid encoding M. tuberculosis and M. leprae marker polypeptides. Also, complexes of the invention's nucleic acids and carrier molecules with cell permeabilizing compounds, such as liposomes, are included within the scope of the invention. Other compounds, such as molecular vectors (EP 696,191, Samain et al.) and delivery systems for nucleic acid vaccines are known to the skilled artisan and exemplified in, for example, WO 93 06223 and WO 90 11092, U.S. Pat. Nos. 5,580,859, and U.S. 5,589,466 (Vical's patents), which are incorporated by reference herein, and can be made and used without undue or excessive experimentation.
- To further achieve the objective and in accordance with the purposes of the present invention, a kit capable of diagnosing mycobacteria infection is described. This kit, in one embodiment, contains the DNA sequences of this invention, which are capable of hybridizing to RNA or analogous DNA sequences to indicate the presence of a mycobacteria infection. Different diagnostic techniques can be used which include, but are not limited to: (I) Southern blot procedures to identify cellular DNA which may or may not be digested with restriction enzymes; (2) Northern blot techniques to identify RNA extracted from cells; and (3) dot blot techniques, i.e., direct filtration of the sample through an ad hoc membrane, such as nitrocellulose or nylon, without previous separation on agarose gel. Suitable material for dot blot technique could be obtained from body fluids including, but not limited to, serum and plasma, supernatants from culture cells, or cytoplasmic extracts obtained after cell lysis and removal of membranes and nuclei of the cells by centrifugation.
- The invention also provides screening assays for identifying agents that modulate (e.g. augment or inhibit) the activity ofM. tuberculosis and M. leprae marker polypeptides. Assays for detecting the ability of agents to inhibit or augment the activity of M. tuberculosis and M. leprae marker polypeptides provide for facile high-throughput screening of agent banks (e.g., compound libraries, peptide libraries, and the like) to identify antagonists or agonists of these marker polypeptides. Such M. tuberculosis and M. leprae marker polypeptide antagonists and agonists may modulate marker polypeptide activity and thereby modulate, inhibit, or even prevent infection of a host by M. tuberculosis and M. leprae
- For example, yeast comprising (1) an expression cassette encoding a GAL4 DNA binding domain (or GAL4 activator domain) fused to a binding fragment ofM. tuberculosis or M. leprae marker polypeptide, (2) an expression cassette encoding a GAL4 DNA activator domain (or GAL4 binding domain, respectively) fused to a binding fragment of a test polypeptide, and (3) a reporter gene (e.g., β-galactosidase) comprising a cis-linked GAL4 transcriptional response element can be used for agent screening. Such yeast are incubated, and expression of the reporter gene (e.g., β-galactosidase) is determined by the capacity of the agent to affect expression of the reporter gene and thereby identify the test polypeptide as a candidate modulatory agent for M. tuberculosis or M. leprae marker polypeptides.
- Yeast two-hybrid systems can be used to screen a mammalian (typically human) cDNA expression library, wherein cDNA is fused to a GAL4 DNA binding domain or activator domain, and either aM. tuberculosis or M. leprae marker polypeptide sequence is fused to a GAL4 activator domain or DNA binding domain, respectively. Such a yeast two-hybrid system can screen for cDNAs that encode proteins that interact with M. tuberculosis or M. leprae marker polypeptides.
- Polypeptides that interact withM. tuberculosis or M. leprae marker polypeptides can also be identified by immunoprecipitation of M. tuberculosis or M. leprae marker polypeptides with antibody, and identification of co-precipitating species. Further, polypeptides that interact with M. tuberculosis or M. leprae marker polypeptides can be identified by screening a peptide library (e.g., a bacteriophage peptide display library) with a M. tuberculosis or M. leprae marker polypeptide.
- Additional embodiments of the invention are directed to methods that employ specific antisense polynucleotides complementary to all or part ofM. tuberculosis or M. leprae marker nucleic acids. Such complementary antisense polynucleotides may include nucleotide substitutions, additions, deletions, or transpositions, so long as specific hybridization to the relevant target sequence corresponding to M. tuberculosis or M. leprae marker nucleic acids is retained as a functional property of the polynucleotide. Complementary antisense polynucleotides include soluble antisense RNA or DNA oligonucleotides that can hybridize specifically to M. tuberculosis and M. leprae marker nucleic acid species and prevent transcription of the mRNA species and/or translation of the encoded polypeptide. See (Ching et al. (1989) Proc. Natl. Acad. Sci. U.S.A. 86:10006; Broder et al. (1990) Ann. Int. Med. 113:604; Loreau et al. (1990) FEBS Letters 274:53; Holcenberg et al., WO91/11535; U.S. Ser. No. 07/530,165; WO91/09865; WO91/04753; WO90/13641; and EP 386563). The antisense polynucleotides, therefore, inhibit production of M. tuberculosis or M. leprae marker polypeptides. Antisense polynucleotides that prevent transcription and/or translation of mRNA corresponding to M. tuberculosis or M. leprae marker polypeptides may inhibit or prevent infection by M. tuberculosis or M. leprae. Antisense polynucleotides of various lengths may be produced, although such antisense polynucleotides typically comprise a sequence of about at least 25 consecutive nucleotides, which are substantially identical to a naturally-occurring M. tuberculosis or M. leprae marker nucleic acids, and typically are identical to a M. tuberculosis or M. leprae marker nucleic acid. For general methods relating to antisense polynucleotides, see Antisense RNA and DNA, (1988) D.A. Melton, Ed., Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.).
- Polypeptides with similar sequence should have similar function. Thus, the functions ofM. tuberculosis and M. leprne marker polypeptides can be assessed by a database search. One method by which structural and functional domains can be identified is by comparison of the nucleotide and/or amino acid sequence data for M. tuberculosis and M. lepree marker polypeptides, or M. tuberculosis or M. leprae marker nucleic acids, to public or proprietary sequence databases. Preferably, computerized comparison methods are used to identify sequence motifs or predict polypeptide conformation domains that occur in other polypeptides of known structure and/or function. For example, methods to identify protein sequences that fold into a known three-dimensional structure are known (Bowie et al. (1991) Science 253:164).
- As other examples, but not for limitation, the programs GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package (Genetics Computer Group, 575 Science Dr., Madison, Wis.) can be used to identify sequences in databases, such as GenBank/EMBL, that have regions of homology withM. tuberculosis or M. leprae marker polypeptides or M. tuberculosis or M. leprae marker nucleic acids. Such homologous regions are candidate structural or functional domains. Alternatively, other algorithms are provided for identifying such domains from sequence data. Further, network methods, whether implemented in hardware or software, can be used to: (1) identify related protein sequences and nucleotide sequences, and (2) define structural or functional domains in M. tuberculosis and M. leprae marker polypeptides.
- Thus, those of skill in the art can recognize sequence motifs and structural conformations that may be used to define structural and functional domains in theM. tuberculosis and M. leprae marker nucleic acids of the invention. Hydrophobicity profiles can be generated and displayed graphically using the ProtScale utility at ExPASy (http://expasy.hcuge.ch/cqi-bin/protscale.pl). There are a number of different ways of predicting transmembrane helices in sequences, the simplest being merely to look for regions of the protein containing a run of 20 hydrophobic residues. However, there are also a number of more sophisticated, and accurate, algorithms which can be used not only to predict the location of transmembrane helices but also their orientation in the membrane.
- Proteins can contain signals within their sequence which assist in their processing within the cell, for example leader sequences or signals which target proteins to specific compartments within cells. Web resources are available to help predict both these types of sites. Different regions of a polypeptide evolve at different rates; some parts of a polypeptide must retain a certain pattern of residues for the polypeptide to function. By identifying such conserved regions, it is possible to make predictions about the polypeptide function. Examples of conserved sequences can be found around the active sites of enzymes, sites of post-translational modification, binding sites for co-factors, protein sorting signals, etc. A number of bioinformatics resources have been developed both to build databases of conserved patterns and to search for instances of such patterns in sequences. One of the best known motif databases is PROSITE, which can be employed in this invention.
- This invention will be described in greater detail in the following Examples.
- The whole genome sequence was obtained from a combination of sequenced cosmids45 and 54,000 end sequences (giving 7.1× coverage) from a pUC18 genomic shotgun library using dye terminator chemistry on ABI373 or 377 automated sequencers The sequences of 42 cosmids previously generated by multiplex sequencing46 were used for scaffolding purposes only. The sequence was assembled using Phrap (P. Green, unpublished), finished using GAP447 then compared with sequences present in public databases using FASTA, BLASTN and BLASTX48. Potential CDS were predicted, and gene and protein sequences analysed as described previously8, 49, using Artemis50 to collate data and facilitate annotation. The genome and proteome sequences of M. leprae and M. tuberculosis H37Rv were compared pairwise to identify conserved genes using the Artemis Comparison Tool (ACT) (K. Rutherford; unpublished; http://www.sanger.ac.uk/Software/ACT/). Pseudogenes had one or more mutations that would ablate expression and were pinpointed by direct comparison with M. tuberculosis
- To illustrate the usefulness of comparative mycobacterial genomics for identifying potentially important proteins, a precise example will now be given. Preproteins transported by the TAT pathway generally bind redox cofactors and fold or oligomerize before crossing the membrane54, 62. After removal of the signal peptide, these proteins usually function in extracytoplasmic electron transfer chains. The specialized machinery that recognizes the twin-arginine motif, and translocates the preprotein across the membrane, is composed of several different Tat proteins. In Escherichia coli, TatA and TatE are 50% identical and share weak similarity with TatB. All three proteins are predicted to be anchored to the cytoplasmic membrane via an N-terminal hydrophobic alpha-helix, and to have cytoplasmic amphipathic helices followed by variable regions. The TatC protein is predicted to be an integral membrane protein with six transmembrane segments. M. tuberculosis and M. leprae both contain clearly identifiable tatA, tatB, tatC, and tatD genes and must, therefore, produce a functional Tat system.
- On examination of the proteome ofM. tuberculosis, eleven potential substrates for the Tat export system were recognized on the basis of their signal peptides containing potential twin arginine motifs (Table 3). During the extensive reductive evolution of the genome of M. leprae only one of the corresponding genes, ML1190, has escaped inactivation. It is orthologous to Rv2525c of M. tuberculosis but shows no similarity to proteins present in sequence databases. The 240 amino acid long precursor protein encoded by Rv2525c (or its counterpart ML1190 contains five histidines and one cysteine residue that may be important for coordinating divalent metal ions. The conservation of this coding sequence by M. leprae , in the face of massive gene loss, is a strong indication that it must play an important biological role. Given the many parallels with Tat systems elsewhere, it is likely to be in electron transport. These indirect arguments suggest on the one hand that, if this function were essential, the ML1190/Rv2525c gene product might represent a novel drug target or, on the other, since it is likely to be located extracellularly it may, therefore, be an important sentinel protein antigen.
- TheMycobacterium tuberculosis strain HRV37 genomic library has been deposited at the Collection Nationale de Cultures de Microorganismes (C.N.C.M.), of Institut Pasteur, 28, rue du Docteur Roux, F-75724 Paris,
Cedex 15, France, on Nov. 19, 1997, under the Accession Number I-1945. This genomic DNA library is disclosed in International patent application No. WO 9954487 (Institut Pasteur). - In summary, Leprosy, a chronic human neurological disease, results from infection with the obligate intracellular pathogenMycobacterium leprae , a close relative of the tubercle bacillus. M. leprae has the longest doubling time of all known bacteria and has thwarted every effort at axenic culture. Comparison of the 3.27 Mb genome sequence of an armadillo-derived Indian isolate of the leprosy bacillus with that of Mycobacterium tuberculosis (4.41 Mb) provides clear explanations for these properties and reveals an extreme case of reductive evolution. Less than half of the genome contains functional genes while pseudogenes, with intact counterparts in M. tuberculosis, abound. Genome downsizing and the current mosaic arrangement appear to have resulted from extensive recombination events between dispersed repetitive sequences. Gene deletion and decay have eliminated many important metabolic activities including siderophore production, part of the oxidative, and all of the microaerophilic and anaerobic respiratory chains, together with numerous catabolic systems and their regulatory circuits.
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M. leprae proteins that are potential targets for the diagnosis, prophylaxis or treatment of mycobacterioses. >BL;ML0007, ML.tab 11195:12106 forward MW:32204 VTSPNESRAFNAADDLIGDGSVERAGLHRATSVPGESSEGLQRGHSPEPNDSPPWQRGSARASQSGYRPSDPLTTTRQSN (SEQ ID NO:1) PAPGANVRSNRFISGMTAPALSGQLPKKNNSTQALEPVLMSNEVPFTESYASELPDLSGPVQRTVPCKPSPDRGSSTPRM GRLEITKVRGTGEIRSQISRRSHGPVRASMQIRRIDPWSMLKVSLLLSVALFFVWMIAVAFLYLLLGGMGVWAKLNSNVG DLLNNTGGNSGELVSNSTIFGCAVLVGLVNIVLMTTMAAIAAFVYNLSSDLVGGVEVTLADLD >BL;ML0012, ML.tab 16566:16979 reverse MW:14690 MQQTAWGPRTARIAGCGGAGIVIAIACSTLDIDTPGFMLTGIAALGLILFAGLSWRARPKLAINPDGLAVQGWFRTRLFG (SEQ ID NO:2) PADIKIIRITEFRRFGRKVRLLEIEAINGDLVILSRWDLGTGPLEVLDALITAGYAG >BL;ML0013, ML.tab 17134:17415 reverse MW:10464 MPKSKVRKKNDFTITSVSRTPVKVKVGPSSVWFVTLFVGLMLIGLVWLMVFQLAALGTQAPTALHWMAQLGPWNYAIAFA (SEQ ID NO:3) FMITGLLLTMRWH >BL;ML0022, ML.tab 27173:28639 reverse MW:52748 MDNQKELIQRIERKLESSIDDAFARMFGGSIVPQEVEALLRREASDGVRSLQGNRLLAPNEYIITLGVHDLEKNKADPDL (SEQ ID NO:4) TSSAFASDLADYINEQGWQTYGDVVVRFDQSSSLHTGQIRARSVVNPDVEPRPTVNDPVRTQSNQAFSAEPGVPPMTDNS SYRGGQGQGRPSDDYYGRPQDDPRGADPQGGQDPRGCYPPKPGSYPQQAGHPPLHRPDQGGYPGQGGYEDQRAYHDQGQG GYPSPYEQRPATPGGYGSQGHDQGYRPGSYGPPSGGQPGYGGYGDYGRGPARPDEGSYTPSGFPAPPEQRVAYPDQGGGY DQGYQHSGLGYGREDYGRQEYTQYAENLPGGVYAPSSGGYAEPAGRDYDYGQPGAANDYSQPVIGGYGGYGALGSAVILQ LDDGSGRTYQLREGSNIVGRGQDAQFRLPDTGVSRRHLEIRWDGQVALLSDLNSTNGTTVNNAPVQEWQLADGDVIRLGH SEIIVRIH >BL;ML0030, ML.tab 34750:35091 reverse MW:11383 MLIAGTLCVCAAVISAVFGTWALIHNQTVDPTQLAMRAMAPPQLAAAIMLAAGGVVALVAVAHTALIVVAVCVTGAVGTL (SEQ ID NO:5) AAGSWQSARYTLRRRATATSCGKNCAGCILSCR >BL;ML0031, ML.tab 35287:36123 reverse MW:28788 MIQSTQTWRVLAGGLAATAMGVTVFAGGTAAADPSPPAPPPAIPGVLPPASLPPIQSVTAVPGGITTNNRFVATPQAPGP (SEQ ID NO:6) AALGQPPLAVAAPVSESLHDYFKAKNIKLVAQKPHGFKALDITLPVPTRWTQVPDPNVPDAFAVIADRLGNSLYTSNAQL VVYNLVGNFDPKEAITHGFVDTQQLSAWQTTNASKADFDGFPSSIIEGTYRENGMTLNTSRRHVIASSGPDKYLVSLSVT TALSQAVADAPATNAIVNGFRVSSPTVSAPVPPQLGTR >BL;ML0042, ML.tab 51993:53396 forward MW:51453 MRNPVWLRFSMGRALLVTALVPPCIILFFHTQYWWAGIALVVLVVILTLVEFSGRWLSGWLMALYSFFRRSSKPLDTPSE (SEQ ID NO:7) PVIGATVKPADQVIMRWQDGFLVSVVELIPRPFTPTVIVDGEAQTDDLLETQLLEHLLSVHCPDLEAVVVSAGYRVGHVA SLDVVNLYQQVIGADPAPAHRRTWIMLRADPVRTRKSAQRRDAGVAGLARYLIASTTRIADQLASHGVDAVCGHSFESVD HATDVGFMQEKWSMMRGQNAYSVAYTAPAGPDAWWSARADHTITRVWVAPGKTPQATVVLTTLGKPKTPCGFYRLHGAQQ PALLGRSFVAYQHCQMPIGSAGVLVGETVNRCSVYMPFDDVDVSVSLGDVQTFTQFVVRAAAAGGIVTLGQQFEKFARMI GGQIGSVAKVAWPNATTYLDPYPGSERVILKHDIIGTPRHRKLPIRRISPPEEGHYQMVLPKSSYEL >BL;ML0044, ML.tab 54698:55039 forward MW:12157 MDLDPTQAQTMALLGQFQSALDEQCNRMTDGVFKASDQEKTVEVTINGYQWLTGIRIESGALREFGHAVVADRINEALQN (SEQ ID NO:8) AQGVATAYNEVSGEQLAARLSALSCSIGEPPPT >BL;ML0047, ML.tab 58020:59558 reverse MW:54486 LSAPAVTAGPATAGITPARPSATRVTILTGKRMTDLVLPSTVSIEAYIDETVAVLSDLLEDAPADVLAGFDFSAQGVWTF (SEQ ID NO:9) ARPGSPPMKLDQSLDDAGVVDGSLLTLVSTSRTERYRPLVEDVIDAIAVLNESPEFNRKAVDRFIGVAIPVLSLPITAVA VWAWWVTGRSPFWSLAIGILSIVALTGSIVAEKFYKNLDLSESLLLTSYPLIASAAALVTPLPNGVDSLGPPQVAAAAAA VLFLTLLTRGGARRHSGYASFTAITTIAIVVIAIAYGFGYQHWVPTGAVAFGLFIVTNAAKLTVAVARIALPPIPVPGET VDNEELLDPVVTPHEATHEETPTWQAIIASVPDSAVRLTERSSLAKRLLIGYVISGTLILCSGAIAVIVRGHFFAHSLVV AFLLTVVCTFRSRLYAERWCAWALLAAAVVIPTGLTVKLCIWYTQIAWLLLTSYLVAAIIALMVFGATVRVRRVSPVTKR IMELIDGAVVASIIPLLLWIAGVYDMVRNLSF >BL;ML0048, ML.tab 59555:61315 reverse MW:63226 MAADYDKLFRLDDGAYASPDQAAEQLFDDAPLYPPPIIPTCTTTPNGEVASPMPDWSEQLPPNPPAASKSPLPPMPIGSS (SEQ ID NO:10) VQPPPASSESPRAPMPVSAPPRSPAASLMPISEPPQWPPAEAPEHQFAKAEPPSVPIPINEPSPAKPATPMPMTPIDGSQ RTPVTSPEPSLAEFEAQPPATPKPSLLPRPMSSPPEAPRPSANQHSRHARRGHHHRDETQQANPASATEPMIAPRARTAE LRQAPHAAAEPAPTQHLTRPDGLVSHRTALHDSTATSAIGVQTGRSTGAKKPSKVVAKRGWRHWVHTVTRINLGLSPDER YELDLRTRVRRPPRGSYQIGILGLKGGAGKTTVTVTLGSMFARVRNDRILVVDADTSCGNLADRAGRFSEANIADLLADK DVKSYNDIRTHTSVNAVNLEVLPAAEYSTAQHALSGEDWNFAAATVSKYYNVMLADCGVGLFDPVTRGVLSTASGVVIVT STSVDAARQAAIALDWLRHNGYQDLLSRACVVINHVMPKEPNIASKDLVQQFEQQIQPGRVVVLPWDKHIAAGTEIRLOR LDPLYRRRILELAAALSDDFERAGRH >BL;ML0049, ML.tab 61406:61693 reverse MW:10464 MIQAWHFPALQGAVNELQGSQSRIDALLEQCQESLTKLQSSWHGSGNESYSSVQRRFNQNTEGINHALGDLVQAINHSAE (SEQ ID NO:11) TMQQTEAGVMSMFTG >BL;ML0050, ML.tab 61720:62022 reverse MW:10964 MAEMITEAAILTQQAAQFDQIASGLSQERNFVDSIGQSFQNTWEGQAASAALGALGRFDEAMQDQIRQLESIVDKLNRSG (SEQ ID NO:12) GNYTKTDDEANQLLSSKNNF >BL;ML0051, ML.tab 62201:63109 reverse MW:32135 MTWPMLWPASVPSECPPNYWHTPAPSAKCEPEQAAVAPIAAAKPMITWLQSAAEQTTTQAEAHRQAMASTPGMAVITENH (SEQ ID NO:13) ITQAILATINFFGINMAPIAFTEAGDFICMRTQTALAMNSYQAETLLNTAFQKLEPMAAILNPSSYSPPSALTSQVNQFT QMISGFSAALPSTQVLQQTVGQVAELARPMQQVKSLFTSIDSTGVYTSAQRGDTESAHRIGLFGASTLSSHPLVGITGTT TDTRLLCAESLPSASGSLAWTPLMTQFQLIDKSIAPEPRQRVMLPPWAAGSPGHNAQDGGTT >BL;ML00S4, ML.tab 67417:68862 reverse MW:51875 MGLRLTTKVQVSGWRFLLRRVEHAIVRRDTRMFDDPLQFYSRSIALGIVVAVALLIGAVLLAYFKPQGKLGASTLLTDRA (SEQ ID NO:14) TNQLYVLLSGHLYPVYNLTSARLALGKPANPAAVKSSELTKLPIGQTIGIPGAPYATPVSGDSSSTWTLCDTVAKIESES PAVQTSVIARSLQIDPAINPLQPNEALLASYRDKTWLVNSKGRHSIDLADRALTSAIGISVNVKPTPLSEGLFNALPDVG RWELPTIPDTGAPNSLGLSPDLVIGSVFQIQMEKSPQYYVVLSDGIAQVNATTADALRATQSHGLVAPPSLVPNVVVQIP ERVYDSPLPDEPLKMVARDDYPTLCWAWERKASDQAPKRTMLIGQHLPLQPSANSTGIKQIRGTATVYIDGGRYVALQSP DPRYSESLYYVDPEGVRYGLANSEAVKALGLASPQTAPWVIVRLLVEGPVLSRDAALLEHDTLIADPSPRKVPAGYSGVR P >BL;ML0056, ML.tab 70584:71093 reverse MW:18452 VNLLGNDDDNHLASLDFYSANRYYEESLFFDELDGYAPTTPVGIEANDLDVFQSLTEPEEELEVELLAVTNPAKSVSALM (SEQ ID NO:15) NGRVHQVELTDQVTRIGEKKPATEAFVLASLARQKARTSQGTCILDSLQGGGENTTARCELVGLTLNLPTSEQAAAEAEM FSNNILRQK >BL;ML0068, ML.tab 89620:90336 reverse MW:26088 MGLFHKRRSRAMRRAEARAIKARAKLEARLAAKNEARRLNSAQRATNKALKAQLKAKRNSDRVALKVAETELKAAKECKL (SEQ ID NO:16) LSPTRIRRVLTVSRLLAPIVVPLIYRAAIATRALIDQRRADQLGIPLAQIGQFSGPSARLSARIARSEQSVLLVQEKKPK DAETKQFVSTITERLIDLSAAVAAVENMPATRRRAVHSTISSQLDGIEADLMARLGVDLTTSMADNRSVADSTRKAAT >BL;ML0069, ML.tab 90521:90919 reverse MW:14807 MSTTFAARLNRLFDTVYPPGRGPHTSAEVIAALKAEGITMSAPYLSQLRSGNRTNPSSATISALANFFRIKPAYFTNDEY (SEQ ID NO:17) YEKLDQELAWLATMRDEGVRRIAMRTIGLSAQAQQDIVDRVDELRRAEHLDV >BL;ML0071, ML.tab 91913:92446 reverse MW:18446 METGSGLPIGVVPFHARGALKGFVISGRWPDSTKEWAQLLMVAVRIASLPGLLSTTTVFGAREELPDEPEPGTVGLVLAE (SEQ ID NO:18) GTVFGESAIQPGYFADHQPPALLMLHPPSETMPSLPECTGAASGCVLLPGLPYLGLEHRAAWVEAEADGTITSMVSRVGV DPISHPDTAILAMLLAA >BL;ML0073, ML.tab 94092:95126 forward MW:38124 VIQVCSQCGTRWNVRERRREWCLRCRGALIAPQAEMPTAVKQWSSHVGLPAGIVPEALGWQRTPPGFRWIAVRPGAAPPN (SEQ ID NO:19) RRRQRHHVPTPRYAVMPRWGLADRVDQDSTWIQAPLKPGPSSAKVRTTLFVAVLVFTLAALVYVVRYVLLVINRNTLLNF GVAAIADWLGVIASLAAIAATLACVMALSRWLIARRAAAYAHHAVPEQRSSWELRAGCLLPLVNLLWAPVYVIELALMEN HYTQLQKPIFMWWIVWVFSYVISVVAVVTSWAKDAQGIANNTVAMVFAYLFAAAAVAAVARVFEGFECKSIKRPVHRWVV VHLGGSVVHPSPGSVELEGQEPAA >BL;ML0081, ML.tab 100648:102000 reverse MW:48150 MLDAPEEEPALADDLTGEDEQPPVEFQWPSTLQARATRRGLLLTALGGLLIGGLVTAIPTVGTGSGLLATYIDSNPVPST (SEQ ID NO:20) GAKSNVAFNRATNGDCLMWPDSTPHTAVIVNCADDHRFEVAESIDMRTFPGSEYGPNAAPPSPARIQQISEEQCETAVRR YLGTKFDPNSKYTISMLWSGDRAWRQSGERRMLCGLQLPGVNNQQVAFKGKVANIDQSKVWPAGTCLSIDLTTNQPIDIP VDCVAPHAMEVTGTVNLADKFPNALPAASEQDTFIKDACTRLTDIYLAAIELRTTTLTLIYPTLSLSSWAAGSRKVACSI GATMGNGGWATLVNSAKGPLLINNQPPTPPPDIPEERLGMPPIPLHHLQVPNSQSNVPVNPIPPGNQQHRKQQPIVTVPQ SPASTAPAASVSPAKHLPKARHTRQMSKRRGRPISPHPWAGRASPGGLAE >BL;ML0091, ML.tab 113153:113863 reverse MW:23752 VPNRRRCKLSTAISTVATLAIASPCAYFLVYEPTASAKPAAKHYEFKQAASIADLPGEVLDAISQGLSQFGINLPPVPSL (SEQ ID NO:21) TGTDDPGNGLRTPGLTSPDLTNQELGTPVLTAPGTGLTPPVTGSPICTAPDLNLGGTCPSEVPITTPISLDPGTDGTYPI LGDPSTLGGTSPISTSSGELVNDLLKVANQLGASQVMDLIKGVVMPAVMQGVQNGNVAGDLSGSVTPAAISLIPVT >BL;ML0093, ML.tab 115371:117302 forward MW:72371 MTAVSLLARVILPRPGDPLDVRKLYLVESITNARRAHALSPTTLQIGAESEVSFATYFNAFPASYWRRWTICKSVVLRVE (SEQ ID NO:22) VTGAGRVDVYRTKANGARIFVEGREFAGVEDDASKAQVVELEVGLQPFEDGGWIWFDITAETRVTLCSGGWYATSPAPGR ANIAVGIPTFNRPADCTNALAELTADPLVDEVIGAVIVPDQGVRKVRDHPDFPEAAARLGDRLSIHDQPNLGGSGGYSRV MYEALKNTDCQQILFMDDDIRIEPDSILRVLAMHRFAKSPMLVGGQMLSLQEPSHLHIMGEVVNRSNFIWTAAPHAEYDH DFVEYPLNDKEDKSKLLHRRIDVDYNGWWTCMIPRQVAEELGQPLPLFIKWDDADYGLRAAEHGYPTVTLPGAAIWHMAW SDKDDAIDWQAYFHLRNRLVVAAMHWDGDVTGLVRSHLKATLKHLACLEYSTVAIQNKAIDDFLAGPDHIFSILESALPE VHRMRKEYPDAVVLPAATELPPPVHKNKVMKPPENPLSIVYRLLRGIFHNLTAADPECHKRPEFNIPTQDARWFRLCTVD GTTVTTADGCGVVYRQRDRAKNFLLLFSSLHRQLQLARRFDELRKIYRDALPVLSSKQKWEMALLPLPDSPTRFPAEQEP EHA >BL;ML0094, ML.tab 117295:117873 forward MW:19928 MPEDKAPTGELAAIAAVQSVLVDRPGVLPTARGMSHFGEHSIGWLAISLLGAILVPCRRRYWLVAGAGVFAAHVAAVLIK (SEQ ID NO:23) RMVRRIRPNHPAVTVNVGTPSPLSFPSAHATSTAAAAILIGRASRLPKGIVAAVLVAPMALSRIVLGVHYPSDVAFGVVL GAAVAGTTARFDSRLSRRWTVQHGLSSGSAVK >BL;ML0096, ML.tab 118819:120768 forward MW:71091 MRRRMVSRQVGWPLFPYHIVVRVSLWASVLLVAALFGWGAWQRRWIADDGLIVLRTVRNLLAGNGPVFNQGERVEANTST (SEQ ID NO:24) VWTYLLYAGSWVGGPMRFEYVALAAALVLSVLGMVLLMLGTGRLYAPSLQGRQAIMLPAGALVYVALPPARDFATSGLES GLVLTYLGLLWWMMVCWAQPLRNRSQSRRFIGALAFVAGCSVLVRPELALMGGSALIMLMIAARTCWLRALIVVAGGSLP VAYQLFRMGYYGLLVPGTALAKDAAGDKWSQGIIYLSNFNQPYVLWVPLVLLVLLGLLLMLIHRWPSFMHPLETPDSGRV ARAVQSPPAVVVFVVFSGLLQAFYWIRQGGDFMHGRVLLAPLFCLLAPVVVIPVVISEGADFSRQTGNWLAGVTSLLWLG VAGWSLWAANSPGMGDDATNVSYSGIVDERRFYAQATGHAHPLTAADYLGYPRMAAVLVALNNTPDGALLLPSGNYIKWD LVPMIQLSPSSPGSPPDSLVSQKPQHTVFFTNLGMLGMNVGLDVRVIDQIGLANPLAQHTERLQHGRIGHDKNLFPDWVI ADGPWVKWYPGIPGYLDQAWIAQAVAALQCSGTQAVLSSVRAPMALHRFISNLLNSFEFTRYRFDRVPLYELVRCGLPVP DVLPATPPE >BL;ML0099, ML.tab 123370:124380 forward MW:35611 MVEKVPRKRHRVLAWTAALSMAAVVALAIVAVVILLRSAESPRSSLPPGVLPIPSTAPHPRKPRPAFQDVSCPDVQLLVV (SEQ ID NO:25) PGTWESSLQDNPLDPVQFPDALLRNSTMTIGQQFPTSRVQTYTIPYTAQFHNPLSGDKQMTYNDSRAEGTRAMVQEMINV NNKCPLTSYVLVGFSQGAVIAGDITSDIGNGHGPVDDDLVLGVTLIADGRRQQGVGNDIGPNPPGEGAEVTLHEVPVLSG LGMTMTCARPGGFGVLHSRTNEICAPGDLICAAPAEAFSVANLPATLNTLASGAGQPIHANYATAQFWDLDGAPATVWTL NWVHRLIEGAPHPKHG >BL;ML0107, ML.tab 147460:149358 reverse MW:68650 MRNALASFGQIVLAAVVASGVAAVSLIAIARVHWPAFPSSNQLHALTTVGQVGCLTGLLAVGGVWQAGRFRRLAQLGGLV (SEQ ID NO:26) FVSAFTVVTLGMPLGATKLYLFGISVDQQFRTEYLTRLTDSAALQDMTYLGLPPFYPPGWFWIGGRVAALTGTPAWEIFK PWAITSITIAVAITLVLWWQMIRFEYALLVTIATAAVTLVYSSPEPYAAMITVLLPPALVLTWSGLRAAEREADRTLGNK RGWATVVGAGIFLGFAATWYTLLLAYTAFTVVLMTLLLATALCRRAGFRATFDPLRRLAGIVVIAAAIGAITWLPFLARA AHDPVSDTGSAQHYLPADGAELAFPMLQFSLLGMICMLGTLWLIVRTSSSVRASALMISVLAVYLWSLLSILTTLARTTL LSFRLQPTLTVLLVTAGVFGFIETAQSLAKHNRAVLSVASAIGLAGAIAFSQDIPNVLRPDLTIAYTDTDGHGQRGDRRP PGSEKYYWAIDEAVLHITGKPRDQTVVLTADYSFLAYYPYWGFQGLTSHYANPLAQFDLRAAQIQQWSRLTTASELIHAL DTLPWPPPTVFVMRHGAGNTYTLRLAKNVYPNQPNVRRYTVDLPAALFADQRFAVQDIGPFVLAIRKPMGNA >BL;ML0115, ML.tab 155413:155937 reverse MW:19053 LNNDNDDSIEIIGGVDPRTMATRGEDESRDSDEPSLTDLVEQPAKVMRIGTMIKQLLEEVRAAPLDEASRNQLREIHATS (SEQ ID NO:27) IRELEDGLAPELREELDRLTLPFNESTAPSNAELRIAQAQLVGWLEGLFHGIQTALFAQQMAARAQLEQMRNSALPPGMG KPGQAGGQGTGQYL >BL;ML0116, ML.tab 155965:157929 reverse MW:70767 VGLCCGTLIALFLLIVPETIVARFAALTWPIAIAVSPALTYGVIALVIIPFGAVGIPWNSWTALAALVAVSMLMIAFRLL (SEQ ID NO:28) LVRYRDTAAETRGISGWPAVTVAVGVLLGALLIGWAAYRGLLHWQSIPSTWDAVWHANTVRFILDTGQASPTHMGELRNV ETHSVLYYPSVLHALAGVYCQLTGAAPTTGYTVSSLAVAVWLFPVSAATLTWHLLRPVTTQKRAAGASATAAALSAAFTS VPYVEFGVAANPNLAAYGVAVPTMVLITSTLRHRDRIPVAILALVGTFSVHLTGGIVVSLFLLGWWLMNALLHPVRSRAA DARTLAAVVMPTALILAPQFIAVLNQADIIAGHSFPSFKSVKQGVIDALLLHTRHLNDFPIQYGLVVLAAIGMAILLYQK IWWPSIAWLVLTVATVYSAAPFRGPIGSAIESFSQFFYNDPRRLSAVVTMLLTPMAGIALFAGVLLLVVGARRVTARFTA LPRPVWTTATVVLLVAATVLTAWHYLFRHLVLFGDKYDSVMVNQKDLDAMSYLATLPGAHNTIIGNSNTDGSSWMYAVAD LHPLWTHYDFPQQTGPGYFRYAFWAYARTGNPWVVEAVRVFNIRYILTTSPTVQGFAIPDGLVSLEESKSWTKIYDNGAA RIFEWSGNATATRA >BL;ML0124, ML.tab 166949:167389 reverse MW:16448 MPVLSKTVEIDTDTATIMAIVTDFESYPQWHEWIKGVWVLAHYDDGRPSQLRIDINFQGMQGTYIQAVYYPGVNQIQTVM (SEQ ID NO:29) QOGOLYSKQEQLFSVTQAEGGSVLTVDLDVELTMPVPAPMVKNLLNTALDRLAEKLKLYAEHLAPS >BL;ML0133, ML.tab 179256:179888 forward MW:24045 MTNRTLSREEIRKLDRDLRILVATNGTLTRVLNVVANEEIVVDIINQQLLDVAPKIPELENLKIGRILQRDILLKGQKSG (SEQ ID NO:30) ILFVAAESLIVIDLLPTAITTYLTKTHHPIGEIMAASRIETYKEDAQVWIGDLPCWLADYGYWDLPKRAVGRRYRIIAGG QPVIITTEYFLRSVFQDTPREELDRCQYSNDIDTRSGDRFVLHGRVFKNL >BL;ML0151, ML.tab 213175:213492 reverse MW:11830 MRPEPPHHENAELTEMNTEVVEAPLLTDIEELREEIDRLDAQILATVKRRAEVSQAIGKVRMASGGTRLVHSREMKVIER (SEQ ID NO:31) YSELGPDGKDLAILLLRLGRGRLGH >BL;ML0158, ML.tab 221657:222601 forward MW:31355 LHCSSGAVTALEITGGVNTYLPGSPGYPLVQPAGSYPGATPSFVKSDVGESQLYHYLTIAVVVLGLAVYLGNFGPTFTSS (SEQ ID NO:32) SDIGPGSGGFAGDAGTAVVVALLAALLAGLDLLPKAKSSAGVVGAIAVLGALLAISEMINMPAGFSIGWANWFILVCSVL QAIAAVAALLLEAGIITAPAPRLSYDPYLQYGQYGAQSYYGQPNRQLQVGLNAHSPQQSPAGYGAQYGAYTSSPTQIQAG MPATGGFSAQHSAQQGPSTPPTGFPSFSPPPSVGAAAGSQAGSAPVSYSNPTDSKQGFGQGRESTSSSSGSAPV >BL;ML0159, ML.tab 222650:223942 forward MW:44093 VGDNRAAGVRQARDLVKVAFGPAVVALAIIAAITLLQLLIANSDMTGALGAIASMWLGVHQVPIAIGGRELSIMPLLPVL (SEQ ID NO:33) LMVWATAHSTSQATSAYSSWLVIRWVVASALGGPLLIAAISLAVIHDASSVLTELQTPKALRAFTGVLVVHAIGAAIGVN SRVGRRVLTASRLPDWVGDSVHAATAGVLALLGLSGLVTAGSLVVHWATMQEFYGITDSIFGQFSLTVLSVLYAPNVIVG TSAVAVGSSAHLGFATFSSFTVFGGDIPALPVLAAAPTPPLAPVWVALLIVGAASGVAVGQQCTRHPLPLLAALAKLLVA AATGALMMALLGYAGSGRLGNFGDIDVDQGALVVGVFFWFAVVGWVTVVVACGIKRFPRHLKPPPALSSEEHADASSKDH EAYFGVDLNVPFDLSGEDEIPKAEPGEAAD >BL;ML0169, ML.tab 234932:235534 forward MW:22082 MSNSAQRDAKGARDEPLRAADTDRIQIAQLLAYAAEQGRLELKDYEDRLAKAYAATTYQELEQLRDDLPGSQVSARRGGN (SEQ ID NO:34) PNPAPSTLLLALMSGFERRGRWNVPRKLTTFSLWGSGVLDLRYADFTSTEVELHAYSVMGVQTILLPPEVNVEISGHGVM GSFDRQVRGQGTPGAPTVKIRGFSLWGGVGIKRKARRPRR >BL;ML0185, ML.tab 250221:251249 forward MW:38250 MPSIPQSLLWISLVVLWLFVLVPMLISKRDVVRRISDVALATRVLNGVAGARLLKRGGPATGHRSDHNWELDEDWRQNPV (SEQ ID NO:35) DGEFADADQDIGEEQDQNVDDTQRTRPVVMEVAVAELTGTDYLDVDVVEDSVALPIEDSADVTESVLLAVGEGGSPGEEA EAEQRQSDRYGYVDASSGLGLEQKDDKSPVPVAPTVSRQRRYDTKTATAVSARKYAFRKRVLMVMAIILVGSAAAAFEVD SNAWWICGSSTTVTVLYLAYLRRQTRIEEKVRSRRMHRIARARVDVENAHDREFDVVPSRLRRPGAVVLEIDDEDPIFEH LDYEMPIRTFGWPRDLPRAVGQ >BL;ML0187, ML.tab 252658:253719 forward MW:38375 VAGSWQCGHCESCASPLGPRDIAVVELIADRAEEFAAMDIFRGLPAEDLMSVAVSVEPVLAAAGEVLMQQGEQAVSFLLI (SEQ ID NO:36) SSGNVEVRRVDDDGAVIVGQASHGMIIGEIALLRDGRRTATVITTEPLTGWVGDIDAFAQMVQIPSITRRLLLTVRQRLA AFITPIPVQLRDGTHLMLRPVLPGDTERSLRGHVRFSRETLYLRFMSARAPSDELMHYLSEVDYVDHFVWVVTDGGDPVA DARFVRDESDPTLAEIAFTVADAYQGRGVGNFLISALSIAAHVNGVNRFSARMLTDNGPMRAIMDHHGAVWRRYDVGVIT TVIDVPRQRDLIIGRAMADQIAGVVRQVIGAVG >BL;ML0190, ML.tab 255125:255742 reverse MW:22988 MCDMLVDVGIAFQGSLFEYHERRQLGDGAFIELRSGWLTDGVELLDTLLSEVPWRIERRRMYDKVVNVPRLVSFHDLTTD (SEQ ID NO:37) DPPHPLLTRLRRRLNDIYAGELGEPFTSVGLCCYRDGSDSIAWHGDTIGRNSSEDTMVAIISLGATRVFALRKRGGGPSL RLPLTHGDLLVMGGSCQRTWEHSVPKTSASTGPRVSIQFRPRNVH >BL;ML0199, ML.tab 265213:265815 forward MW:21217 VSQLSFFTAESLLPAIADLAGVLAASGQIVVVSASGQSPAPAARLSVVVDQLWRASALAEMISEAGLVPEISRTEEDTPL (SEQ ID NO:38) VRTAVDPLLCPIAAEWTRGAVKTVPPRWLPGPRELRAWILAAGVPEAANRYLLGLDPHAPDTHSPLASALMRVGIAPTLI GTRSGRPALRISGRRRLSRLLENVGEPPDWAEALALWPRV >BL;ML0208, ML.tab 279784:280125 forward MW:12884 MNWIQVLLIGSIIVLLIYLLRSRRNVRSRAWVKVGYIAFVLGGVYAVLRPNDTTVVAHWFGVCRGTDLMLYALIMAFSFT (SEQ ID NO:39) TLSIYIRFKDLELRYACLARVVALEGARAPEPF >BL;ML0227, ML.tab 298516:298992 forward MW:17121 MGPTRKRDLTAANIGAAVVGYLLVLVLYRWFPPITVWTGLSLLAVAIPEALWARYVRTKISDGEIGDGPGWLHPLAVAHS (SEQ ID NO:40) LMVAKASAWVGALVLGWWVGVLVYFLPRWPWLRVADKDTSGTVVAALSALALLVAALWLQHCCKSPQDPTEHGEGAEN >BL;ML0229, ML.tab 300537:301466 forward MW:32734 MVQFDGLRSARLNIAILSTGRVGVALERADQVVVACSAVSHASRQWVQFRLPETSVASPPEVASSAELLLLAVPDCEFAG (SEQ ID NO:41) LMSGVAVTSVPRPGTIVAHTSWANGVGILAQLGKDGCIPLAIHPANMFSGSDEDLSQCQLRDTYFGITKTDDVGYAIAQS LVLEMGGEPFCVVEYARILYHSVSPHVGNNIVTVLADALEVRRSALRGSELLGLGVPPACRGEVVDDQLDVIVERIVGSL ARAACENTLQRGQAGLTKLVARGDLDALAGHLVALMRIGPELAQAYRVNALRKTQRAHAPYDVVEALAP >BL;ML0256, ML.tab 335129:335812 forward MW:24402 MSEAKRLDPKRRSPASRPGKAGDSVRGRRSTKPVAKLSVKPSRTTPASSHSGRNSTRMLTQHVVEPIRQSIIESRERRSD (SEQ ID NO:42) QQLGFTARRAAVLAAVVCVLTLTIAGPVRTYFAQHAEIEQLAATEATLRRQIADLEQQKGKLADSAYIAARARERLGFVM PGDVPFQVQLPSTAAVSSQPGGRAAKPANNDPWYTSLWHNIADAPHLPPGAGTPPFSLTPLSTTSGG >BL;ML0257, ML.tab 335805:336308 forward MW:17960 VVDRADLEAVARHLGREPRGVLEIAYRCPSGEPGVVKTAPKLDDGTPFPTLYYLTHPVLIAAASRLESTGLMREMTERLG (SEQ ID NO:43) QDPELAAGYRRAHESYLTERDAIESLGTTFSAGGMPDRVKCLHVLIAHSLAKGPGLNSLGDEVLALLAADPKTAATLVAG QWKECDR >BL;ML0271, ML.tab 354849:355220 reverse MW:12992 MRLGQALAWLATDIVAVSVFCAVGRCSHAEGLTVADLAVTLWPFLTGTAIGWLASRGWQRPTAVVPTGVVVWLCTVVVGV (SEQ ID NO:44) ALRKASSAGVVANFMVVAASTTAALFLGWRAVVELILRRRSTR >BL;ML0279, ML.tab 361297:361953 reverse MW:24062 VTYYSSLRPEDLPPERPKHEHYSGFPEYELANPGVGFRRFVATMRRLQDLAVSADPSDEVWYAAADRAVALVELLGPFAT (SEQ ID NO:45) DEGKAPAGRVPDMPGMGSLLLPPWTLTRSGPDSVEMTGYFTRFHVGFNHAVIIGGVLPLVFDHLFGMISYTAGRSISRTAF LHVDYRKITPIDEPLVMRGRVTRTEGRKAFVSAELVDGDEMLLAEGNGMMVRLLAGQP >BL;ML0281, ML.tab 363432:364121 forward MW:25240 LNTSDSAPGVAVLLFGDDRTRQRWNTLTALSTYRAGGPDDIDSIDATIGPYRRLVVVGGDGDLAAVLGRLLRADRLDIEV (SEQ ID NO:46) AYVPHQRTAATRVYRLPTGRRAARRARRGYATRVPLIRDETGSVIVGRADWLPVVDRQPLNGEAIVDDIPLFDGDVAGVR IAPTLANPGLRARLHTSRTGIGIWSRWLTGRAVQLGSTGVAVVRDGVPTRRRERRSTFYRNVEGWMLVR >BL;ML0284, ML.tab 365860:366273 reverse MW:14541 MTSMGDLLGPDPILLPDDSAAEVELRANKDPGTVAAAHIPSASVAWAALAEGALADDKATTAYAYARTGYHRGLDQLRCNG (SEQ ID NO:47) WKGFGPVPYSHEPNRGFLRCVAALARAANAIGETDEYRRCLNLLDDCDPAARNELGL >BL;ML0285, ML.tab 366385:367263 forward MW:31593 MPNASEPERGITLNRPGLAPRTLDKNVVSNLPEAKDNPANTHGEEIAAGYPLAHSDSETEAMVLTKTEPDQDPGADRQHH (SEQ ID NO:48) ERRFTAPGFDARATAIMATAPDPATEAIHPPLSSSDPPGHLGISPKAAVPQSIPPVLGTKLRSARHFHWGWVVALLMMVL ALAAIAILGTVLLTRGKHVKASPAEQVRHAIQSFDVAVQTGNLTALRSITCGTTRDGYVEYDESSWDETYHRVSAAKQYP VIASIDQVVVNGQHAEANITTFMAYDPQVRSTRSLDLQFCDDQWKICQSPSG >BL;ML0298, ML.tab 381423:381647 reverse MW:7851 MIVXTVNERPVEVNEQTTVAALLESLGFPASGIAVAVEFSVLPRSYWATKISELPAVTGRSEPIRLEVVTAVQGG (SEQ ID NO:49) >BL;ML0370, ML.tab 461945:462814 reverse MW:30055 VRYRRQVAHTRKLLAALSRRGPHRVLRGDLSFAGLPGVVYTPAGGLNLPGVAFGHDWLTGTARYAGLLEHLASWGIVTGA (SEQ ID NO:50) PDTQRGLTPSVLNLAFDLGSALDIVAGVRLGPGNISVHPAKLGLVGHGFGGSAAVLAAAGLPGLAGLPAKSAVAIFPTVT SPAPEQPAATCKVPGLILTAPGDPKTLNSNALSLYRAWDDATLRIVSKAKAGGLVEGWRMTKVVGLAGPHRATQKAVRSL LTGYLLYALGGDKEYRDFADPDMHLPHTVPVDPEAPLVTPEQKIVTLLK >BL;ML0383, ML.tab 476440:477285 forward MW:29301 VTSVSIVVEIGHTSAAEPMLAAAAFGNQPGRWPLPTATTPHQLWLRAVAAGGQGHYSSAYRDLAVLRRSVPAGRLASLAH (SEQ ID NO:51) STEGSFLRQLGWHSLARGWDGRALVLAGTDSEARADALIGLAADALGVGRLAAAATLLRRVGSALAPAQLPAQVADRLAV RRRWVAAELAMAVGDGATAVRNAREAVELAQVGRVSVRHQVKSDVVLALCSAATEPRVVAEAALAATGRLGLIPLR WALACLLIDIGSVTFSEPELSELRDVCADQVRRAGGTWRTA >BL;ML0386, ML.tab 480093:480506 reverse MW:15294 VRDHLPPGLPPDPFADDPCDPSAALDAVEPGQPLDQQERIAVEADLADLAVYEALLAHKGIRGLVVCCDECQQDHYHDWD (SEQ ID NO:52) MLRANLLQLLIDGTVRPHEPAYDPEPDSYVTWDYCRGYADASLNQATSDADGYRRRH >BL;ML0405, ML.tab 503217:504401 forward MW:40754 MSGAFIIDPTLKAIEAWHALLGIGVPNDGGVLYSSLSFFEKALEHLAAAFPGDGWLGSAADKYAGQNRKRVDIFQELAEL (SEQ ID NO:53) DKELIELIHNQANSVQTTRGILDGAKKALLFVRPVAIDLNYIPLVGSVMSASIQAQACAAAMAAVSGGLAYLLVQTAIHT AKFVALLARLAHLLASAVADVVSDGVAIIKGIVDHLWHFIAGALTGLKDIVEKIIHWFFGLFSHWWSRLHSFFGGIPGLS GATSGLSQVTGLFGVPGLAGSSGLLSGESLLSTENLPSLAGVGAGLGLGSLPQLAQLHAASTRQGTRSQAGVSAELSTEQ FGGQQEPVSAQGSQGMGGSQGMGGMTPASTKSKKDERKKKKYSEGAAAGTDDAERAPIEVQSGGGKRALAQHVV >BL;ML0406, ML.tab 504459:504779 forward MW:11110 MRSMIDNLTVQSEHLNSLASQHENEAACASSGVSAAAGLANAVSTSHGSYCAQFNDTLKMYEDAHRTLGESLHTGGIDLA (SEQ ID NO:54) RVLRVAAANYCDADEICGSDIKSAFG >BL;ML0407, ML.tab 504793:505443 forward MW:24227 MGSRRRINRRLLPMSTFPAWQEFRRDVVVVFPGNDFDRDDCDTVDPWGVGGAAHWTIDPIVGFASSSAPQDRGTDVDNTR (SEQ ID NO:55) GQAEEDEKQKEPEVAIFTVTNPPRTVSVSVLMDGRIDHVELSKRVTWMSESQVASEILVLADLARQKAQSAQYTFILDKL SQLADGDEHRVALLRESVGNTWNLPSPEQAAEAEAEVFATRYSDYCPAQDTENDQW >BL;ML0410, ML.tab 508327:508629 forward MW:10951 MSFFLRVEVGGLMMAAGRLERITSESMACNAKLTPVTTKVVPPAADQVSKLVSQVFSSYGKQYEGYAAQGVDQSRLFVQS (SEQ ID NO:56) LKDAAGDYMDSDHMYLNTED >BL;ML0411, ML.tab 508755:509981 forward MW:42466 MFDFMVYSPEVNAFLMSRGPGSTPLWGAAEAWISLAEQLMEAAQEVSDTIVVAVPASFAGETSDMLASRVSTFVAWLDGN (SEQ ID NO:57) AENAGLIARVLHAVAYAFEEARAGMVPLLTVLGNIIHTMALKAINWFGQVSTTVAALEADYDLMWVQNSTAMTTYRDTVL RETGKMENFEPAPQLVSRYCMDRRDSVNSFHSSSSSDSLYESIDNLYDSVAQSEEHGSDSMSQSYNTCGSVAQSELCDSP FGTPSQSSQSNDLSATSLTQQLGGLDSIISSASASILLTTNSISSSTASSIMPIVASQVTETLGRSQVAVEKMIQSISSTA VSVDVAASKVVAGVGQAVSVGALRVPENWATASQPVMATAHSVPAGCSAITTAVSGPLEGVTQPAEEVLTASVAGGSGTG GPAFNEAV >BL;ML0418, ML.tab 517644:518276 forward MW:23558 LLSVDEVLTTTRSVRKRLDFDKPVPRDVLMECLQLALQAPTGSNSQGWHWVFVEDAEKRKAIGDIYLVNARCYLSQPAPEY (SEQ ID NO:58) PEGDTRGERMRLVRDSATYLAEHMHEVPVLLIPCLLGRAEESPLGAVSYWASLFPAVWSFCLALRSRGLGTCWTSLHLLG DGEQRAAEVLGIPSDKYSQGGLFPIAYTKGTDFRPANRLPAENVTHWDIW >BL;ML0425, ML.tab 524416:524643 forward MW:8231 VADRHPDTIKLEIDVAREQFAATVDSLAERANPRRLAGDLKARVVEFGRRPAVIAALVSCAVLTVIVVVRKVKNR (SEQ ID NO:59) >BL;ML0431, ML.tab 530916:531695 reverse MW:27233 MNNPRRSEWLGPSLAGSGPIEPQVHQYPPLTDPAYAEQAPYAPAYGASLPPWTPKKPPQQLPRYWQQDQPPPTDIPPEGL (SEQ ID NO:60) TLPPPHEPKSPHWFLWVVAGASVVLVVGLVMALIIANGAIKTQTAVPPLPAITESSSATPTPTTKTSPTPTAGPAPSTTG SGTLTQTIGPSAMLDVVYSITGQGRAISVTYMDTGDVIQTEFNVVLPWSKQVSLSKSAVHPASVTIVNIGHDVTCSVTVA GVQIRQHTGVGLTICDAPR >BL;ML0451, ML.tab 551191:552240 reverse MW:37930 MLTLLVLLVALATLAGGWGYQTANRLNRLHVRYDLSWQALDGALARRAVVARAVAIDAYSGTSPGRRLAALADAAECAPR (SEQ ID NO:61) HTRENAENELSAALAMVDPASLPTALIAELADAEARVLLARRFHNDAVRDTLALGEQRLVRTLRLRGTASVPTYFEIVER PHALTHGDHGVPNQRTSARVVLLDETGAVLLLCGSDPAITNGHAPRWWITVGGEVRPGERLAAAAARELAEETGLRVIPT HMVGPIWRRDAIFEFNGSVIDSEEFYLVYRTRRFEPSTVGWTELEHLCLHGSRWCDANDIAELVASGEQVYPRQLGELLP VANQLADASTGTARGTAAARNTYVLLSIC >BL;ML0486, ML.tab 589652:589996 forward MW:12749 MESLVLLLLFLLIMGGFMFFASRRQRRSMQATIDLYNSLQPGDRVNTTSGLQATIIVVGDDTVDLEIAPGVVTTWMKLAI (SEQ ID NO:62) RDRILPDDAYMDEHEAEPGDFVYCDELEESDGSS >BL;ML0520, ML.tab 631179:631787 reverse MW:21872 MNNWMLRGLVFAALMIVVRLMQGTMINVWQAQSVLISVVLLAVFIIAVVVWAARDGRADAIANPDPDRRRDLAMTWLLTG (SEQ ID NO:63) ILVGVLSDAVAWVISLLYNGIYTGGLVSELTTFSAFTALIVFLTGIIGVACGRWRVDRRSPPVPEHSRSGQNRADSNVFA AVCTDDDTPTGELSAAQTKEQTAAVATAESEAPTEIIYIIQRA >BL;ML0542, ML.tab 657980:658312 forward MW:11942 VSIPQSNTSLSAVIAVDQFDPSSGGQGVYDTPLGITNPPIDELLDRVSSKYALVIYAAKRARQINDHYNQLGEGILEYVG (SEQ ID NO:64) PLVEPGLQEKPLSIANREIHADLLEHTEGE >BL;ML0561, ML.tab 678085:678555 forward MW:17254 MTAQLDRDDWDVELRPYWTPLFAYAAAFLIAAAHITVGLLLRIKSSGVVFRTADQVAIGALGLVIASAVLLLTRPRLRVG (SEQ ID NO:65) AAGLLVRNIMFYRIIPWSHVVDVSFPLGSHWARIDLPDDEYIPLMAIQAVDKERAVEAMDAVRALLARYRAGPYGP >BL;ML0577, ML.tab 699950:700183 forward MW:8150 MELALQITLVVTSILVVLLVLLHRAKGGGLSTLFGGGVQSSLSGSTVVEKNLDRLTLFVTGIWLVSIIGVALLTKYR (SEQ ID NO:66) >BL;ML0580, ML.tab 704001:704798 reverse MW:29039 MSRVLTLVITPYSKANLKESIEAANGASHKYPNRIIIANRVNSYANKARLDAQLWVGADTGAGVVVSRTLAVYAHSVVIS (SEQ ID NO:67) ILLPDIPMVAWWPNIAPTMSGQDSLGKLAIQRITNATNSIDPLATIKSRLSDYTADDTHLAWDLITYWRALLTSAVNLPP HEPIDLALVSGMKTEPALDVLAGWLANRINRPLRRAVADLKVELIRNSETIVLSRPQTWVTSTLIRTVKPDALVPWGAQG SRGVPSRKSATTGSRQVLLQCLRRH >BL;ML0603, ML.tab 735002:736117 forward MW:39051 VLVLWRCFRVANISALMVAVACLPDWLSGFLTGGLIAGSSARRATIYGVSNKFSSLHLVLGNEELLVERAVGEVLRSARQ (SEQ ID NO:68) RAGTQDVPVSRMRAGDVGTYELTELLSPSLFADERIVVLEAAAEAGKEAAALIVSAAADIPQGTVLVVVHSGGGRAKALA NELQSLGATVHPCARITKLSERTDFVRKELRSLRVKVDEGAVTALLNAVGSDVRELASACSQLVADTAGDVDADAVQRYH SGKAEVKGFDIADKAVGGDVSGAVEALRWANMRGEPLVVLADALAEAVHTIGRVGPLSGDSYRLASRLGMPPWRVQKAQQ QARRWSRDTVAAAMRVVAALNADVKGAAADAYYALESAVRKVAELAADGSR >BL;ML0630, ML.tab 763032:763358 forward MW:11114 MAELLNTEDAKLVVLVRAAMARTEAGSGAVVRDFDGRTYAAAPVTLSTLELIGLQEEAAAAFSASSVVSGLEVGVLVAGS (SEQ ID NO:69) VDEPDIAMVRELASTAVVILIDRNGNRV >BL;ML0642, ML.tab 774506:775945 reverse MW:50246 VAHSGSPVSTVDGVANPPFGFSSGNDSPNDESGRDKHGKNGPDSGSSGSDPLASFGMSGDFGMSDLGQIFTHLGQMFTNA (SEQ ID NO:70) GTAMTADKQLGPVNYELARRVASSSIGFVAPIPATTSSAIGDAVHLAETWLDGVTALPAGTTKAEGWTPDDWVNNTLETW KRLCDPMAQQISTVWAASLPEEAKSMASPLLSMMSQMGGMAFGSQLGQAFGQLSREVLTSTDIGLPLGPRGVAAIMPQAV ESFADGLEQPRCEILTFLATREAAHHRLFSHVPWLASQLLGAVEAYAAGMKIDMNGIEELARDFNPASLSDPTAIEELLG QGVFEPQATPAQTQALERLEALLALIEGWVQVVVTAALGDRIPGAAALGETLRRRRASGGPAEQTFATLVGLELRPRKLR EAAVLWERLTQAAGVDARDAVWQHPDLLPSGKDLDDPASFIDRIIGGDTSGIDEAIAKLDLDRGNSDGRTPGSGGPVDN >BL;ML0676, ML.tab 811815:812291 reverse MW:16889 MFLRLMLSALKALQRLGAVMNSLARIDHWIWLFRCQPLTIRLLVATAALFTAATAFEVPAEADAIDDTFIKALNHAGVNF (SEQ ID NO:71) GEPRSAMTMGHYVCPILAKSGGNFAAAVQRIRGNSDMSPQMAETFAKIAISIYCPTMMANVASGNLPSLPPGPGIPGI >BL;ML0703, ML.tab 840882:842153 reverse MW:46028 MVADLVPICLSLPAGDRYTVWAPRWRDGGDEWEAFLGKDDNLYACETVADLVAFVRTDSDNDLVDHPAWKDLTSVHAHKL (SEQ ID NO:72) DPSEDNQFDLVVVEELVAEKPTAESVTTLAATLAIVASIGSVCELPAVSKFFNGNPSLGAVSGGIEHFTGRAGQRRWNSI AEIIGRSWDDVLSAIDKVISTPRVNAAMSAKAADELAEEPVEPEVEPDDEDGADSATAQANNSDDTEDESRTAGDTVVLG SDKDFWLQVGIDPVRIMTGAGTFYTLRCYLDDHPIFLGRNGRISVFSSERALARYLADEHDHDLSYLSTYDDIRTAATDG SLAIDITDDNIYVLSGLSDDLADGPDAVDRDQLDLAVELLRDIGQYSEESAVDTALETNRPLGKLVAHVLSPSAVDKPVA PYSAAVREWEKLEQFVESRLRLE >BL;ML0730, ML.tab 871757:872011 reverse MW:9373 VSAANDGSETNKLPTTQNPHIQITKGQPTDQELAALIVVLSSIGGASQVKQPEPTRWGLPVDKLRYPVFSWQRITLHEMT (SEQ ID NO:73) HMRR >BL;ML0733, ML.tab 874677:875195 forward MW:19913 MRYPGNTLVAGEQVVLHRHPHWKRLIWPAVVLILATGLVSFGSGYVNSTHWAQVAKNVIYGVLWGVWLVIVGWLTLWPFL (SEQ ID NO:74) NWLTTHFVVTNRRVMFRQGTLTRSGVDIPLARINSVEFRDRLFERMFRTGTLIIESASQDPVEFYNIPRLRQMYALLYHE VFDTLGSEESPS >BL;ML0734, ML.tab 875150:875836 reverse MW:25515 VSFPDATITRLPTVLQPYAQRYHELIKFAIVGGTTFIIDSAIFYTLKLTILEPKPVTAKVVAGIVAVIASYVLNREWSFR (SEQ ID NO:75) DRGGRERHNEALLFFAFSGIGVLLSNAPLWFSSYVLQLRAPTVSLTVENLADFLSAYIIGNLLQMAFRFWAFRRWVFPDA FARNPEKTLESALTAGGIAEVFEDAIDGVFEDFGDALLRAWRNRSRRLDLSPASQLGDSSEPRVSKTS >BL;ML0748, ML.tab 890981:891259 reverse MW:9830 MVQGLLAKAATMVITGLTGVTAYEMLRKAVTKVPLHQIAVSALELGLRGSRKAEEAAESARLKLADVMAEARERIGKETT (SEQ ID NO:76) APAVSDIHQHDH >BL;ML0761, ML.tab 903525:904028 reverse MW:18775 VSNSCSSSRHGQWSRRFSSRRAAKRGRDIRGPLLPPTVPGWRSRAERFDMAVLEAYEPIEQRWQGRVSELDVAVDEIPRI (SEQ ID NO:77) AARNPENVQWPPEVIADGPIALARLIPAGVDVRSNATRARIVLFRKPIERRAHDTVELGELLHDILVAQVAIYLDVEPSA IDPTMDD >BL;ML0762, ML.tab 904068:904565 forward MW:17248 MRVSGASATFSHDSLSVVNVPRRCCRPGCPHYAVATLTFVYSDSTAVVGPLATVREPHSWDLCVDHAARITAPRGWELVR (SEQ ID NO:78) HAGPLPSNPDEDDLVALADAVREGPGGEHGSYGNGARASLGGFADPQLQSAGAHATVPSGGLLAPSELRSGRRRGHLRVL PDPSD >BL;ML0764, ML.tab 906078:907175 forward MW:37464 VNATRLIDLEDTKGLIAADRDGLLRAASSAGAQVRAIAAAAEEGALETLRAHDRPRTVIWVAGRGTAETAGAMLAATSGG (SEQ ID NO:79) ATTEPIVVASEAPPWVGPLDVLIVAGDDPGDPALVGAAATAVGRGARVVVVAPYEGPLRDATAGRVAVLEPRLRIPNEFG LCRYLAAGLAALQTVDPRLRLDLANLADELDSEALHNSVGYEVFTNPAKTLAASVSGHRVALAGDCAATLALARHGSSVL LRIAHQVTSATGLSDAVVAVRSSVDVADYAPTSVDVLFHDEEIDGSLPERLRVLALTLASERTVVAARVVGLDDVYLVAA EDVPDGPSGLAGLPVSGGADRAEQELANLAVRLEMAAVYLRLVRG >BL;ML0776, ML.tab 920258:920515 forward MW:8946 VAGCGVFATRWSDACTAELSVAAGEPRVVSLCVDPLVPVVVLGRYVGARRQAILAMKEHGRRNLVALPTRQCVSRLGSCT (SEQ ID NO:80) LPGRG >BL;ML0806, ML.tab 955206:955727 forward MW:17808 VDRVIALLSSGAIVGPCDYADVVTLPHKRAVFSRAPAAVRGAGLIVVVQGAVALVVAAALVVRGLTGADQRIVNGLGTAI (SEQ ID NO:81) WFVVVGVAVLAAGCALLVGKRWGRGLAVFTQLLLLPVAWYLVVGSHQSAFGFPMGIVALIALILLFSPPAVRWSAGAYQR SVASSANRKADSR >BL;ML0810, ML.tab 958882:960105 reverse MW:42979 MVRPERRTKADTIAAMTITVVMAAMVSLIWWTSDAQATHSRPATIPAPNPTPAREVPTAFNQLWAAASPATTAPVVVGGA (SEQ ID NO:82) VITGDGHQIDGRNPVTGESRWSYARDSDLCGVSWVYHYAVAVYRDDRGCGQVSTIDGSTGRREAARSSYADPNVRLSSDG TAVLSAGDTRLELWRSDMVRMLAYGEIDARVKPPARGLHSGCTLESTAASSSAVAVLEACANQDDLQLVLLRPGKEDDEP QQHLVAEPRVRSGSGARVLTVSDTHTAVYLPGEAGTQPRVDVIDETGTTVASTLLTKPPSSSAVVSQAGNLVTWWTGDTL MVFNQSNLTLRYTIAAGETTAPVGPGVMMAGQLLVPVTGKIGVYDLFSGANNRYIPVRRPPSSSAVIPAVSGSTVFEQRG DTLVALG >BL;ML0813, ML.tab 962707:963294 reverse MW:20353 MRLTETTSIRRTTTTSYSGHPIVDGRQVAALLGSVAALCAIATAVIINSGDNATTKAIVGAPTPRPVLTTPSIPLPATPS (SEQ ID NO:83) STPPLLLLFDTATATIPHKAAPPALHPRTVVYNVTGMKELLDLVTVVYTDARGYPKTEFNVVLPWTKAVVLNLGVKTQSV VATSFHSQLHCSIVNAEGQPVVASTNNAVIATCTR >BL;ML0814, ML.tab 963593:963841 forward MW:8652 VEVKIGITDSPRELTFSSAQTPGEIEELVSAALREGLGLLVLTDERGRRFLIHGAKIAYVEIGVADARRVGFGIGAESAT (SEQ ID NO:84) NG >BL;MLO816, ML.tab 964701:965726 forward MW:37443 VSSPGPVGSPGRVPVLREEWRAPLRAQREPLARGEGRVRVNRGRSRRWRKQTRLGRFVSVFGWRAYALPFLMALTAVVLY (SEQ ID NO:85) QTVTGTNAPEPAASEPITEPPVIGAVGTAIMDVPPRGLAAFDANLPAGTLPDGGAFTEAGDKTWHVVPGTMPQISQSATK VFKYSIEIENGLDPTMFGGDGAFAQMVDQTLANPKGWTHNPQFAFTRIDTGMPDFRISLVSPLTIRAGCGYEFRLETSCY NPSFGPDRQARVLINEARWLRGALPFEGDVGSYRQYVINHEVGHAIGYVRHEPCDKQGGLAPVMMQQTFSTSNNDGAKFD PEWVKPDGKTCRFNPWPYPIA >BL;ML0818, ML.tab 967172:968065 forward MW:32374 LRSPRSGSTRLTRVTVEPPPEHVLSAFGLTGVQPVPLGASWEGGWRCGEVVLSMVADNARAAWSARVRETLFVDGIRLAR (SEQ ID NO:86) PVRSTDGRYVVSCWRANTFVAGTPEARHDEVVSAAVRLHEATGKLERPRFLTQGPTARWADVDIFIAADRAAWEGRPLQS VPSGVWAAPMTTDGQRSVDLINQLAGLRKPTRSPNQLVHGDLYGTMLFVGTAAPGITDITPYWRPASWAAGVVVVDALSW GEADDGLIERWNALPEWPQMLLRALMFRLAVHALHPRSTAEAFPGLARTAALVRLVL >BL;ML0834, ML.tab 990401:990703 reverse MW:10909 VRQDGASRTVVGGTALIRYVIVLGLGYVLGAKAGRRRYEQIVGIYRTLTGSPMAKSMIAEGRRKVANRISPDEGFVTLAE (SEQ ID NO:87) IDNQTTVIERSAEWRENGGN >BL;ML0857, ML.tab 1019690:1020442 reverse MW:26808 MAKPRNAAAHKAARAEAKAARKAASRQRRLQLWQAFTIQRTEDKRLIPYMIAAFSLMVSASVTAGVLVGGLTMITLILLG (SEQ ID NO:88) VVLGALVAFIIFGRRTQQSVYHKAEGQTGGAAWALDNLRGKWRVSPGVAANGHFDAVHRVIGRPGVIFVAEGSAARVKPL LAQEKKRTARLVGDVPIYDI IVGNGDGEVALVKLERHLARLPANISVKQVDILESRLAALGSRAGASLIPKCPLPNACKN RGVQRTVRRK >BL;ML0869, ML.tab 1033201:1033575 reverse MW:13804 MMAGEEAYLPPRDQGPVRRYIRDLVDARRNALGLFTPSALVLLFITFGVPQLQLYMSPAMLVLLSVMGIDGIILGRKISK (SEQ ID NO:89) LVDVKFPSNTESHWRLGLYAAGRASQMRRLRVPRPQVEHGSSVG >BL;ML0872, ML.tab 1035615:1036130 reverse MW:19047 MLPPAVSYPRRRSKRLI ISVLVAIALVAAMTAVI IYGVRTNGSKTGGTFSEVTAKTAI EDYLKALEQSNINTIARNALCG (SEQ ID NO:90) MYDSVRDQRPDQALAQLSSDAFRKQFSQVELTS IDQIVYWSPYQAQVLFTMRTSPATGGPKRRQIQGIAQLLYRRNQVLV CSYMLRTADSH >BL;ML0876, ML.tab 1040896:1041315 forward MW:14969 MHI EARLFEFVAVFFVIMAVLYGVLTSMFATGGVDWVGTTALALTGGLALIVATFFRFVARRLDI RPEDYEGAEISDGAG (SEQ ID NO:91) ELGFFSPHSWWPVLVALSGSVAAVGIALWLPWLIVAGVVFVLASAAGLVFEYYVGPEKH >BL;ML0878, ML.tab 1042383:1043021 forward MW:22756 MMNRYSPY2RGSDTIASDVIDRILVGVCAAVWLVLIGVSVAAAVALEDLGRGFHKIASDPHTTWVLYGIIVVSVLIIAGA (SEQ ID NO:92) VPVLLWARRVARVEPPIRPAGVPERGGVRQLVSAGRSTARIEVERVCAEERVQSVAQPGEWFDAAVDRIWLRGTVGLTGT MGAALVAVAASTYLMAVGRDGASWVGYVLAGIVTAVMPVIEWIYVRQLRRVG >BL;ML0888, ML.tab 1055260:1055667 forward MW:15125 MNSTNS IQIADETYVAADRALIGAAVADRSSWHRWWPDLRLQVVEDRAEKGIRWAVTGTLTGTMEIWLEPLTEELDGVVL (SEQ ID NO:93) HYFLHAEPAGVAAWQLAKMNMAKVTHRRRVAGKAMAFEVKKTLERSRSIGVSPVI >BL;ML0889, ML.tab 1055786:1056220 forward MW:16483 VADKTTQTFYIDANPGEVMKTIADIESYPQWISEYKEVEVLEVDDEDFPKRARMLMDAKIFKDTLIMSYDWTADHQSVSW (SEQ ID NO:94) ILESSSLLKSLEGSYRLVPKGSTTEVTYELAVDFAIPMIGMLKRKAEHRLIDGALKDLKKRVEG >BL;ML0891, ML.tab 1057485:1057877 forward MW:13550 MSGGYADIGPELRKLAQMTLDGIGPAVRSAAALVAGARGTGKCQQAWCPVCALTALVIGEQHPLLTVIADHSVALLDVIR (SEQ ID NO:95) AIVDDIDQSNKIPPDSPHGGGLDTETPAQTNTSNGTVRRRYQPIPVSVED >BL;ML0895, ML.tab 1061008:1061523 forward MW:19954 MRYPYDTEFIEDGRTIELVSIGVVAEDGREYYAVSNEFDPERAGNWVRVNVLSKLPPLASQLWRSRRQIRLDLEEFFGVD (SEQ ID NO:96) GSEPTEPIELWAWVGAYDHVALCQLWGPMPDLPEALPRFTREIRQLWEDRGCPRMPPRPRDLHDALVDARDQLRRFRIIM SADDVGSLPTH >BL;ML0898, ML.tab 1064343:1064747 forward MW:14698 VGSIPAGDDVLDPDEPTYDLTQVAELLGIPVSRVHRKLCEGYLVAVRRGDSLVVPQIFFTNSGAVVKSLPGLLTILHDGS (SEQ ID NO:97) FHETEIVRWLFTPDPSLTLTRDGSRDVVSNARPVDALHTHQAREVVRRAQAMAY >BL;ML0902, ML.tab 1068511:1069230 reverse MW:25542 VRARFPPLFTRGCTAQRRRTLTIALLLVAMVPLATGCLRVTASITISPDNLVSGKIIAAAKPKNKNDAGPQLNDNLPFSQ (SEQ ID NO:98) KIAVSNYNSDGYVGSQAVFSDLTFAELPQLANMNSSTTDVTLSLRRNGNLVILESRADLTSVTDPDADVELTVAFPGVVT STNGDRIETKVVAWKLKPGVVSTMSARARYTDPDTRSFTGAAVWLGIASFSAASVVVLLAWNERKSSARLQIPRDSSSS >BL;ML0903, ML.tab 1069302:1069934 reverse MW:23864 LAIFLINLSPNEMERRLNEALEVYVDAMRYPRNTENLRAGIWLEHIRRPGWQAVAAVEVRIEVADVADMADGPAHPAPSA (SEQ ID NO:99) DELNNAPLRGVAYGYPGAPGQWWQQQVVQGLQRSGLSTLEIARLMNSYFELTELHIHPHTQGRGIGEALTRRLLAHRREN NVLLSTPETNGETNRAWRLYRRLGFMDIIRRHYFAGDPRAFAILGRTLPL >BL;ML0904, ML.tab 1070251:1070655 forward MW:14614 MPLSDHEQRMLDQIESALYAEDPKFVSSVRGGGLRVPTARRRTQGAALFVIGLGMLVCGVAFKATMIGSFPILSVFGFVV (SEQ ID NO:100) MFGGVLFAITGSRLSGREDHPGLAPGTSRQRRSKGAAGSFTSRMEDRFRRRFDE >BL;ML0907, ML.tab 1072702:1073835 forward MW:39543 MKAQRDTPIRRGDSGRPGGRDGAARSGKRTANEAGSRRLRTHAGKISASAREVGVPKSGPRTSPMSRPVERPARPRNTTQ (SEQ ID NO:101) AKARAKARKAKAPKVVRPRLGECLIARLALIDLRPRTLVNKVPFVVLVISSLGVGLGLTLWLSTDSAERSYQLGDAREQA RMLQQQKEALERDVREAESAPALAETARKQGMIPTRDTAHLVQGPGGNWVVVGTPKPADGVPPPPLNTKLPDAGPPSLKP PEIPLEVPVRVVPGPGGPPPPARSGPQMWLRVPDGATTLGGQHLPQELPQLPGMLNGPAAAQVQVPGFMPTPGLPIPGST MRVPVPAPAPTEVPVRLQPGLVSPAVTSPVISTSPVPTPVNSEQFGPVTATAPGTSR >BL;ML0920, ML.tab 1090054:1090686 forward MW:24016 MSTLHKVKAYFGMAPMEDYDDEYYDDRSPTHGYGRSRFEEGYGRYEGRDYSDLRGDPTGYLPLGYRGGYGDEHRFRPREF (SEQ ID NO:102) DRPDLSRPRLGSWLRNSTRGALAMDPRRMAMLFDEGSPLSKITTLRPKDYSEARTIGERFRDGTPVIIDLVSMDNADAKR LVDFAAGLAFALRGSFDKVATKVFLLSPADVDVSPEERRRIAETGFYAYQ >BL;ML0921, ML.tab 1090811:1091101 forward MW:10769 LALFYQILGLALFVFWLLLIARVVVEFIRSFSRDWRPNGVTVVILETIMSITDPPVKLLRRLIPQLTIGAVRFDLSIMVL (SEQ ID NO:103) LLVAFIGMQLALSAAA >BL;ML0923, ML.tab 1092221:1092613 forward MW:13650 MLIIALVLALIGLVVLVFAVATSNLLMAWVCIGASVLGVLLLIVDAVREHQCIDAANNEDKEDTDQDDGAVYVDYLDEVP (SEQ ID NO:104) AGTSTEAPDAGSQEGDTNSGELSGYWGRLTIDTGEQSAVAADDHDNDRAT >BL;ML0984, ML.tab 1151024:1151473 reverse MW:16902 VAIAELTEASVQGVENIRTVEVFLAALQDAGLRNRIRDVGRQPRVYQNVGLPTIHGRSKTITLWRKMADCIGFEIKIHRI (SEQ ID NO:105) AAVAIAVLCERADAVIVGPLWMQFWVCGTFEVQNKRIMLWPNYFDLFDLFKATMRSLVALRIPSLNAAF >BL;ML0986, ML.tab 1152702:1152905 forward MW:7514 LAGVRLTEFHERVVLRFGAAYGASVLVDHVLTGFDGRTVAQAIEDGVELRDVWRALCVDFDVPRDQW (SEQ ID NO:106) >BL;ML0990, ML.tab 1157281:1157910 forward MW:22743 MNEEPNIVDFPDSNPLQAALEAEELRVVREIDSGAKIFVLIAVLVFMLLGSFILPHTGQVRGWDVLFDSHGAGAAAVALP (SEQ ID NO:107) LRIFAWLSLVFGVGFSMLALMTRRWVLAWIALAGAANASIVGLLAVWSRQTVAVGQPGPGVGLIVAWITLILLTFHWARV VWSSTIVQLATEEQRRRVVAQQQSKTLLDGLYSAGNRDTRTRSDPQVGS >BL;ML0994, ML.tab 1162620:1163318 forward MW:23576 VLSAIAIVPSAPVLVPELTGAAAAEVADLRSAVLAVAACLPPCWIVVGTGRADDVVGPGGCLGTFAGFGADVRVRLSPQV (SEQ ID NO:108) GGEAELLVDFPVCALIAAWVRGQSQLDASAQVRVYCGDHDPDMALACGRQLRVEIEQAPDPIGVLVVADGATTLTSSSPG GYDPSAADAELVLDDALASGDVAALTRLSCQISGRVAFQVLAGLVEPGPRLAKELYRGAPYGVGYFVGVWQP >BL;ML1001, ML.tab 1172599:1172874 reverse MW:10150 MPDPVVMPVPCPTSGFTQYSPYYRGAQITLLQQTILAKLNQKYYNNRYRVDVEMVLSHTGVEADSAASHTILGLSSSILP (SEQ ID NO:109) PYGCRTKKQRS >BL;ML1004, ML.tab 1176008:1176502 forward MW:17108 MLVIYAVPPLIGNVRHPMSRPILGPRCGSGESAGSRRPAPSRSASAPMRYSGASVANLVAPHRGRTVSLAKTIGLALLAG (SEQ ID NO:110) MITLWLGLMADVSQVIDGDATGFVTHVPNRLAVVRVEAGESLQDVAARVAPDAPVRQVSERIRELNVLDSSMLVAGQTLI APVG >BL;ML1009, ML.tab 1179519:1180499 reverse MW:36153 MSHSHYQDPDDEQHYQPGQPGMYVLEFPAPQLLASDGRGPVLIHALEGFSDAGHAIRLAATHLKAALNTELVASFAIDEL (SEQ ID NO:111) LDYRSRRPLMTFKTDHFTHYDDPELSLYALRDSVGTPFLLLAGMEPDLKWERFITAVRLLAERLGVRQTISLGTVPMAVP HTRPITLTAHSNNGELIADFTPWITEIQVPGSASNLLEYRMGQHGHEVVGFTVHVPHYLTQTDYPAAAQALLEQVAKTGA LQLPLSALAEAAAEIRAKIDEQVQASTEVAQVVAALERQYDAFIDAQENRSLLRRDEDLPSGDELGAEFERFLAQQAEKK RDDDLT >BL;ML1015, ML.tab 1185456:1185875 reverse MW:15761 VGKLSTAPNRGTTDTFDDNSRPVLITTAAPSYEEERRTRVRKYMTLMAFRIPALMLTTVAYSAWHNGLISLLIVAASVPL (SEQ ID NO:112) PWMAVLIANDRPLRRTEEPRRFDSRRRRTPLLLTTEQPAFKSLRRPPPKPTSLATDSRS >BL;ML1016, ML.tab 1185903:1186226 forward MW:11848 VSGFCFSVGRVRRHNVTMLGRHNVTMLGMQTQTIEHTYTDEHVDDGTGSDTPKYFHYVKKDKIVESAVMGSNVVALCGEV (SEQ ID NO:113) FPVTRAAKPGSPVCSDCKRVYDMLKKG >BL;ML1O2S, ML.tab 1192722:1193372 reverse MW:22931 VVTQITEGTAFDKHGRPFRRRNARPAIFVVVFLVIVAGVSWTIALTRPAKVREPEVCNPPTQSTGSVPTQLGKQVPRTEM (SEQ ID NO:114) TDVTPAKLSDTKVHVLNASGRDGQAADIAGALRDLGFAQPTAANDPMYADTLLNCQGQLRFGTAGQATVAAVWLVAPCTE LLHDNRTDDSVDLALGTDFTALAHNDDIDAVLASLRPGATEPSDPALLQKIHANSC >BL;ML1026, ML.tab 1193568:1193870 forward MW:10969 MPTDYDAPRRTETDNVPEDSLEELKARRNEAASAVVDVDESESAESFELPGADLSGEELSVRVIPKQADEFTCSSCFLVQ (SEQ ID NO:115) NRSRLASEKNGVMICTDCTA >BL;ML1027, ML.tab 1193875:1194348 reverse MW:17131 VSGTPVAPHNVRYRERLWVPWWWWPLAFALASLIAFEVNLSGATLPSWLPFAVAAGTLLWLGRVEIQVIADAPLGGSVEL (SEQ ID NO:116) WAGNAMLPITAIAQSAAISRSAKSAALGRQLDPAAYVLHRAWVGPMILVVLDDPDDPTPYWLVSCRHPERVLSALRS >BL;ML1029, ML.tab 1194835:1195656 forward MW:29018 VTADDDAERSDEDGAAVMATFGKRTGKDGASRTLTEPADPEATELPAASEPDSEEVDELEGPFDIDDFEDPAVAVLARLD (SEQ ID NO:117) LGSVLIPLPEGSQLQVELTDVGVPNAVWVVTANGRFTITAYAAPKTGGLWREVAGELADSLRNDSAKVTVKDGPWGREVV GTNTGVVRFIGVDGYRWMIRCVVNGPLETIDVLSEEARAALADTVVRRGDTPLPVRTPLPVQLPEQMAEQLREAAVAQQS AQHADARQQSRELAPRRGAAGSAMQQLHNTTGG >BL;ML1030, ML.tab 1195701:1196399 reverse MW:23579 VAVDLRNVTTVLLPGTGSDDDYVYRAFSGPLHRVGAAVLTPPPQPNRLIDGYLSALDDAARAGPIGVGGVSIGAAVAAAW (SEQ ID NO:118) ALAPERAVAVLAALPAWNGAPESAPAALAARYSASHLRRDGLAATTLQMQASSPPWLADELARSWCGQWPLLPDANEEA AAYIAPSCAELARLATPLGVAAAVDDPIHPLQVGVDWVTAAPHAALQTVTLNQIGTNAAALGTACLAALALT >BL;ML1037, ML.tab 1200579:1201133 reverse MW:19903 VSHEYWSTAVSCNPGIHHIVRLDVAJ4TPRTTQTYRHSMLAEDIAEDFPAISINSSALDAARMLAEHGLPGLLVTDMSDKP (SEQ ID NO:119) YAVLPASQVVRFIVPRYIQDDPSLAGVLNESTADQAAEKLSSKKVRDVLPDHLVNVSPVNADDTIIEVAATMSRQRSPLL AVVKGGQLLGVITASRLLRAALKH >BL;ML1O41, ML.tab 1206538:1207128 reverse MW:21153 VAPVTAAEPTPFREAVAAMNAFTVRPEIELGPIRPPQRLAPYSYALGAQVKHPELDIVPEQSEDNAFGRLILLYDPDGSD (SEQ ID NO:120) AWDGTIRLVAYIQSDLDSREAIDPLLPEVAWSWLIEALESRIDHVTALGGTVTATTSVRYGDISGPPRAHQLELRASWTA TTPEVGVNVKAFCEVLENAAGLPPAGVIDLGSRSRS >BL;ML1053, ML.tab 1220374:1220673 forward MW:10117 MPLFLNAEPQALTAAANTLEGLSAATVASNAAAAQLTTEIAPPAADDVSILLAHFFSGHGRQYQAHASQGATNHQDLIQS (SEQ ID NO:121) LLTSSSAYAGTETANIHDSL >BL;ML1055, ML.tab 1221433:1221735 forward MW:11298 MTAAHFMTDPQAMRDMARKFDMHAQNVRDESHKNFMSSMDIAGAGWSGTAQLTSHDTMGQINQAFRHIVTLLQDVRDQLG (SEQ ID NO:122) TAADRYEHQEENSRKILSGS >BL;ML1056, ML.tab 1221787:1222074 forward MW:10260 MGNINYQFGEIDAHGAAIRAQAAALETTHQAILATVRDAAEFWGGQGSTAHEMFIADLGRNFQMIYEQANSHGQKVQRAS (SEQ ID NO:123) SSMADTDRSVSSAWS >BL;ML1065, ML.tab 1230644:1230988 forward MW:11933 VALVLLYLVVLVLVAIVLFGAASLLFGRGERLPPLPRGTTATVLPAHGVTGADVDAVKFTQVLRGYKPSEVDWVLDRLGR (SEQ ID NO:124) ELEALRGQLAAIADAEADADVSNVPSGDDGQDVT >BL;ML1067, ML.tab 1231777:1232004 forward MW:7998 MLGAEWVREGGPARVWREHTMAAMKPRTGDGPLEATKEGRGIVMRVPLEGGGRLVVELTPDEAAALSDELKGVTS (SEQ ID NO:125) >BL;ML1077, ML.tab 1240278:1240697 forward MW:15219 VMADRGQVFRRVFSWLPAQFASQNDAPVGAPRRFGSTEHLSVEAIAAFVDGELRMNAHLRAAHHISLCAQCAAEVDDQSR (SEQ ID NO:126) TRAALRDSHPIRIPSTLFGLLTAIPRCSPDYTSPVSEPFSEGSVSDRFVDGVAREQGKR >BL;ML1079, ML.tab 1242373:1242735 forward MW:13348 VFANIGWGEMLVLVVVGLVVLGPERFPGAIRWTLGALRQTRDYLSGVTNQLREDIGPEFDDLRGQFGELQKLRGMTPRAA (SEQ ID NO:127) LTKHLLDGDDSLFTGNFDRPAAAKQQDRDNHQTPFDTDAT >BL;ML1093, ML.tab 1257729:1258586 forward MW:29736 MRVGRLAALLLAGVGVFVAGGCATDRGDRHPELVVGSKPDSESTLLAAIYVAALRSYGFGARGETGADPMAMLDSGGFTV (SEQ ID NO:128) VPGFTGKVLQILQPRAAVLSAARVYRANVSALPEGIAAGDYTTAAEDKPTLVVTPDTAKAWSGSOLSLVLSHCNELVVGI VAGTHTPSAVGSCRLPAAREFPDYPTMFAALRAGQLTAGWTTTANPDLPADLIVLTDGKATLIQAENVVPLYRRNVLTDR QMLAINEVAGVLDTAALIEMRRQVIRGADSQAIADGWLAEHPMGR >BL;ML1096, ML.tab 1263932:1264606 reverse MW:23505 LAQVIERSVWIQGPAAEAYVARLRRTHPSASPTEIVAKLEKHYLAALTASGAVVGSVATLPGIGTLAAVSANAGETVFFL (SEQ ID NO:129) EATAVFVLTIASVYGIPANHRERRRALVLAVLAGDDTRLTIGELIGPGRTNGGWLLEGMASLPLSTWSQLHTRMLRYAAK RCTVRRGALMFGKILPIGIGAAVGGAGNRVVGKKIISNTRNAFGTAPSRWPATLILLPTVHNAG >BL;ML1098, ML.tab 1266648:1270106 reverse MW:126012 VFVTDETIVYSASDLAAASRCEYALLRDFDARLGRGPVVATTEDELFARTSALGADHEQRHLDQLRHEFGDAVAVIGRPA (SEQ ID NO:130) YTYAGFAAAAEATQRAIANRAPAVYQAANFDGRFVGFIDFLVRDGEQYRVVDTKLARSPKVTALLQLAAYADALAHSGVP VAPEAELRLGDGMVVSYRICDLIPVYRSQRSLLQRLLDRHYTAGTAVRWQDDEVRSCFRCPQCTEQLRATDDLLLIAGMR ISQRSKLLNVGITTIAELADHSGPVPDLSSSALSELTAQAKLQVQQRNTGTPQFEIVDPQPLALLPDPDPGDLFFDFEGD PLWTVDGQEWGLEYLFGVLDSEISGTFRPLWAHNRVEERKALTEFLKMVTKRRKQRPHMHVYHYAPYEKTALLRLAGRYG VCEDEVDELLRSGTLVDLYPLVSKSIRVGAESFSLKALEPLYMGKQLRSGDVTTATDSITCYGRYCELLSAGNFDEAATV LKEIEDYNHYDCRSTRELRNWLLLQAYEAGVVPVGAQPVPEGNTVKDDDELSAILSALSGFTGDVAVGDRTPEQTAIALV AAARGYHRREDKPFWWGHFDRLNFPVGEWADNTDVFVADDASIIIDWHTPPRARKPQRRVRLRGRLARGNLGSAVFALYD PPAPLANDVHPGRRAAGRAEVVEADDLSIPTEVVIVERVGNDGNTFHQLPFALTPGPPIATTALRDSIESTATTLAASLP QLPRTALIDILLRRIPRTHSGATLPRGTDTVADITAAVLDLDSSYLAVHGPPGTGKTHTAAHVITQLVSNHSWRIGVVAQ SHAAVENLLDGVITAGLDARQVAKKRHDRSAPPWQEIDGNDYPTFIADPMGCVIGGTAWDFANRNRVPPGSLDLLVIDEA GQFCLANTIAVAPAAANLMLLGDPQQLPQVSQGTHPEPVNTSALDWLVEGQRTLPNERGYFLDRSYRMHPAICAAVSTLS YEGKLHAHTEYTAARRLNEYQPGVHVLAVHHQGNSTESPEEAGAITAEIERLLGTPWTDEHGTRPLDVSDILVLAPYNAQ VALVRQQLMSAGFSGVRVGTVDKFQGGQAPVVFISMTSSSVEVVPRGISFLLNRNRLNVAVSRAQYAAVIVRSETLTEYL PATPVGLIDLGAFLTLTTFNGTGRLESRLDKP >BL;ML1099, ML.tab 1270157:1270765 reverse MW:20773 VRDVWSLPCRKSLLGVAAVVLVSGTLTGCSSGDSTVAKTPVPPSTTTGTISTIISSAPSPPFATAAPPTSNTPPDDPCAV (SEQ ID NO:131) NLASPTIARVVSELPRDPRSAQPWNPEPLAGNYNECAQLSAVIIKANTNAVNPTTRAVLFHLGRFIPQGVPDTYGFNGID PAQTTGDTVALTYPSSIDGLATAVRFHWNGNAVELISNIAGG >BL;ML1105, ML.tab 1279262:1279951 forward MW:24905 VLSGGAGSIPELNAQISVCRACPRLVDWREEVAVVKRRAFADQPYWGRPVPGWGSEQPRLLIVGLAPAAhGANRTGRMFT (SEQ ID NO:132) GDRSGDQLYAALHRAGLVNLPISMDAADGLQANQIRITAPVRCAPPGNAPTQAEWVTCSPWLEAEWRLVSEYVRAIVALG GFAWQIVLRLPGVSANRKPRFSHGVVAQLYAGVRLLGCYHPSQQNMFTGRLTPANLDDIFRDAKKLAGI >BL;ML1115, ML.tab 1291563:1292129 forward MW:19913 VRCDVRALALAARGLIELMIVIPMVAGCSNAGSNKSVGTISSTPGNTEGHHGPMFPRCGGISDQTMSQLTKVTGLTNTAR (SEQ ID NO:133) NSVGCQWLAGGGIVGPHFSFSWYRGSPIGRERKTEELSRASVDDININGHSGFIAVGNEPSLGDSLCEVGIQFQDDFIEW SVSFSQKPFPSPCGIAKELTRQSIANSK >BL;ML1116, ML.tab 1292138:1292701 forward MW:19839 MRLSVRGRRSVFAGVAVLVSAALVVTGCSRSIGGTAVKAGSHDVPRNNNSQQQYPNLLKECEVLTTDILAKTVGADSLDI (SEQ ID NO:134) QSTFVGAICRWQAANPASLIDITRFWFEQGSLANERKVADFLKYKVENRSIAGVDSIVMRPDDPNGACGVASDAAGVVGW WINPQASGIDACGQAIKLMELTLATNS >BL;ML1117, ML.tab 1292709:1293194 reverse MW:17617 MRHAKSSYPRGFPDHIADHDRRLAPRGVREASLAGGWLRTNVPAIEKVLCSTAMRARETLTHSGIEAPVRYTERLYRADP (SEQ ID NO:135) DTVIKEIKAISDEVTTSLIVSHEPTISAVALALTGSGTNNDAAQRISTKFPTSGIAVLNVAGRWQHLELESAELVAFHVP R >BL;ML1119, ML.tab 1294763:1295914 forward MW:41281 MRFLHTADWQLGMTRHFLAGDAQPRYSAARRDAVAGLGALAAEVGAEFVVVAGDVFEHNQLAPQVVSQSLEAIRAIGIPV (SEQ ID NO:136) YLLPGNHDPLDASSVYTSALFTAECFDNINVLDRAGVHQVRPGLEIVAAPWRSKAPTTDLVAEMLGGLTADIVTRVLVAH GSIDVFDPDRDKPSLIRLAGIDDALAGGAVHYVALGDRHSLTQVGSSGRVWYSGSPEVTNFDDIESNSGNVLVVEIDEND PRRPVTVTARHVGHWRFFTLHWQVDNGRDIADLDMNLDQMMDKDRSVVRLALTGSLTITDRAVLDACLDRYARLFAWLGL WERRSDLAVIPADGEFTDIGIGGFAAAAVDELVATAREGDTESAIDAQAALALLLRLADRGVA >BL;ML1120, ML.tab 1295911:1298532 forward MW:94011 MKLHRLALTNYRGTARREIEFPDRGVILVCGANEIGKSSMIEALDLLLEFRDRSTKKEVKQVKPANADIGSEVCAEISSG (SEQ ID NO:137) TYRFVYRKRFNKKCETALTVLAPHREQLTGDEAHERVRAMLAETVDNDLWHAQRVLQAASTAAVDLSGCDALSRALDLAA GDHAELSGTEPLLIERIEAEYRRYFTSTGRPTGEWAVAISRLSDAETAVGECAAAVAEVDDRVRRHAVLTERVAGLAQQR FAAGPRLAVAQAAADKVAVLTRQAREAELVAAAATATNAAAVAAHTSRLRLLAEIDTRAVVLAATQDEAQEAVDAVSTMR ADAEASDAAVEESTEALMAAQQRADIARSTVDQLVDRQEADRLSTRLAKIDAIQGERDLICAELSAVTLTEQLLQRIENA AAIVDRTGEQLKLISAAVEFTATADIEISVGQQRVSLEAGQSWSTTATGPTEVEVLGVLTACVIPGATALDAQSKYVAAQ EELSVALADGGVVDLAAARCANQRRRELQSSLDQLSAALAGVCGDDQIDQLRARLEQLRDGYPGEPDLLAVDIGSARAEL EAAETVRAAVDFEREVCRRTAAAANCRLVETSARANFLLKKAETQRAELDQDIDQLAQQRASVSDEDLASAAEAGLRAVQ IAEQRVAKLTEELVAAEPEAVTAELVAATAAAESLRDQHEDAAGALREISIELSVFGTEGRQGKLDTAEAEREHAISQNT QIGRRARAAQLLRSVMARHRDTTRLRYVEPYRTELQRLGRPVFGPTFEVDIDSDLRIRSRTLDGITVPFESLSGGAKEQL GILARFAGATLVAKEDNVPVVVDDALGFTDPDRLAKMGEMFDTVGAHGQVIVLTCSPDRYDGFTGAHRIDLNV >BL;ML1138, ML.tab 1329962:1330423 forward MW:16168 VTTPAQDAPLVLPAVAFRPVRLFIINIVLTGLANLAAGLSGHLMVGVFFGIGLLLGLLNALLVRCSVESITAQGHPLKRS (SEQ ID NO:138) MALNSASRLAIITVFGLIIAYAFPLAGLGVVFGLALFQVLLVLSTMLPVWRKFRFGEADGGVLKGSEGEEQQR >BL;ML1147, ML.tab 1337937:1338380 forward MW:16518 MSAPMVGMVVLVVTLGAAVLALSYRLWKLRQGGTAGIMRDIPAVGGHGWRHGVIRYRGEAAAFYRLSSLRLWPDRRLSRR (SEQ ID NO:139) GVEIVARRGPRGDEFDIMTDKIVVLELRDTTQDRRSGYEIALDQGALAAFLSWLESRPSPRTRRRSV >BL;ML1159, ML.tab 1354280:1355185 forward MW:31923 MAGAVDLSGLKQRARQKASTSDPASRATLGARGTGSSENTSVIEITEANFEDEVLVRSHEVPILVLVWSPRSDACVKLLE (SEQ ID NO:140) TLSGLAVADSGTWLLATVNVDAVPRVAQIFGVDAVPTVVALAAGQPLSSFQGMQSVDQLRRWLDSLLSVTAGKLRGPTRS EDSAEIDPAIAQARQQLEAGDFLTAKQSYHAILDADPASVEAKAAIRQIDFLTRATAQHPDAVAVADAAPGDIAAAFAAA DVQILNQDVTAAFERLIVLVRSTSGDERSSVRTRLIELFELFDPDDPNVIVGRRNLANALY >BL;ML1166, ML.tab 1364964:1365551 forward MW:21484 VRKWKRVETANGPRFRSVVAPHEVALLKHLVGALLGLLNERESSSPLDELEVITGIKAGNAQRPEDPTLRRLLPDFYTPD (SEQ ID NO:141) DKDQLDPAALDAVDSLNAALRSLHEPEIVDAKRSAAQQLLDTLPESDGRLELTEASANAWIAAVNDLRLALGVILEIDRP APERVPAGHPLSVIIFDVYQWLTVLQEYLVLALMAT >BL;ML1176, ML.tab 1372485:1372844 reverse MW:13792 MTRPETPQAPDFDFEKSRTALLGYRIMAWTTGIWLIALCYEIVSNLVFHHEIRWIEVVHGWVYFVYVLTAFNLAIKVRWP (SEQ ID NO:142) IGKTVGVLLAGTVPLLGIIVEHFQTKflVKTRFGLRRSRT >BL;ML1177, ML.tab 1372841:1373221 reverse MW:14447 VSTTRRRRPALVALVTIAACGCLALGWWQWTRFQSASGTFQNLGYALQWPLFAGFCLYTYHNFVRYEESPPQPRHMNCIA (SEQ ID NO:143) EIPPELLPARPKPEQQPPDDPALRKYNTYLAELAKQDAENHNRTTT >BL;ML1180, ML.tab 1380300:1380587 reverse MW:10260 MGNINYQFGEIDAHGAAIRAQAAALETTHQAILATVRDAAEFWGGQGSTAHEMFIADLGRNFQMIYEQANSHGQKVQRAS (SEQ ID NO:144) SSMADTDRSVSSAWS >BL;ML1181, ML.tab 1380639:1380941 reverse MW:11298 MTAAHFMTDPQAMRDMARKFDMHAQNVRDESHKMFMSSMDIAGAGWSGTAQLTSHDTMGQINQAFRHIVTLLQDVRDQLG (SEQ ID NO:145) TAADRYEHQEENSRKILSGS >BL;ML1182, ML.tab 1381004:1382269 reverse MW:43120 MFDFAALSPETNSTRMYLGPGSSPILTAAAAWVVLAKELTAAAQGLQSAVEALLTTFEGESAAALAERVTPYEKWLTQNA (SEQ ID NO:146) ASAELTATQLTVAANAYETAFTMTVPPLMVFVNRAQACLLIMSNIFGQNSTAIAEKEAEYTEMWIQDAAAMTSYQASVLE AVGATKAFTAPPLGVNEVGLAQEVVEEVVEEVVEEVVEEVVEAEQAISQAALDQAVNEGMEATVVPQVDQQVNVDVATPQ TAVPDSSSAAAPQLWGGFAQHLSPINDTLSMINNHAGMANAGLSLVNGMGSANKSLAPTTTKAAESAFKANGSAVQSTGR GLLGSSSGGHVTAQLGRAASIGSLRVPQTWTTASQPVTAATRALSPARVAVATESESAPLLGGGLPMAPMVPGGGSGTGG VNTALRLQPRAFVMPRNPAAG >BL;ML1183, ML.tab 1382326:1382625 reverse MW:10117 MPLFLNAEPQALTAAANTLEGLSAATVASNAAAAQLTTEIAPPAADDVSILLARFFSCHGRQYQAHASQCATNHQDLIQS (SEQ ID NO:147) LLTSSSAYAGTETANHDSL >BL;ML1190, ML.tab 1395291:1396010 forward MW:25342 MSVSRRDVLKFATVTPGLLGLGVAAAALCAVPASTAGSLGTLLDYAAGVIPASQIRATGAVGAIRYVSDPRGTWAVGKPI (SEQ ID NO:148) QVTEARDLINNGLKIVSCYQYGKGNTADWLGGATAGLRHAQRGVQLHTAAGGPVSAPIYASIDSNPTYEQYKQQVAPYLR SWESVIIGHQRTGVYANSRTIAWALQDGLASYFWQHNWGSPKGYTHPAANLHQVEIDRRTVGGVGVDVNTILKPQFGQWA >BL;ML1221, ML.tab 1443565:1443807 forward MW:8793 VVQDLPTPIGAGIYNIYTGVHRDELAGASMPTVAQLGLEPPRFCAECGRRMVVQVRPDGWRAKCSRHGQVDSVDMEAKR (SEQ ID NO:149) >BL;ML1222, ML.tab 1443804:1444400 forward MW:20601 VTEHCASDISDVSCPPRGRVIVGVVLGLAGTGALIGGLWAWIAPPIHAVVGLTRTGERGHDYLGNESEHFFVAPCLMLGL (SEQ ID NO:150) LTVLAVTASVLAWQLRQHRGPGMVIGLAIGLMICAATAAAVGALLVWMRYGALNFDAVPLSYDHKVAHVIQAPPVFFAHG LLQVAATVLWPAGIAALVYAVLAAANGRDDLGGRLCSR >BL;ML1232, ML.tab 1465612:1466688 reverse MW:38687 MKRLLATTLAALTVGTVSGFGSTVASSEPGEPWLPPSPVPVRENSPAKIVYALGGARPPTFDWDYYTIRAGDEFFPDVNR (SEQ ID NO:151) KLIDYPARAPFRYVPTFLVPGPRDEVTIGEAIAVATKNLNQAIHRGTEPAAVVGLSQGSLALDTEQEQLATDPTAPPPDQ LTFNTFGDPSGYHGFGKSVLASIFRPGDYIPLIDYTMPQRMDSQYDSNRVVAAYDGLSEFPDRADNLLAQLNCFAGGAIS HTPSGFFNPEDVPPQNIRTTVNSRGAKTTTYLIPVNHLPLTLPLRYLGWSDALVDQIDAVLQPKIDAAYAYNDNPLNKPI SVDPVNGMDPIAGIDAELRDSILNVFAQLRSILPPPPG >BL;ML1233, ML.tab 1466853:1467545 reverse MW:24400 MWITILLMAIAISLEPFRIGMTVLMLNRPRPTLQLLVFLCSGFTMGMTVGFVVLFVFRRRLMASMQLTLPKVQILIGVLA (SEQ ID NO:152) LLVAAVLTVQVCISSEPPAESPVDSASGPPKPSKWAPRPLARLLNGDSLWVAGVAGLGIALPSVDYLAALAVILTSGAAA TTQVGALLMFNVVAFALIEIPLAAYLLAPDTTRAWTAALNNWIRSRRRLEVATLLAGVSCLLLAVGIAGL >BL;ML1244, ML.tab 1482817:1484292 forward MW:52449 MADSVEGIGPFDELGALDYLLHRGEANPRTRAGIMAVELLDTTPDWNRFRSRIEDVSQRVLRLRQKVVVPTLPTAAPRWV (SEQ ID NO:153) VDPDFELDFHVRRVRVPDPGTLREVFDLAEVIQQSPMDVSRPLWTATLVEGLAAGRAANLLQISHAITDGVGSVEMFAENI YDLERDPPSRPRSPQPIPQDLSRNDLMLQGINHLPVALAGGVXTGGLSGVASVAGRAILRPASTVSGVVGYVRSGIRVLSQ AAEPSPLLRQRSLATRTEAIEIQLSDLHKAAKAGDGSINDAYLAGLVGALRRYNEALGVSISTLPMAVPVNVRTEADVVG SNRFVGVTLAAPLGTNDPAARMQKIRSQMTQRRDEPAMNIIGSLAPLMTVLPASVLDFIVDSVASSDVNASNIPAYPGDT YFAGAKILRQYGIGPRPGVAMMAVLMSRGGFCTVTVRYDRASVKSEALFARCLLEGFDEVLALAGDPTPHAVPASFAARS SGSPAGWLSSS >BL;ML1249, ML.tab 1490899:1495767 forward MW:177878 MTIDPGATHVAELCTTFTQGADVPDWISKAYIDSYRGSHGDVREAPETSRVNPNALVTPAMLSAHYRLGQCRPNGRNCVR (SEQ ID NO:154) VYPADDPAGFGPALQIVTDHGGMVMDSITVLLHRLGVTYTAMMTPVFMVLRSPTGELLGVEPRASSTSHSIEGTWVGEVW IYIQLLPAVDSKSLAEVEQLLPRTLVDVQRVAADAAALNATLSGLAADVKTNKEGHFSASDRDDVAALLHWLGNGNFLLL GYQRCRVHYGLVSCDRSTGLGVLRARTGSRPRLTDDNELLVLAQAAVGNYLRYGAYPYAIAVREYDDGGDCGIIEHRFVG LFTVAAMNADVLEIPSISHRVRAALAMANSDPIYPGQLLLDVIQTVPRSELFTLSAERLFTMAKEVVDLGSGRRALLFLR ADRLQYFVSCLVYVPRDRYTTGVRLQIEDILVREFGGTQVEFTARVSESPWALMHFMVRLSEGAATGSVDVSEGNRIRIQ AMLSEAARTWSDRLIAAAASFSEGSVSYAEAEHYAATFSETYKQAVTPADAIDHIAIIKELADDSVKLVFFERKADGFAQ LTWFLGGRSASLSQLLPMLQSMGVVVLEERPFTVARTDGLPVWIYQFKISPHPTIPLASTANERELTAKRFSDAVTAIWQ GRVEIDRFNELVMRARLTWQQVVLLRAYAKYLRQAGFNYSQSYIESVLNEHPSTARSLVALFEALFDPSPLSSSTNCDAQ AAAAAVAADIDALVSLDTDRILRAFASLVQATLRTNYFVTQKFSARSKGVLVLKLDAQLINELPLPRPKFEIFVYSPRVE GVHLRFGAVARGGLRWSDRLDDFRTEILGLVKAQAVKNAVIVPVGAKGGFVLKRPPLPTGDAAADRDAMRAEGIACYQLF ISGLLDITDNVDHATGKVNAPPQVVRRDSDDAYLVVAADKGTATFSDIANDVAKSYGFWLGDAFASGGSVGYDHKAMGIT AKGAWEAVKRHFREMGVDTQNEDFTVVGIGDMSGDVFGNGMLLSKHIRLIAAFDHRHVFLDPDPDAAVSWAERQRMFDLP RSSWDDYNKSLISEGGGVYSREQKAIPTSPQVRTALGIDGEVTEMAPPNLIRAILQAPVDLLFNGGIGTYIKAETESVAD VGDRANDPVRVNANQVRAKVIGEGGNLGVTALGRVEFDLSGGRINTDAMDNSAGVDCSDHEVNIKILIDSLVTAGKVKVE ERKHLLESMTDEVARLVLTDNEDQNDLIGTSRANAANMLSVHAMQIKYLVDERGVNRELEALPSEKEIQRRSEAGIGLTS PELSTLMAHVKLALKEQMLATELPDQOVFVSRLPRYFPKPLRERFTPEIRSHQLRREIVTTMLINDLVDTAGISYAFRIA EDIGVGPIOAIRTYVATDAIFGVGOVLRRIRAANLSVVLSDRMTLDTRRLIORAGRWLLNYRPQPLAVGAEINRFAAKVK ALTPRMSEWLRGODQAIVEQQATEFVSQGAPEDLAYRVAVGLYRYSLLDIIDIADITELDPAEVADTYFSLMDRLGTDGL LTAVSKLPQNDRWHSLARLAIRDDIYASLRSLCFDVLAVGEPDESGEEKIAEWEHISASRVERARLMLAEIHASGEKDLA TLSVAARQIRRMTRTSGRGSSG >BL;ML1255, ML.tab 1499768:1500259 forward MW:16842 MGNQSSQSEVAPVVRGDVVTELPKGWVITTSGRVSGVTEPGDRSVHYPFPIKDLVALDDALTYSSRASHARFAVYLGDLG (SEQ ID NO:155) NDTAALAREILAQVPTPDDAVLVAVSPNQCAIEVVYGSQVRGRGAESAAPLGVAAASSAFEQGNLIDGLISAVRVLSAGI SRS >BL;ML1270, ML.tab 1513725:1514522 forward MW:27833 VMAPDIKSARAGRLTIQIAQLLLVVAAGALWMAARLPWVVIRSFDGLGPPKEVALSGASWSAVLLPLALLMLAATVAAIA (SEQ ID NO:156) VRGWPLRVLAGLLAVASFLVGYLGVSLWVLPDVTVRGAVLAHVSLLSLVGSQRHHLGAGAAVAASGCTLIAAVLLMRSAS VIGSARQGTSKYVVPAQRRSIARRDGAATAISQMSERMIWDALDEDRDPTDRLREPDTEGRWWTACRRSLPFMNVVEIGG CTGSVAGRWVTSGKGNDTHVSGNCA >BL;ML1296, ML.tab 1545740:1546075 forward MW:12349 MYRFGMRYLDSMTVDRHVAGNEFTVEEISTGIFASGYGQVGDGRSFSFHIEHWSLWEIYRTRLAGLVPQTEEVVPRA (SEQ ID NO:157) IRGLVNIDLTDERSLAAAVRDLVARTLTVSG >BL;ML1299, ML.tab 1547791:1548381 forward MW:21454 MARAIHVFRTPDRFVAGTVGQPGNRTFYIQAVHDSRVVSVVLEKQQVAVLAERIGALLLEVHRRFGTPVPPEPAEINDLN (SEQ ID NO:158) PLVMPVDAEFRVGTMGLGWDSEAQTVVVELLAVTDAEFDASVVLDDTDEGPDAVRVFLTPESARQFATRSNRVILAGRPP CPLCDEPLDPEGHVCARTNGYKRSALLGPKDDDTEW >BL;ML1300, ML.tab 1548392:1549180 forward MW:28681 VLRNGELTVLGRIRSASNATFLCESTLDQRSVHCVYKPVSGEQPLWDFPEGTLAGRELSAYLVSTDLGWNIVPYTVIRDG (SEQ ID NO:159) PAGPGMLQLWVQQPGDVADSAPRSGPDMVDLFPADKLQSGYLPVLRSYNYAGDEVILMHADDTQLRRLAVFDVLINNADR KGGHILYGLDGHVYGVDHGVSLHVEDKLRTVLWGWAGKPIDNQTLEEVAGLADALSGPLADTLAGQITWAEIIALRRRAY ANLDNPVMPGPNRDRAIPWPAF >BL;ML1306, ML.tab 1555819:1556643 reverse MW:30377 VAAFEGWNDASDAASGALEHLNAVWEADPIVEIDDEAYYDYQVNRPVIRQVDGVTRELVWPAMRISYCRPPGSDRNVVLM (SEQ ID NO:160) HGVEPNMRWRTFCTELLTIADRLNVDTVVILGALLADTPHTRPVPVSGAAYSPESARRFGLEETRYEGPTGIAGVFQDAC VAARIPAVMFWAAVPHYVSHPPNPKATVALLRRVEDVLDVEVPLADLPTQAEDWEQAITEIAAEDDELAEYVHSLEQRGD AEVDVNDALGKIDGDALAAEFERYLRRRRPGFGR >BL;ML1315, ML.tab 1567372:1567956 reverse MW:20428 VSRWTHRTFFIALSAIVTTAGFGSSGCAHGNSSTSESAVPSTFPGISSSITAPPATGLPAPEVLTNVLSRLADPNIPGID (SEQ ID NO:161) KLPLIESATPDSAVTLDKFSNALRONGYLPMTFTANNIAWSNKNPSDVLATISVNIAQTNNSVFSFPMEFTPFPPPQQSW QLSKRTADMLLEFGNSSGLTNPAPIKAPTPTPSH >BL;ML1321, ML,tab 1575493:1575684 forward MW:7067 MAQEQTRRGGGGDDDEFTSSTSVGQERREKLTEETDDLLDEIDDVLEENAEDFVRAYVQKGGQ (SEQ ID NO:162) >BL;ML1334, ML.tab 1587322:1588140 forward MW:29047 MSEPQGSDPGKQWQSPGEGVENHSSDQPTQAASPWQQQPSTQDSTWHPPAYASPECYNYPQLTEPVYPHQYPSATPGYGQ (SEQ ID NO:163) PGYFGAQFSQCGIPGQYPQSGSPGQYGSPGQYGPPGQYGPPGQYGPPGQYGPPGQYGPPGQYGPPGQYSQQFQPYEQPGT KGFVALIGSIAGVIGVLIFAAILVTGFLWPAWLVTTKLDVNKAQASVQQVLTDETNGYGAKNVKDVKCNNGADPTVKKGD TFDCSVSIDGMQKRVTVTFQDDKGTYEVGRPQ >BL;ML1338, ML.tab 1595449:1596771 reverse MW:50163 VYGALVTAADSTQTGLRNWLLAVFHPRTHTPSTATIVRSALWPAAILSVLHRSTVITTNGNITDDFKPVYRAVLNFRHGW (SEQ ID NO:164) DIYNEHFDYVDPHYLYPPGGTLLMAPFGYLPFAPSRYLFILINTGAILIAWYLILRLFKYTLSSVAAPTLLLAMFCTETV TSTLVFTNINGCIMLLEVLFLWWLINGSEPKTVSQQWWAGGAIGLTLVLKPLLGPLLCLPLLNRQWQALVPAIALPVVIN LAALPLVSHPMDFFTRTVPYILGTRDYFNSSIEGNGVYFGLPTWLIVFLRLLFTVLAICSLWLLNRYYRTRDPLFWFTCS TGVLLLWSWLVLPLAQGYYSMMLFPFLMTVVLPNSLIRNWPAWLGIYGFLTLDRWLLFNWMRYGRALEYLKITYGWSLLL IVVSTVLCFRYLDAKAENRLDHGIDPAWLTAERERASVNA >BL;ML1357, ML.tab 1617916:1618101 forward MW:6609 MTIDPDQIRAEIDALLAQLPDFADLEDSVSGLSLAQLEEVALRFSEVHSVLLQALESAEKG (SEQ ID NO:165) >BL;ML1361, ML.tab 1621823:1623004 forward MW:42405 MRMSALLSRNNSRPGLVGTARVDRNIDRLLRRICPGDIVVLDVLDLDRITADALVEADIVAVVNASPSVSGRYPNLGPEV (SEQ ID NO:166) LVNNGVTLIDETGPEVFKKIKDGAKIRLHEGGVYSGDRRLICGTERTDHDIADLMREAKSGLATHLEAFAGNTIEFIKSE SPLLIDGIGIPDIDVDLRRRHVVIVADEPSAADDLKSLKPFIKEYQPVLVGVSGGADVLRKAGYRPQLIVGDPEQISTEA LRCGAHVVLPADADGHAPGLERIQDLGVGAMTFPAAGSATDLALLLADHHGAALLVTAGHTANIETFFDRTRTQSNPSTF LTRLRVGEKLVDAKAVATLYRNHISFGAIALLALIMLIAVIVALWVSRTDGVVLNGVIDYWNRFSLWIQRLIA >BL;ML1362, ML.tab 1623026:1623979 forward MW:32360 MISLRQHAFSLAAVFLALAVGVVLGSGFLSDTLLSSLRDEKRDLYTQISGLNDQKNMLNEKVSAANNFDNQLLGRIVHDV (SEQ ID NO:167) LGGTSVVVFRTPDAKDDDVAAVSKIVVQAGGTVTGTVSLTQEFVDANSTEKLRSVVNSSILPAGAQLSTKLVDQGSQAGD LLGITLLVNANPAVPNVGDAQRSTVLVALRDTGFITYQTYNRNDHLGAANAALVITGGLLPQDAGNQGVSVARFSAALAP HGSGTLLAGRDGSATGVAAVAVARADAGMAATISTVDNVDAEPGRITAILGLHDLLSGGHTGQYGVGHGATSITVPQ >BL;ML1389, ML.tab 1665174:1666757 reverse MW:57894 VTSIMSVSALEQSAADVGDNSARQHAHGALPDSLAIAMLATVISGAWASRPSLWFDEAATISASASRTVPELWRLLSHID (SEQ ID NO:168) AVHGLYYLLMHGWFAIFPSTEFWSRVPSCLAIGAAAAGVTVFTRQFATRTTAVYAGIVFAILPRITWAGIEARSSALSVA AANWLTVLLVASVQRNRPRLWLCYALTLMLSILLNLTLATLVLVYAVILPWLAPNKFRNSPFIWWAVTSVVALGTITPFI LFAHGQVWQVDWIFRVSWHYVFDITQRQYFDHSVSFAIATAVIIVPAIATRLAGLRAPAGDLRSLVIICTAWIVIPTTLM VGYSAVIEPVYYPRYLILTAPAAAIVIAVCIVTVARKPWPIAGVLVLFAVAAFPNYLFTQRGRYAKEGWDYSQVADVISS QAAPGDCLIVDNTVPWRPGPIRALLAARPAAFRSLIDIERGFYGPTVGTLWDGHVPVWLVTAKINKCSTVWTVSDRDTSL PDHQAGQLLSPGLILGRAPAYQFPSYLGFRIVERWQFHYSQVIKSTR >BL;ML1399, ML.tab 1679214:1680188 forward MW:34653 LPPSAKSTYPGQVEGAPHDGTPSAPQEPDEDTVTVPAPALIRRSSVSMPNAAQWLHTTNRSPRLVANVRRARRLLPGDPD (SEQ ID NO:169) FGDPLSTAGEGGPRAAARAADRLLGDRGAASREVSLSVLQVWQALTEAIARRPVNPEVTLVFTDLVGFSGWSLQAGDEAT LALLRQVARAVESPLLDAGGHIVKRMGDGIMAVFRDPSVAVQAVLAATEAMKSVEVGGYTPRIRVGIHTGRPQRLAADWL GVDVNIAARVMERATKGGIMISGPTLDLIPQSDLKELGIITRRVRKPMFTSKFTGIPPDMVIYRIKARRELTASDETAQT NSLT >BL;ML1439, ML.tab 1733347:1733682 forward MW:12946 MADRVLRGSRLGAVSYETDRNHDLAPRQIARYRTDNGEEFEVPFADDADIPGTWLCRNCMEGTLIEGDLPEPKMVKPPRT (SEQ ID NO:170) HWDMLLERRSIEELEELLKERLDLIRSRRRG >BL;ML1444, ML.tab 1738595:1739293 forward MW:25220 MTKIQIDAPDGPIDALLSVPPGPEPWPGVVVIHDAIGYEPDKESTNNHIAMAGYVAITPNLYSRGSRARCITRVMRELLT (SEQ ID NO:171) KRGRAFDDILATRDYLLAMPKCSGRVGIAGFCMGGRFALVMSPKGFDASAPFYGTPLPRNLSETLNGACPIVASFGGRDP LGIGAPKRLRQATQTRHITTDIKVYPDAGHSFANKLPGQPLMRITGFGYNQAATEDAWSRVFAFFDKHLRTD >BL;ML1446, ML.tab 1740098:1740484 reverse MW:13769 VTPTFADLAKAKYILLTTFTKDGRPKPTPIWAAADGDRLLAISAGKAWKVKRIRNNPRITLATCNVRGCATSAGVQGNAT (SEQ ID NO:172) ILDKLQTGSVYDAICKQYGIQGRLFNFVSKLRGGMQNNVGLELRVSGS >BL;ML1470, ML.tab 1768618:1768989 reverse MW:12909 MTDSPGEHGPQKPLPSADPWKSFAGVMAAILFLEAIVVLLALPVLGASGGLTLSALSFLIGLAGLLIVLVGLQRKAWAIW (SEQ ID NO:173) VNLGVQVVVLVGCAVYPVLGFVGVLFAGLWALIVYFRAEVSRR >BL;ML1485, ML.tab 1787915:1788538 reverse MW:23064 MPEKASVKYQADLWFDPLCPWCWITSRWILEVEKVRDVEVHFHVMSLAILNENREDLTENYLENITKAWGPARVVIAAEQ (SEQ ID NO:174) ANGASVLDPLYTAMGIRIHNEDNKNLDEVIKRSLADTGLPAELAAAAQSNAYDDALRESHHAGMDPVGDDVGTPTVHVNG VAFFGPVLSKIPRGEEAGKLWDASLTLAAYPHFFELKRTRTEPPQFA >BL;ML1494, ML.tab 1801370:1801723 reverse MW:12353 MRIVVLVLFAADGVLSAVVGANLMPLYIGSVPFPISGLISGLVNAVLVWAARLWTRSPWLVALPLWVWLLTVGLLSLGGP (SEQ ID NO:175) GVDVVSGQSVMASGALWLILLGVSPPACVLWRCNRYG >BL;ML1503A, ML.tab 1815091:1815375 forward MW:10624 MTVLTDEQVDAALLDLNDWKHTDGALCRSIKFPTFLAGIDAVCRVAEHAETKDHHPDIDIRYRTVTFILVTHYADGITKK (SEQ ID NO:176) DITMARDIDRLIGD >BL;ML15OS, ML.tab 1816758:1817306 forward MW:17516 MATIWTYLRATAIVVGSSAALLTGGIAHADTAPAPAPAPAPAPAPALNIPQQLISSAANAPQILQNLATALGATPPVTPS (SEQ ID NO:177) APGISFPGLTPAAATVPTSSAATLPSLPGIMAPAISNTPTTPGLPASTPGFPQARVDMPAMPPLPVSVPPQISLPGDLQA LASSASAAAAPVAAPTLLSALP >BL;ML1506, ML.tab 1817334:1818380 forward MW:34620 LKTGGFVTSAWNLPKGLVAVVTASTAAFGLCQNAAADPANPYGTPPNPTQQLPGLPALAQLSPIVQQAANNPQQATQLLM (SEQ ID NO:178) EAVSALTQNPTAPIASKNLATSVSQFMQEPNNPNPGASALDIPTSGVPAPAANGITPLDVVLVPHLPSAGAEPGAQAHLP TGIDPVHAAGPATAATPTPGSPTNRTAAPPTPVASPAPTTPELPATTPGFGPDAPPTQDFIYPSISTNCLADGSSSIATA LSVAGPAKIPLPGPGPGQAAYVFTAVGTPGPADVQKLPLNVTWVNLTTGKSGSATLKPRPDINPEGPTTLTVIADTGSGS IMSTIFGQVTTKEKQCQFMPTIGSTVVP >BL;ML1508, ML.tab 1819557:1820048 reverse MW:18221 MRFGASLLRVRRRLYGMGSQVFDDKLLAVISGNSIGVLATIKRDGRPQLSNVQYHFDPRDLAVRVSITEPGVKTRNLRRD (SEQ ID NO:179) PRASILVDVDDGWSYAVAEGTAELTPPAAAPDDDTVEALIVLYRNIVGEHLDWDEYRQAMVTDRRVLLTLPILHVYGLPP GIR >SL;ML1525, ML.tab 1840011:1840466 reverse MW:15892 MTKTLLVVHHTPSPTTRELLEAVLAGANDSEIDGVEVVSRPALAATIPDMLNADGYLFGTTANFGYMSGALKHFFDTVYY (SEQ ID NO:180) PILDNVSGRPYGLWVHGMNDTVGAAVAVGKLATGLSLTHAADVLEVVGPVDAMVCERAHELGGTLAAMLME >BL;ML1526, ML.tab 1840474:1840956 reverse MW:17670 MNDTVMTKRSLYILYIQLLIAALCFANLAYLVLLGRMAVANIGSGQAAAVSLGLALLIMPVIGLWANIATLRAGFAHQKL (SEQ ID NO:181) ARLIAADGMELDTSVLLRRPSGRIQRDAADALFATVRAELAGDPDNWRCWYRLARAYDYAGDRRRAREANKTALELHGRD >BL;ML1537, ML.tab 1853559:1854764 reverse MW:43686 MKAQRRLGLALSWSRVTTVFVVAIVVLVLASHVPELWQAGHHVAWCVGVGITVVVMVLVLVSYHGITLMSGLATWVWDCF (SEQ ID NO:182) ADPRAALAAGCTPAIDHQRRFGRDVVGVREYKGRLVTVIAVDDGEDDPVGRHRHRTTPAGLPVQAVADGLRQFDIRLDSI DIVSVKIRRGGNAAKFSALDNWGSEEWGLVCACPPTYQRCTWLVLRMNPQHNVVAVAARDSLASTLVAATERLAQDLDGQ NCAARPLAAGELAEVDSAVLADLEPTWSYPGWRHIKYVNGFATSFWVTPSDIDSETLNELWLSDLPDIKATVITIRLASR SCQTRLSAWVRHHSETRLSKEACRGLNQLTGRQLAAVRASLPAPATRPVLVVPSRELSDHDELVLPVGQGREGSASLFAG Q >BL;ML1540, ML.tab 1858295:1859197 reverse MW:32551 MDHQSTRTDITVNVDGFWLLQALLDIRHVAPELRCRPFVSTDSNDWLHEHPGMAVMREQGIVVNGNVNEHVATRMRVFAA (SEQ ID NO:183) PDLEVVALLSRGKLLYGAVNDENQPPGSRDIPENEFRVVLVRRGSHWASAVRVGNDITIDDVAIADSASITSLVMDGLES IHHADPAAINAVNVPLEEMLEATKSWQDAGFNVFSGRDLRRMGISAATVAALGQALSDPAAEAAVYARQYRDDAKGPSAS VLSLKDSSSGRIAIYQQARTAGLGDAWLAICPATPQLVQLGLKTVLDTLPYGDWKTHSRV >BL;ML1544, ML.tab 1866369:1867889 reverse MW:53849 VAEESSGRRGSEYGLGLSTRTQVTGYQFLARRTAMALTRWRVRMEVEPGRRQTLAVVASVSAALLGCLGALLWSFISPSG (SEQ ID NO:184) QLNESPIIIDRDSGALYVRVGDRLYPALNLASARLITGRPDNPHAVRSSQIATLPHGPLVGIPGAPSELSPETPQTSSWL VCDTVATSTGIGSSSGVTVTVIDGSPDLSGHRRVLTGSDAVVLHYGGDAWVIRQGRRSRIDAMNRSVLLPLGLTPEQVSQ ARPMSRALFDALPVGPDLVVPDVPNEGNPASFPGAPGPVGTVIVTPQISGPQQYSLVLADGVETVSPLVAQIMQNAGKPG NTKLITVAPSVLVKMPVVNKLDLSVYPDTPLQVVDLRENPSTCWWWERTAGESRSRIQVITGSTIPINSADVKKVVSLVK ADTTGREADQVYFGSNYANFVAVTGNNPAAQTTESLWWVTRTGARFGVEDTKDVRDALGLNGTPNLAPWVALRLLSQGPT LSRADALMEHDTLPMDMTPAELVVPK >BL;ML1548, ML.tab 1872638:1873603 reverse MW:37427 VAKQEPMCGVEPTLWAISDLHTGHVGNKPVAESLYPLSPDDWLIVAGDVAECTDEIRWTLELLRRRFAKVIWVPGNHELW (SEQ ID NO:185) TTNRDPMQIFGRARYDYLINMCDQMGVVTSEHPFPLWTERGGPATIVPMFLLYDYTFLPTGADSKAKGLAIARERNVVAT DEYLLSSEPYATREAWCRDRLDVTRSRLEQLDWMTPTVLVNNFPLVREPCDALFYPEFSLWCGTTKTADWHIRYNAVCSV YGHLHIPRTTWYNEVRFEEVSVGYPREWRRRKPYSWLRQVLPDPQYAPGYLNDFGGHFVITSEMRAQAVQFRERLRQKQS R >BL;ML1557, ML.tab 1883016:1883336 reverse MW:11540 VRTCVGCRKRELAVELLRVVAPSTGKGSYAVIVDTASSLSGRGAWLHPDMQCVQQAIRRRAFTGALRIAGSPDTSAVVEH (SEQ ID NO:186) IEFLSELDRPGNRTGSKEHEHTVKSR >BL;ML1560, ML.tab 1885239:1885775 forward MW:17494 MLLVPSAVPVINRRGVLAGGATLTVLGVCFSACSKSPSKTPEIEELLGPLDQARHDSALASAAAAAIGNLPQITAALAVV (SEQ ID NO:187) ATQFAAHARALVTEISRATGKLASSSSDTTSPGLSPASPPSKPPPPVSDVIDALRTSAEGAGRLVSTASGYRAGLLASIA ASCTASYTVALVSGGPSI >BL;ML1561, ML.tab 1885772:1886269 forward MW:17495 MTSIEPSAPTPVATPKRTPVSQDSDNAGLSEALVVEHSTIYGYGIVLALSPPNANSLVVDALIQHRQRRDDIIVMLTARR (SEQ ID NO:188) VSPPVAASGYQLPMLVGSAADAARLAVRMENDGATAWRAVAEHAETADDRTFAAMALAQSAVMAARWNKMLGAWPITTTF PGSNE >BL;ML1584, ML.tab 1909590:1909844 forward MW:9465 VASTEGEHNAGVDPAEVPSVAWGWSRINHHTWHIVGLFAIGLLLANLRGNHIGHVENWYLIGFAALVFFVLIRDLLGRRR (SEQ ID NO:189) GWIR >BL;ML1607, ML.tab 1932700:1932990 reverse MW:11018 MTTHKAMTRVQLEANGEVFAVDNLTRMGLRGLHCNWRCRYGECDVIASETAHRTVVSRLRSIAATVMEGSRRSAPEQKVR (SEQ ID NO:190) WLRWLAGLWPANQDEF >BL;ML1610, ML.tab 1935020:1935325 reverse MW:12258 MSAEDLEKYETEMELSLYREYKDIVGQFSYVVETERRFYLANSVEMMPRNTDGEVYFELRLADAWVWDMYRPARFVKQVR (SEQ ID NO:191) VVTFKDVNIEEVEKPELRLPE >BL;ML1624, ML.tab 1947637:1949427 forward MW:65207 MTQSDHRHTRPSSYGGTVLTQRVSQATVEDSRPLRGWQRRAMVKYLASQPRDFLAVATPGSGKTTFALRVMTELLNSHAV (SEQ ID NO:192) EQVTVVVPTEHLKVQWTRAAATHGLALDPKFSNTNPRTSPEYHGVTMTYAQVAAHPTLHRVRTEGRRTLVIFDEIHHCGN AKAWGDAIREAFSDATRRLALTGTPFRSDDKPIPFVTYALDADGLMHSQADHTYSYAEGLADGVVRPVVFLVYSCQARWR NSAGEEHAARLGEPLSAEQTARAWRTALDPSGEWMPAVISAADQRLRQLRTHVPDAGGMIIASDQTAARAYANLLAQMTS ETPTLVLSDDPGSSARITEFAKNTSQWLIAVRMVSEGVDIPRLSVGIYATSASTPLFFAQAIGRFVRSRHPGETASIFVP SVPNLLQLASELETQRNHVLGKPHRESTDNPLGGNPATMTQTEQDDTEKYFTAIGADAELDQIIFDGSSFGTATPAGSEE EAYYLGIPGLLDADQMRALLHRRQNEQLQKRTAAQQASSTPDRTSGAPASVHGQLRELRRELNSLVSIAHHHTGKPHGWI HNELRRRCGGPPIAAATHDQLKARIDAVRQLNAEPS >BL;ML1638, ML.tab 1975122:1975820 reverse MW:25842 LSKLDDELSRIAHRANYLPQREAYERMRVERTGANDRLVAVQIALEDVDTQVFLLESEIDAMRQREDRDRLLLNSGATDA (SEQ ID NO:193) KQLSDLQPEFGTWQRRKNSLEDSLREVMKRRGELQDQLTAELGAIERMQTDLVGARQTLDVAPAEIDQVGQPHSSQCDVL IAELAPALSAPYERLCAGGGLGVGQLQGHRCGACRSEIGRGELSCISVDVDDEVVKYPESGAIQLLDKGFFQ >BL;ML1644, ML.tab 1978961:1979773 forward MW:30049 MRHLALLLRPGWIALTLVVTAFTYLCFMVLAPWQLGKNTRMSRENNQIEYSLNTPPVPVKTLLSHQDLSTSKSQWRQVTA (SEQ ID NO:194) TGRYLPDVQVLARLRVVDSGQAFEVLAPFVVDDGPTVLVDRGYVRPEPGSHVPPIPRPPNEAVSITARLRDSEPVMKDKE PFSRDGVQQVYSINIEQVARLTKIPLAGSYLQLVDNQPGGLGVIDIPHLDAGPFLSYGIQWISFGIIAPIGLGYLAYAEI RTHRQEKLAKPSQAPMAVEEKLADRYGHPR >BL;ML1649, ML.tab 1987829:1988251 reverse MW:15144 VVAADHTPSFARKLGIQQGQVVQEWGWDEDTDDDIRASVEEACGGELLDEDTDEVVDVVLLWWRDGDGDLVDTLMDAITP (SEQ ID NO:195) RAEDGVIWVLTPKTGKPGHVPPAEIAEAAPTAGLMLTSSVNLGDWSASRLVQPKSRIGKR >BL;ML1652, ML.tab 1992060:1993304 forward MW:44873 VNNNHFVPAPFRRLPLELLDTVPDSLLRRLKQYSGRLATEAVTAMQERLPFFADLEASQRASVTLVVQTAVVNFVQWMQN (SEQ ID NO:196) PHSDVSYTAQAFELVPQDLARRIALRHTVDMVRVTMEFFEEVVPLLARSEEQLTALTVGILKYSRDLAFTAATAYADAAE ARGTWDSRMEASVVDAVVRGDTGPELLSRAAALNWDTTAPATVVVGTPTPNHDGPNGQVSSERASQEVREIAARHGRAAL TDVHGTWLVAIISGQLAPTDKFFSDLLHAFSDGPVVIGPTAPMLTAAYHSASEAVSGMNAVAGWSGAPRPVQARELLPER ALMGDASAIVALNTDVMLPLADAGPTLIETLDAYLDCGGAIEACARKLFVHPNTVRYRLKRITDFTGHDPTLPRDAYVLR VAATVGKLNYPTHH >BL;ML1660, ML.tab 2001607:2002260 reverse MW:23449 VTVALALRDGCRRISTMTRQYGVTTQRHLISPVVFDITPLGRRPGAIIALQKTVPSLARIGLELVVIEWGAPINLDLRVE (SEQ ID NO:197) SVSEDVLVAGTVTAPTVSECVRCLTAVHGHVQVTLNQLFAYPYSATKVTTEEDAVGHVVDGTIDLEQSIIDAVGIELPFA PMCRSDCPGLCAECGTSLVVEPGHPHDRIDPWWAKLTDMLAPDVPQTSETDGSRSEW >BL;ML1666, ML.tab 2009601:2010245 reverse MW:23370 VSAQPVERPGDLKPAPASVLPMPVPTAWWVLIAGVIGLVASMMLTVEKIRILLNSAYVPSCNVNPIVACGSVMSTPQASV (SEQ ID NO:198) LGFPNPLLGIVGFTLVTVTGVLSVAEVSLPQWYWIGLAVGTLAGVGFVHWLIFQSLYRIGALCAYCMVIWAVSVSLLVVV TAIVFRPLLEVLPGRTSAIARGIYQWRWSIATLWFITVFLLIMVRFWNYWQTLL >BL;ML1677, ML.tab 2021235:2021810 forward MW:19668 VTSNSDAGSAVDAGGPPRTVIIAAVVLTAATIGTILVLAATLHEPPQPVVITAVPAPQATTAACRSLTQALPQRLGDYER (SEQ ID NO:199) APVAQPAPDAVAAWRTGSDTEPVVLRCGLDGPAEFVVGSPIQAVDQVQWFEVDAKPKPAIDAGRSTWYTVDRPVYVALTL PSGSGPTPIQELSDVIDRTLAAIPISPAQSH >BL;ML1698, ML.tab 2046984:2047817 reverse MW:29424 VTGQSHDEHWRRPGECPEPIPGRPASASLVDPEDDLTPVGYPGDFGTTTVIPYSDPDHLKGPGGTGYNLLDQQEPLPYVQ (SEQ ID NO:200) PQARHAVAEPTEIDSDQDNERLHTVGRRGTQHLGLLVLRVGLGVVLAAQGLHKLFGWWGGQGLTGFKNSLTQVGYQHADI LAYVSAGGEAVAGVLLVLGLFAPVVAAGALAFLINGLLAAWPHSPLFSFFLPDGNEHQITLIVMDVTVILCGPGRYGLDA GRRWAYRPFIGSFIVLIAGIAAGIAVWVLLNGVNPLA >BL;ML1704, ML.tab 2055043:2055741 forward MW:24598 VEMPLTQRYATVLAVPSYLLRIELADRPGSLGSLAVALGSVGGDILSLDVVERSGGYAIDDLVIEVPSGAMPDKLITAFE (SEQ ID NO:201) SLPGVRVDSVRPHSGLLEAHRELELLDQVAAADDNASKLQVLADEAPKVLRVSWCTVLRSSQGKLLRLAASVGAPETRAN SAPWLPIERAAPLDGTAEWVPQSLRDMNTTMIAAPLGDPHTAVVLGRPGPEFRPSEVARLGYLAGIVATMLR >BL;ML1706, ML.tab 2057887:2058900 reverse MW:34564 MSVFATASGVGSWPGSSPYPAAKVVVGELAGALAHIVELPARGVGADMLGRAGALLIDVAIDTVPRGYRIAARPGAVTRR (SEQ ID NO:202) AFSLLDEDMDAFEAAWEMAGLRGRGRVVKVQAPGPITLAAGLELANGHRAITDSCAVRDLAESLAEGVAAHRAALARRLD TQVVVQFDEVSLPAALGGLLTGVTAFSPVAPLDETLAATLFDSCVATVGADVLLHSCAAELPWNFLQRSAIRAVSVDVNV LRTGDLDGIAAFVESGRTVVLGVVPATAPQRLPSVEQVAAAVVGVTDRLGFGRSALRDRIGVSPACGLAGATPHWACTAI ELARKTAEAFAQDPDAI >BL;ML1720, ML.tab 2076101:2077195 forward MW:38298 LAAGPALSARGYLAMNAQTQAGCSLMEWENNDNGRQRWCVRLVQGGGFGGPLFDGFENLYVGEPGTIFSFPMTQWTRWRQ (SEQ ID NO:203) PVIGMPSTPRFLGNGQLLVTTHLGQVLVFDAHRGMVVGSPLDLVDGVNPTDPTRGLADCVSAQRGCPVASAPAYSPASOT VVLDIWQPGAPTAGLIGLKYHSRQTPLLARAWTSDAIGAGVLASPVLSADGSTVYVNGRDQHLWALHAANGKPKWSVPLE FLAQTPPTVTPQGLIVSGGGPDTRLAAFKDAGDHAQQIWRRDDLTPLSTSSLAGVSVGYTVVSSSPAADAPGMSLLAFDP RNGHTLNSYPLPAATGYPVGVSIANNRRVITVTSDGQLYSFAPT >BL;ML1723, ML.tab 2079775:2080758 reverse MW:36615 MTRSTEISANAVPNPHATAEQVAAARKDSKLAQVLYHDWEAENYDEKWSISYDQRCVDYVRHCFDAIVPDELFTELPYDC (SEQ ID NO:204) ALELGCGTGFFLLNLIQSGVARRGSVTDLSPGMVKIATRNGQSLGLDINGRVADAEGIPYDDNTFDLVVGHAVLHHIPDV ELSLREVLRVLKPGGRFVFAGEPTDVGNRYARVFADLTWKVTIRVVQLPGLSAWRRTQVEIDENSRAAALEWVVDLHTFE PKVLETMATNAGAVQVKTVTEEFTAAMLGWPLRTFESTMPPSKLGWGWARFAFTSWKTLSWVDANVWRRVIPKSWFYNII ITGVKPS >BL;ML1781, ML.tab 2157673:2158185 reverse MW:18049 MRASNQFADATAGVVYVHASPAAVCPHVEWALSSTLQTKAINLVWTPQPAMPGQLRAVTNWTGPVGTGARLANALRSWSVL (SEQ ID NO:205) RFEVTEDPSPGVDGQRFSHTPQLGLWSGSMSANGDIMVGEMRLRANMAHGADTLAAELDSVLGTAWDDALEVYRDGGDVG EVTWLSRGVG >BL;ML1782, ML.tab 2158324:2159145 reverse MW:29017 MVALDALDDWPVPTTAAAVVGPTGVLAARGDTEQVFPLASVTKPLVARAVQIAIEEGVVDLDTVAGPPGSTIRHLLAHAS (SEQ ID NO:206) GLAMHSKYVMAPPGTRRIYSNYGFRVLAETVQREAGIGFSRYLTEAVLEPLAMTATKLEDGTWAAGFGATSTVADLAAFA NDLLRPATVSAQIHAEATSVQFPDLDGVLPGHGVQRPNDWGLGYEIKNSKLPHWTGTLNSARTYGHFGQSGGFIWADPEA ELALVVLTDRDFGEWALQLWPAISDAVISEYAR >BL;ML1791, ML.tab 2165620:2166063 reverse MW:16468 LGKIFIMLPTVTHQAITCTVRRVRWIVDAMNVIGTRPDCWWKDRRGAMVRLVGKLERWASTERNHVTVVFERPPSPSIRS (SEQ ID NO:207) SVIVIAHAPKAFPDSADDEIVRLVQADPEPQGICVVTSDSALTDRVQEVGALAYPAARFRKHIDSID >BL;ML1813, ML.tab 2194277:2194849 reverse MW:20227 MTGQDVVVQQPQTIPMLPIYIPQDVDMTVVKSEVAAAGVSASPAAMPGLLEVVSHAQAEGINLKIVLLDHNLPNDTPLRD (SEQ ID NO:208) IATVVGADYPDVTVLTLSPNYVGSYSTHYPRVTLEAGEDISKTGNPVQSAQNFLGELNVPEFPWTVLTIVLLIGVLVAAI GTRFMQLRSKRLATSLDAAGILAEDVNRAD >BL;ML1908, ML.tab 2293144:2293644 reverse MW:18864 VALKTDIRGMVWRYSDYFIVGREQCREFARAIKCDHPAYFSEDAAAELGYDAIVAPLTFVTIFAKYVQLDFFRNVDVGME (SEQ ID NO:209) TNQIVQVDQRFVFHKPVLVGDKLWARMDIHSVSERFGADIVVTKNSCTSDDGELVMEAYTTLMGQQGDNSSQLKWDKESG QVIRSA >BL;ML1909, ML.tab 2293648:2294076 reverse MW:14875 MARREFSSVKVGDLLPEKTYPLTRQDLVNYAGVSGDLNPIHWDDEIAKVVGLDTAIAHGMLTMGIGGGYVTSWVGDPGAV (SEQ ID NO:210) IEYNVRFTAVVPVPNDGQGAVLVFSGKVKSVDPDTKSVTIALSATTGGKKIFGRAIASAKLA >BL;ML1910, ML.tab 2294063:2294542 reverse MW:17608 VGLTTNIVGMHYRYPDHYEVEREKIREYAVAVQNEDTSYFEEDAAAELGYKGLLAPLTFICLFGYKAQSAFFKHANIAVT (SEQ ID NO:211) DQQIVQIDQVLKFVKPIVAGDKLYCDVYVDSMREAHGTQIIVTKNVVTNEVGDIVQETYTTLAGRVGEGGEEGFSDGAA >BL;ML1911A, ML.tab 2295156:2295371 reverse MW:7998 MLKKVEIEVDDDLVQEVIRRYGLLGRREAVHLALKALLGEPGVGGLSEQDPEYDEFSNPDAWRTRRSSDTG (SEQ ID NO:212) >BL;ML1918, ML.tab 2301835:2302626 reverse MW:27133 VLDLEPRGPLPTEIYWRRRGLAVGITVIVIVIAAIVAVVGNGAAAQPANVDKPGSSQNHPGSATPKVLPPNGHEGNLAPA (SEQ ID NO:213) PPQGRNPESSTSTAAVQPPPVLREGDDCPDSTLAVKGLTNVPQYFLGDQPKFTMVVTNIGLVSCKRDVGAAVLAAYVYSL DNKRLWSNLDCAPSNETLVKTFTPGEQVTTAVTWTGMGSSPHCPLPRPAIGPGTYNLVVQLGNLHSMPVPFILNQPPPPP GSSGPALAPSPEAPPANVPVSGG >BL;ML1926, ML.tab 2311558:2312061 reverse MW:17296 LVDTVGLVNKCVPDSSGLPLRAMVMVLLFLGVIFLLLGWQALGSSGNSDDYSALPMSSMPNTPTTPAATSTSSTSAANQA (SEQ ID NO:214) EVRVYNISSKEGIAARTRDQLTTAGFKVTEVDNLVVSDVSATTVYYSDAEGEYATADAVGQKLGAPVEPRIAAITNQPPG VIVLVTS >BL;ML1927, ML.tab 2312092:2312400 reverse MW:11799 MDGAMARAHRAGDDVEIVDGLTRREHDILAFERQWWKFAGVKEEAIKELFSMSATRYYQVLNALVDRPEALAVDPMLVKR (SEQ ID NO:215) LRRLRASRQKARAARRLGFEVT >BL;ML1937, ML.tab 2323320:2324552 forward MW:46582 MERPNEYMARQRSILNKVFTGFSAYCRYGQHVSKQQARSTVESTYRSILPNIPGVPWWAALLIATTASAIGYAIDAGNTD (SEQ ID NO:216) LTTVFTGFYITGCVAAVLAVRQSGLFTAVIQPPLILFCAVPAAYWLFHGSKIKSLKDLLINCGYPLIERFPLMLGTAGSV LLIGLVRWFFQLMYRTTASSNSEDDTVSKPNSLISGITAVLNSILCIYSNDQNHRANQDTADTELMHSDPPLRTRQTARD NRSARTHSGQARRVVEYTSEPLVEPWQHSSQRSSEQARDFDAGESPRRSRRQPTPQSDPELRSQPPREIRRDAYGHRSGP YEWPTNHSSHLEPYRRYKQPGPPEHFTEHGQLYERYKQPRRRATPPRASSVNPISQVRYRGSTARDDPRVDRQRSQTPRR PVTESWEFDV >BL;ML1945, ML.tab 2331776:2332549 reverse MW:27316 MVNDCPRSRSATWSWALAVNQQGWDTRRVTFEWQPNSEVANKPGSVSWSAKPRLLQDGRDMFWSLVPLVVGCILLAGMAG (SEQ ID NO:217) TCTFAPGGTTKSTVSSYDAAAALRADARALGFPVRLPELPTGWRSNSGSRGSIEDGRMDLSTGKRLPAVTSTVGYITPTG MYLSLTQSNADEDRLVASIHPSSHPTGTVDVAGTKWVVYQGSDQKKDHSGAAAEPVWTSRFASPVGAAQIAITGAGCSSQ FRMLASATQSQQPLPAR >BL;ML1983, ML.tab 2367418:2367885 forward MW:16955 MSNRKFSFEVTRTSSASAAVLFRLVTDGANWAKWAKPIVLQSSWARLGDLRPGGIGAVRKIGIWPILVREETVEYEQDRR (SEQ ID NO:218) HLYKLIGPPNPAKDYLGEVLLAPNAAGGTNIHWSGSFTENIPGTGPVMRAALKGAVRCLTVRLVKTAERESDGVQ >BL;ML1988, ML.tab 2375705:2376418 reverse MW:25568 MDCEVAREALSARLDGEREAVPSVRVDEHLGECSACRAWFDQVADQARDLRQLVDSRPAITPVDALGIVAPPRRRRPLMT (SEQ ID NO:219) WQRWALLCVGIAQIVLATVQGLGVSVGLTHDRAMSFGSYLLHESTAWSASLGVIMMAAVLWPGVAAGLAGVLTVFVGLLT VYVVVDVVAGATITLRILMHLPVAIGAVLAIAVWRHSSTPRPTFDDEVDVDLDIVLPRNASRGRRRGHLWPTDGSAV >8L;ML1993, ML.tab 2380915:2381466 forward MW:20576 MSAELAPSLQNAAESTNTFPMAEDLLGSILEPYSYKGCRYLIDAQYRASPDSVFAYGNFGIEESAYIRGTGHFNAVELML (SEQ ID NO:220) CFNQLGYSAYAQSVVNKDISALRGWSIADYCRNQLSGILIKNTSSRFKKLINPQKFSARLHVYDLRIVERTWRYLQLSNT IEFWDDNGGSAIGEFEVAILNIP >BL;ML1995, ML.tab 2383087:2383323 forward MW:8810 VTETARERILTAVCEVLYIAESDLVDGDETDLRDLGLDSVRFTLLMKQLGLSQEAEMQSKLMDNFSIANWVRQLESST (SEQ ID NO:221) >BL;ML1997, ML.tab 2387532:2388164 reverse MW:23261 MIDDLLLRWVTGLFVLSAAECGFACLACRRPWTLVPSNGLHFAMAIAMAVMAWPRGAQLPTTGTVVFCGLVGAWFVILA (SEQ ID NO:222) TVSSRRIAERAAYAYPALMMLANVWMYVIMDSHLHDHWATGHHTSPHTSMLGVDMTTTWPASGIPGWISIINWLWFAFF CIATVFWTYRSFATSRRNAGFSRYCSLHPSGQAMMSTGMAIMFGVLLFHV >BL;ML2010, ML.tab 2402973:2403434 forward MW:15613 MWLTAAPAAARFVVASVIAASCAASTGVAGADPQSPSAPKTTIDHDGTYAVGTDIAPGTYSSAGPVGNGTCYWKRIDNPD (SEQ ID NO:223) GPIDNAMSKKPKIVQIEASNKAFKTTGCQPWQQTSNTTVSTDLPGPIAGIQLESNLGILNGLLASNGQQVPRS >BL;ML2022, ML.tab 2413644:2414168 reverse MW:18955 MSGPSSSCRCLPCCPHDRSSQPRCGESLGWQGYGRVYLESPWPFGLKQILQILRYGAEYAGKILAQPSKPTDVSSGPRRK (SEQ ID NO:224) TQVFAKATVVPKILQPKETQMTFDPKNAVNAARDIATNFVEKASDIVENVSDIIKGDIAGGANDIVQNSIDIATHAVDKA KEIFIGKGEYDELE >BL;ML2023, ML.tab 2414264:2414668 reverse MW:14091 MIRELLAISAIASGAVNSAPRAAANPHYDGDVPGMSYDASLSAPCFSWERYIFGRGPSGQAEACHFPPPNQFPPANTGYW (SEQ ID NO:225) VISYPLYGVQQAGAPCPKTQAAAQSADGLPMLCLGGQGWQPGWFTDKGFFPPAG >BL;ML2030, ML.tab 2420647:2421120 forward MW:16613 LDMPGEMLDVRKLCKLFVKSAVVSGIVTASMALSTSTGMANAVPREPNWDAVAQCESGRNWRANTGNGFYGGLQFKPTIW (SEQ ID NO:226) ARYGGVGNPAGASREQQITVANRVLADQGLDAWPKCGAASDLPITLWSHPAQGVKQIINDIIQMGDTTLAAIALNGL >BL;ML2031, ML.tab 2421151:2421606 forward MW:17306 MEGSVTVHMAAPADKVWNLIADVRNTGRFSPETFEAEWLDDVTGPALNAKFRGHVRRNEIGPVYWTTCKVTACEPGREFG (SEQ ID NO:227) FTVLLGNKPVNNWHYRLVTSGDGTYVTESFRFNRSPLLTVYWLLGGFLRKRRNIRDMTKTLRRIKDVVEAE >BL;ML2048, ML.tab 2437805:2438062 forward MW:9877 MTNLWDLKQKVIYSIQWLWNSLGHQLPRTMLETIRRKTGQPWRTAAGVHPVDNQFGMVCENSEYSDYVYNIKANTAVRT (SEQ ID NO:228) HKSKI >BL;ML2054, ML.tab 2442182:2442481 reverse MW:10350 MDVMAATEYLARSTTLTSVGWIGYIIIGGIAGWIAGKIVQGGGSGILMNIVIGVVGALIGGFLLSFFVNTAAGGWWFTLF (SEQ ID NO:229) TSILGSVILLWVVGRVRKT >BL;ML2063, ML.tab 2450656:2451084 forward MW:16160 MAKLTRLGDLERAVMDHLWSRQEPQTVRQVHEALSARRDLAYTTVMTVLQRLAKKNLVSQIRNNRAHRYAPVHGRDELVA (SEQ ID NO:230) GLMVDALDQAEDSDSRQAALVHFVERVGADEADALRRALAELETHQRHVRHLVALQRTTEGD >BL;ML2064, ML.tab 2451089:2452039 forward MW:32995 VSALAFTILAVLLVGPTPTLVARSTWPLRAPRAAMVLWQTIALAAALSTFSAGIAIASRVLMPGPDGRLLTASVIGAAGRL (SEQ ID NO:231) GWPLWAAYVAAFALTVLVGARLIVAIVRVAIATRRRRAHHRMVVDLVGVGHNAALAQPCARARDLRVLEVAQPLAYCLPG VRSRVVVSEGALTKLNDTEVTAILTHERAHLRARHDLVLEAFTAVHAAFPRLVRSSAALSAVRLLVELLADDAAVRAAGR TPLARALVACASGQAPSGALAAGGNTTVLRVRRLSGRSNSAVVSAAAYLAAAIVLLVPTVALAVPWLTELQRLFNI >BL;ML2070, ML.tab 2460317:2462518 forward MW:77018 MTKLGAEFKPDQTRINRKAANTGMGRHSMPDPEDSIDQPSNQFAASGPDQSDEIDHGYQSRMGYPEPVFEPAATGSPSYR (SEQ ID NO:232) SYPHGAEHPADSTPEALDETIDYQSYWAEDRNEDLFVDGAADDHPDFPPRPAGSSTSSQAPTSLSHLFKASHRSVGKWQG GHRSDGGRRGVSIGVIATLVAVVVLVGAVIMWSFLGHILNNRKHQAAARCVGGHQTVAVVADPSIADYLQEFAQSYNASA RPVGDHCMMVTVKPVGSEAALTGFNDSWPANLGDKPALWIPGSSISAARLAVTADQKTISESHSLVTSPVLLAVRPEFEQ ALANKGWAALPGLQTNPNSLADLNLPAWGSLRLALPMNGNSDATFLAGEAVATASVPAGAPAIQGVGAVRTLMSAQPKLA DSTWAEAMSTLLKPGDVATAPVHAVITTEQQLFQRGQSLSDAKSALGSWLPHGPAPVADYPAVLLNGSWLTQEQAAAASE FARFVQKPDQLAKLAKAGFRVNGVTPPSSSVTSFAAVPSTVSVGDDGMRATLVEEMIQPSSGVAATIMLDQSMPTDEGGK TRLANVVAALDDKINAMPPTSVMGLWTFDGHKGQTEVTTGQLADPVNGQPRSAALTAALDKQYSSNGGAVSFTTLRMIYQ EMLANYHVGQTNSVLVITAGPHTDQTLDGARLQDFIRTSADPAKPIAVNVIDFGTDPDQATWKAVAQISGGSYQNLSTSA SLDLATAINTFLS >BL;ML2073, ML.tab 2466445:2467140 reverse MW:24857 MTHLVTRARSARGNTVSEQPRQGQLDLADYRDTPTATTHGDIGLNGPTAVSGPAQPGLFPDDSVPDELVGYRGPSACQIA (SEQ ID NO:233) GITYRQLDYWARTSLVVPSIRGAAGSGSQRLYSFKDILVLKIVKRLLDTGISLHNIRVAVDHLRQRGVQDLANITLFSDG TTVYECTSAEEVVDLLQGGQGVFGIAVSGANRELTGVIDDFRGERADGGESIAAPEDELASRRKHRDRKIG >BL;ML2075, ML.tab 2467984:2468739 reverse MW:26531 VSAPDSPALVOMSIGAVLDLLRSDFPDVTISKIRFLEAEGLVTPQRSASGYRRFTAYDCARLRFILTAQRDHYLPLKVIR (SEQ ID NO:234) AQLDAQPDGELPSFGSPYVAPRLFSVTGGPGAGVGSGVGSDIPAVSPAGVRLSREDLLDRSGVADDLLTALLKAGVITTG PGGFFDEHAIVILQCARALSEYGVEPRHLRAFRSAADRQSDLIVQIAGPIVKAGKAGARDRADDLAREVAALAITLHTSL IKSAVRGVLHR >BL;ML2111, ML.tab 2512539:2512973 reverse MW:15031 MIHRLRLGWLVAFFATIVLISVWIPWLTTKVNDEGWANAIGGTNGNLELPSGFGAGQLIVLLSSTLLVAGAMMGRGLSVK (SEQ ID NO:235) VASIAALIISLLIVVIVVWYYQLNVNPPWAECGLYLGAAGAVCAMVCSVWAVIAAVAAGRSSL >BL;ML2113, ML.tab 2513870:2514415 reverse MW:19748 VTSRIKRMAKLTGSIDVPLPPNEAWMCASDLARFGEWLTIHRAWRSKLPEVVEKGTVIESYVEVKGMPNRIRWTVVRYKA (SEQ ID NO:236) PEANTLNGOGVGGVKVKLIAKVSPKDDGSVVSFDVNLGGSALFGPIGMIVAVALRTDIRESLQNFVTAFSRPEPGLIRSR ALVVDQHSRAVVEQRSASAGL >BL;ML2114, ML.tab 2514412:2514582 reverse MW:6182 VLDKAKDILVQNADKVETVLDKAGEFVDEKAKGKYTDTIYQVAEETKKAASFDTFC (SEQ ID NO:237) >SL;ML2135, ML.tab 2537496:2538521 reverse MW:40179 MARTRMVRRWRNNMEVRDDTDYVGMLTTLSEGSVRRNFNPYTDIDWESPAFAVKDNDPRWILPDTDPLGRHPWYLAQPEQ (SEQ ID NO:238) RKIEIGMWRQANVAKVGLHFESILVRGLMNYTFWMPNGSPEYRYCLHECVEECNHTMMFQEMVNRVGADVPGMPRRLRWL SPLVPLVAGPLPVAFFIGVLAGEEPIDHMQKNVLREGKSLHPIMERVMAIHVAEEARHISFAHEFLRKRLTHLTKRQLFW VSLYYPLTMRVLCNAIMVPPKAFWQEFNIPREVKKELFFRSPESRKLLRDIFADVRMLAYDTRLMETRSARLMWHICKID GQPSRYRGEPQRQHPATTSAA >BL;ML2137, ML.tab 2539983:2540738 forward MW:27365 MRELKVVGLDPDSKTILCEGDIPGERFKLPADDRLRAAVRGDTTLLDQPQLDIQVTNMLSPKEIQARIRAGASVEQVANA (SEQ ID NO:239) SGSDIARIRRFAHPVLLERSRAAELATAAHPVLADGPAVLTLLETVSAALVKRGLEPDKLSWDAWRNEDSRWTVQLMWHA GRSDNLAHFCFTPGAHGGTVTASDDAANELIDPDFNRPLRPLARVAHLDFVEPATPATVTPDNQLVSSRRGKPTIPAWED VLLGVRSAGQP >BL;ML2141, ML.tab 2542620:2542895 forward MW:9766 MLVEPDRSREPPPLPSMLLEVWPVIMVGALAWLIAVVAAFVVSSLQSWRPVALAGLVVGLFGTGIFVWQLAAARRGARGA (SEQ ID NO:240) QGGLETYLDPR >BL;ML2142, ML.tab 2543007:2543816 reverse MW:28190 VTGPVEDSAVATVAEWPEELAAVLTNAADDARAAIEEFSGSVTVGDYLGVGYEDPNAATHRFLAHLPGYQGWQWAVVVAA (SEQ ID NO:241) YPGAEHATVSEVVLVPGPTALLAPEWVPWEQRVRPGDLGPGDLLAPTSEDLRLVPGYNASGDPAVDEIAAEIGLGRRWVM SVWGRSAAAERWHGGDYGPDSPMARSTKRVCRDCGFFLSLVGSLGANFGVCGNEMSADGHVVDKLYGCGAHSDTPAPAGS GSSVYEPYDDGVLDILEPSTVQLPESPAD >BL;ML2143, ML.tab 2543926:2545665 forward MW:61675 VSGRRRNHPGRLASIPGLRTRTGSRNQHPGIANYPADSSDFRPAQQRRALEQREQQAGQLDPARRSPSMPSANRYLPPLG (SEQ ID NO:242) QQQSEPQHNSAPPCGPYPGERIKVTRAAAQRSREMGYRMYWMVQRAATADGADKSGLTALTWPVVTNFAVDSAMAVALAN TLFFAAASGESKSKVALYLLITIAPFAVIAPLIGPALDRLQHGRRVALATSFVLRTGLATLLIMNYDGATGSYPSMVLYP CALAMMVLSKSFSVLRSAVTPRVMPPSIDLVRVNSRLTVFGLLGGTIAGGAIAAGVEFVCAHLFKLPGALFVVAAITISG ALLSMRIPRWVEVTAGEIPATLSYRLHRKPLRQSWPEEVKKVSGRLRQPLGRNIITSLWGNCTIKVMVGFLFLYPAFVAK EHQANGWVQLGMLGLIGTAAAIGNFAGNFTSARLQLGRPAVLVVRCTIAVTVLALAASVAGNLLMTTIATLITSGSSAIA KASLDASLQNDLPEESRASGFGRSESTLQLAWVLGGALGVMVYTDLWVGFTAVSALLILGLAQTVVSFRGDSLIPGLGGN RPVMIEQESMRRAAAVSPQ >BL;ML2144, ML.tab 2545673:2546161 forward MW:18046 VQRRVTVLLPAVVMLLAAAAGFGVWLLVREPDPQRPEISVYSHGHLTRVGPYLHCNMLNLDECQTPQAQGVLSADEHNPV (SEQ ID NO:243) QLSVPETISRAPWRLLRIYEDPTGTTSTLYRPNTRLAVTIPTLDPHRGRLTGIVVQLLTLVVDPAGEVHDVPHTEWLVRL TF >BL;ML21S1, ML.tab 2554745:2555269 forward MW:17666 MSESYRKLTTSSIIVAKITFTGAMLDGSIALAGQASPATDSEWDQVARCESGGNWSINTGNGYLGGLQFSQGTWASHGGG (SEQ ID NO:244) EYAPSAQLATREQQIAVAERVLATQGSGAWPACGHGLSGPSLQEVLPAGMGAPWINGAPAPLAPPPPAEPAPPQPPADNF PPTPGDVPSPLARP >BL;ML2155, ML.tab 2556716:2556940 reverse MW:8095 MKSVNYYVVADIAKSKAHKSRYVDNGWPTTDPDHHAVSELVTDCAGALSPFGDLVFPVPADDLPYVHPVTVVNR (SEQ ID NO:245) >BL;ML2156, ML.tab 2557038:2559299 forward MW:80254 MTDNTPDIPLGSWLADLSDERLIQLLELRPDLAQPPPGSIAALAARAQARQSIKAATDELNFLQFAVIDALLVLQADSTP (SEQ ID NO:246) VPTTKLKALIGDRAPQADVVSALDNLRQRALAWGETTVRIAAAAAAALPWHPGQVTLEDISSTGEQIAELIARLSQTQRD VLQKLLEGSPLGRTRDAAPGAPPDRPVPQLLAMGLLRRIDADTVILPRRVGQVLRGEQSGPTQLTQPYPVVSVTTPNDAD AEAAGAVIEALHELDVLLETLGSAPVYELRNGGLGVREFKRLAKATGINEPRLGLLLEVTAAAGLIASGIPDPEPATGDS PYWAPTVATDRFTANPPAERWHLLASTWLDLQCRPALIGSRGPDAKSYGALSNSLYSTAAPLDRRLLLGMLAELPAGVGV EAAEASAALIWRRPRWARRLQPGPVADMLAEGHTMGLVGRGAISTPGRALLDEAIASADPAIAVAAMTRALPEPIDHFLV QADLTVVVPGPLQRNLAKELGTVATVESAGTANVYRISEQSIRHALDIGKTRDWMHALFTNHSKTPVPQRLTYLINDVAR RHGQLRIGMAASFVRCEDPALLTQTVAAAEELQLRALAPTVAVSPAPIAEVLVTLQSAGFAPAAEDSSGSIVDVRPRRAR LPTPQHRRPYRPLQRPNLETLNAVIAVLRKVAATPFGGIRVDPTVTMSLLQRATKEKTTLVIGYLDAAGIATQRMVSPIA IRGGQLVAFDPGTGRLRDFVIHRITSVVSSDSQ >BL;ML2193, ML.tab 2608113:2609048 reverse MW:33819 MVLNWRFALSADEQRLVREIISAATEFDEVSPVGEQVLRELGYDRTEHLLVTDSRPYAPIIGYLNLSSPRDAGVANAELV (SEQ ID NO:247) VHPRERRRGVGAANVRAALAKTGGRNRFWAHGTLASARATASVLGLVPVRELVQMQRSLRTIPDPMVPDQLGVWVRTYVG TVDDAELLRVNNAAFAGHPEQGGWTATQLAERRSEPWFDPAGLFLAFGDSSSNQPGKLLGFHWTKVHAAHPGLGEVYVLG VDPSAQGRGLGQMLTSIGIASLAQRLVGPSAEPTVMLYVESDNVAAARTYERLGFTTYSVDTAYALARIDD >BL;ML2195, ML.tab 2609965:2610816 forward MW:30382 MVKDATCIKVRHNMRMRKVLTSVIATVVTMAVLVVGVLGIDYGTSIYAEYLLSVNVRNAANLGSDPFVAILAFPFIPQAM (SEQ ID NO:248) RDHYTELEIKANAVDHANVGKASLEATMYSIDLTYASWLIKPDAKLPVDRLESRIIIDSMHLGQYLGISDLMVEAPHRET NNATGGTTESGISSGHGLVLSGTPKSANFDHRVSVLVDLSIAPEDQATLVFTPTGIATGPDTANQPVPDDKRNPVLRAFS ARMSDQRLPFGVAPTSEGARGSDVIIEGITQGVTITLDGFKQS >BL;ML2199, ML.tab 2612896:2613198 forward MW:10570 MCSEPKQRLALPANVNLEKETVITGRVVDRKGQAVGGAFVRLLDSSNEFTAEVVTSATGDFRFFAAPGSWTLRALSSVGN (SEQ ID NO:249) GDAMMSPSGTGIHKVDVKIT >BL;ML2200, ML.tab 2613457:2614143 forward MW:24489 VTSDEVRDGAGSPADSSKGNKCTAAGMFQAAKRSTVSAARNIPAFDDLPVPSDTANLREGANLNSTLLALLPLVGVWRGE (SEQ ID NO:250) GEGRGPNGDYHFGQQIVVSHDGGNYLNWEARSWRLNDAGEYQETSLRETGFWRFVSDPYDPTESQAIELLLAHSAGYVEL FYGRPRNASSWELVTDALACSKSGVLVGGAKRLYGIVEGGDLAYVEERVDADGGLVPNLSARLYRFAG >BL;ML2204, ML.tab 2619139:2619327 forward MW:7054 MGRGRAKAKQTKVARELKYSSPQTDFQRLQRELSSTGAADPGQLDGDDRVSEDSWDEDAWRR (SEQ ID NO:251) >BL;ML2207, ML.tab 2622297:2622692 reverse MW:13959 MAVCDRADPAKTRQAVLALADWLKDRTLPAPDRDAVATAVRLTVRTLATLAPGASVEVRIPPYVAVQCVSGPSHTRGTPP (SEQ ID NO:252) NVVETDSRTWLLVATGLMQLVEAVATGALRMSGSRAGDIEVWMPLINLRCT >BL;ML2219A, ML.tab 2636676:2636915 reverse MW:8613 VARAVVMVMLRAEILDPQGQAIAGALGRLGHTGISDVRQGKRFELEIDDTVDDSELAMIAESLLANTVIEDWTITRESQ (SEQ ID NO:253) >BL;ML2228, ML.tab 2645990:2646610 forward MW:21778 MNSRFLPYATSPGRLTIQLLSDIAVVMWTTFWVLVGIAVYNTISTIADTGAQVESGAHGIADNLASASHGMQLIPVLGNA (SEQ ID NO:254) VSKPLTLTSAAALDIADAGHSLNTTASWLAVLLALAVIALPILVAVVPWLVLRFWFFRHKWTVTTLAATPAGKQLLALRA LTLRSPSKLAAVSADPVGGWRREDPGTIRGLAALELQSSGITLRVH >BL;ML2253, ML.tab 2676319:2676534 reverse MW:8295 MPNNIAFSRSYIGKRCYSEQEVGVFIDLAEQERTRHIEEDVEFRNRNAELRNQDGAPQPRSCADRARNCHV (SEQ ID NO:255) >BL;ML2258, ML.tab 2682528:2682830 reverse MW:11299 VNRFLTSIVSWLRAGYPEGIPATDTFAVLALLARRLTNDEVKIVARELIRRGEFDKIDIGVMISHLTDELPSPQDIERVR (SEQ ID NO:256) TRLNAKGWLLDNARDNGEPT >BL;ML2259, ML.tab 2682860:2683150 reverse MW:10541 LSPWFNYEATLKILLFSTLAGAALPGLFALGIRLQVNDAGDASTNNATPNRKPILVTLAWVIYALVLMVVILGVLYIVSR (SEQ ID NO:257) DFIAHHTHYPFLGIKP >BL;ML2261, ML.tab 2684489:2684905 reverse MW:15612 MEILASRMLLRPTDYQRSLSFYRDQIGLAIAREYGTGTVFFAGQSLLELAGYVIQGAPDHSRGAFPGALWLQVRDIAVTQ (SEQ ID NO:258) ADLEGRGVSITREPRREPWGLHEMHVTDPDEITLIFVEVPANHPLRRDTRSERPRTPD >BL;ML2271, ML.tab 2695503:2696030 forward MW:19222 VILSKSLLRILIHGRSDEPPSTRARVIMRWGRIAVLIVTGLITLQSVLLVAGAWRNDLTIQHNMGVAQAEVLSAGPRRST (SEQ ID NO:259) IEFVTPERVTYRPELGVLYLSELSTGMRIYVEYNKNDPNLVRVRHRNAGLAIIPAGSIAVVCWLAATVVLVALAVLDKRL DRHTESSAVPSQPTS >BL;ML2274, ML.tab 2698017:2698355 reverse MW:11815 MKGTGLAANVAMAAAATVLAAPALADDYDAPFNAQLHSYGIYGAQDYNAWLGKIACQRLAKGVDGDVNKSATF IQRNLPL (SEQ ID NO:260) YTTEGQSLQFLGAAINHYCPNQIGILQRAGAR >BL;ML2289, ML.tab 2713408:2714178 reverse MW:26191 VTADLLAPLMELPGVATASDRARDALGRAHRHRANLRGWPVTAAEAALRAARASSVLDGGPVRLDHLPGASPQAGGVSDP (SEQ ID NO:261) VFGGALRVAQALEGGAGPLVGVWQRAPLQALARLHVLAAADQVGDEWLGRPRMDAEVGLRLGLLVDVVSGRTFAAAPVVA AVVHGELLTLQPFGSADGVVARAVSRLVTIATGLDPHGLGVPEVSWMRRAAVYRDAACGFAGGTPKGVAAWLVLCCRALH AGAQEALSIAESLPSR >BL;ML2295, ML.tab 2720556:2721260 reverse MW:23836 LVLRRGHWCILVALVAVLLAVVSMPAKTVFADGRLPMGGGAGIVINGDTMCTLTTIGTDSAAELIGFTSAHCGGPGAQVA (SEQ ID NO:262) AEGAENRGPMGTMIAGNDNLDYAVIKFDPAKVMPVAAYNGFVISGIGQDPAFGQIACKQGRTTGNSCGVAWGMGETSGTL VMQVCGRPGDSGAPVTVNNLLVGMIHGAFTDNLPVCITKFIPLHTPAVVMSMNAILADVNKNNRPGAGFVPQPV >BL;ML2296, ML.tab 2721464:2722009 forward MW:20041 MSKGDRKNGVPSTLTTIPLVDPHAEPTEPSIGDLIKDATTQVSTLVRAEVELARAEIIRDVKKGLTGSVFFIAALVVLFY (SEQ ID NO:263) STFFFFLFLAELLDTWLWRWVALLIVFAIMVMVTAALALLGYVKIRRIRGPHQTIESVKETRTALTPGHDKAQARPRKLT GSGTNPENNPDRRTPADPSGW >BL;ML2306, ML.tab 2730213:2731358 forward MW:40804 MTAPTSHRPPTLDMAAILADTSNRVVVCCGAGGVGKTTTAAAMALQAAEYGRTVVVLTIDPAKRLAQALGVNDLGNTPQR (SEQ ID NO:264) VPLAPEVPGELHAMMLDMRRTFDEMVVQYSGPERAQAILNSEFYQTVATSLAGTQEYMAMEKLGQLLSQDRWDLVVVDTP PSRNALDFLDAPKRLGNFMNSRLGRLLLTPGRGIGRLVTGANGLAMRALSTVLGSQMLADAATFVQSLDATFGGFRGKAD RTYALLKQRGTQFVVVSAAEPDALREASFFVDRLSQENMPLAGLMLNRTHPTLCALPVEQAIDASKTLQDEITNSAAASL ATAVLRINDRGQTAKREARLLSRFTGANPHVPVIGIPLLPFDVSDLEALRAIADRLTASH >BL;ML2307, ML.tab 2731463:2731708 reverse MW:9325 LCRATDPDELFVRGAAQRKAAVICRHCPVMQECRADALDNKVEFGVWGGMTERQRRALLKQHPEVVSWADFFDTRKHRNV (SEQ ID NO:265) S >BL;ML2320, ML.tab 2747152:2747799 reverse MW:22771 VSWVIRISAVVMSVGLGLGVPVASARPSEPGVVSYAVLGKGSVGNIIGRPMGWESLLTEPLQAYSVDLPMCNNWADIGLP (SEQ ID NO:266) EVYHDVDLASFNGAITQTSANDQTHFVKQAVGVFATNDAAVRAFHRVVDRTVGCSGQTTAMHLDNGTTQVWSFVGGTPTY ADANWTKQEAGTDRRCFVQTRLRENVLLQTKVCQPGNAGPAVNVLAGAMQNALGQ >BL;ML2330, MLtab 2761253:2761603 reverse MW:11931 MQPGGDMSALLAQAQQMQQKLLETQQQLANAQVHGQGGGGLVEVVVKGSGEVVSVAIDPKVVDPGDIETLQDLIVGAMAD (SEQ ID NO:267) ASKQVTKLAQERLGALTSAMRPTAPPPTPPTYMAGT >BL;ML2332, ML.tab 2762489:2762926 reverse MW:15496 MGPVSAVSTILVNVEPVATLAAVADYQKNRPKILSPQYNEYQVVQGGQGPGTVVKWKLQVTRSRVRDVQVNVDVAGHTVI (SEQ ID NO:268) EKDANSSMVTSWTVAPAGPGSSVTMKTAWTGAGGVKGFFEKTFAPLGLKKIQAEVLANLKNELER >BL;ML2337, ML.tab 2769442:2770194 forward MW:27248 MGYKVATLWHASFSIGAGVLYFYFVLPRWPELIGETTHTLGTTLRIVTGVLFGLAALPVVFTLLRSQTSELGIPQLALSI (SEQ ID NO:269) RTWSIVAHVLSGVLIVSTAIGEIWLSSDTAVQCLFGIYGAAAASAVLGFVAFYLSFVAALPPPSPKPVKLKKANQRRIRR RKGRKDNEAEDEEADAGEHNEAETPAQAEEVTSENPQPAPESGAQKEPDELLANKTEETDEPRRGLHNRRPTGKVSHQRR RARSGIAVEN >BL;ML2366, ML.tab 2834617:2834958 reverse MW:11956 MAFMTSNPSGPPSQPAPAVGLTPGERAVPVTRAGALWSALFAGFLILILLLIFIAQNTTSTPFTFFGWHWSLPLGVAIML (SEQ ID NO:270) SAVGGGLLAVAVGTARILQLRRTVKKRYVAAHR >BL;ML2377, ML.tab 2846366:2846830 forward MW:16863 MSKRQRGKGISIFKLLSRIWIPLVILVVLVVGGFVVYRVHSYFASEKRESYADSNLGSSKPFNPKQIVYEVFGPPGTVAD (SEQ ID NO:271) ISYFDANSDPQRIDGAQLPWSLLMTTTLAAVMGNLVAQGNTDSIGCRIIVDGVVKAERVSNEVNAYTYCLVKSA >BL;ML2380, ML.tab 2850483:2850944 reverse MW:17491 MSRLSTSLCKGAVFLVFGIIPVAFPTTAVADGSTEDFPIPRRQIATTCDAEQYLAAVRDTSPIYYQRYMIDMHNKPTDIQ (SEQ ID NO:272) QAAVNRIHWFYSLSPTDRRQYSEDTATNVYYEQMATHWGNWAKIFFNNKGVVAKATEVCNQYQAGDMSVWNWP >BL;ML2388, ML.tab 2858302:2858607 forward MW:10942 VAAGDNRLIGNDTPEIAVGAIGGVATGYVLWLVVMSIGYNITTVSQWSLIVLILSMVSVFCSGMCGWWLRQRRKHAWGAF (SEQ ID NO:273) TFGLPVFPVVLTLAVLAKIYL >BL;ML2390, ML.tab 2861300:2861605 reverse MW:10840 VSHIFLTLIADGELQYHGPDFGKASPMGLLVIVLLLVATLLLLWSMNRQLKKIPASFDSEHPELDQAADEGTELGGYLDE (SEQ ID NO:274) EPSDTDRNGPSLPPEPGADSG >BL;ML2392, ML.tab 2862579:2863013 forward MW:15303 MNQAFTPLTETRYGRSRLPGRSRHRGVIALTVLAVAASTGIAVIGYQRLGTSDVAGSLASYRVLDDETVSVTISVMRSDP (SEQ ID NO:275) SRPVDCIVRVRAKDGSETGRREVLVAPAEATTVQVVTTVKSARPPVMADIYGCGTDVPGYLRPA >BL;ML2407, ML.tab 2878350:2878685 reverse MW:12141 VSKGPNSICAADHNRDHLVVNVLLYAAARLLLVILLGSVIYGVARLLGVTQLPIVVAALFALIIAMPLGIWLFSPLRRA (SEQ ID NO:276) TAALAVVGERRRSEREQLRARLRGEPLPDEE >BL;ML2410, ML.tab 2881021:2882649 reverse MW:59195 LMQVLMRLLAWVRNTWRALTSMGTALVLLFLLALGAIPGALLPQRDLNVGKVDDYVAAHPVIGSWLDQLQAFNVFSSVWF (SEQ ID NO:277) TAIYTLLFVSLVGCLTPRMIEHARSLRAMPVIAPRNLARLPKHASFQVIGDDKTLAGTIAGRLRGWRTVIRTQDGVVPET VVSAEKGYLREFGNLVFHFSLLGLLVAVAVDKLFGYEGNVVVIADGGPGFCSASPAAFDAFRAGNTVDGTSLHPICIRVN DFAAHYLPSGQAMSFTADIDYQDGHDLTVNSWRPYRLEVNHPLRVAGNRVYLQGHGYAPTFTVTFPDGQTRTSTVQWRPE NQQTLLSSGVVRIDPPAGSYPNMSERRQHEIAIQGLLAPTEQLDGTLLLSRFPALNAPAVAIDIYRGDTGLDSGRPQSLF TLDPRLINQGRLTKEKRVNLQAGEQVRLGQGPGAGTVVRFDGAVPFVNLQVSHDPGQAVFVFAIAMMVGLVVSLMVRRR RVWVRLTPAAGTVNVELGGLARTDNSGWGDEFERLTERLLAGLVAADRTLAAARRSSQMDVK >BL;ML2425, ML.tab 2901005:2901505 forward MW:18654 MTVPLEAEGLIGKYRQLDHFQVGREKIREFAIAVKDDHPTHYNETAAFEAGYPALVAPLTFLAIACRRVQLEIFTKFNI (SEQ ID NO:278) PINVARVFHRDQKFRFYRTILAQDKLYFDTYLDSVIESHGTVIAEVRSEVTDTEGKAVVTSIVTMLCELARQDATAEETV AAIASI >BL;ML2428A, ML.tab 2904745:2904846 reverse MW:4145 MGSVIKKRRKRMSKKKHRKLLRRTRVQRRKLGK (SEQ ID NO:279) >BL;ML2432, ML.tab 2907135:2907977 reverse MW:30442 LRPVIKVGLSTASVYPLRAEAAFEYAAKLGYDGVELMVWGESVSQDIDAVKGLSRRYRVPVLSVHAPCLLISQRVWGANP (SEQ ID NO:280) VPKLERSVRAAEQLGAQTVVVHPPFRWQRRYAEGFSDQVAELEAASDVMIAVENPFPFRADRFFGADQSRERMRKRGGGP GPAISVFAPSFDPLAGNHAHYTLDLSHTATAGSDSLEMVRRMGSGLVHLHLCDGSGLPADEHLVPGRGTQPTAAVCQLLA GADFAGHVVLEVSTSSVRSATERETMLTESLQFARTYLLR >BL;ML2433, ML.tab 2908008:2909075 reverse MW:37938 MTGPHNDTESPHARPISVAELLARNGTIGAPAVSRRRRRRTDSDAVTVAELTCDIPIIHDDHADEQHLAATHAHRANIGV (SEQ ID NO:281) RVVEPAAQSPLEPVCEGIVAEPPVDDHGHVPPGCWSAPEPRWPKSPPLTHLRTGLQRSACSRPLPHLGDVRHPVAPDSIA QKQSDAEGMSPDPVEPFADIPVDVMGSEVRAAELVAEESAYARYNLQMSAGALFSGHTLTNELAERRGDEHAAGGLLAVG IDLDEDHLDLHTDLAGITSPARGWQSRFEALWRGSLIVLQSILAVVFGAGLFVAFDQLWRWNSIVALVLSVLVILGLVVG VRVVRRTEDIASTLIAVVVGALITLGPLALSLQSG >BL;ML2435, ML.tab 2910195:2911028 forward MW:31007 VSSCPESGSTFEYVANSHLEPVHPGEEVDLDFTREWVEFYDPDNSEQLIAADLTWLLSRWTCVFGTPACRGTVAGRPDDG (SEQ ID NO:282) CCSHGAFLSDDADRTRLDDAVKKLSHDDWQFREKGLGRKGYLELDEHDGQSQFRTRKHKNACIFLNRPGFPIGAGCALHS KALKLGVPPRTMKPDICWQLPIRHSQEWVTRPDGTEILKTTVTEYDRRSWGSGGADLHWYCTGDPASHVDSKQLWESLAD ELTELLGAKAYAKLAAICKRRNRLGIIAVHPATQEAK >BL;ML2442, ML.tab 2917372:2917926 reverse MW:20820 MSTAWDTVWHACSVIEHALQASHLTYSEFSGVPDGLLRLVVELPGERRLKTNAILSIGEHSVNVEAFVCRKPDENHEGVY (SEQ ID NO:283) RFLLKRNRRLFCVSYTLDNVGDIYLVGRMSLASVDTDEIDRVLGQVLEAVESDFNTLLELGFRSSIQKEWDWRISRGESL NNLQAFAHLIDDEGDGDASIYARP >BL;ML2446, ML.tab 2921383:2922708 reverse MW:46863 VIASTPRQNRESINRRVALTALGVGVFAPSVFVACAGSAIKPSEKKTTPAPHLTFQPATATDDVIPVAPISVQIADGWFQ (SEQ ID NO:284) RVTLTNPVGKVVAGVFNQDRTVYTITEPLGYDTTYTWNGSAVGHDGKAVPVTGKFSTVTPVKKVNGGFQLADGQTVGVAA PITIQFDAPISDKSAVEKALTVTTTPPVEGSWAWLPDEAKGARIHYRPREYYPAGTTVNVDAKLYGLPFGDGAYGLQDMS LNIQIGRRQVVKAEVSSHRIQVVTDAGVIMDFPCSYGEADQARNVTRNGIHVVTEKYSDFYMSNPAAGYSNVYERWAVRI SNNGEFIHANPASVGAQGNTNVTNGCINLSTGDAEQFYRSAIYGDPVEVTGSSIQLSYSDGDIWDWAVDWDTWVGMSALL SFPTVHQPATQIPVTAPVTPPGAPILSGTPTSGSGTARPGG >BL;ML2450, ML.tab 2925762:2926499 forward MW:26174 LLRDPLAIVLILIIVVALVISGLIGAELFARHTANSKVARVVTCEIKDQATAKFGVTPLLLWQFATQHFTNISVETAGNQ (SEQ ID NO:285) IRDAKGMKIAIDIQNVQIRDTPTSRGTIGVLDAIITWSSDGIRQSVQNSIPVLGGVVTTSVTTHPTNGTIELKGMLNDIV AKPVVSNGGLQLQIVSFNTLGFSLPKETVQFTLDDFTTNLTKNYPLGIHADNVEVTSTGVTSHFSARNTNIPNSTGGQDP CFANL >BL;ML2452, ML.tab 2927236:2927607 reverse MW:13492 MSSPLSPLYVLPFVDHTKWTRWRSLISLQAYSNLFGRTSAMQPDVAAGDEAWGDVLTLSPDADTADMHAQFICHGQFAEF (SEQ ID NO:286) VQPSNTSSNLEPWRPVVDDSEIFAAGCHPGISEGIQQADEGPR >BL;ML2453, ML.tab 2927710:2927997 reverse MW:10004 MSHLVGTVMLVLQLAVLVTAVYAFVHAALQRPDAYTAAEKLTKPVWLVILGAAVSLTSILGFVFGVLGIVIAACAAGVYL (SEQ ID NO:287) VDVRPKLLDIQGKSR >BL;ML2454, ML.tab 2928117:2928683 reverse MW:20421 MAENPNVDDLRAPLLAALGAADLALTTVNELVGNMRERAEETRIDTRSRVEESRARVAKLQEVLPEHLSELREKFTADEL (SEQ ID NO:288) RKAAEGYLEAATNRYNELVERGEAALERLRSRPVFEDASARAEGYVDQAVELTQEALGTVASQTRAVGGRAAKLVGIELP KKAAAPARKAPAKKAPAKKAPAKKVTQK >BL;ML2463, ML.tab 2936751:2937545 reverse MW:30332 VSLDKIMMPVPEGHPDVFDREWPLRVGDIDRTGRLRLDAGVRHIQDIGQDQLREMGFEETHPLWIVRRTMVDLIRPVEFQ (SEQ ID NO:289) EMLRLRRWCSGTSNRWCEMRVRIDGRKGGLIESEAFWININRETQMPARIADDFLAGLHRTTSVDRLRWRGYLQPGSRDD ASEIHEFPVRVTDIDLFDHMNNSVYWSVIEDYLVSHSELLKGPLRTTIEHEAPVALGDKLEIVLHVHPAGSTDQFGPGLV DRSVITLTYTVGDETKAIAAIFAL >BL;ML2465, ML.tab 2939177:2939743 forward MW:21174 MSGGTGTGPVGRIPPGSLRQLGPINWVIAKLAASLLRTSEMHLFTILGQRQLLFWAWLIYGGRLLRGKLPRVDTELVILR (SEQ ID NO:290) VAHLRTCEYELQHHRRMARKRGLDTKIQAMIPAWPDVPTGAGLSVRQQALLAATDEFVKDRKITSSSWQQLETHLDRRRL IEFCMLISQYDGLAATISSLDIPLDNSC >BL;ML2473, ML.tab 2948272:2948751 forward MW:17160 MPDGFGVAVVREEGQWRCSAMASKSLTSLTAAETELRELRSVGAVFGLLDVDDEFFIILRPAPSGTRLLLSDATAALDYD (SEQ ID NO:291) IAAEILDSLDAEIDPEDLEDAYPFEEGDLGLLSDVGLPEATLGVILDQTDLYADEQLGHIAREMGFAEQLSAVINRLGR >BL;ML2489, ML.tab 2962275:2963135 reverse MW:32001 MVPLWFTLSALCFVGAVVLLYVDIDRRRGRSRRRKSWARSHGFDYERESTEILQRWKRGVMSTVGDISAHNVVLGQIRGE (SEQ ID NO:292) AVYIFDLEEVATVIALHRKVGTNIVVDLRLKGLKEPRESDIWLLGAIGPRMVYSTNLDAARRACDRRMVTFAHTAPDCAE VMWNEQNWTLVSMPIGSTRVQWDEGLRTVRQFNDLLRVLPPLPADTSQEAGASARNAAPSRPLASVGRAELPPDRGVESD VAGLLGSGVQAGRSAEPISRDEGRWDGIRRPPSVERNGHQTTNYQY >BL;ML2491, ML.tab 2966697:2967698 forward MW:36545 VTGPNSPNKTLQRFGISGTDLGIPWDNGDPTNHQVLMAFGDSFGYCSVKGQQRRYNILFRSSNQDLSHGIRIADGVPNDK (SEQ ID NO:293) YSGSPVWTTGLAKQVVNTIHRAPHETGIIPTTAISIGKTQYMNYMSIKKWGRDGEWTTNYSAIARSIDNGQSWGTYPGTI RTASPDAIPGTHFVPGNQNFQMGAFMRGNDGYLYSFGTPSGRSGAAYLARVPQNLVPDLSKYQYWNGNWVPNNPGAATPL FSGPVGEMSAQYNDYLKQYIILYSNGDSNDVVARTAPAPQGPWSPEQPLVSSFQMPGGIYAPMIHPWSSGRDLYFNLSLW SAYDVVLMHTVLP >BL;ML2518, ML.tab 2999816:3000208 reverse MW:14353 VGEYSAFGFDPDDFDRLIKEGSEGLRDAFERISRFVGGPGVRTAWSAIFEDLSRRARPAQETADEAGDGVWAIYTVTGDG (SEQ ID NO:294) AARVEQVYATELDALRANKNNVDPKRKVRFLPYGIAVSVLDSHQESTQQL >BL;ML2522, ML.tab 3004590:3005246 reverse MW:22735 MCRLIALLSAVVCAAWATLILAPIGAAAGAAWFANKVGNATQVVSVVSTGGSNAKMDIYQRTGTGWQPLKTGIPTYVGSA (SEQ ID NO:295) GLVAQAKSGYPATPMGVYSLDSAFGTAPNPGSQLPYTQVGPNHWWSGDDHSPTFNTMQVCQKSHCRFNTAESENLQIPSY KHAVVMGVNKAKVPGSGSAFFLHTTGGGPTEGCVAIDDVTLVQILRWLRPGAVIAITK >BL;ML2527, ML.tab 3009256:3010275 reverse MW:36773 VSAHRSRPAAMWPGSSRITLALLAVMPALMAYPWWFTRSYWLLGIVALVVVVLFGWWRGLYLTTILRRRLAMMWRRGRPV (SEQ ID NO:296) SASGSATRTTVLLRLGPPVGGSDVIPLPLITRYLNCYGIRADSIRITSRNNESDGALCETWIGLTVSAAKNLAALQARSS RIPLQETAQVAARRLADHLREIGWEVSLAVPDGIPRLITAAGDETWRGMQQGSDYLTAYRVNVDDELPGTLDAVRLYPAR ETWTALEIACPDSSSNRNTIAAACAFLTDTAPQGAAPLAGLTPQHGNHRPALAVLDLFSAQRLDGHTDTDADLLTRLRWP APAAGVSSCTATRSPAVSA >BL;ML2529, ML.tab 3011710:3013167 reverse MW:49866 MVYVFAEEFCEGPVTSGAVMPIVRVAILALSRLIEMALPTELPLREILPAVKRLVVPAASDNDSPLAANASLHLSLAPIG (SEQ ID NO:297) GAPFSLDASLDTVGVVDGDLLALQPVPVGPAAPGIVEDIADAAMIFSTARLQSWGPTHIRRGALAATTAVTFAATGLGVT YRAVTGALTGLLVVIVIAVLIALGGLVLRSRAARTGLVLSIAALVPIGAVFALAVPGIFGPAQVLLASAGVTAWSLIALI VPGPERVRIVAFFTATVVIGVAVMLEAGAALLWQLTPLTIGCGLILAALLVTVEAAQLSALWARFPLPVIPAPGDPTPSA PSFQVLEDLPRRVRISSAHQSGFIAAATLLSMLGSVAIALRPEAVSSVGWYLVAATAVAATLRARVWDSVACKAWLLAQP YLVASVLLGLYTATGRYVAASAALLVLVVVVLAWAVVALNPRIASSDSYSLPLRRLLGMVASGLDASLIPAMAYLVSLFS WVLNR >BL;ML2530, ML.tab 3013309:3014178 reverse MW:31518 MKVDPNAVELTVDHAWFIAEVIGAGSFPWVLAITTPYRDAGERSAFVERQVDELTRMGLLVAENSVDPTVADWIRVVCFP (SEQ ID NO:298) DRWLDLRYLRSTSAVGDSELLRGMVAQRAGVSDKTVVALRSAQLITFTAMDIDDPLRLVPILGAGLAQRPPARFDEFSMP MRVGVRADERLRSGTSLAEVADYLGIPKSAQPVVESVFSGPRSYVEIVAGCRRDGKHATTEVGMSIVDTTTGRVLVNPSR AFDGEWVSTFSPGTPFAIAVGIEQLTATLPEGQWFPGQRLCRDFSGQTS >BL;ML2531, ML.tab 3014189:3014479 reverse MW:10392 MTQIMYNYPAMLDHAGNMSACAGALQGVGIDIAAEQAALQACWGGDTGISYQAWQVQWNQATEEMVRAYHAMANTHQNNT (SEQ ID NO:299) LAMLTRDQAEAAKWGG >BL;ML2532, ML.tab 3014518:3014814 reverse MW:10191 VSLLDVHIPQLVASESAFAAKAALMRSQINQAECEAISAQAFHQGESSAAFQSAHAQFVTAAEKINALLDIAQQHLGEAA (SEQ ID NO:300) ETYVATDATAASTYTTGL >BL;ML2534, ML.tab 3016103:3016411 reverse MW:10243 MTLRVVPEKLAATSEAMKALTARLEAAHAAAFPCLVAVVPPAADPVSLQTAAGFSARGQEHALVAAQGVEELGRAGIGVG (SEQ ID NO:301) QSSTHYAISDALAASTYGIVES >BL;ML2536, ML.tab 3020432:3022090 reverse MW:57975 MTSNELPGEWSGERRSFFSRTPVNDNPDKVVYRRGFVTRHQVTGWRFVMRRIASGIALHDTRMLVDPLRTQSRSVLVGAL (SEQ ID NO:302) LVITGLIGCFVFSFIRPNGAAGNNAVLADRSTAALYVRVGDELHPVLNLTSARLIVGRSVNPITVKSSELDRFPRGNLIG IPGAPERMVQNTTHDANWTVCDVVSGEGGHAAHSMGVTVIAGPPDSHGMRAAVLGSAHGVLVDAPSERGGsTWLLWDGKR SEIDLADHAVTDALGFGVGFAEVPAPRPIGAOLFNAIPEAPPLKAPVIPNAGATPSFGVRAPIGAVVVSFGLAALGKNPY DSVRYYAVLPDGLQPISPVLAAILRNINSYGLQQPPRLGADEVDKLPVSRMLDTERYPEQQISLIDAGYAPVSCAYWSKP AGAATSFLSLMSGAALPVPDAARAVELVSAPSRGDSSTASRVVLTPGTGYFAQTVGVGSAAPATASLFWVSDTGVRYGID TEADARSEATAGPGKIVEALGLKLPAVPIPWSILSLFAVGPTLSRADALLEHDGLAPDTRAGRTTTAYGEHR >BL;ML2557, ML.tab 3049294:3049590 forward MW:10997 LYATTELAELHDLIGRMRRSVASFKARYGDSPNRRIAIDADRILSDIELLDADISELDLARATVQQSNEKIAIPDTQYD (SEQ ID NO:303) SDFWRDVDDEGVGGHSRS >BL;ML2566, ML.tab 3061369:3062271 forward MW:32889 LTFGFVLRRLRRHFSVKENTVNQPSGLKNILRAIVGALPLLPRTDQLPSRTVTIEELPIDHTNVSAYASVTGLRYGNHVP (SEQ ID NO:304) LTYPFALTFPANMSLVTGFDFPFAANGSVHTENHITQYRPIAVTDVVGVQVHAENLREHRKGLLVDLVTDVSVGNDTAWH QVTTFLHLQRTSLSDEPKPPSQKQPKLLPPSAVLQITPRQIRRYAAVGGDHNPIHTNPIVAKLFGFPTTIAHGMFSAAAV LANIEARLPDAVHYSARFVKPVVLPATTGLYVDESAGNWDLTLRNIAKGYPHLAGTVQGV >BL;ML2569A, ML.tab 3065268:3065441 forward MW:5896 MSRIVAPAAASVVVGLLLGAATIFGMTLMVQQDTKPPLPGGDPQSSVLNRVEYGNRT >BL;ML2570, ML.tab 3065557:3069774 forward MW:147681 VAAMSRWWLVLVGVVAVALTFAQSPGQISPDTKLDLTTNPLRFLARATNLWNSDLPFGQVQNQAYGYLFPHGTFFLIGQL (SEQ ID NO:305) LGSPGWITQRLWWALLLTAGFWGLLRVAETLSIGSPTSRAIGAVAFALSPRVLTTLGSISSETLPMMLSPWVLLPTILAL QGAPGRSVRTRAAQAGLAVALMGAVNAIATLAGCLPAVIWWACHRPNRLWWRYTGWWLLALCLATLWWVVALVLLHGVSP PFLDFIESSGVTTQWSSLVEMLRGTDSWTPFVAQTATAGTPLVTESVAILGTCLVAAAGLAGLASTGMPARGRLVTMLVI GVVLLSAGYSGGLGSPLAQAVQAFLDSSGAALRNVHKLESVIRTPFALGIAGLLGRIPLPGSAPVLVWLSSFAHPERDKR VAATVAVLTALLVSTSSAWTGRLTPPGTFSAIPQYWNDTSDWLSEHNTGIPTPGRVLVVPGAPFATQVWGTSHDEPLQVL GNSPWGVRDSIPLTPPQAIRALDSVQRLFASGRPSVGLADTLARQGISYVVLRNDLDPDTSRSARPILVHRAIAGSPQLE KVAQFGAPVGTNMLKGFVADSELRPWYPAVEIYRVAVSDGTNPGKPYFADTDQLPRIDGGPEVLLRLDERRRLLGQPALG PALMTADAQFAGLPLPSRAEVTITDTPVARETDYGRVDQNSSAIRAVNDARHTFNRVPDYPVPGAEMVFGGWSGGRITAS SSSSDATSMPDVAPATSPAAAIDGDPATSWVSNALQPAVGQWLQVDFDHPVNNAVITVTPSATAVGAQVRRIEIETVNGT TNLRVDEAGKPLAVALPYGETPWVRITAAATDDGSSGVQFGITDLTITQYDASGFAHPVNLRHTALVPGSPPGWAVAGWD LGSELLGRPGCAPAPDNVRCAASMTLAPEEPVNFSRTLTVPYPISVTAMLWVRPRQGPKLADLIAEPKTTRAYGEADTVD ILGSAYAATDGNPATSWTAPQRVVQHKTPPTLTLVLPRPTEVNGLRLAPSRSALPARPTLVAVNLGNGPQVRELQAGEPQ ALSLKPRITDTVTISLLDWHDVIDRNALGFDQLKPPGLAEVTVLGTDGNPTAPANASENRIREVTVDCDHGPIIAVAGRF VHTSIRTTAAALLDGEPVAAVPCERAPIVLPAGQQELLISPGAAFIVDGAQLSTQDGTELPSARTISADTGKWGPSRREV RAPGSATSQVLVMPDSINPGWVAHTSTGVRLMPVAVNGWQQGWLVPAGNPGTITLTFTANSLYRPGLAAGLALLPLLALL ALWGRRNERAADAAAQPWTPGAWSAVAVLSAGAVIAGAAGVVVVGAALSLRYALRHQQRWRNGLTVGLSAGGLVLAGAAL SRQPWRSVDGYSGHSANVQLLALISLAALAASVVSPRCGSTGVAT >BL;ML2581, ML.tab 3081538:3082821 forward MW:46681 VNRAVILRFTACGIIGLGAAFLIAALLLATYTSSRITKIPLDIDATLVSEGNGTALDSSSLSSEHIIVNQNVPLVSQQQI (SEQ ID NO:306) TVESPANVDVVTFQVGVSIRRTDKQKDTGLLLAVVDTVTLNRKTANAVSDDTHTGGSIQKPRGFTDENPPTAIPLRHDGL SYRFPFHTEKKTYPYFDPVAQKTFDVNYQNQEDINGLTTYRFTQNVGYDADGKLVAPITYPSLYASDEDGKITTTAJUWG LSGDPSEQITMTRYYAAQRTFWVDPVSGTIVKETEHVNIYFARDTLKPEVTLADYKVTSTEETIESQVNSARDERDRLAL WSRVLPITFTAVGLITLLSGGFLASFSLRTESALTESGLDRANRDAFGHCRTEEPVPGAEAETEKLPTQRPELRDSSILS VSAHRRRSSESSPPNSGPADPGHPERG >BL;ML2582, ML.tab 3082923:3084725 forward MW:61888 VSRELYHRSMSWSRPSYALGMALLVVGPLMRPGYLLLRDAVSTPRSYLSDAALGLTSAPRSTPQDFAVAMASHLVDGGIV (SEQ ID NO:307) VKSALVLGLWLAGWGAARLVVTALPSAGVAGQFVASTLAVWNPYVAERLLQGHWSLLVGYGCLPWVAEAMLMLRSSDNAS RPGLLGFFALACWIALAGLTPTGLMLAATVALICVAVPVEGPGEPRPRWLCAAATLGSALGAALPWLTASAVGTSLTAHT VANTLGVTVFAPRAEPGLGTLASLASLGGIWNGEAVPTSRTTLFAVLSATVLLGVVVAGLPVAVRRPAVVPLLVLAAVAV ATPAALATGPGIDMLKAVVNAVPGLGVLRDGQKWVALAVPGYSLAGAGAVVTLGRWLRPSRPLSPVVTALACCLALILAL PDLAWGVWGKVQPVHYPSGWAAVAATINDRGEGPGWVAVLPAGTMRRFSWSGTAPVLDPLPRWVRDDVLTTGDLIISGVM VAGEGNHARAAQDLLLSGPNPSALTAAGVAWLVVESDTAGDMGASARTLAALQPTYRDDAIGLYRIGGSNAKTAPSPYRG LLIAAHLTWLVILVMAVVGMQITRHTHFRDVSSVALLSRR >BL;ML2595, ML.tab 3100808:3101356 forward MW:19619 LPESQVAADDSGVTLNRSRLGRGWLTGIAVALLLAGCGIGTGGYCMLRYHQDSQAMARNDNAALKTALDCVAATQAPDTN (SEQ ID NO:308) TMAASEQKIIDCGTDAFHAQALLYTNMLVQAYQAANVHVQVSDMRAAVERHNNDGSIDVLVALRVKLSNDRAHNQETGYR LRVKNALAEGQYKISKLDQVTK >BL;ML2596, ML.tab 3101353:3102330 forward MW:35970 VTVVVAKSQTAAVIPEPLSNRLAPWHLRLVALAVDVLPGLVAVSTMTLVVFTVPLRSAWWWLCMAVGGIVILSMLVNRLL (SEQ ID NO:309) LPTIIGWSLGRALCGISVIMRDGVAIGPWRLLLRDLTNLLDTAAVFAGWLWPLWDSRRRTFADILLRTEVRCVQAVERQR TIRWWASVALLTAAGVSLGGASVSWAVVYSHDRAIDQTRSEIAIQGPKMVAQMLTYNPKSLRDDFTHAQSLASDKYRRQL AAQQDVVKKGHPVINEYWPTAGAIQSATRDRATMLLFMQGRRGAAPGERYISATVRVSFAKGEHNHWLVDDLTVLTKPKT TGNGR >BL;ML2597, ML.tab 3102327:3102881 forward MW:20340 MSPRRKFQAGEGLLLVSHTVASQRRWGLPLAATFAALVMVAAITASTLMSISHASRELAVAKDQQVLSYVKWFMTQFTTL (SEQ ID NO:310) DPYHANDYVARILAQATGDFAKQYNEKVNEILLQVAQAEPATGTVLDAGVERWNDDGSANVLVATEVTSKYPDEKQVLEN TNRWTATATRECNQWKISNLLQVI >BL;ML2598, ML.tab 3102971:3103525 forward MW:19619 VAAAEGGGSWRNRRAGQRTAIAVVVAAVLFVGSAAFAGAAVQPYLADRATVAVKLEVARTAANAITVLWTYTPENMDTLA (SEQ ID NO:311) DRAATYLSGDFGAQYRKFVDAIVGPNKQAKITNSTEVTGVAVESLDASNAIAIVYTNTTSTSPLTKNIPALKYLSYRLFM KRSAVRWLVTRMTTITSLDLTPQL >BL;ML2604, ML.tab 3108446:3109195 forward MW:26859 MTDNKMLARIAALLRQAEGTDNAHEADAFMATAQRLATAASIDLAVARSHVANRSTAQAPTQRTITIGTAGTRGLRTYVQ (SEQ ID NO:312) LFVLIAAANDVRCDVASNSTFLYAYGFAEDIDATHALYASLVVQMVRESDAYLASGAYRPTPTITARLNFQLGFGMRVGQ RLTEARDHIRSAVTEAWDRPTATAIALRDKEIELIDYYRSASKARGTWQAARASAGYSSAARNAGDQAGRRAWIDNSTEL PGARAALGR >BL;ML2605, ML.tab 3109192:3109698 forward MW:18602 MNLLDSVRDAQRSKVYAAEEFIRTLFDRAVEHGSPAVEFFGAQLSLPPEARFGSVAAVQRYVDDVLALQAVRQRWPRMLP (SEQ ID NO:313) LTVRARRAATAAHYENLDGAGVIAVPGNNADWAMRELVVLHEVAHHLCKDPPPHGPEFVATICALTELVMGPELGYVFRV VYAKEGVR >BL;ML2614, ML.tab 3120828:3121502 forward MW:24144 VNWPKTPGTLAAMPDEEQTELPVHKEFAGIADYSDPGLSDGSVFSQYGIASTVLAVLSAAAVVFGVVIWRAHHDNSAERA (SEQ ID NO:314) YLTHVMQTAFDWTGVLINMNTSNVDASLQRLHAGTVGELNTDFDAAVQPYRKVVEKLQTQSRGQIEAVAIESVHHDLDTQ PGVAHPVVTTKLLPPAARTDSVMLVATSVSENVGGKPTTVHWSLRLDVSDVDGKLMISHLESIR >BL;ML2615, ML.tab 3121499:3122188 forward MW:24416 MRNRWRLLAFDVVAPLVAIAALVMIGVVLDWPRWWVSACSVLVLLIVEGVGVNFWLLRRDSVTIGTDDDAPGLRLAXIXISV (SEQ ID NO:315) CTAALCAAVLIGYMHWTSPDRDFSLDSREVVQIATGMAEAFVIASFTPSAPTSSIDRAAAMIMPDQAGVFKEQYRKSSADLA RRNVTAQASVLAAGVEAIGSSAASVAVILRVTQNTPGQPPSQAAPAVRVTLIKRGSDWLVTDVLSINAR >BL;ML2616, ML.tab 3122267:3122779 reverse MW:18682 VTLADDHRRPAAPPEQPAADQGRYDPDQPVEFWSTAAIRSALHAGSIEIWKLITAAVKHDPYGRTAHQVEEVLEGTRPYG (SEQ ID NO:316) ICKALGEVLQRARTHLEINERAEVARHVRLLIDRSGLGHQEFASRIGVAPEGLASYLDGSTSPSAALMVRMRRVSDRFVK VKAARSANSD >BL;ML2621, ML.tab 3131780:3132367 reverse MW:21956 MLIWDAPNLDMGLDAIVDHHHRNALERPCFDALGRWLFTCNTEVAVGYPDSTIGLKGTMFTNIAQASADVVRLWVDTLRN (SEQ ID NO:317) VEFVIFVKPKIDEDSHMLGRIKGRYNEGLAVQVVVSAYSQALRQTLERTAHAVIDVQMIGFREHTSWALASAILEFADLE DIAGVFRESLPRISLDSLPAQGEWCAPFPGRWLRY >BL;ML2627, ML.tab 3140261:3141280 forward MW:36081 VTANGHAGRREGGPYFDDLSIGQVFDWAPAVTLTSGMAAVHQAILGDRMRLALDAELSTTVIGTHAMLAHPGLVDDVAIG (SEQ ID NO:318) QSTLVTQRVKANLFYRGLTFHRFPVIGDTLYTSTEVVGLQANSAKPGRPPTGMAALRITTTDQHDRLVLDFYRCAMLPAS AAWHPHDALNRNDDLANVGADAVASASDPTGQWDAAAFRERVPGPHFDAGITGAVLRSTGDIVSSAPDLARLTLNIASTH HDSRVRGLRLVYGGHTIGLALAQAGRMLPNLATVLNWRSCDHTGPVHEGDTLYSELHVESAEATEQGGVLGLRSLVYAVS AAGGSDHLVLDWRFTVLQF >BL;ML2629, ML.tab 3144572:3145042 reverse MW:17022 LGSVPGYASPMPVMSKTVEVRATAASIMAIVTDFEAYPQWNDGVKGVWVLARYDDGRPSQLRLDTEIQGTKCTYIQAVYY (SEQ ID NO:319) PATNQIQTIMQQGDLFTKQEQLFSAVEIGAASLLTVDIDVESSMPVPAPMVKALLNNVLDNLAENLKLRAEQLAAN >BL;ML2630, ML.tab 3145226:3145597 reverse MW:12982 LLTDGVLLPELLFGYLNKCCLLPQLFDTAINTSVGVTSPNESRAFNAADDLIGDGSVERAGLHRATSVPGESPEGLQRGH (SEQ ID NO:320) SPEPNDSPPWQRGSAQASQSGYRPSDPLTTTRQSNPAPGANVR >BL;ML2640, ML.tab 3159055:3159987 reverse MW:34454 MRTHDDTWDIKTSVGTTAVMVAAARAAETDRPDALIRDPYAKLLVTNTGAGALWEAMLDPSMVAKVEAIDAEAAAMVEHM (SEQ ID NO:321) RSYQAVRTNFFDTYFNNAVIDGIRQFVILASGLDSRAYRLDWPTGTTVYEIDQPKVLAYKSTTLAEHGVTPTADRREVPI DLRQDWPPALRSAGFDPSARTAWLAEGLLMYLPATAQDGLFTEIGGLSAVGSRIAVETSPLHGDEWREQMQLRFRRVSDA LGFEQAVDVQELIYHDENRAVVADWLNRHGWRATAQSAPDEMRRVGRWGDGVPMADDKDAFAEFVTAHRL >BL;ML2664, ML.tab 3190775:3191530 forward MW:26919 MYQAVRYLLVMAAIILMAVAESGSPSVAAIPALKPTPEVASVLPTNGAVVGVAHLVVVTFTAPVTDRSAAERSIRITSPN (SEQ ID NO:322) NMTGHFEWLDGDVVQWIPTKYWPAYTHVSVEVQALTTGFETGDALLGVASLSTHTFTVSRNGEVLRTMPASMGKPTRPTP IGKFTALSKERTVVMDSRTIGIPLNSPEGYLITAQYAVRVTWSGVYVHSAPWSVNSQGYTNVSHGCINLSPDDATWYFNT VNVGDPIEVVA >BL;ML2687, ML.tab 3234968:3236662 reverse MW:61392 VINAQTHSTTISPRPLAADRQSADNRDCPSRTDYLGAALADAIGGPVGCHALIGRSWLMTPLRVMFLIGLVFLALGWSTK (SEQ ID NO:323) AACLQTTGTGPGGQRVPNWDNQRAYYELCYSDIVPLYGTELLSQGKFPYKSSWIETDSSGTPRTRYDGRLAVRYMEYPVL TGIYQYVSMAVAKSYTALSEPVSLPAVAEVVMFFDVVAFGLALAWLATIWATAGLAGLRIWDAALVAASPLVIFQVFTNF DALAIAFATGGLLAWSRCRPISAGVLIGLGAAAKLYPLLFLVPLFVLGVRTGRLGGVACAAVTAATTWLLVNLPVLLLFP RGWSEFFRFNTRRGDDMDSLYNVVKSLTGWRGFDTKLGFCELPLVLNTVVTVLFALCCAAVAYIALTAAQRPRVVQLAFL LVAVFLLTNKVWSPQFSLWLVPLAVLALPHRRVLLAWMTIDALVWVPRMYYLYGNPSRSLPEQWFTATVLLRDIAVVALC ALVIRQIYRPDEDPVRLGGRVDDPAGGPFDRAPYAPPSWLPDWLHPAGMRRVVTLAASSVTETELAAAATPSGPMHHPHA PSSI >BL;ML2689, ML.tab 3239183:3239599 reverse MW:15278 VVNYSLRRRFLLAEVYSGRTGVSEVCDANPYLLRAAKFHGKPSQVMCPICRKEQLTLVSWVFGNQLGAISGSARTAEELV (SEQ ID NO:324) LLATRYEEFAVYVVEVCRTCSWNYLVRSYVLGAARSAPPPRGTPVTRTACNGARMAIE >BL;ML2699, ML.tab 3250667:3253060 forward MW:84667 VTASRLRLAGSLSIALVVDIVASFAVLLVAPTATPHAAADEPRATSFVRVRIDKVTPDVVTTSSEPVVTVSGVVTNIGDR (SEQ ID NO:325) PVRDLMVRLEHESAVISSAVLRTYLDDGADQFQTAADFVTVAEELQRGQEAGFTLVAPIRSTTKPSMAIDQPGIYPVLVN VNGTPDYGTPARLDNARFLLPVAGVPPAKSDAMDSAVAPDITKPVWITMLWPLADRPRLSPGAPGGTIPVRLVDDDLASS LAPGGRLDILLTAAETATGRDVDPDGAVSRALCLAVDPDLLVTVNAMTGGYIVSNSPDGPAQQPGTPTHPGTGQDAAVIW LNRLRALAHRMCVASLPYAQADLDALQRINDTELSTTATTSVGDIVDHILDVTSIRGVTMLPDSPLTNRVVDLLNDNNST VAIAAAAFSAQDSTSGSLVDIDTEPRRLSPRVVVAPFDPAVGAALAAAGTDPIVPTYLDSSLNIRIVHDSDTARRQDALS SILWRALERDAAPRSQILVPPTSWHLQADDARVMLTTLSTVIRSGLAVARPLPTVIADALARTKLSDTVGSYTSARGRFN DDIIADIASQVGRLWGLTSALTADGRTGLTGVQYTAPLREDMLRALSQLEPPATRNGLAQQRLAVVSKTIKDLIGAVTIV NPGGSYTLATEHSPLPLALHNGLAVPIRVRLQVDAPPGMTVTDVSQIELPPGYLPLRVPIEVNFTQRVAVDVALQTPEGI QLGEPVRLLVHSNAYGKVLFEITLTAATILIVLAGRRLWHRFRIQTEGADSNRPDPLIVDAHPQHQYDDWVDEENRI >BL;PE, ML.tab 654129:654437 forward MW:10295 MTLGVIPEGLEGASAVIEALTAHLATVHAEAAPFIMEVIPPGSGSVSVQNQVGFNVHGCQYVAMTAHGAEELGRWGVGVA (SEQ ID NO:326) ESGVSYALRDAFAVASYLGGGL >BL;desA2, ML.tab 2339270:2340097 reverse MW:31139 MAQKPVPNALILQLEPVVKDNMARHFANEELWFAHDYVPFDRGENFAFLGGRDWDPSQATLAKAVTDACEILLILKDNLA (SEQ ID NO:327) GYHRELVEHFILEGWWGRWLGRWTAEEHLHAIALREYLVVTREVDPVANEQVRVEHVMKGYRVNSYTQIETLVYMAFLER SYAFFCGSLAAQIKEPALFGLINQIVKDEVRHEEFFANLVAHCLECNRDETVAAIAARAAGLDVLGADIDAYHDKVENIS AAGIFGSVELRQVISDRITAWGLINEPQLAQFVTS >BL;embA, ML.tab 139821:143156 reverse MW:118457 VPHDGHEPPQRIIRLIAVGAGITGLLLCAVVPLLPVKQTTATIRWPQSATRDGWVTQITAPLVSGTPRALDISIPCSAMA (SEQ ID NO:328) TLPDSVGLVVSTLPSGGVDTGKSGLFVRANKNAVVVAFRDSVAAVAPRPAVAAGNCSVLHIWANTRGAGANFVGIPGAAG ILTAEKKPQVGGIFTDLKVPVQPGLSAHIDIDTRFITAPTAIKKIAVGVGAAAVLIAILALSALDRRNRNGHRLINWRVS MAWLAQWRVILATPPRAGGASRIADGGVLATLLLWHIIGATSSDDGYNLTVARVSSEAGYLANYYRYFGATEAPFDWYFT VLAKLASVSTAGVWMRIPATLAGIACWLIINHWVLRRLGPGTGGLSTNRVAVLTAGAMFLAAWLPFNNGLRPEPLIALGV LFTWVLVERAIALRRLASAATAAVVAILTATLAPQGLIAIAALLTGARAITQTIRRRRTTDGLLAPLLVLAASLSLITLV VFHSQTLATVGESARIKYKVGPTIACYQDFLRYYFLTVESNADGSMTRRFPVLVLLLCMFGVLVVLLRRSRVPGLASGPT WRLIGTTATSLLLLTFTPTKWAIQFGALAGLTGTFGAIAAFAFARISLHTRRNLTVYITALLFVLAWATAGINGWFGVSN YGVPWFDIQPVIAGHPVTSIFLTLSILTGLLAGGQHFRLDYAKHTEVKDTRRNRFLATTPLVVVATTMVLCEVGSLAKGA VARYPLYTTAKANLAALRSGLAPSVCAMADDVLTEPDPNAGMLQPVPGQIFGPTGPLGGMNPIGFKPEGVNDDLKSDPVV SKPGLVNSDASPNKPNVTFSDSAGTAGGKGPVGVNGSHVALPFGLDPDRTPVMGSYGENTLAASATSAWYQLPLHWKESI ADRPLVVVSAAGAIWSYKEDGNFIYGQSLKLQWGVTRPDGIIQPLAQVMPIDIGPQPAWRNLRFPLTWAPPEANVARVVA YDPNLSPDQWLAFTPPRVPVLQTLQQLLGSQTPVLMDIATAANFPCQRPFSEHLGIAELPQYRILPDHKQTAASSNLWQS SEAGGPFLFLQALLRTSTISTYLRDDWYRDWGSVEQYYRLVPADQAPEAVVKQGMITVPGWIRRGPIRALP >BL;embB, ML.tab 136573:139824 reverse MW:117159 MSVIYRAHRVAIANRTASRNVRVARWVAAIAGLIGFVSSVVTPLLPVVQTTATLNWPQNGQLNSVTAPLISLTPVDITAT (SEQ ID NO:329) VPCAVVAALPPSGGVVLGTAPKQGKDANLNALFIDVNSQRVDVTDRNVVILSVPRNQVAGDAGAPGCSSIEVTSTHAGTF ATFVGVTDSAGNPLRGGFPDPNLRPQIVGVFTDLTGGAP5GLRLSATIDTRFSSTPTTLKRFAMMLAIITTVGALVALWR LDQLDGRRMRRLIPARWSMFTLVDVAVIFGFLLWHVIGANSSDDGYQMQMARTADHSGYMANYFRWFGSPEDPFGWYYNL LALMIHVSDASMWIRLPDLICGVACWLLLSREVLPRLGPAIVGFKPALWAAGLVLLAAWMPFNNGLRPEGQIALGALITY VLIERAITYGRMTPVALATLTAAFTIGIQPTGLIAVAALLAGGRPMLYILVRRHRAVGAWPLVAPLLAAGTVVLTVVFAE QTLSTVLEATKVRTAIGPAQAWYTENLRYYYLILPTVDGSLSRRFGFLITALCLFTAVLITLRRKQIPGVARGPAWRLIG TILGTMFFLTFAPTKWVHHFGLFAALGAAVAALTTVLVSHEVLRWSRNRMAFLAALLFVMTLCFATTNGWWYVSSYGVPF NSAMPRIDGITFSTIFFILFAIVALYAYYLHFTNTGHGEGRLIRTLTVSFWAPIPFAAGLMTLVFIGSMVAGIVRQYPTY SNGWANIRALTGGCGLADDVLVEPDSNAGYMTALPSNYGPLGPLGOVNAIGFTANGVPEHTVAEAIRITPNQPGTDYDWE APTKLKAPGINGSVVPLPYGLNPNKVPIAGTYTTGAQQQSRLTSAWYQLPKPDDRHPLVVVTAAGKITGNSVLHGHTYGQ TVVLEYGDPGPNGGLVPAGRLVPDDLYGEQPKAWRNLRFARSQMPFDAVAVRVVAENLSLTPEDWIAVTPPRVPELRSLQ EYVGSSQPVLLDWEVGLAFPCQQPMLHANGVTDIPKFRITPDYSAKKIDTDTWEDGANGGLLGITDLLLRAHVMSTYLAR DWGRDWGSLRKFDPLVDTHPAQLDLDTATRSGWWSPGKIRIKP >BL;embC, ML.tab 144115:147327 reverse MW:114723 VSGAGANYWIARLLAVIAGLLGALLAMATPFLPVNQNTAQLNWPQNSTFESVEAPLIGYVATGLNVTVPCAAAAGLTGPQ (SEQ ID NO:330) SAGQTVLLSTVPKQAPKAVDRGLLIQRANDDLVLVVRNVPVVSAPMSQVLSPACQRLTFAAYFDKITAEFVGLTYGPNAE HPGVPLRGERSGYDFRPQIVGVFTDLSGPIPTGLNFSATIDTRYSSSPTLLKTIAMILGVVLTIVALVALHLLDTADGTQ HRRLLPSRWWSIGCLDGLVITILAWWHFVGANTSDDGYILTMARVSEHAGYMANYYRWFGTPEAPFGWYYDLLALWAHVT TTSAWMRVPTLAMALTCWWLISREVIPRLGHAAKASRAAAWTAAGMFLAVWLPLDNGLRPEPIIALGILLTWCSVERAVA TSRLLPVAVACIVGALTLFSGPTGIASIGALLVAVGPLLTILQRRSKQFGAVPLVAPILAASTVTAILIFRDQTFAGESQ ASLLKRAVGPSLKWFDEHIRYERLFMASPDGSVARRFAVLALLVALSVAVAMSLRKGRIPGLAAGPSRRIIGITVTSFLA MMFTPTKWTHHFGVFAGLAGSLGALAAVAVASAALRSRRNRTVFAAVVLFVVALSFASVNGWWYVSNFGVPWSNSFPKLR WSLTTALLELTVIVLLLAAWFHFVATTNGSAKTRFGVRIDRIVQSPIAIATWSLVIFEVASLTMAMIGQYPAWTVGKSNL QALTGQTCGLAEEVLVEQDPNAGMLLPVSTPVADALGSSLAEAFTANGIPADVSADPVMEPPGDRSFVKENGMTTGGEAG NEGGTNATPGINGSRAQLPYNLDPARTPVLGSWQSGIQVVARLRSGWYRLPARDKAGPLLVVSAAGRFDHHEVKLQWATD SGAASGQPGGAFQFSDVGASPAWRNLRLPLSAIPSMATQIRLVADDEDLAPQHWIALTPPRIPQLRTLQDVVGYQDPVFL DWLVGLAFPCQRPFDHQYGVDETPKWRILPDRFGAEANSPVMDNNGGGPLGVTELLLKATTVASYLKDDWSRDWGALQRL TPYYPNAQPARLSLGTTTRSGLWNPAPLRH >BL;1ppS, ML.tab 524929:526143 forward MW:43242 VGTATRRVQPKAWRALLTLLVISVVMPGVACNRGGGNVPVNVIGDKGTPFADLLVPKLTASVTDGAVGVNVDMPVTVTVA (SEQ ID NO:331) DGVLAAVTMINDNGRMINGQFSPDGLRWSTTEPLGFNRCYTLSAKALGLGGVVNRQMTFQTSSPAHLTMPYVNPGNGEIV GIGEPVAIRFDENIANRLAAQKAITITANPPVEGAFYWLNNREVRWRPEHFWKSGTAVDVAVNTYGVDLGEGMFGEDNVK THFTIGDEVFATADDATKMLTVRVNGEVVKIMPTSMGKDSTPTANGIYIVGARFKHIIMDSSTYGVPVNSPNGYRADVDW ATQLSYSGVFLHSAPWSVGAQGHTNTSHGCLNVSPSNAQWFYDHVKRGDIVEVVNTVGDTLPGAEGLGDWNIPWEQWKAG NANI >BL;1ppX, ML.tab 188551:189252 forward MW:24411 MNDRKWVTSSVMLVTLSACLALGLSGCSSTKPDAQEQSSSSSPASSDPALTAEIKQSLETTKALSSVHVVVQTTGKVDAL (SEQ ID NO:332) LGISNADVDVQANPLAVKGTCTYNDQPGVPFRVLGDNISVKLFDDWSNLGSISDLSTSHVLDPNTGITQVLSGVINLQAQ GTEVVDRIPTNKITGTVPTSSVKMLDPKAKGSKLATVWIAQDGSHHLVRASIDLGSGSIQLTQSKWNEPVNTN >BL;1pqB, ML.tab 918368:920137 forward MW:61768 VMRGVLVIMRLLCLGMLFTGCAGVPNSSAPQAIGTVERPVPSNLPKPTPGMDPDVLLREFFKATADPANRHLAARQFLTQ (SEQ ID NO:333) SASNAWDDAGRALLIDHVVFVETRGAERVSATMRADILGSLSDMGVFETAEGVLPDPGPVELIKTSGCWRIDRLPNGVFL DWQQFQATYKRNTLYFADPTGKTVVPDPRYVAVLGHDQLATELVSKLLAGPRPEMAHAVRNLLAPPLRLRGPVTRADGSK SGIGRGYGGARIDLEKLSTTDPHSRQLLAAQIIWTLARADIRGPYVINADGAPLDDRFADGWTTSDVAATDPGVADGAGA GLHALVGGALVSLIGQNTTTVLGAFGRMGYQTGAALSRSGRQVASVVTLRRGAPDMAASLWIGDLGGEAVQSADGHSLSR PSWSLDDAVWVVVDTNNVLRAIPEPASGQPARIPVDSAAVASRFPGPITDLQLSRDGTRAAMVIGGQVILAGVEQTQAGQ FALTYPRRLGFGLGSSVVSLSWRTGDDIVVTRTDATHPVSYVNLDGVNSDAPARGLQVPLSVIAANPSTVYVAGPQGVLQ YSASVAESQQGWSEVAGLTVMGAEPVLPG >BL;1pqE, ML.tab 409442:409993 reverse MW:19242 VSRFKISLPALATRVAVLGFLTLMASVLGGCGAGQISQTATQEPAVNGNRVTLNNLALRDIRIQAAQTGDFLQSGRTVDL (SEQ ID NO:334) MLVAINNSPYVTDRLVSITSDIGTVALNGYTQLPTNGMLFIGTSEGQRIKPPPLQSNNIAKAIVTLAKPITNGLTYNFTF NFEKAGQANVAVPVSAGLAPRQT >BL;1pqT, ML.tab 322399:323055 reverse MW:23455 MQAIRLGLHTAAAVVTLSISAVSCGTKTPDYQLILSKSSTTTTTTPDKPIPLPQYLESIGVTGQQVAPSSLPGLTVSIPT (SEQ ID NO:335) PPGWSPYSNPNITPETLIIAKSGKYPTARLVAFKLRGDFDPTQVIKHGNDDAQLFENFRQLDVSTANYNGFPSAMIQGSY DLEGRRLHAWNRIVIPTGPPPSKQQYLVQLTITSLANEAVAQSNDIEAIIRGFVVAPK >BL;1prG, ML.tab 674679:675395 reverse MW:24874 MQAPKHHRRLFAVLATLNTATAVIAGCSSGSNLSSGPLPDATTWVKQATDITKNVTSAHLVLSVNGKITGLPVKTLTGDL (SEQ ID NO:336) TTHPNTVASGNATITLDGADLNANFVVVDGELYATLTPSKWSDFGKASDIYDVASILNPDAGLANVLANFTGAKTEGRDS INGQSAVRISGNVSADAVNKIAPPFNATQPMPATVWIQETGDHQLAQIRIDNKSSGNSVQMTLSNWDEPVQVTKPQVS >BL;1sr2, ML.tab 305368:305706 forward MW:12164 MAKKVTVTLVDDFDGAGAADETVEFGLDGVTYEIDLTNKNAAKLRGDLRQWVSAGRRVGGRRRGRSNSGRGRGAIDREQS (SEQ ID NO:337) AAIREWARRNGHNVSTRGRIPADVIDAFHAAT >BL;mihF, ML.tab 656895:657212 forward MW:11474 VALPQLTDEQRAAALEKAAAARRARAELKDRLKRGGTNLTQVLKDAESDEVLGKMKVSALLEALPKVGKVKAQEIMTELD (SEQ ID NO:338) IAPTRRLRGLGERQRKALLEKFGSA >BL;mmpS3, ML.tab 1041502:1042383 forward MW:30891 MSGPNPPGRENEESDSGNELSGELDPHNGVESVDELVPVPDSDLVTASDHTSETEVYSQAYSAPEAEHFTAVPYVPADLR (SEQ ID NO:339) LYDYDESSVYDEPGAAPRWPWVVGVAAILAAISLVVSVSLLFTRTDTSKLSTPTTGRSTPPVQDEITTVKPPPPSTETST ATETQTVTVTPLPPPSATSTAVPPSSVVPPPPTTPTTTVTTLTGPRQVTYSVTGTKAPGDIISVTYVDASCRRRTQHMVY IPWSMTVTPISQSDVGSVEAFSLFRVSKLNCLITTSDGTVLSSNSNDAPQTSC >BL;mtb12, ML.tab 753532:754035 forward MW:17130 MTMKSIATYAALAIIGAAVDGLTSMAIPTGPAASHIQPVAFGVPLPQDPAPAADVPTAAELTSLLNKIVDPDVSFMHKSQ (SEQ ID NO:340) LVEGGIGSAEAHIGDRELKNAAQKGELPLLFSVTNIRPGTSGSATADVSVSGPKLNPPVTQNITFINKGSWVLSRHSAME LLQAAGR >BL;whiB1, ML.tab 953665:953919 reverse MW:9318 MDWRHKAVCRDEDPELFFPVGNSGPAIAQIADAKLVCNRCPVTTECLAWALNTGQDSGVWGGMSEDERRALKRRNTRTKA (SEQ ID NO:341) RSGV >BL;whiB2, ML.tab 903227:903496 forward MW:10119 VVPKALVAFEVESEPESSDQWQDRALCAQTDPEAFFPEKGGSTREAKKICLGCEVRHECLEYALAHDERFGIWGGLSERE (SEQ ID NO:342) RRRLKRGVI >BL;whiB3, ML.tab 475771:476079 reverse MW:11576 MPQPKQLPGPNATIWNWQLQGLCRGVDSSMFFHPDGERGRARMQREQRAKEMCRRCPVIEECRAHALDVGEPYGVWGGLS (SEQ ID NO:343) ESERDLLLKGDLARSRSIPRSA H. tuberculosis proteins that are potential targets for the diagnosis, prophylaxis or treatment of mycobacterioses. >BL;RV0007, H37RV2.tab 9914:10825 forward MW:31041 VTAPNEPGALSKGDGPNADGLVDRGGAHRAATGPGRIPDAGDPPPWQRAATRQSQAGHRQPPPVSHPEGRPTNPPAAADA (SEQ ID NO:344) RLNRFISGASAPVTGPAAAVRTPQPDPDASLGCGDGSPAEAYASELPDLSGPTPRAPQRNPAPARPAEGGAGSRGDSAAG SSGGRSITAESRDARVQLSARRSRGPVRASMQIRRIDPWSTLKVSLLLSVALFFVWMITVAPLYLVLGGMGVWAKLNSNV GDLLNNASGSSAELVSSGTIFGGAFLIGLVNIVLMTALATIGAFVYNLITDLIGGIEVTLADRD >BL;Rv0010C, H37RV2.tab 13136:13558 reverse MW:15166 MQQTAWAPRTSGIAGCGAGGVVMAIASVTLVTDTPGRVLTGVAALGLILFASATWRARPRLAITPDGLAIRGWFRTQLLR (SEQ ID NO:345) NSNIKIIRIDEFRRYGRLVRLLEIETVSGGLLILSRWDLGTDPVEVLDALTAAGYAGRGQR >BL;Rv0011c, H37RV2.tab 13717:13995 reverse MW:10429 MPKSKVRKKNDFTVSAVSRTPMKVKVGPSSVWFVSLFIGLMLIGLIWLMVFQLAAIGSQAPTALNWMAQLGPWNYAIAFA (SEQ ID NO:346) FMITGLLLTMRWH >BL;RV0020C, H37RV2.tab 23864:25444 reverse MW:56880 MGSQKRLVQRVERKLEQTVGDAFARIFGGSIVPQEVEALLRREAADGIQSLQGNRLLAPNEYIITLGVHDFEKLGADPEL (SEQ ID NO:347) KSTGFARDLADYIQEQGWQTYGDVVVRFEQSSNLHTGQFRARGTVNPDVETHPPVIDCARPQSNHAFGAEPGVAPMSDNS SYRGGQGQGRPDEYYDDRYARPQEDPRGGPDPQGGSDPRGGYPPETGGYPPQPGYPRPRHPDQGDYPEQIGYPDQGGYPE QRGYPEQRGYPDQRGYQDQGRGYPDQGQGGYPPPYEQRPPVSPGPAAGYGAPGYDQGYRQSGGYGPSPGGGQPGYGGYGE YGRGPARHEEGSYVPSGPPGPPEQRPAYPDQGGYDQGYQQGATTYGRQDYGGGADYTRYTESPRVPGYAPQGGGYAEPAG RDYDYGQSGAPDYGQPAPGGYSGYGQGGYGSAGTSVTLQLDDGSGRTYQLREGSNIIGRGQDAQFRLPDTGVSRRHLEIR WDGQVALLADLNSTNGTTVNNAPVQEWQLADGDVIRLGHSEIIVRMH >BL;Rv0039C, H37RV2.tab 42007:42351 reverse MW:11292 MFLAGVLCMCAAAASALFGSWSLCHTPTADPTALALRAMAPTQLAAAVMLAAGGVVAVAAPGHTALMVVIVCIAGAVGTL (SEQ ID NO:348) AAGSWQSAQYALRRETASPTANCVGSCAVCTQACH >BL;Rv0040c, H37RV2.tab 42434:43365 reverse MW:31923 MIQIARTWRVFAGGMATGFIGVVLVTAGKASADPLLPPPPIPAPVSAPATVPPVQNLTALPGGSSNRFSPAPAPAPIASP (SEQ ID NO:349) IPVGAPGSTAVPPLPPPVTPAISGTLRDHLREKGVKLEAQRPHGFKALDITLPMPPRWTQVPDPNVPDAFVVIADRLGNS VYTSNAQLVVYRLIGDFDPAEAITHGYIDSQKLLAWQTTNASMANFDGFPSSIIEGTYRENDMTLNTSRRHVIATSGADK YLVSLSVTTALSQAVTDGPATDAIVNGFQVVAHAAPAQAPAPAPGSAPVGLPGQAPGYPPAGTLTPVPPR >BL;Rv0049, H37RV2.tab 52831:53241 forward MW:15000 VDYTLRRRSLLAEVYSGRTGVSEVCDANPYLLRAAKFHGKPSRVICPICRKEQLTLVSWVFGEHLGAVSGSARTAEELIL (SEQ ID NO:350) LATRFSEFAVHVVEVCRTCSWNHLVKSYVLGAARPARPPRGSGGTRTARNGARTASE >BL;Rv0051, H37RV2.tab 55696:57375 forward MW:61209 VTGALSQSSNISPLPLAADLRSADNRDCPSRTDVLGAALANVVGGPVGRHALIGRTRLMTPLRVMFAIALVFLALGWSTK (SEQ ID NO:351) AACLQSTGTGPGDQRVANWDNQRAYYQLCYSDTVPLYGAELLSQGKFPYKSSWIETDSNGTPQLRYDGQIAVRYMEYPVL TGIYQYLSMAIAKTYTALSKVAPLPVVAEVVMFFNVAAFGLALAWLTTVWATSGLAGRRIWDAALVAASPLVIFQIFTNF DALATGLATSGLLAWARRRPVLAGVLIGLGSAAKLYPLLFLYPLLLLGIRAGRLNALARTMAAAAATWLLVNLPVMLLFP RGWSEFFRLNTRRGDDMDSLYNVVKSFTGWRGFDPTLGFWEPPLVLNTVVTLLFVLCCAAIAYIALTAPHRPRVAQLTFL TVASFLLVNKVWSPQFSLWLVPLAVLALPHRRILLAWMTIDALVWVPRMYYLYGNPSRSLPEQWFTTTVLLRDIAVMVLC GLVWQIYRPGRDLVRTGGPGALPACGGVDDPVGGVFANAAPPGRLPSWLRPRLGDEHRERTPDAGRDRTFSGQHRA >BL;RV0093C, H37RV2.tab 102818:103663 reverse MW:29599 VLAQATTAGSFNHHASTVLQGCRGVPAAMWSEPAGAIRRHCATIDGMDCEVAREALSARLDGERAPVPSARVDEHLGECS (SEQ ID NO:352) ACRAWFTQVASQAGDLRRLAESRPVVPPVGRLGIRRAPRRQHSPMTWRRWALLCVGIAQIALGTVQGFGLDVGLTHQHPT GAGTHLLNESTSWSIALGVIMVGAALWPSAAAGLAGVLTAFVAILTGYVIVDALSGAVSTTRILTHLPVVIGAVLAIMVW RSASGPRPRPDAVAAEPDIVLPDNASRGRRRGHLWPTDGSAA >BL;RV0098, H37RV2.tab 107600:108148 forward MW:20528 MSHTDLTPCTRVLASSGTVPIAEELLARVLEPYSCKGCRYLIDAQYSATEDSVLAYGNFTIGESAYIRSTGHFNAVELIL (SEQ ID NO:353) CFNQLAYSAFAPAVLNEEIRVLRGWSIDDYCQHQLSSMLIRKASSRFRKPLNPQKFSARLLCRDLQVIERTWRYLKVPCV IEFWDENGGAASGEIELAALNIP >BL;Rv0100, H37RV2.tab 109783:110016 forward MW:8660 VRDRILAAVCDVLYIDEADLIDGDETDLRDLGLDSVRFVLLMKQLGVNRQSELPSRLAANPSIAGWLRELEAVCTEFG (SEQ ID NO:354) >BL;Rv0116c, H37Rv2.tab 140270:141022 reverse MW:26915 MRRVVRYLSVVVAITLMLTAESVSIATAAVPPLQPIPGVASVSPANGAVVGVAHPVVVTFTTPVTDRRAVERSIRISTPH (SEQ ID NO:355) NTTGHFEWVASNVVRWVPHRYWPPHTRVSVGVQELTEGFETGDALIGVASISAHTFTVSRNGEVLRTMPASLGKPSRPTP IGSFHAMSKERTVVMDSRTIGIPLNSSDGYLLTAHYAVRVTWSGVYVHSAPWSVNSQGYANVSHGCINLSPDNAAWYFDA VTVGDPIEVVG >BL;Rv0146, H37Rv2.tab 172211:173140 forward MW:34016 MRTHDDTWDIKTSVGATAVMVAAARAVETDRPDPLIRDPYARLLVTNAGAGAIWEAMLDPTLVAKAAAIDAETAAIVAYL (SEQ ID NO:356) RSYQAVRTNFFDTYFASAVAAGIRQVVILASGLDSRAYRLDWPAGTIVYEIDQPKVLSYKSTTLAENGVTPSAGRREVPA DLRQDWPAALRDAGFDPTARTAWLAEGLLMYLPAEAQDRLFTQVGAVSVAGSRIAAETAPVHGEERRAEMRARFKKVADV LGIEQTIDVQELVYHDQDRASVADWLTDHGWRARSQRAPDEMRRvGRWVEGVPMADDPTAFAEFVTAERL >BL;Rv0164, H37Rv2.tab 193626:194180 forward MW:20165 MTAISCSPRPRYASRMPVLSKTVEVTADAASIMAIVADIERYPEWNEGVKGAWVLARYDDGRPSQVRLDTAVQGIEGTYI (SEQ ID NO:357) HAVYYPGENQIQTVMQQGELFAKQEQLFSVVATGAASLLTVDMDVQVTMPVPEPMVKNLLNNVLEHLAENLKQPAEQLAA S#GMCGLSRRLRSQPGPPSACVPHR >BL;Rv0175, H37Rv2.tab 206814:207452 forward MW:22324 VKAADSAESDAGADQTGPQVKAADSAESDAGELGEDACPEQALVERRPSRLRRGWLVGIAATLLALAGGLGAAGYFALRS (SEQ ID NO:358) HQESQSIAREDLAAIEAAKDCVAATQAPDAGANSASMQKIIECGTGDFGAQASLYTSMLVEAYQAASVHVQVTDMRAAVE RNNNDGSVDVLVALRVKVSNTDSDAHEVGYRLRVRMALDEGRYKIAKLDQVTK >BL;Rv0176, H37Rv2.tab 207452:208417 forward MW:35405 VTVVVEKTPTTLPQATPNGAAPWHVRAGAFAIDVLPGLAVAATMALTALTVPPGSAWRWLCACLLGLTILLLAVNRLLLP (SEQ ID NO:359) TITGWSLGRALTGIRVVRRDGSAIGPWRLLVRDLAHLVDTLSLFVGWLWPLWDSRRRTFADLLLRTEVRRVEPVQRPAVI RRLTAAVALAAAGACASATAVGAAVVYVNEWQTDHTRAQLATRGPKLVVDVLSYDPETVQRDFERARSLATDRYRPQLSI QQDSVRESGPVRNQYWVTDSAVLSATPAQATMLLFMQGERGTPPNQRYIQSTVRAIFQKSRGQWRLDDLAVVMKPRQPTG EK >BL;Rv0177, H37Rv2.tab 208417:208968 forward MW:20164 MSPRRKFEPGEGALLAPQSIEPSRRWGLPLALTASAVVMAAAISACALMRISHESHQRAAHKDIVMLSDVRSFMTMFTSP (SEQ ID NO:360) DPFHANEYAERVLSHATGDFAKQYHERANDILIRISGVEPTTGTVLDAGVQRWNEDGSANVLVVTQITSKSADGKRVVSN ANRWLVTAKQEGNEWKISSLLPVI >BL;Rv0178, H37Rv2.tab 208938:209669 forward MW:25879 VEDQQSASGDLTQKSVANGESTDTASAATEGHRGEIDAAGEPDERGAAVADSQADEDDSAATAARGGKTRARRSRGRRLA (SEQ ID NO:361) ITVGVAAALFVGSAAFAGATVEPYLSERAVVATKLMVARTAANAITTLWTYTPENMDTLADRAANYLSGDFAAQYRRFVD QIAAANKQAXITNDTEVTGAAVESLSGRDAVAIVYTNTTTTSPVTKNIPALKYLSYRLFMKRYDARWLVTRMTTITSLDL TPQV >BL;Rv0184, H37Rv2.tab 214969:215715 forward MW:26826 MTNDKMLARIAALLRQAEGTDNPHEADAFMSTAQRLATAASIDLAVARSHAGNRSPAQAPTQRTITIGAAGTRGLRTYVQ (SEQ ID NO:362) LFVLIAAANDVRCDVASNSTFVYAYGFAEDIDTSHALYASLVVQMVRASDAYLASGAHRPTPTITARLNFQLAFGARVGQ RLADAREQTRQEATKDRDRPPGTAIALRDKDIELHEYYRRSSKARGAWRASRATAGYSSAARRAGDRAGRQARLGNNPEL PGARAALGR >BL;Rv0185, H37Rv2.tab 215715:216221 forward MW:18365 VIGADVPRDSQRARVYAAEAFVRTLFDRvTAHGSPTVEFFGTQLTLPPEGRFGSVASVQRYVDDVLALPAVGQNWPTVSP (SEQ ID NO:363) VRVRARRAATAAHYENHGGTGTIAVPDRHTAGWANRELVVLHEVAHHLCQVPPPHGPEFVATVCTLTELVMGPEVGHVFR VVYAQEGVR >BL;Rv0199, H37Rv2.tab 236550:237206 forward MW:23520 MPDGEQSQPPAQEDAEDDSRPDAAEAAAAEPKSSAGPMFSTYGIASTLLGVLSVAAVVLGAMIWSAHRDDSGERTYLTRV (SEQ ID NO:364) MLTAAEWTAVLINMNADNIDASLQRLHDGTVGQLNTDFDAVVQPYRQVVEKLRTHSSGRIEAVAIDTVHRELDTQSGAAR PVVTTKLPPFATRTDSVLLVATSVSENAGAKPQTVHWNLRLDVSDVDGKLMISRLESIR >BL;Rv0200, H37Rv2.tab 237206:237892 forward MW:24029 MRNAWRLVVFDVLAPLATIAALAAIGVLLGWPLWWVSTCSVLVLLVVEGVAINFWLLRRDSVTVGTDDDAPGLRLAVVFL (SEQ ID NO:365) CAAAISAAVVTGYLRWTTPDRDFNRDSREVVHLATGMAETVASFSPSAPAAAVDRAAANMVPEHAGGFKEQYAKSSADLA RRGVTAQAATLAAGVEAIGPSAASVAVILRVSQSIPGQPTSQAARALRVTLTKRGSGWLVLDVTPINAR >BL;Rv0201c, H37Rv2.tab 237895:238395 reverse MW:18484 VTLAAEPHPAPPQQPTVAWSEPDVDRRVEFWPTVAIRSALESGDIATWQRIAAALKRDPYGRTARQVEEVLEGIPATGIA (SEQ ID NO:366) NAFWEVLDRARTHLDANERAEVARQVGLLLDRSGLQRQEFASRIGVTAQDLTAYLDGIVSPSASLMIRMRRLSDRFVRAK SVRAADS >BL;Rv0207c, H37Rv2.tab 247387:248112 reverse MW:26175 MSLTEDVTSQTSESLARHSVLAEDLSQDGLTSLGAPGARvLLVWDAPNLDMGLGSILGRRPTALERPRFDALGRWLLART (SEQ ID NO:367) AEIVAGRPGISTEPEATVFTNIAPGSAEVVRPWVDALRNVGFAVFAKPKVDEDSDVDRDMLAHIDERYREGLAALVVASA DGQAFRQPLEAVARSGTPVQVLGFREHASWALASDTLEFVDLEDIAGVFREPLPRIGLDSLPEQGAWLQPFRPLSSLLTS RV >BL;Rv0216, H37Rv2.tab 258913:259923 forward MW:35756 VASGYGGIRvGGPYFDDLSKGQVFDWAPGVTLSLGLAAAHQSIVGNRLRLALDSDLCAAVTGMPGPLAHPGLVCDVAIGQ (SEQ ID NO:368) STLATQRVKANLFYRGLRFHRFPAVGDTLYTRTEVVGLRANSPKPGRAPTGLAGLRMTTIDRTDRLVLDFYRCANLPASP DWKPGAVPGDDLSRIGADAPAPAADPTAHWDGAVFRKRVPGPHFDAGIAGAVLHSTADLVSGAPELARLTLNIAATHHDW RVSGRRLVYGGHTIGLALAQATRLLPNLATVLDWESCDHTAPVHEGDTLYSELHIESAQAHADGGVLGLRSLVYAVSDSA SEPDRQVLDWRFSALQF >BL;Rv0226c, H37Rv2.tab 269837:271564 reverse MW:59107 VRWFRPGYALVLVLLLAAPLLRPGYLLLRDAVSTPRSYVSANALGLTSAPRATPQDFAVALASHLVDGGVVVKALLLLGL (SEQ ID NO:369) WLAGWGAARLVATALPAAGAAGQFVAITLAIWNPYVAERLLQGHWSLLVGYGCLPWVATAMLTMRTTVGAGWFGLFGLAF WVALAGLTPSGLLLAATVAVVCVANPGAGRPRWQCGVAALGSALVGALPWLTASALGSSLTSHTAANQLGVTAFAPRAEP GLGTLGSLASLGGIWNGEAVPSSRTTLFAVASAVVLLANVAIGLPTVARRPVAVPLLTLAAVSVMVPAVLATGPGLHALR VVVDAAPGLGVLRDGQKWVALAVPGYTLSGAGTVLTLRRWLRPATAAVVCCLALVLTLPDLAWGVWGKVAPVHYPSGWAA VAAAINADPRTVAVLPAGTMRRFSWSGSAPVLDPLPRWVRADVLTTGDLVISGVTVPGEDAHARAVQELLLTGPHPSTLA AAGVGWLVVESDSAGDMGAAARTLGRLAAAHRDDELALYRVGGQTSGASSARLKATMLAHWAWLSMLLVGGAGAAGYWVR RHLHHCEDTPASRAQD >BL;Rv0227c, H37Rv2.tab 271577:272839 reverse MW:45528 MLRFAACGAIGLGAALLIAALLLSTYTTSRIAEIPLDIDATLISDGTGTALDSASLATEHIVVNQDVPLVSQQQVTVESP (SEQ ID NO:370) ANADVVTLQVGSSLRRTDKQKDSGLLLAIVDTVTLNRKTAMAVSDDTHTGGAVQKPRGLNDENPPTAIPLRHDGLSYRFP FHTEKKTYPYFDPIAQKAFDANYEGEEDVNGLTTYRFTQNVGYTPEGKLVAPLKYPSLYAGDEDGKVTTSAANWGLPGDP NEQITMTRYYAAQRTFWVDPVSGTIVKETERANNYFARDPLKPEVTFADYOVTSTEETVESQVNAARDERDRLALWSRVL PITFTAAGLVALVGGGLFASFSLRTEGALMAASGDRDDHDYRRGGFEEPVPGAEAETEKLPTQRPDFPREPSGSDPPRLG SAQPPPPPDAGHPDPGPPERR >BL;Rv0236A, H37Rv2.tab 286898:287071 reverse MW:5833 MNRIVAPAAASVVVGLLLGAAAIFGVTLMVQQDKKPPLPGGDPSSSVLNRvEYGNRS (SEQ ID NO:372) >BL;Rv0236c, H37Rv2.tab 282652:286851 reverse MW:146250 VAPLSRKWLPVVGAVALALTFAQSPGQVSPDTKLDLTANPLRFLARATNLWNSDLPFGQAQNQAYGYLFPHGTFFVIGHL (SEQ ID NO:373) LGVPGWVTQRLWWAVLLTVGFWGLLRvAEALGVGGPSSRvVGAVAFALSPRVLTTLGSISSETLPMMLAPWVLLPTILAL RGTSGRSVRALAAQAGLAVALMGAVNAIATLAGCLPAVIWWACHRPNRLWWRYTAWWLLAMALATLWWVMALTQLNGVSP PFLDPIESSGVTTQWSSLVEVLRGTDSWTPFVAPNATAGAPLVTGSAAILGTCLVAAAGLAGLTSPAMPARGRLVTMLLV GVVLLAVGHRGGLASPVAHPVQAFLDAAGTPLRNVHKVGPVIRLPLVLGLAQLLSRVPLPGSAPRPAWLRAFAHPERDKR VAVAVVALTALMVSTSLAWTGRVAPPGTFGALPQYWQEAADWLRTHHAATPTPGRVLVVPGAPFATQVWGTSHDEPLQVL GDGPWGVRDSIPLTPPQTIRALDSVQRLFAAGRPSAGLADTLARQGISYVLVRNDLDPETSRSARPILLHRSIAGSPGLA KLAEFGAPVGPDPLAGFVNDSGLRPRYPAIEIYRVSAPANPGAPYFAATDQLARvDGGPEVLLRLDERRRLQGQPPLGPV LMTADARAAGLPVPQVAVTDTPVARETDYGRVDHHSSAIRAPGDARHTYNRVPDYPVPGAEPVVGGWTGGRITVSSSSAD ATAMPDVAPASAPAAAVDGDPATAWVSNALQAAVGQWLQVDFDRPVTNAVVTLTPSATAVGAQVRRILIETVNGSTTLRF DEAGKPLTAALPYGETPWVRFTAAATDDGSAGVQFGITDLAITQYDASGFAHPVQLRHTVLVPGPPPGSAIAGWDLGSEL LGRPGCAPGPDGVRCAASMALAPEEPANLSRTLTVPRPVSVTPMVWVRPRQGPKLADLIAAPSTTRASGDSDLVDILGSA YAAADGDPATAWTAPQRvVQHKTPPTLTLTLPRPTVVTGLRLAASRSMLPAHPTVVAINLGDGPQVRQLQVGELTTLWLH PRVTDTVSVSLLDWDDVIDRNALGFDQLKPPGLAEVVVLSAGGAPIAPADAARNRARALTVDCDHGPVVAVAGRFVHTSI RTTVGALLDGEPVAALPCEREPIALPAGQQELLISPGAAFVVDGAQLSTPGAGLSSATVTSAETGAWGPTHREVRVPESA TSRVLVVPESINSGWVARTSTGARLTPIAVNGWQQAWVVPAGNPGTITLTFAPNSLYRASLAIGLALLPLLALLAFWRTG RRQLADRPTPPWRPGAWAAAGVLAAGAVIASIAGVMVMGTALGVRYALRRRERLRDRvTVGLAAGGLILAGAALSRHPWR SVDGYAGNWASVQLLALISVSVVAASVVATSESRGQDRMQ >BL;2V0241c, H37Rv2.tab 289815:290654 reverse MW:30163 VTQPSGLKNLLRAAAGALPVVPRTDQLPNRTVTVEELPIDPANVAAYAAVTGLRYGNQVPLTYPFALTFPSVMSLVTGFD (SEQ ID NO:374) FPFAAMGAIHTENHITQYRPIAVTDAVGVRVRAENLREHRRGLLVDLVTNVSVGNDVAWHQVTTFLHQQRTSLSGEPKPP PQKKPKLPPPAAVLRITPAKIRRYAAVCGDHNPIHTNPIAAKLFGFPTVIAHGMFTAAAVLANIEARFPDAVRYSVRFAK PVLLPATAGLYVAEGDGGWDLTLRNMAKGYPHLTATVRGL >BL;Rv02500, H37Rv2.tab 301738:302028 reverse MW:10878 LSTTAELAELHDLVGGLRRCVTALKARFGDNPATRRIVIDADRILTDIELLDTDVSELDLERAAVPQPSEKIAIPDTEYD (SEQ ID NO:375) REFWRDVDDEGVGGHRY >BL;Rv0257, H37Rv2.tab 309699:310071 forward MW:13053 MTRVSWLPDRCLPRLPACGRGLRGSLPGDSGGTAPDSHRLPASSSPDGKNIGMQSVDLHVERHLPSRGRSNRTVATVTCV (SEQ ID NO:376) TALGDIRSAQLSATGAWPAVLFPSWSWLCGIGGGVDLQKPSCRA >BL;Rv0283, H37Rv2.tab 344022:345635 forward MW:55943 MTNQQHDHDFDHDRRSFASRTPVNNNPDKVVYRRGFVTRHQVTGWRFVMRRIAAGIALHDTRMLVDPLRTQSRAVLMGVL (SEQ ID NO:377) IVITGLIGSFVFSLIRPNGQAGSNAVLADRSTAALYVRVGEQLHPVLNLTSARLIVGRPVSPTTVKSTELDQFPRGNLIG IPGAPERMVQNTSTDANWTVCDGLNAPSRGGADGVGVTVIAGPLEDTGARAAALGPGQAVLVDSGAGTWLLWDGKRSPID LADHAVTSGLGLGADVPAPRIIASGLFNAIPEAPPLTAPIIPDAGNPASFGVPAPIGAVVSSYALKDSGKTISDTVQYYA VLPDGLQQISPVLAAILRNNNSYGLQQPPRLGADEVAKLPVSRVLDTRRYPSEPVSLVDVTRDPVTCAYWSKPVGAATSS LTLLAGSALPVPDAVHTVELVGAGNGGVATRVALAAGTGYFTQTVGGGPDAPGAGSLFWVSDTGVRYGIDNEPQGVAGGG KAVEALGLNPPPVPIPWSVLSLFVPGPTLSRADALLAHDTLVPDSRPARPVSAEGGYR >BL;Rv0288, H37Rv2.tab 351848:352135 forward MW:10390 MSQIMYNYPMLGHAGDMAGYAGTLQSLGAEIAVEQAALQSAWQGDTGITYQAWQAQWNQANEDLVRAYHAMSSTHEANT (SEQ ID NO:378) MAMMARDTAEAAKWGG >BL;Rv0289, H37Rv2.tab 352149:353033 forward MW:31559 MDATPNAVELTVDNAWFIAETIGAGTFPWVLAITMPYSDAAQRGAFVDRQRDELTRMGLLSPQGVINPAVADWIKVVCFP (SEQ ID NO:379) DRWLDLRYVGPASADGACELLRGIVALRTGTGKTSNKTGNGVVALRNAQLVTFTAMDIDDPRALVPILGVGLAHRPPARF DEFSLPTRvGARADERLRSGVPLGEVVDYLGIPASARPVVESVFSCPRSYVEIVAGCNRDGRHTTTEVGLSIVDTSAGRV LVSPSRAFDGEWVSTFSPGTPFAIAVAIQTLTACLPDGQWFPGQRvSRDFSTQSS >BL;Rv0290, H37Rv2.tab 353083:354498 forward MW:47944 MSGTVMQIVRVAILADSRLTEMALPAELPLREILPAVQRLVVPSAQNGDGGQADSGAAVQLSLAPVGGQPFSLDASLDTV (SEQ ID NO:380) GVVDGDLLVLQPVPAGPAAPGIVEDIADAANIFSTSRLKPWGIAHIQRGALAAVIAVALLATGLTVTYRvATGVLAGLLA VAGIAVASALAGLLITIRSPRSGIALSIAALVPIGAALALAVPGKFGPAQVLLGAAGVAAWSLIALMIPSAERERVVAFF TAAAVVGASVALAAGAQLLWQLPLLSIGCGLIVAALLVTIQAAQLSALWARFPLPVIPAPGDPTPSAPPLRLLEDLPRRV RVSDAHQSGFIAAAVLLSVLGSVAIAVRPEALSVVGWYLVAATAAAATLRARVWDSAACKAWLLAQPYLVAGVLLVFYTA TGRYVAAFGAVLVLAVLMLAWVVVALNPGIASPESYSLPLRRLLGLVAAGLDVSLIPVMAYLVGLFAWVLNR >BL;Rv0292, H37Rv2.tab 355880:356872 forward MW:35932 MNPIPSWPGRGRVTLVLLAVVPVALAYPWQSTRDYVLLGVAAAVVIGLFGFWRGLYFTTIARRGLAILRRRRRIAEPATC (SEQ ID NO:381) TRTTVLVWVGPPASDTNVLPLTLIARYLDRYGIRADTIRITSRVTASGDCRTWVGLTVVADDNLAALQARSARIPLQETA QVAARRLADHLREIGWEAGTAAPDEIPALVAADSRETWRGMRHTDSDYVAAYRVSANAELPDTLPAIRSRPAQETWIALE IAYAAGSSTRYTVAAACALRTDWRPGGTAPVAGLLPQHGNHVPALTALDPRSTRRLDGHTDAPADLLTRLHWPTPTAGAH RAPLTNAVSRT >BL;Rv0309, H37Rv2.tab 377931:378584 forward MW:22528 MSRLLALLCAAVCTGCVAVVLAPVSLAVVNPWFANSVGNATQVVSVVGTGGSTAKMDVYQRTAAGWQPLKTGITTHIGSA (SEQ ID NO:382) GMAPEAKSGYPATPMGVYSLDSAFGTAPNPGGGLPYTQVGPNHWWSGDDNSPTFNSMQVCQKSQCPFSTADSENLQIPQY KHSVVMGVNKAKVPGKGSAFFFHTTDGGPTAGCVAIDDATLVQIIRWLRPGAVIAIAK >BL;Rv0313, H37Rv2.tab 382490:382873 forward MW:13916 VGDYGPFGFDPDEFDRVIREGSEGLRDAFERIGRFLSSSGAGTGWSAIFEDLSRRSRPAPETAGEAGDGVWAIYTVDADG (SEQ ID NO:383) GARVEQVYATELDALRANKDNTDPKRKVRFLPYGIAVSVLDDPVDEAQ >BL;Rv0356c, H37Rv2.tab 434833:435474 reverse MW:22879 VTDASVHPDELDPEYHHHGGFPEYGPASPGAGFGQFVATMRRLQDLAVAADPGDAVWDEAAERAAALVELLSPFEADEGK (SEQ ID NO:384) APAGRTPGLPGMGSLLLPPWTVTRYGTDGVEMRGSFSRFHVGGNSAVHGGVLPLLFDHMFGMISHAAGRPISRTAFLHVD YRRITPIDVPLIVRGRVTNTEGRKAFVCAELFDSDETLLAEGNGLMVRLLPGQP >BL;Rv0358, H37Rv2.tab 436860:437504 forward MW:23102 MYTAENAPGVAVLLSGDADVPGPLTGLPTHQDNLDTVIGRYSRLIVVGADADLGAVLTRLLRTDRLDVEVGYVPRRRSPA (SEQ ID NO:385) TRAYRLPAGRRAARRARCGVARRVPLIRDETGSVIVGRAQWLPAEEQALIHGEAVVDDTVLFDGDVAGVCIEPTLTLPGL RAAVDGAGKWRRWIGGRAAQLGTTGAAVLRDGVAAPFPVRRSTFYRNVEGWLLVR >BL;Rv0360c, 1137Rv2.tab 438305:438739 reverse MW:15297 VTKRTITPMTSMGDLLGPEPILLPGDSDAEAELLANESPSIVAAAHPSASVAWAVLAEGALADDKTVTAYAYARTGYHRG (SEQ ID NO:386) LDQLRRHGWKGRGPVPYSHQPNRGFLRCVAALARAAAAIGETDEYGRCLDLLDDCDPAARPALGL >BL;Rv0361, H37Rv2.tab 438822:439646 forward MW:29982 MSNAPEPDRSAGESGSEPAGERSADPGEERTESYPLVPHDAETETVVITTSDNDAAVTQPEAQRERRFTAPGFDAKETQV (SEQ ID NO:387) IVTAHEAATEVFQTNQAPTTPPRMPTGMPPKTAVPQSIPPRTEATSVRQRTWGWALAVVVIVLALAAIAILGTVLLTRGK HSKMSQEDQVRQAIQSLDIAIQTGDLTALRSLTCGSTRDGYVDYDERDWAETYRRvSAAKQYPVIASIDQVVVNGAHAEA NVTTFMAFDPQVRSTRSLDLQFRDDQWKICQSSSN >BL;Rv0383c, H37Rv2.tab 458464:459315 reverse MW:31801 MVPLWFTLSALCFVGAVVLLYVDIDRRRGRSRRRKSWARSHGFDYERESTEILKRWTRGVMSTVGDVAAHNVVLGQIRGE (SEQ ID NO:388) AVYIFDLEEVATVIALHRKVGTNVVVDLRLKGLKEPRESDIWLLGAIGPRMVYSTNLDAARRACDRRMVTFAHTAPDCAE IMWNEQNWTLVSMPIASTRAQWDEGLRTVRQFNDLLRVLPPLPQEMPQQTGVGPRGAAPGRPVAPGGPAELPPRRAQPDP ATTVLPDPARRAPEPIRRDEGRSEGVRRPPPAGRNGQQATNYQH >BL;Rv0401, H37Rv2.tab 479789:480157 forward MW:12641 MRPRRALAGLAADVVAVLVFCAVGRRSHAEGLSVTGLAATAWPFLTGTGIGWVLARGWRRPTALAPTGVIVWLCTIWGM (SEQ ID NO:389) VLRKVSSAGVAASFVVVASAVTAVLLLGWRAAVALMAPHRADG >BL;Rv0416, H137Rv2.tab 502167:502370 forward MW:7367 MIVVVNEQQVEVDEQTTIAALLDSLGFGDRGIAVALNFSVLPRSDWATKICELRKPVRLEVVTAVQGG (SEQ ID NO:390) >BL;Rv0430, H37Rv2.tab 518733:519038 forward MW:11723 MDSAMARAIRSGDDAEVADGLTRREHDILAFERQWWKFAGVKEEAIKELFSMSATRYYQVLNALVDRPEALAADPMLVKR (SEQ ID NO:391) LRRLRASRQKARAARRLGFEVT >BL;Rv0431, H37Rv2.tab 519073:519564 forward MW:16905 VLVTVGSMNERVPDSSGLPLRAMVMVLLFLGVVFLLLVWQALGSSPNSEDDSSAISTMTTTTAAPTSTSVKPAAPRAEVR (SEQ ID NO:392) VYNISGTEGAAARTADRLKAAGFTVTDVGNLSLPDVAATTVYYTEVEGERATADAVGRTLGAAVELRLPELSDQPPGVIV VVTG >BL;Rv0455c, H37Rv2.tab 545378:545821 reverse MW:16639 MSRLSSILRAGAAFLVLGIAAATFPQSAAADSTEDFPIPRRMIATTCDAEQYLAAVRDTSPVYYQRYMIDFNNHANLQQA (SEQ ID NO:393) TINKANWFFSLSPAERRDYSEHFYNGDPLTFAWVNHMKIFFNNKGVVAKGTEVCNGYPAGDMSVWNWA >BL;Rv0463, H37Rv2.tab 554016:554306 forward MW:10111 MTRRASTDTPQIIMGAIGGVTGYILWLAAISVGDGLTTVSQWSRVVLLLSVLVAVCGAAGGLRLRSRGKLAWSAFAFSL (SEQ ID NO:394) PIPPVVLTVAVLADIYL >BL;Rv0464C, H37Rv2.tab 554316:554885 reverse MW:21304 MTGQNGQVARISPGKFRQLGPVNWLVAKLAARAVGAPQMHLFTTLGYRQYLFWTFAIYTGRLLHGRLPGVDTELVILRVA (SEQ ID NO:395) HLRSCEYELQHHRRMARRRGLDANTQATIFAWPDVPDGDGPRKVLSARQQALLQATDELIKDRTITAGTWERLATNLDPR LLIEFCLLATQYDAIAATITALAIPPDNPQ >BL;Rv0466, H37Rv2.tab 556458:557249 forward MW:30153 VSLDKKLMPVPDGHPDVFDREWPLRVGDIDRAGRLRLDAACRHIQDIGQDQLREMGFEETHPLWIVRRTMVDLIRPIEFG (SEQ ID NO:396) DMLRCRRWCSGTSNRWCEMRVRVDGRKGGLIESEAFWIHVNRETEMPARIADDFLAGLHRTTSVDRLRWKGYLKPGSRDD ASEIHEFPVRVTDIDLFDHMNNAVYWSVIEDYLASHAELLRGPLRVTIEHEAPVALGDKLEIISHVHPAGSTEIFGPGLV DRAVTTLTYVVGDEPKAVASLFNL >BL;Rv0476, H37Rv2.tab 566508:566768 forward MW:9166 MLVLLVAVLVTAVYAFVHAALQRPDAYTAADKLTKPVWLVILGAAVALASILYPVLGVLGMAMSACASGVYLVDVRPKLL (SEQ ID NO:397) EIQGKSR >BL;Rv0477, H37Rv2.tab 566776:567219 forward MW:15658 MKALVAVSAVAVVALLGVSSAQADPEADPGAGEANYGGPPSSPRLVDHTEWAQWGSLPSLRVYPSQVGRTASRRLGMAAA (SEQ ID NO:398) DAAWAEVLALSPEADTAGMRAQFICHWQYAEIRQPGKPSWNLEPWRPVVDDSEMLASGCNPGSPEESF >BL;Rv0479C, H37Rv2.tab 567924:568967 reverse MW:37016 VTNPQGPPNDPSPWARPGDQGPLARPPASSEASTGRLRPGEPAGHIQEPVSPPTQPEQQPQTEHLAASHAHTRRSGRQAA (SEQ ID NO:399) HQAWDPTGLLAAQEEEPAAVKTKRRARRDPLTVFLVLIIVFSLVLAGLIGGELYARHVANSKVAQAVACVVKDQATASFG VAPLLLWQVATRHFTNISVETAGNQIRDAKGMQIKLTIQNVRLKNTPNSRGTIGALDATITWSSEGIKESVQNAIPILGA FVTSSVVTHPADGTVELKGLLNNITAKPIVAGKGLELQIINFNTLGFSLPKETVQSTLNEFTSSLTKNYPLGIHADSVQV TSTGVVSRFSTRDAAIPTGIQNPCFSHI >BL;Rv0483, H372V2.tab 571710:573062 forward MW:47858 VVIRVLFRPVSLIPVNNSSTPQSQGPISRRLALTALGFGVLAPNVLVACAGKVTKLAEKRPPPAPRLTFRPADSAADVVP (SEQ ID NO:400) IAPISVEVGDGWFQRVALTNSAGKVVAGAYSRDRTIYTITEPLGYDTTYTWSGSAVGHDGKAVPVAGKFTTVAPVKTINA GFQLADGQTVGIAAPVIIQFDSPISDKAAVERALTVTTDPPVEGGWAWLPDEAQGARVHWRPREYYPAGTTVDVDAKLYG LPFGDGAYGAQDMSLHFQIGRRQVVKAEVSSHRIQVVTDAGVIMDFPCSYGEADLARNVTRNGIHVVTEKYSDFYMSNPA AGYSHIHERWAVRISNNGEFIHANPMSAGAQGNSNVTNGCINLSTENAEQYYRSAVYGDPVEVTGSSIQLSYADGDIWDW AVDWDTWVSMSALPPPAAKPAATQIPVTAPVTPSDAPTPSGTPTTTNGPGG >BL;2V0487, H37Rv2.tab 576787:577335 forward MW:20684 VTSSLPTVQRVIQNALEVSQLKYSQHPRPGGAPPALIVELPGERKLKINTILSVGEHSVRVEAFVCRKPDENREDVYRFL (SEQ ID NO:401) LRRNRRLYGVAYTLDNVGDIYLVGQMALSAVDADEVDRVLGQVLEVVDSDFNALLELGFRSSIQREWQWRLSRGESLQNL QAFAHLRPTTMQSAQRDEKELGG >BL;Rv0495c, H37Rv2.tab 585427:586314 reverse MW:32960 VWRPAQGARWHVPAVLGYGGIPRRASWSNVESVANSRRRPVHPGQEVELDFAREWVEFYDPDNPEHLIAADLTWLLSRWA (SEQ ID NO:402) CVFGTPACQGTVAGRPNDGCCSHGAFLSDDDDRTRLADAVHKLTDDDWQFRAKGLRRKGYLELDEHDGQPQHRTRKHKGA CIFLNRPGFAGGAGCALHSKALKLGVPPLTMKPDVCWQLPIRRSQEWVTRPDGTEILKTTLTEYDRRGWGSGGADLHWYC TGDPAAHVGTKQVWQSLADELTELLGEKAYGELAANCKRRSQLGLIAVHPATRAAQ >BL;Rv0497, H37Rv2.tab 587377:588306 forward MW:33092 MTGPHPETESSGNRQISVAELLARQGVTGAPARRRRRRRGDSDAITVAELTGEIPIIRDDHHHAGPDAHASQSPAANGRV (SEQ ID NO:403) QVGEAAPQSPAEPVAEQVAEEPTRTVYWSQPEPRWPKSPPQDRRESGPELSEYPRPLRHTHSDRAPAGPPSGAEHMSPDP VEHYPDLWVDVLDTEVGEAEAETEVREAQPGRGERHAAAAAAGTDVEGDGAAEARVARRALDVVPTLWRGALVVLQSILA VAFGAGLFIAFDQLWRWNSIVALVLSVMVILGLVVSVRAVRKTEDIASTLIAVAVGALITLGPLALLQSG >BL;Rv0498, H37Rv2.tab 588325:589164 forward MW:30433 VRPAIKVGLSTASVYPLRAEAAFEYADRLGYDGVELMVWGESVSQDIDAVRKLSRRYRVPVLSVHAPCLLISQRVWGANP (SEQ ID NO:404) ILKLDRSVRAAEQLGAQTVVVHPPFRWQRRYAEGFSDQVAALEAASTVMVAVENMFPFRADRFFGAGQSRERMRKRGGGP GPAISAFAPSYDPLDGNHAHYTLDLSHTATAGTDSLDMARRMGPGLVHLHLCDGSGLPADEHLVPGRGTQPTAEVCQMLA GSGFVGHVVLEVSTSSARSANERESMLAESLQFARTHLLR >BL;RvO500B, H37Rv2.tab 591475:591573 forward MW:4145 MGSVIKKRRKRMSKKKHRKLLRRTRVQRRKLGK (SEQ ID NO:405) >BL;Rv0504c, H37Rv2.tab 594805:595302 reverse MW:18360 MTVPEEAQTLIGKHYRAPDHFLVGREKIREFAVAVKDDHPTHYSEPDAAAAGYPALVAPLTFLAIAGRRVQLEIFTKFNI (SEQ ID NO:406) PINIARVFHRDQKFRFHRPILANDKLYFDTYLDSVIESHGTVLAEIRSEVTDAEGKPVVTSVVTMLGEAAHHEADADATV AAIASI >BL;Rv0528, H37Rv2.tab 618305:619891 forward MW:57131 MWRSLTSMGTALVLLFLLALAAIPGALLPQRGLNAAKVDDYLAAHPLIGPWLDELQAFDVFSSFWFTAIYVLLFVSLVGC (SEQ ID NO:407) LAPRTIEHARSLRATPVAAPRNLARLPKHANARLAGEPAALAATITGRLRGWRSITRQQGDSVEVSAEKGYLREFGNLVF HFALLGLLVAVAVGKLFGYEGNVIVIADGGPGFCSASPAAFDSFRAGNTVDGTSLHPICVRVNNFQAHYLPSGQATSFAA DIDYQADPATADLIANSWRPYRLQVNHPLRVGGDRVYLQGHGYAPTFTVTFPDGQTRTSTVQWRPDNPQTLLSAGVVRID PPAGSYPNPDERRKHQIAIQCLLAPTEQLDGTLLSSRFPALNAPAVAIDIYRGDTGLDSGRPQSLFTLDHRLIEQGRLVK EKRVNLRAGQQVRIDQGPAAGTVVRFDGAVPFVNLQVSHDPGQSWVLVFAITMMAGLLVSLLVRRRRVWARITPTTAGTV NVELGGLTRTDNSGWGAEFERLTGRLLAGFEARSPDMAEAAAGTGRDVD >BL;Rv0531, H37Rv2.tab 622329:622643 forward MW:11436 VSEAPNDKTTRGVVDILVYATARLLLVVAVSAAIFGVARLIGLTEFPVVVATLFGLIIAMPLGIWVFSPLRRRATAALAV (SEQ ID NO:408) AGERRRAERERLRARLRGESLPEEQ >BL;Rv0543c, H37Rv2,tab 635576:635875 reverse MW:11279 VNRFLTSIVAWLRAGYPEGIPPTDSFAVLALLCRRLSHDEVKAVANELMRLGDFDQIDIGVVITHFTDELPSPEDVERVR (SEQ ID NO:409) ARLAAQGWPLDDVRDREEHA >BL;2V0544c, H37Rv2.tab 635938:636213 reverse MW:9747 VSAWFNYTATLKILIFSLLAGALLPGLFAVGVRLQAAGDGADATARRRPLLVAVSWAIFALVLAVVIIGVLYIARDFIAH (SEQ ID NO:410) HTGWAFLGATPK >BL;RvOS46c, H37Rv2.tab 637586:637969 reverse MW:14346 MEILASRMLLRPADYQRSLSFYRDQIGLAIAREYGAGTVFFAGQSLLELAGYGEPDNSRGPFPGALWLQVRDLEATQTEL (SEQ ID NO:411) VSRGVSIAREPRREPWGLHEMHVTDPDGITLIFVEVPEGHPLRTDTRA >BL;Rv0556, H37Rv2.tab 647959:648471 forward MW:18725 VISPKPLLHILIHGLSDELPDTRGRIVLRWLRIAVLIVTGLVTLQSVLLVAGAWRNDIAIQRNNGVAQAEVLSAGPRRST (SEQ ID NO:412) IEFVTPDRITYRPQLGVLYPSELSTGMRIYVEYNKRDPNLVRvQHRNAGLAIIPAGSIAVVAWLIAAAALVVLAVLDKRL ERRENSASATG >BL;Rv0559c, H37Rv2.tab 650410:650745 reverse MW:12116 MKGTKLAVVVGMTVAAVSLAAPAQADDYDAPFNNTIHRFGIYGPQDYNAWLAKISCERLSRGVDGDAYKSATFLQRNLPR (SEQ ID NO:413) GTTQGQAFQFLGAAIDHYCPEHVGVLQRAGTR >BL;Rv0634A, H37Rv2.tab 731113:731364 forward MW:9408 LGSDCGCGGYLWSMLKRVEIEVDDDLIQKVIRRYRVKGAREAVNLALRTLLGEADTAEHGHDDEYDEFSDPNAWVPRRSR (SEQ ID NO:414) DTG >BL;Rv0635, H37Rv2.tab 731930:732403 forward MW:17448 VALSADIVGMHYRYPDHYEVEREKIREYAVAVQNDDAWYFEEDGAAELGYKGLLAPLTFICVFGYKAQAAFFKNANIATA (SEQ ID NO:415) EAQIVQVDQVLKFEKPIVAGDKLYCDVYVDSVREAHGTQIIVTKNIVTNEEGDLVQETYTTLAGRAGEDGEGFSDGAA >BL;Rv0636, H37Rv2.tab 732393:732818 forward MW:14934 MALREFSSVKVGDQLPEKTYPLTRQDLVNYAGVSGDLNPIHWDDEIAKVVGLDTAIAHGMLTMGIGGGYVTSWVGDPGAV (SEQ ID NO:416) TEYNVRFTAVVPVPNDGKGAELVFNGRVKSVDPESKSVTIALTATTGGKKIFGRAIASAKLA >BL;Rv0637, H37Rv2.tab 732825:733322 forward MW:18929 MALKTDIRGMIWRYPDYFIVGREQCREFARAVKCDHPAFFSEEAAADLGYDALVAPLTFVTILAKYVQLDFFRHVDVGME (SEQ ID NO:417) TMQIVQVDQRFVFHKPVLAGDKLWARMDIHSVDERFGADIVVTRNLCTNDDGELVMEAYTTLMGQQGDGSARLKWDKESG QVIRTA >BL;Rv0779c, H37Rv2.tab 872675:873292 reverse MW:21572 MRSRFLPYATTPGRLLAQLISDITVAVWTTLWMLVGLAVHDAISIIGEAGRQIEIGSHGIAGNLAAAGQDAQRIPVVGDA (SEQ ID NO:418) LSNPITAASQAALDIAGAGHNLDTTAGWLAVVLALAVAATPILAVAMPWLFLRLRFCRRKWTVTTLAATPAGRQLLALRA LANRPPGKLAAVSTDPVGAWRREDPATMRALAALELRAAGIPLRGD >BL;Rv0807, H37Rv2.tab 901635:902021 forward MW:13480 MSARDRVDPAKTRQVVLALADWLRDETLPAPDTDVLAAAVRLTARTLAALAPGASVEVRIPPFAAVQCISGPRHTRGTPP (SEQ ID NO:419) NVVQTDPRTWLLVATGLSGVAQARGSGALQLSGSRAGEIEAWLPLVDLG >BL;Rv0810c, H37Rv2.tab 904908:905087 reverse MW:6900 MGRGRAKAKQTKVARELKYSSPQTDFQRLQRELSGTGTDRLDGDGPSDDDSWNDEDDWRR (SEQ ID NO:420) >BL;Rv0813C, H37Rv2.tab 907341:908018 reverse MW:23868 VSSGAGSDATGAGGVHAAGSGDRAVAAAVERAKATAARNIPAFDDLPVPADTANLREGADLNNALLALLPLVGVWRGEGE (SEQ ID NO:421) GRGPDGDYRFGQQIVVSHDGGDYLNWESRSWRLTATGDYQEPGLREAGFWRFVADPYDPSESQAIELLLAHSAGYVELFY GRPRTQSSWELVTDALARSRSGVLVGGAKRLYGIVEGGDLAYVEERvDADGGLVPHLSARLSRFVG >BL;Rv0817C, H37Rv2.tab 910033:910842 reverse MW:28567 MPMRKVLVGVTGAAIVVAVLIVGAVGADFGASIYAEYRLSTTVRKAANLRSDPFVAILRFPFIPQAMREHYAELEIKAFA (SEQ ID NO:422) VEHAGSGTATLEATMHSIDLSYASWLIRPDAKLPVGELESRIIIDSMHLGRYLGISDLMVAAPRQESNDATGGTTESGIS GSRGLVFSGTPISANFAHRVSVLVDLSVASDDRATLVITPTAVVTGPDTADQPVPDDKRDAVLHAFASKLPNQKLPFGVV PNTVGARGSDVIIEGITRGVTISLDEFKQS >BL;Rv0819, H37Rv2.tab 911736:912680 forward MW:33567 VTALDWRSALTADEQRSVRALVTATTAVDGVAPVGEQVLRELGQQRTEHLLVAGSRPGGPIIGYLNLSPPRGAGGANAEL (SEQ ID NO:423) VVHPQSRRRGIGTAMARAALAKTAGRNQFWAHGTLDPARATASALGLVGVRELIQMRRPLRDIPEPTIPDGVVIRTYAGT SDDAELLRVNNAAFAGHPEQGGWTAVQLAERRGEAWFDPDGLILAFGDSPRERPGRLLGFHWTKVHPDHPGLGEVYVLGV DPAAQRRGLGQMLTSIGIVSLARRLGGRKTLDPAVEPAVLLYVESDNVAAVRTYQSLGFTTYSVDTAYALAGTDN >BL;Rv0862C, H37Rv2.tab 960345:962612 reverse MW:79667 MTEHTPDIPLGSWLAALPDERLTQLLELRPDLAQPPPGSIAALAARAQARQSVKAATDELDFLRLAVFDALLVLQADTAP (SEQ ID NO:424) VPIVRLLAVIGDRAAQADVLGALADLKQRALAWGETAVRVATDAGTALPWHPGQVTLEGSSRSGDQLADLIAGLDPAQRD VLDKLLQGSPVGRTRDAAPGAPSDRPVPRLLAMGLLRRIDAETVILPRHVGQVLRGEQPGPMELTAPDPVVSTTTPDDAD AAAAGAVIDLLREVDVLLENLGATPVAELRSGGLGVREFKRLAKATGIDEPRLGLILEIAAAAGLIASGMPDPEPPHSDG PFWAPTVAADRFATMSPAERWHLLASAWLDLPGRPALIGTRGPDAKPYGALSDSLFSTAAPLDRRLLLGMLAELPAGAGV DASRASATLIWRRPRWARRLQPAPIADLLTEGHALGLVGRGAISTPARALLDEALEPATAPAAAVGVMARALPKPIDHFL VQADLTVVVPGPLQRELADDLTTVATVESAGTAMVYRVSEQSIRHALDVGKSRDWLQEFFANRSKTPVPQGLTYLIDDVA RRHGQLRIGMAASFVRCEDPTLLAQVVAAPEADGLALRALAPTVAVSPAPISEVLVTLRCAGFAPAAEDSTGAVVDVRTR GARVPTPQRRRPYRPPPRPNSEALKAVVAVLREVTAAPFANVRVDPAVTMSLLQRAAKDQATLVISYLDAAGVATQRVVA PITLRGGQLVAFDSSSGRLRDFAIHRITLVVSAHDR >BL;Rv0863, H37Rv2.tab 962599:962877 forward MW:10079 VCSVIADQRRPDQPCGVGGCKTCQNGFVADIAEGKARKTRYVDHGWPTTDPDDHAVSELVTDRTGALSPFGELTFPVPSD (SEQ ID NO:425) DLPYIHPVTVINR >BL;Rv0875c, H37Rv2.tab 973809:974294 reverse MW:17800 VKRGVATLPVILVILLSVAAGAGAWLLVRGHGPQQPEISAYSHGHLTRVGPYLYCNVVDLDDCQTPQAQGELPVSERYPV (SEQ ID NO:426) QLSVPEVISRAPWRLLQVYQDPANTTSTLFRPDTRLAVTIPTVDPQRGRLTGIVVQLLTLVVDHSGELRDVPHAEWSVRL IF >BL;Rv0876C, H37Rv2.tab 974294:975937 reverse MW:57938 MAPTPGRRTRNGSVNGHPGMANYPPDDANYRRSRRPPPMPSANRYLPPLGEQPEPERSRVPPRTTRAGERITVTRAAAMR (SEQ ID NO:427) SREMGSRMYLLVHRAATADGADKSGLTALTWPVMANFAVDSAMAVALANTLFFAAASGESKSRVALYLLITIAPFAVIAP LIGPALDRLQHGRRvALALSFGLRTALAVVLIMNYDGATGSFPSWVLYPCALANMVFSKSFSVLRSAVTPRVMPPTIDLV RVNSRLTVFGLLGGTIAGGAIAAGVEFVCTHLFQLPGALFVVVAITIAGASLSMRIPRWVEVTSGEVPATLSYHRDRGRL RRRWPEEVKNLGGTLRQPLGRNIITSLWGNCTIKVMVGFLFLYPAFVAKAHEANGWVQLGMLGLIGAAAAVGNFAGNFTS ARLQLGRPAVLVVRCTVLVTVLAIAAAVAGSLAATAIATLITAGSSAIAKASLDASLQHDLPEESRASGFGRSESTLQLA WVLGGAVGVLVYTELWVGFTAVSALLILGLAQTIVSFRGDSLIPGLGGNRPVMAEQETTRRGAAVAPQ >BL;Rv0877, H37Rv2.tab 976075:976860 forward MW:27437) VTGPTEESAVATVADWPEGLAAVLRGAADQARAAVVEFSGPEAVGDYLGVSYEDGNAATHRFIAHLPGYQGWQWAVVVAS (SEQ ID NO:428) YSGADHATISEVVLVPGPTALLAPDWVPWEQRvRPGDLSPGDLLAPAKDDPRLVPGYTASGDAQVDETAAEIGLGRRWVM SAWGRAQSAQRWHDGDYGPGSAMARSTKRVCRDCGFFLPLAGSLGAMFGVCGNELSADGHVVDRQYGCGAHSDTTAPAGG STPIYEPYDDGVLDIIEKPAES >BL;Rv0879c, H37Rv2.tab 978484:978756 reverse MW:9512 MSVENSQIREPPPLPPVLLEVWPVIAVGALAWLVAAVAAFVVPGLASWRPVTVAOLATGLLGTTIFVWQLAAARRGARGA (SEQ ID NO:429) QAGLETYLDPK >BL;Rv0883C, H37Rv2.tab 980509:981267 reverse MW:27373 MRELKVVGLDADGKNIICQGAIPSEQFKLPVDDRLRAALRDDSVQPEQAQLDIEVTNVLSPKEIQARIRAGASVEQVAAA (SEQ ID NO:430) SGSDIARIRRFAHPVLLERSRAAELATAAHPVLADGPAVLTMQETVAAALVARGLNPDSLTWDAWRNEDSRWTVQLAWKA GRSDNLAHFRFTPGAHGGTATAIDDTAHELINPTFNRPLRPLAPVAHLDFDEPEPAQPTLTVPSAQPVSNRRGKPAIPAW EDVLLGVRSGGRR >BL;Rv0885, H37Rv2.tab 982762:983781 forward MW:39798 MDRTRIVRRWRRNMDVADDAEYVEMLATLSEGSVRRNFNPYTDIDWESPEFAVTDNDPRWILPATDPLGRHPWYQAQSRE (SEQ ID NO:431) RQIEIGMWRQANVAKVGLHFESILIRGLMNYTFWMPNGSPEYRYCLHESVEECNHTMMFQEMVNRvGADVPGLPRRLRWV SPLVPLVAGPLPVAFFIGVLAGEEPIDHTQKNVLREGKSLHPIMERvMSIHVAEEARHISFAHEYLRKRLPRLTRMQRFW ISLYFPLTMRSLCNAIVVPPKAFWEEFDIPREVKKELFFGSPESRKWLCDMFADARMLAHDTGLMNPIARLVWRLCKIDG KPSRYRSEPQRQHLAAAPAA >BL;Rv0909, H37Rv2.tab 1014681:1014857 forward MW:6403 MGILDKVKNLLSQNADKVETVINKAGEFVDEQTQGNYSDAIHKLHDAASNVVGMSDQQS (SEQ ID NO:432) >BL;Rv0910, H37Rv2.tab 1014866:1015297 forward MW:15754 MAKLSGSIDVPLPPEEAWMhASDLTRYREWLTIHKVWRSKLPEVLEKGTVVESYVEVKGMPNRIKWTIVRYKPPEGMTLN (SEQ ID NO:433) GDGVGGVKVKLIAKVAPKEHGSVVSFDVHLGGPALLGPIGMIVAAALRADIRESLQNFVTVFAG >BL;Rv0912, H37Rv2.tab 1016236:1016682 forward MW:15438 MTRRLRPGWLVALSAAVIAASTWMPWLTTTVGGGGWVNAIGGTHGSLELPHGFGPGQLIVLLSSTLLVVGAMAGRGLSVK (SEQ ID NO:434) LSSIAALVVSLLIVALTVWYYKLNVNPPVSAEYGLYFGAAGGVCAVGCSLWAAVSAASPGRRRHREVVR >BL;Rv0948C, H37Rv2.tab 1057649:1057963 reverse MW:11770 MRPEPPHHENAELAAMNLEMLESQPVPEIDTLREEIDRLDAEILALVKRRAEVSKAIGKARMASGGTRLVHSREMKVIER (SEQ ID NO:435) YSELGPDGKDLAILLLRLGRGRLGH >BL;Rv0954, H37Rv2.tab 1065127:1066035 forward MW:30203 MTYSPGNPGYPQAQPAGSYGGVTPSFAMADEGASKLPMYLNIAVAVLGLAAYFASFGPMFTLSTELGGGDGAVSGDTGLP (SEQ ID NO:436) VGVALLAALLAGVALVPKAKSHVTVVAVLGVLGVFLMVSATFNKPSAYSTGWALWVVLAFIVFQAVAAVLALLVETGAIT APAPRPKFDPYGQYGRYGQYGQYGVQPGGYYGQQGAQQAAGLQSPGPQQSPQPPGYGSQYGGYSSSPSQSGSGYTAQPPA QPPAQSGSQQSHQGPSTPPTGFPSFSPPPPVSAGTGSQAGSAPVNYSNPSGGEQSSSPGGAPV >BL;Rv0955, H37Rv2.tab 1066078:1067442 forward MW:46056 VNRVSASADDRAAGARPARDLVRvAFGPGVVALGIIAAVTLLQLLIANSDMTGAWGAIASMWLGVHLVPISIGGRALGVM (SEQ ID NO:437) PLLPVLLMVWATARSTARATSPQSSGLVVRWVVASALGGPLLMAAIALAVIHDASSVVTELQTPSALRAFTSVLVVHSVG AATGVWSRvGRRALAATALPDWLHDSMRAAAAGVLALLGLSGVVTAGSLVVHWATMQELYGITDSIFGQFSLTVLSVLYA PNVIVGTSAIAVGSSAHIGFATFSSFAVLGGDIPALPILAAAPTPPLGPAWVALLIVGASSGVAVGQQCARRALPFVAAN AKLLVAAVAGALVMAVLGYGGGGRLGNFGDVGVDEGALVLGVLFWFTFVGWVTVVIAGGISRRPKRLRPAPPVELDADES SPPVDMFDGAASEQPPASVAEDVPPSHDDIANGLKAPTADDEALPLSDEPPPRAD >BL;Rv0966c, H37Rv2.tab 1077236:1077835 reverse MW:22210 MSNSAQRDARNSRDESARASDTDRIQIAQLLAYAAEQGRLQLTDYEDRLARAYAATTYQELDRLRADLPGAAIGPRRGGE (SEQ ID NO:438) CNPAPSTLLLALLGGFERRGRWNVPKKLTTFTLWGSGVLDLRYADFTSTEVDIRAYSIMGAQTILLPPEVNVEIHGHRVM GGFDRKVVGEGTRGVPTVRIRGFSLWGDVGIKRKPRKPRK >BL;Rv0970, H37Rv2.tab 1081052:1081681 forward MW:22887 MIHDLMLRWVVTGLFVLTAAECGLAIIAKRRPWTLIVNNGLHFANAVAMAVMAWPWGARVPTTGPAVFFLLAAVWFGATA (SEQ ID NO:439) VVAVRGTATRGLYGYHGLMMLATAWMYAAMNPRLLPVRSCTEYATEPDGSMPANDMTAMNMPPNSGSPIWFSAVNWIGTV GFAVAAVFWACRFVMERRQEATQSRLPGSIGQANMAAGMAMLFFAMLFPV >BL;Rv0996, H37Rv2.tab 1112384:1113457 forward MW:39519 MPSIPQSLLWISLVVLWLFVLVPMLISKRDAVRRTSDVALATRvLNGGAGARLLKRGGPAAGHRWGYLPPEGQGDDPDWK (SEQ ID NO:440) PEEDWRDDPVEDGFADVEHDIDEDQEADDARRRGAVVMKVAAPQTAGADEPDYLDVDVVEEDSEALPVGAGAAVGESADE ADAEAADGVAGHADPEADPVEYEYEYEYVEDTCGLELEEDDQEAPPTVASGTSRRRRFDTKTAAAVSARKYTFRKRALIV MAVILVGSAAAAFELTPVAWWICGSATGVTVLYLAYLRRQTRIEEKVRRRRMQRIARARLGVENTRDREYDVVPSRLRRP GAVVLEIDDEDPIFTHLESAAPIRNYGWPRDLPRAVGQ >BL;Rv0998, H37Rv2.tab 1114748:1115746 forward MW:35608 LDGIAELTGARVEDLAGMDVFQGCPAEGLVSLAASVQPLRAAAGQVLLRQGEPAVSFLLISSGSAEVSHVGDDGVAIIAR (SEQ ID NO:441) ALPGMIVGEIALLRDSPRSATVTTIEPLTGWTGGRGAFATMVHIPGVGERLLRTARQRLAAFVSPIPVRLADGTQLMLRP VLPGDRERTVHGHIQFSGETLYRRFMSARVPSPALMHYLSEVDYVDHFVWVVTDGSDPVADARFVRDETDPTVAEIAFTV ADAYQGRGIGSFLIGALSVAARVDGVERFAARMLSDNVPMRTIMDRYGAVWQREDVGVITTMIDVPGPGELSLGREMVDQ INRVARQVIEAVG >BL;Rv1000, H37Rv2.tab 1116531:1117148 reverse MW:22648 MCDKLGGVAIAVQGALFEHNERRQLGDGAFIDIRSGWLTGGEELLDALLSTVPWRAERRQMYDRVVDVPRLVSFHDLTIE (SEQ ID NO:442) DPPHPQLARMRRRLNDIYGGELGEPFTTAGLCYYRDGSDSVAWHGDTIGRGSTEDTMVAIVSLGATRVFALRPRGRGPSL RLPLAHGDLLVMGGSCQRTFEHAVPKTSAPTGPRVSIQFRPRDVR >BL;Rv1024, H37Rv2.tab 1145858:1146541 forward MW:24570 MPEAKRPESKRRSPASRPGKAGDSVRGGRATKPSAKPSTPAPHASRKTTRTPHEHIVEPIKRAITESVEKRSEQRLGFTA (SEQ ID NO:443) RRAAILAAVVCVLTLTIARPVRTYFAQRAEMEQLAATEANLRRQIADLEEQQVKLADPAYIAAQARERLGFVMPGDIPFQ VQLPSTPLAPPQPGSDAATATNNEPWYTALWHTIADDPHLPPAAPPAPEPGRPGPLPPASPNPEQPGG >BL;Rv1025, H37Rv2.tab 1146561:1147025 forward MW:16593 VVTRQLGRAPRGVLAIAYRCPNGEPGVVKTAPRLPDGTPFPTLYYLTHPVLTAAASRLETTGLMREMNRRLGQDAELAAA (SEQ ID NO:444) YRRAHESYLSERDALEPLGTTVSAGGMPDRvKCLHVLIAHSLAKGPGLNPFGDEALALLAAEPRTAATLVAGQWR >BL;Rv1081c, H37Rv2.tab 1205987:1206418 reverse MW:15384 MTHTPIPRPDARYGRPRLSRRARRRvAIALGVLVAAAGIVIAVIGYQRISTSAVTGSLVGYRLVDDETASVTISVTRSDP (SEQ ID NO:445) SRPVACIVRVRATNGSETGRRELLVPPSEATTVQVTTTVKSSQPPVMADVYGCGTEVPSYLRLP >BL;Rv1083, H37Rv2.tab 1207383:1207646 forward MW:9263 VNQILLSVIAEGGPGNTGPDFGKASPVGLLVIVLLVIATLFLVRSMNQQLKKVPKSFDRDHPELDQAADEGTDRDGPARP (SEQ ID NO:446) PGPPHESG >BL;Rv1100, H37Rv2.tab 1228683:1229381 forward MW:24562 MVGDCPRSRTVRWSWDTGHVTAEPQPTPRPAKPRLLQDGRDMFWSLAPLVVGCILLAGLVGMCSFQLGGTKRGPIPSYDA (SEQ ID NO:447) AQALRADAKTLGFPIRLPQLPGGWTPNSGGRGGIENGRADPATGQRRNAATSIVGFISPTGRYLSLTQSNADEDKLVGSI HPSMYPTGTVDVGGTRWVVYEGSDENGAVEPVWTTRLTGPGGATQLAITGAGSIDQFRTLASATQSQPPLPAR >BL;Rv1109c, H37Rv2.tab 1235460:1236095 reverse MW:22957 MATAPYGVRLLVGAATVAVEETMKLPRTILMYPMTLASQAAHVVMRFQQGLAELVIKGDNTLETLFPPKDEKPEWATFDE (SEQ ID NO:448) DLPDALEGTSIPLLGLSDASEAKNDDRRSDGRFALYSVSDTPETTTASRSADRSTNPKTAKHPKSAAKPTVPTPAVAAEL DYPALTLAQLRARLHTLDVPELEALLAYEQATKARAPFQTLLANRITRATAK >BL;Rv1111c, H37Rv2.tab 1237212:1238192 reverse MW:36985 VSAQRARSAVQASHRSIHPHIPGVPWWAAILIAVTATAIGYAIDAGSGHKALTLVFTGCYIAGCVGAVLAVRQSDLFTAL (SEQ ID NO:449) VQPPLILFCAVPGAYWLFHGGTIGKFKDLLINCGYSLIERFPLMLGTAAGVLLIGLVRWYLGTALFDSIARKLSSLMTGD SDDDGGRRSAQRPARTRSRHARPPSEDNREPIAERRSRRRPRPQNDPHPRRNAMERPAPRSSRFDSYRSYQPSEPSGPAE PVNRYERRGARYQPYARYEPTYEPQRRRARPSEPTNPTHHPISQVRYRCSATRDARRDNYREEQRFDRRDRSRAPRRPPA ESWEYDV >BL;Rv1155, H37Rv2.tab 1281429:1281869 forward MW:16300 MARQVFDDKLLAVISGNSIGVLATIKHDGRPQLSNVQYHFDPRKLLIQVSIAEPRAKTRNLRRDPRASILVDADDGWSYA (SEQ ID NO:450) VAEGTAQLTPPAAAPDDDTVEALIALYRNIAGEHSDWDDYRQAMVTDRRvLLTLPISHVYGLPPGMR >BL;Rv1157c, H37Rv2.tab 1283059:1284171 reverse MW:36448 VRRLTNTEHRENTTVASTWSVCKGLAAVVITSAAAFALCPNAAADPATPQPNPTQQLPGLPALAQLSPIIQQAAMNPAQA (SEQ ID NO:451) TQLLMAAASAFAGNPAVPTESKNVASSVNQFVAEPTNPDSAALGVPAPHGVALPEAIPVPHVPPLGAEPGVQAHLPTGID PSHAAGPAPAVAPTVTPPVAAPPASAPAPAPDAAQPVAVPGPPPAPPAPRAAAPAPASAAPAPAAAPAPASGFGADAPPT QDFMYPSIGPNCVADGSNSIATALSVAGPAKIPLPGPGPGQTAYVFTAVGTPGPADVQRLPLNVTWVNLTTGKSGSATLR PRSDINPDGPTTLTVIADTGSGSIMSTIFGQVTTKDRQCQFMPTIGSTVVP >SL;Rv1158c, H37Rv2.tab 1284182:1284862 reverse MW:21401 MPTIWTFVRAAAVLVGSSAALLTGGIAHADPAPAPAPAPNIPQQLISSAANAPQILQNLATALGATPPLSAPKVAEPAPA (SEQ ID NO:452) APGITATFPGLTPAAPAAAAAPALTPSIPGVNAPIPGITPAAPALPVTAPAAAPTIPGVNAPIPGITAPAPAAAAVPASV PGVPSAKVDLPQLPYLPLQVPQQLSLPADLPALASGVIPAAPIAPTPPAPGAPALPPGPPSLLAALP >BL;Rv1159A, H37Rv2.tab 1286284:1286568 reverse MW:10379 MAVLTDEQVDAALHDLNGWQRAGGVLRRSIKFPTFMAGIDAVRRVAERAEEVNHHPDIDIRWRTVTFALVTHAVGGITEN (SEQ ID NO:453) DIAMAHDIDANFGA >BL;Rv1171, H37Rv2.tab 1301307:1301744 forward MW:15185 VGHRVDTLSDRQRANLTTGATDRAIRLVVLALLTVDGVVSALAGALLMPWYIGSAPFPISALISGLVNAALVWAAARWTT (SEQ ID NO:454) SSRVAALPLWAWLLTVAAMSFGGPGDDVILGGQGLLVYGALVFVVAGAVPPAWVLWRRRVQADGSG >BL;Rv1184c, H37Rv2.tab 1324535:1325611 reverse MW:37818 MKRvIAGAFAVWLVGWAGGFGTAIAASEPAYPWAPGPPPSPSPVGDASTAKVVYALGGARMPGIPWYEYTNQAGSQYFPN (SEQ ID NO:455) AKHDLIDYPAGAAFSWWPTMLLPPGSHQDNMTVGVAVKDGTNSLDNAIHHGTDPAAAVGLSQGSLVLDQEQARLANDPTA PAPDKLQFTTFGDPTGRHAFGASFLARIFPPGSHIPIPFIEYTMPQQVDSQYDTNEVVTAYDGFSDFPDRPDNLLAVANA AIGAAIAHTPIGFTGPGDVPPQNIRTTVNSRGATTTTYLVPVNHLPLTLPLRYLGMSDAEVDQIDSVLQPQIDAAYARND NWFTRPVSVDPVRGLDPLTAPGSIVEGARGLLGSPAFCG >BL;Rv1209, H37Rv2.tab 1353157:1353522 forward MW:13089 VALVLVYLVVLVLVAIVLFAAASLLFGRGEQLPPLPRATTATTLPAFGVTRADVDAVKFTQVLRGYKTSEVDWVLERLGR (SEQ ID NO:456) ELEALRSQLGAIHASSEDAEAESDASNPSRGETVVHYRSDPA >BL;Rv1211, H37Rv2.tab 1354243:1354467 forward MW:7810 MLGADQARAGGPARIWREHSMAAMKPRTGDGPLEATKEGRGIVMRVPLEGGGRLVVELTPDEAAALGDELKGVTS (SEQ ID NO:457) >BL;Rv1222, H37Rv2.tab 1365344:1365805 forward MW:16250 MADPGSVGHVFRRAFSWLPAQFASQSDAPVGAPRQFRSTEHLSIEAIAAFVDGELRMNAHLRAAHHLSLCAQCAAEVDDQ (SEQ ID NO:458) SRAPAALRDSHPIRIPSTLLGLLSEIPRCPPEGPSKGSSGGSSQGPPDGAAAGFGDRFADGDGGNRGRQSRVRR >BL;Rv1249c, H37Rv2.tab 1393197:1393982 reverse MW:27571 MSARRIRSWKRFDNRSANAAEPDPQLAGTGGRPKVSTRALAQVIERSSRIQGPAAQAYVARLRRAHPGASPAKIVAKLEK (SEQ ID NO:459) RFLSVVTASGAAVGAAATLPGIGTLAAWFAAAGEVVVFLEATALFVLALASVHAIPLDHRERRRALVLAVLVGDNTTAVA DLLGPGRTSGGWVSETMASLPLPAISSLNSRMLKYVVKRFALKRGALMFGKLVPMGIGAIIGAIGNRLVGKKLVRNARSA FGTPPARWPVTLNVLPTVRDAS >BL;Rv1251c, H37Rv2.tab 1395824:1399240 reverse MW:123118 VFVTGDSIVYSASDLAAAARCQYALLREFDAKLGRGPAVAVDDELMARAAVLGSAHEGRRLDQLRHEFGDAVAIIGRPAY (SEQ ID NO:460) TPAGLAAAADATRRAIANHAPVVYQAAMFDGRFVGFADFLIRDGHRYRVADTKLARSPTVTALLQLAAYADALVHSGVPV AADAELELGDGTIVRYRVGELIPVYRSQPALLQRLLDGHYTAGTAVRWDDERVQACFRCPQCTERLRASDDLLLVGGMRV RQRDKLLEAGITTIAELADHTAPVPGLTTNALGKLTAQAKLQIRQRDTGAPQFEIVDPRPLTLLPEPNPGDLFFDFEGDP LWTADGKQWGLEYLFGVLEAGRAGVFRPLWAHDRTAERQALTDFLAIVARRRRRHPNMNIYHYAPYEKTALLRLVGRYGI GEDDVDDLLRNGVLVDLYPLVRKSIRVGTDSFSLKALEPLYLGTQPRSGDVTTAADSINSYARYCELRAAGRIDEAATVL KEIEGYNHYDCRSTRALRDWLLMRAWEAGVTPIGAQPVPDADPIDDGDSLASVLSKFTGDAAAGERTPEQTAVALLAAAR GYHRREDKPFWWAHFDRLNYPVDEWSDSTDVFLASEASVTVDWHMPPRARKPQRRVRLTGELARGDLNGNVFALYEPPAP PGMTDNPDRRAAGPAAVVETDDPTVPTEVVIVERTGSDGNTFQQLPFALAPGPPVPTTALRESIESTAAAVASGSPQLPS TALMDVLLRRPPRTRSGAALPRSSDPVTDIAAAALDLDSSYLAVHGPPGTGKTYTAARVIAELVTEHAWRIGVVAQSHAT VENLLEGVISAGLDPGQVAKKPHDHTAGRWQSIDGSQYTEFIRDTAGCVIGGTAWDFANGNRvPKASLDLLVIDEAGQFC LANTIAVAPAATNLLLLGDPQQLPQVSQGTHPEPVDTSALSWLVDGQHTLPDERGYFLDRSYRMHPAVCAAVSALSYEGR LCSHTERTAVRRLDGYPPGVHTRGVHHKGNSIESPEEAEAILAELRQLLGSPWTDEHGTRPLAASDVLVLAPYNAQVALV RRRLASAGLGGADGVRVGTVDKFQGGQAPVVFISMTASSADDVPRGISFLLNRNRLNVAVSRAQYAAVIVRSELLTQYLP ATPDGLVDLGAFLGLTSTS >BL;Rv1259, H37Rv2.tab 1407339:1408235 forward MW:31783 MNIAAESSAKPVWGPPNFCAAAARMQDVRVLMHPKTGRAFRSPVEPGSGWPGDPATPQTPVAADAAQVSALAGGAGSICE (SEQ ID NO:461) LNALISVCRACPRLVSWREEVAVVKRRAFADQPYWGRPVPGWGSKRPRLLILGLAPAAHGANRTGRMFTGDRSGDQLYAA LHRAGLVNSPVSVDAADGLRANRIRITAPVRCAPPGNSPTPAERLTCSPWLNAEWRLVSDHIRAIVALGGFAWQVALRLA GASGTPKPRFGHGVVTELGAGVRLLGCYHPSQQNMFTGRLTPTMLDDIFREAKKLAGIE >BL;Rv1276c, H37Rv2.tab 1425441:1425914 reverse MW:16461 MRHAKSAYPDGIADHDRPLAPRGIREAGLAGGWLRANLPAVDAVLCSTATRARQTLAHTGIDAPARYAERLYGAAPGTVI (SEQ ID NO:462) EEINRVGDNVTTLLVVGHEPTTSALAIVLASISGTDAAVAERISEKFPTSGIAVLRvAGHWADVEPGCAALVGFHVFR >BL;Rv1277, H37Rv2.tab 1426164:1427414 forward MW:44758 VSPRPGPAGRGPAPCRCADLHSLCVDSHALRRDGMRFLHTADWQLGMTRHFLAGDAQPRYSAARRDAVAGLKALAADVGA (SEQ ID NO:463) EFVVVAGDVFEHNQLAPQIVGQSLEANRVIGLPVYLLPGNHDPLDASSVYTSTLFRAERPDNVVVLDRAGVHEVRPGVQI VAAPWRSKAPTTDPVAEVLAGLPTDAAIRLLVAHGGVDALDPDHDKPSLIRLAALDDALTRQAIHYVALGDKHSLTQVGS SGRVWYSGAPEVTNFDDVEPDPGHVLVVDIDESDPRHPVTVDARRIGRWRFVTLHHQVDTSRDIADLDLNLDLMTDKDRT VVRLALTGSLTVTDRAALDTCLDKYARLFAWLGLWERNTDLAVIPVDAEFTDLGIGGFAAAAVDELVATARGGODESAVD AQAALALLLRLADRGAA >BL;Rv1278, H37Rv2.tab 1427414:1430038 forward MW:93319 VKLHRLALTNYRGIAHRDVEFPDHGVVVVCGANEIGKSSMVEALDLLLEYKDRSTKKEVKQVKPTNADVGSEVIAEISSG (SEQ ID NO:464) PYRFVYRKRFHKRCETELTVLAPRREQLTGDEAHERVRTMLAETVDTELWHAQRVLQAASTAAVDLSGCDALSRALDLAA GDDAALSGTESLLIERIEAEYARYFTPTGRPTGEWSAAVSRLAAAEAAVADCAAAVAEVDDGVRRHTELTEQVAELSQQL LAHQLRLEAARVAAEKIAAITDDAREAKLIATAAAATSGASTAAHAGRLGLLTEIDTRTAAVVAAEAKARQAADEQATAR AEAEACDAALTEATQVLTAVRLRAESARRTLDQLADCEEADRLAARLARIDDIEGDRDRVCAELSAVTLTEELLSRIERA AAAVDRGGAQLASISAAVEFTAAVDIELGVGDQRVSLSAGQSWSVTATGPTEVKVPGVLTARIVPGATALDFQAKYAAAQ QELADALAAGEVADLAAARSADLCRRELLSRRDQLTATLAGLCGDEQVDQLRSRLEQLCAGQPAELDLVSTDTATARAEL DAVEAARIAAEKDCETRRQIAAGAARRLAETSTRATVLQNAAAAESAELGAAMTRLACERASVGDDELAAKAEADLRVLQ TAEQRVIDLADELAATAPDAVAAELAEAADAVELLRERHDEAIRALHEVGVELSVFGTQGRKGKLDAAETEREHAASHHA RVGRRARAARLLRSVMARHRDTTRLRYVEPYRAELHRLGRPVFGPSFEVEVDTDLRIRSRTLDDRTVPYECLSGGAKEQL GILARLAGAALVAKEDAVPVLIDDALGFTDPERLAKMGEVFDTIGADGQVIVLTCSPTRYGGVKGAHRIDLDAIQ >BL;Rv1303, H37Rv2.tab 1459766:1460248 forward MW:16863 VTTPAQDAPLVFPSVAFRPVRLFFINVGLAAVAMLVAGVFGHLTVGMFLGLGLLLGLLNALLVRRSAESITAKEHPLKRS (SEQ ID NO:465) NALNSASRLAIITILGLIIAYIFRPAGLGVVFGLAFFQVLLVATTALPVLKKLRTATEEPVATYSSNGQTGGSEGRSASD D >BL;Rv1312, H37Rv2.tab 1467688:1468128 forward MW:16594 MSAPMIGMVVLVVVLGLAVLALSYRLWKLRQGGTAGIMRDIPAVGGHGWRHGVIRYRGGEAAFYRLSSLRLWPDRRLSRR (SEQ ID NO:466) GVEIISRRAPRGDEFDIMTDEIVVVELCDSTQDRRVGYEIALDRGALTAFLSWLESRPSPRARRRSM >BL;Rv1324, H37Rv2.tab 1487161:1488072 forward MW:32138 VTRPRPPLGPAMAGAVDLSGIKQRAQQNAAASTDADRALSTPSGVTEITEANFEDEVIVRSDEVPVVVLLWSPRSEVCVD (SEQ ID NO:467) LLDTLSGLAAAAKGKWSLASVNVDVAPRVAQIFGVQAVPTVVALAAGQPISSFQGLQPADQLSRWVDSLLSATAGKLKGA ASSEESTEVDPAVAQARQQLEDGDFVAARKSYQAILDANPGSVEAKAAIRQIEFLIRATAQRPDAVSVADSLSDDIDAAF AAADVQVLNQDVSAAFERLIALVRRTSGEERTRvRTRLIELFELFDPADPEVVAGRRNLANALY >BL;Rv1332, H37Rv2.tab 1500926:1501579 forward MW:24054 MPPVCGRRCSRTGEIRGYSGSIVRRWKRVETRDGPRFRSSLAPHEAALLKNLAGAMIGLLDDRDSSSPSDELEEITGIKT (SEQ ID NO:468) GHAQRPGDPTLRRLLPDFYRPDDLDDDDPTAVDGSESFNAALRSLHEPEIIDAKRVAAQQLLDTVPDNGGRLELTESDAN AWIAAVNDLRLALGVMLEIGPRGPERLPGNHPLAAHFNVYQWLTVLQEYLVLVLMGSR >BL;Rv1342c, H37Rv2.tab 1508187:1508546 reverse MW:13382 MTAPETPAAQHAEPAIAVERIRTALLGYRIMAWTTGLWLIALCYEIVVRYVVKVDNPPTWIGVVNGWVYFTYLLLTLNLA (SEQ ID NO:469) VKVRWPLGKTAGVLLAGTIPLLGIVVEHFQTKEIKARFGL >BL;Rv1343c, H37Rv2.tab 1508546:1508923 reverse MW:14241 VSTTRRRRPALIALVIIATCGCLALGWWQWTRFQSTSGTFQNLGYALQWPLFAWFCVYAYRNFVRYEETPPQPPTGGAAA (SEQ ID NO:470) EIPAGLLPERPKPAQQPPDDPVLREYNAYLAELAKDDARKQNRTTA >BL;Rv1390, H37Rv2.tab 1565093:1565422 forward MW:11810 VSISQSDASLAAVPAVDQFDPSSGASGGYDTPLGITNPPIDELLDRvSSKYALVIYAAKRARQINDYYNQLGEGILEYVG (SEQ ID NO:471) PLVEPGLQEKPLSIALREIHADLLEHTEGE >BL;Rv1417, H37Rv2.tab 1592150:1592611 forward MW:16351 VTAAPNDWDVVLRPHWTPLFAYAAAFLIAVAHVAGGLLLKVGSSGVVFQTADQVAMGALGLVLAGAVLLFARPRLRVGSA (SEQ ID NO:472) GLSVRNLLGDRIVGWSEVIGVSFPGGSRWARIDLADDEYIPVMAIQAVDKDRAVAANDTVRSLLARYRPDLCAR >DL;Rv1476, H37Rv2.tab 1666204:1666761 forward MW:19601 MTGPYFPQTIPFLPSYIPQDVDMTAVKAEVAALGVSAPPAATPGLLEVVQHARDEGIDLKIVLLDHNPPNDTPLRDIATV (SEQ ID NO:473) VGADYSDATVLVLSPNYVGSYSTQYPRvTLEAGEDHSKTGNPVQSAQNFVHELSTPEFPWSALTIVLLIGVLAAAVGARL MQLRGRRSATSTDAAPGAGDDLNQGV >BL;Rv1590, H37Rv2.tab 1791334:1791570 forward MW:8602 MVEIVAGKQRAPVAAGVYNVYTGELADTATPTAARMGLEPPRFCAQCGRRMVVQVRPDGWWARCSRHGQVDSADLATQR (SEQ ID NO:474) >BL;Rv1591, H37Rv2.tab 1791570:1792232 forward MW:23151 VTEPPGFGGPSEPSGAPRTSRTRAVLFVMLGLSATGVLVGGLWAWIAPPIHAVVAITRAGERVHEYLGSESQNFPIAPFM (SEQ ID NO:475) LLGLLSVLAVVASALMWQWREHRGPQMVAGLSIOLTTAAAIAAGVGALVVRLRYGALDFDTVPLSRGDHALTYVTQAPPV FFARRPLQIALTLMWPAGIASLVYALLAAGTARDDLGGYPAVDPSSNARTEALETPQAPVS >BL;Rv1610, H37Rv2.tab 1809443:1810147 forward MW:24586 VAANAGSVRPNRRARPMIGIAQLLLVVAAGALWMAARLPWVVIGSFDELGPPKEVTLTGASWSTALLPLALLMLAAAVAA (SEQ ID NO:476) LAVRGWPLRALAVLLAAASFAVGYLGISLWVVPDVAARGADLAHVPVVTLVGSARHYWGAVAAVLAAVCALLAAVFLMSS AAIRGSAGEDMARYAAPRARRSIARRQHSNAAGRAAPQDDGPDMGPRMSERMIWEALDEGRDPTDREQESDTEGR >BL;Rv1635c, H37Rv2.tab 1840575:1842242 reverse MW:60035 MNASRPGAPPHAGLPSRRTAGDQDHRADPKVTRIMSASTLEQPAAAHVDELVARMRGRLLDPLAIAVLAAVISGAWASRP (SEQ ID NO:477) SLWFDEGATISASASRTLPELWSLLGHIDAVHGLYYLLMHGWFAIFPPTELWSRLPSCLAIGAAAAGVVVFAKQFSGRTT AVCAGAVFAILPRVTWAGIEARSSALSVAAAVWLTVLLVAAVRCNTQRRWLLYALVLMLSILVSINLALLVPAYATMVPL LASGKSRKSPVIWWTVVTAAALGAMTPFILFAMGQVWQVGWIAGLNRNIILDVIHRQYFDHSVPFAILAGLIVAAGIAAH LAGARGPGGDTHRLVLVSAAWIVVPTAVVLIYSATVEPIYYPRYLILTAPAAAVILAVCVVTIARKPWLIAGVVFLLAAA AFPNYFFTQRGPYAKEGWDYSQVADVISAHAKPGDCLLVDNTAGWRPGPIRALLATRPAAFRSLIDVERGTYGPKVGTLW DGHVAVWLTTAKIDKCPTLWTIANRDKSLPDHQVGEMLSPGTGFGRTPVYRFPSYLGFRIVERWQFHYSQVVKSTR >BL;Rv1647, H37Rv2.tab 1856774:1857721 forward MW:33939 LAGSARTTYPCHVEVGPQDSESGAPDETATAMASPVPRQRSALRWLRTVNRSPGLVSFIHRARRLLPGDPEFGDPLSTAG (SEQ ID NO:478) EGGPRAAARAADRLLRDRDAASREVGLSVLQVWQALTEAVSRRPANPEVTLVFTDLVGFSTWSLHAGDDATLTLLRQVAR AVESPLLDAGGHIVKRLGDGIMAVFRNPTVALRAVLVAQDAVKSLEVQGYTPRMRIGIHTGRPQRLAADWLGVDVNIAAR VMERATKGGIMISQPTLDLIPQSELDALGVVARRVRKPVFASKPTGIPPDLAIYRIKTVSESTAADNFDEMSPDAQ >BL;Rv1693, H37Rv2.tab 1917756:1917929 forward MW:6094 MTIDPDQIRAEIDALLASLPDPADAENGPSLAELEGIARRLSEAHEVLLAALESAEKG (SEQ ID NO:479) >BL;Rv1697, H37Rv2.tab 1921542:1922720 forward MW:42423 MRMSALLSRNTSRPGLIGIARVDRNIDRLLRRvCPGDIVVLDVLDLDRITADALVEAEIAAVVNASSSVSGRYPNLGPEV (SEQ ID NO:480) LVTNGVTLIDETGPEIFKKVKDGAKVRLYEGGVYAGDRRLIRGTERTDHDIADLMREAKSGLVAHLEAFAGNTIEFIRSE SPLLIDGIGIPDVDVDLRRRHVVIVADEPSGPDDLKSLKPFIKEYQPVLVGVGTGADVLRKAGYRPQLIVGDPDQISTEV LKCGAQVVLPADADGHAPGLERIQDLGVGANTFPAAGSATDLALLLADHHGAALLVTAGHAANIETFFDRTRvQSNPSTF LTRLRVGEKLVDAKAVATLYRNHISGGAIALLALTMLIAIIVALWVSRTDGVVLHWIIDYWNRFSLWVQHLVS >BL;Rv1698, H37Rv2.tab 1922745:1923686 forward MW:32391 MISLRQHAVSLAAVFLALAMGVVLGSGFFSDTLLSSLRSEKRDLYTQIDRLTDQRDALREKLSAADNFDIQVGSRIVHDA (SEQ ID NO:481) LVGKSVVIFRTPDAHDDDIAAVSKIVGQAGGAVTATVSLTQEFVEANSAEKLRSVVNSSILPAGSQLSTKLVDQGSQAGD LLGIALLSNADPAAPTVEQAQRDTVLAALRETGFITYQPRDRIGTANATVVVTGGALSTDAGNQGVSVARFAAALAPRGS GTLLAGRDGSANRPAAVAVTRADADMAAEISTVDDIDAEPGRITVILALHDLINGGNVGHYGTGHGAMSVTVSQ >BL;Rv1754c, H37Rv2.tab 1984982:1986670 reverse MW:60608 MYRYQVRVQQRRSEMNRWVATRSRRHTYQWITDHKSPRDHYRHISELRTSIATSSPGRCDMSPIPRIVSVSLAWAAAIGL (SEQ ID NO:482) MVPIGLAPPAMAAPCSGDAANAPPPPSAIVTDPGATALGPVRPGHGPIPTGRKPRGANDRAPLPKLGPLISALLNPGARN AAPLQQQALVPRANPGPNPAPNPPATGPQPPNATQLTPNFAPAPDPAPAAAPDPGATLAGATTSLAEWVTGPDSPNKTLE RFGISGTDLGIPWDNGDPANRQVLMIFGDTFGYCAVDGHQWRYNTLFRSQDRDLGNGVHVTSGDASNRYSGSPVRQPGFS KQLINSIKWARDETGIIPTAGIAVGKTQYVNFMSIRNWGRDGEWTTNYSGIAVSKDNGQTWGVFPGTIRASGPDSGGKAR FVPGNENFQMGAYLKSNDGYLYSFGTPPGRGGSAYLARvPQRFVPDLTKYQYWNGDSNSWVPNKPDAATPVIPGPVGEMS VQYNTYLKQYLALYTNGMNDVVARTAPAPQGPWSAEQMLVSSWQMPGGIYAPMMHPWSTGKDVYFNLSLWSAYNVNLMHT VLP >BL;Rv1782, H37Rv2.tab 2017740:2019257 forward MW:53689 VAEESRGQRGSGYGLGLSTRTQVTGYQFLARRTANALTRWRVRMEIEPGRRQTLAVVASVSAALVICLGALLWSFISPSG (SEQ ID NO:483) QLNESPIIADRDSGALYVRVGDRLYPALNLASARLITGRPDNPHLVRSSQIATMPRGPLVGIPGAPSSFSPKSPPASSWL VCDTVATSSSIGSLQGVTVTVIDGTPDLTGHRQILSGSDAVVLRYGGDAWVIREGRRSRIEPTNRAVLLPLGLTPEQVSQ ARPMSRALFDALPVGPELLVPEVPNAGGPATFPGAPGPIGTVIVTPQISGPQQYSLVLGDGVQTLPPLVAQILQNAGSAG NTKPLTVEPSTLAKMPVVNRLDLSAYPDNPLEVVDIREHPSTCWWWERTAGENRARVRVVSGPTIPVAATEMNKVVSLVK ADTSGRQADQVYFGPDHANFVAVTGNNPGAQTSESLWWVTDAGARFGVEDSKEARDALGLTLTPSLAPWVALRLLPQGPT LSRADALVEHDTLPMDMTPAELVVPK >BL;Rv1794, H37Rv2.tab 2031066:2031965 forward MW:32399 MDQQSTRTDITVNVDGFWMLQALLDIRHVAPELRCRPYVSTDSNDWLNEHPGMAVMREQGIVVNDAVNEQVAARMKVLAA (SEQ ID NO:484) PDLEVVALLSRGKLLYGVIDDENQPPGSRDIPDNEFRVVLARRGQHWVSAVRvGNDITVDDVTVSDSASIAALVMDGLES IHHADPAAINAVNVPMEEMLEATKSWQESGFNVPSGGDLRRMGISAATVAALGQALSDPAAEVAVYARQYRDDAKGPSAS VLSLKDGSGGRIALYQQARTAGSGEAWLAICPATPQLVQVGVKTVLDTLPYGEWKTHSRV >DL;Rv1797, H37Rv2.tab 2035483:2036700 forward MW:44178 MKAQRSFGLALSWPRVTAVFLVDVLILAVASHCPDSWQADHHVAWWVGVGVAAVVTLLSVVSYHGITVISGLATWVRDWS (SEQ ID NO:485) ADPGTTLGAGCTPAIDHQRRFGRDTVGVREYNGRLVSVIEVTCGESGPSGRHWHRKSPVPMLPVVAVADGLRQFDIHLDG IDIVSVLVRGGVDAAKASASLQEWEPQGWKSEERAGDRTVADRRRTWLVLRMNPQRNVAAVACRDSLASTLVAATERLVQ DLDGQSCAARPVTADELTEVDSAVLADLEPTWSRPGWRHLKHFNGYATSFWVTPSDITSETLDELCLPDSPEVGTTVVTV RLTTRVGSPALSAWVRYHSDTRLPKEVAAGLNRLTGRQLAAVRASLPAPTHRPLLVIPSRNLRDHDELVLPVGQELEHAT SSFVGQ >BL;Rv1828, H37Rv2.tab 2073081:2073821 forward MW:26411 VSAPDSPALAGMSIGAVLDLLRPDFPDVTISKIRFLEAEGLVTPRRASSGYRRFTAYDCARLRFILTAQRDHYLPLKVIR (SEQ ID NO:486) AQLDAQPDGELPPFGSPYVLPRLVPVAGDSAGGVGSDTASVSLTGIRLSREDLLERSEVADELLTALLKAGVITTGPGGF FDEHAVVILQCARALAEYGVEPRHLRAFRSAADRQSDLIAQIAGPLVKAGKAGARDRADDLAREVAALAITLHTSLIKSA VRDVLHR >BL;Rv1830, H37Rv2.tab 2074841:2075515 forward MW:23988 VTQLVTRARSARGSTLGEQPRQDQLDFADHTGTAGDGNDGAAAASGPVQPGLFPDDSVPDELVGYRGPSACQIAGITYRQ (SEQ ID NO:487) LDYWARTSLVVPSIRSAAGSGSQRLYSFKDILVLKIVKRLLDTGISLHNIRVAVDHLRQRGVQDLANITLFSDGTTVYEC TSAEEVVDLLQGGQGVFGIAVSGAMRELTGVIADFNGERADGGESIAAPEDELASRRKHRDRKIG >BL;Rv1836c, H37Rv2.tab 2082606:2084636 reverse MW:69677 MGRHSKPDPEDSVDDLSDGNAAEQQNWEDISGSYDYPGVDQPDDGPLSSEGHYSAVGGYSASGSEDYPDIPPRPDWEPTG (SEQ ID NO:488) AEPIAAAPPPLFRFGHRGPGDWQAGHRSADGRRGVSIGVIVALVAVVVMVAGVILWRFFGDALSNRSHTAAARCVGGKDT VAVIADPSIADQVKESADSYNASAGPVGDRCVAVAVTSAGSDAVINGFIGKWPTELGGQPGLWIPSSSISAARLTGAAGS QAISDSRSLVISPVLLAVRPELQQALANQNWAALPGLQTNPNSLSGLDLPAWGSLRLANPSSGNGDAAYLAGEAVAAASA PAGAPATAGIGAVRTLMGARPKLADDSLTAANDTLLKPGDVATAPVHAVVTTEQQLFQRGQSLSDAENTLGSWLPPGPAA VADYPTVLLSGAWLSQEQTSAASAFARYLHKPEQLAKLARAGFRvSDVKPPSSPVTSFPALPSTLSVGDDSMRATLADTM VTASAGVAATIMLDQSMPNDEGGNSRLSNVVAALENRIKAMPPSSVVGLWTFDGREGRTEVPAGPLADPVNGQPRPAALT AALGKQYSSGGGAVSFTTLRLIYQEMLANYRVGQANSVLVITAGPHTDQTLDGPGLQDFIRKSADPAKPIAVNIIDFGAD PDRATWEAVAQLSGGSYQNLETSASPDLATAVNIFLS >BL;Rv1845c, H37Rv2.tab 2095221:2096168 reverse MW:32704 VSALAFTILAVLLAGPTPALLARATWPLRAPRAANVLWQAIALAAVLSSFSAGIAIASRLLMPGPDGRPTTSFVGAAGRL (SEQ ID NO:489) GWPLWAAYITVFALTVLVGARLAVAVVRVATATRRRRAHHRMVVDLVGVGHNGALAQPCARARDLRVLDVAQPLAYCLPG VRSRVVVSEGTLTALADAEVAAILTHERAHLRARHDLVLEAFTAVHAAFPRLVRSANALGAVQLLVELLADDAAVRAAGR TPLARALVACASGRAPSGALAVGGPSTVLRVRRLSGRGNSAVLSAAAYLAAAAVLVVPTVALAVPWLTQLQRLFIA >BL;Rv1846c, H37Rv2.tab 2096186:2096599 reverse MW:15211 MAKLTRLGDLERAVMDHLWSRTEPQTVRQVHEALSARRDLAYTTVMTVLQRLAKKNLVLQIRDDRAHRYAPVHGRDELVA (SEQ ID NO:490) GLMVDALAQAEDSGSRQAALVHFVERVGADEADALRRALAELEAGHGNRPPAGAATET >BL;Rv1861, H37Rv2.tab 2109165:2109467 forward MW:10330 MDITATTEFSAMNLDGKTGIGWLGYIVIGGIAGWLASKIVKGGGSGILMNVVIGVVGAFGAGLVLNALGVDVNHGGYWFT (SEQ ID NO:491) FFVALGGAVVLLWIVCMVRKT >BL;Rv1871c, H37Rv2.tab 2121498:2121884 reverse MW:14663 LNAAMNLKREFVNRVQRFVVNPIGRQLPMTMLETIGRKTGQPRRTAVGGRVVDNQFWMVSEHGEHSDYVYNIKANPAVRV (SEQ ID NO:492) RIGGRWRSGTAYLLPDDDPRQRLRGLPRLNSAGVRANGTDLLTIRVDLD >BL;Rv1883c, H37Rv2.tab 2133234:2133692 reverse MW:17280 MCLDQVMEGSATVHMAAPPDKIWTLIADVRNTGRFSPETFEAEWLDGATGPALGARFRGHVRRNGIGPVYWTVCEPGREF (SEQ ID NO:493) GFAVLLGDRPVNNWHYRLTPTADGTEVTESFRLPPSVLTTVYYRVFGGWLRQRRNIRDMTKTLQRIKDLVEAG >BL;Rv1891, H37Rv2.tab 2139741:2140145 forward MW:14108 MIRELVTTAAITGAAIGGAPVAGADPQRYDGDVPGMNYDASLGAPCSSWERFIFGRGPSGQAEACHFPPPNQFPPAETGY (SEQ ID NO:494) WVISYPLYGVQQVGAPCPKPQAAAQSPDGLPMLCLGARGWQPGWFTGAGFFPPEP >BL;Rv1893, H37Rv2.tab 2140486:2140701 forward MW:7467 MSFNPKDAVDAVRDIAANAVEKASDIVENAGHIIRGDIAGGASGIVKDSIDIATHAVDRTKEVFTGKTDDEG (SEQ ID NO:495) >BL;Rv1906c, H37Rv2.tab 2152428:2152895 reverse MW:15536 MRLKPAPSPAAAFAVAGLILAGWAGSVGLAGADPEPAPTPKTAIDSDGTYAVGIDIAPGTYSSAGPVGDGTCYWKRMGNP (SEQ ID NO:496) DGALIDNALSKKPQVVTIEPTDKAFKTHGCQPWQNTGSEGAAPAGVPGPEAGAQLQNQLGILNGLLGPTGGRVPQP >BL;Rv1919c, H37Rv2.tab 2171064:2171525 reverse MW:16803 MSGRKFSFEVTKTSSAPAATLFRLVTDGGNWATWAKPIVAQSSWARRGDPAPGGIGAIRKLGMWPVFVQEETVEYEQDRR (SEQ ID NO:497) HVYKLVGARTPVQDYFGEVVLTPNASGGTDLRWSGSFTEKVRGTGPVMRAALGGAVRFFAGQLVKAAEREAVRR >BL;Rv1976c, H37Rv2.tab 2218847:2219251 reverse MW:14997 VRWIVDGMNVIGSRPDGWWRDRHRANVMLVERLEGWAITKARGDDVTVVFERPPSTAIPSSVVEVAHAPKAAANSADDEI (SEQ ID NO:498) VRLVRSGAQPQEIRVVTSDKALTDRVRDLGAAVYPAERFRDLIDPRGSNAARRTQ >BL;Rv2050, H37Rv2.tab 2307821:2308153 forward MW:12971 MADRvLRGSRLGAVSYETDRNHDLAPRQIARYRTDNGEEFEVPFADDAEIPGTWLCRNGMEGTLIEGDLPEPKKVKPPRT (SEQ ID NO:499) HWDMLLERRSIEELEELLKERLELIRSRRRG >BL;Rv2054, H37Rv2.tab 2313125:2313835 forward MW:25183 MTTIEIDAPAGPIDALLGLPPGQGPWPGVVVVHDAVGYVPDNKLISERIARAGYVVLTPNMYARGGRARCITRVFRELLT (SEQ ID NO:500) KRGRALDDILAARDHLLANPECSGRVGIVGFCMGGQFALVLSPRGFGATAPFYGTPLPRHLSETLNGACPIVASFGTRDP LGIGAANRLRKVTAAKNIPADIKSYPGAGHSFANKLPGQPLVRIAGFGYNEAATEDAWRRVFEFFGQHLRAGSPGEP >BL;Rv2061c, H37Rv2.tab 2316684:2317085 reverse MW:14782 VTPTFSDLAEAQYLLLTTFTKDGRPKPVPIWAALDTDRGDRLLVITEKKSWKVKRIRNTPRVTLATCTLRGRPTSEAVEA (SEQ ID NO:501) TAAILDESQTGAVYDAIVKRYGIQGKLFTFVSKLRGGMRNNIGLELKVAESETG >BL;Rv2091c, H37Rv2.tab 2348561:2349292 reverse MW:26019 MSGPQGSDPRQPWQPPGQGADHSSDPTVAAGYPWQQQPTQEATWQAPAYTPQYQQPADPAYPQQYPQPTPGYAQPEQFGA (SEQ ID NO:502) QPTQLGVPGQYGQYQQPGQYGQPGQYGQPGQYAPPGQYPGQYGPYGQSGQGSKRSVAVIGGVIAVMAVLFIGAVLILGFW APGFFVTTKLDVIKAQAGVQQVLTDETTGYGAKNVKDVKCNNGSDPTVKKGATFECTVSIDGTSKRVTVTFQDNKGTYEV GRPQ >BL;Rv2111c, H37Rv2.tab 2370601:2370792 reverse MW:6944 MAQEQTKRGGGGGDDDDIAGSTAAGQERREKLTEETDDLLDEIDDVLEENAEDFVRAYVQKGGQ (SEQ ID NO:503) >BL;Rv2125, H372V2.tab 2386293:2387168 forward MW:31808 VTPSEGNAPLPELHNTVVVAAFEGWNDAGDAAGDAVAHLAASWQALPIVEIDDEAYYDYQVNRPVIRQVDGVTRELQWPA (SEQ ID NO:504) MRISHCRPPGSDRDVVLMCGVEPNMRWRTFCDELLAVIDKLNVDTVVILGALLADTPHTRPVPVSGAAYSAASARQFGLQ ETRYEGPTGIAGVFQSACVGAGIPAVTFWAAVPHYVSHPPNPKATIALLRRvEDVLDVEVPLADLPAQAEAWEREITETI AEDHELAEYVQTLEQHGDAAVDMNEALGNIDGDALAAEFERYLRRRRPGFGR >BL;Rv2133c, H37Rv2.tab 2393854:2394639 reverse MW:28284 VLADGELTVLGRIRSASNATFLCESTLGLRSLHCVYKPVSGERPLWDFPDGTLAGRELSAYLVSTQLGWNLVPHTIIRDG (SEQ ID NO:505) PAGIGMLQLWVQQPGDAVDSDPLPGPDLVDLFPAHRPRPGYLPVLRAYDYAGDEVVLMHADDIRLRRMAVFDVLINNADR KGGHILCGIDGQVYGVDHGLCLHVENKLRTVLWGWAGKPIDDQILQAVAGLADALGGPLAEALAGRIAAAEIGALRRRAQ SLLDQPVMPGPNGHRPIPWPAF >BL;Rv2134c, H37Rv2.tab 2394653:2395237 reverse MW:21217 MARAIHVFRTPDRFVAGTVGQPGNRTFYLQAVHDSRvVSVVLEKQQVAVLAERIGALLFEVNRRFGTPVPPEPTEIDDLS (SEQ ID NO:506) PLIMPVDAEFRVGTMGLGWDSEAQSVVVELLAVTDAEFDASVVLDDTEEGPDAVRVFLTPESARQFATRSYRVISAGRPP CPLCDEPLDPEGHICARTNGYRRDVLLGSGDDPAG >BL;Rv2137c, H37Rv2.tab 2396905:2397315 reverse MW:14965 MRNMKSTSHESESGKLLSISSCRPREMVLQRYSLGMTVTADRHLADKREEFAVEDISTGIFASGYGQVGDGRSFSFHIEH (SEQ ID NO:507) RSLVVEIYRPRvAGPVPQAEDVVAMAVRGLVDIDLTDERSLAAAVRDSVASAAPVSR >BL;Rv2144c, H37Rv2.tab 2404168:2404521 reverse MW:12027 MLIIALVLALIGLLALVFAVVTSNQLVAWVCIGASVLGVALLIVDALRERQQGGADEADGAGETGVAEEADVDYPEEAPE (SEQ ID NO:508) ESQAVDAGVIGSEEPSEEASEATEESAVSADRSDDSAK >BL;Rv2146c, H37Rv2.tab 2405669:2405956 reverse MW:10804 LVVFFQILGFALFIFWLLLIARvVVEFIRSFSRDWRPTGVTVVILEIIMSITDPPVKVLRRLIPQLTIGAVRFDLSIMVL (SEQ ID NO:509) LLVAFIGMQLAFGAAA >BL;Rv2147c, H37Rv2.tab 2406121:2406843 reverse MW:27629 VNSHCSHTFITDNRSPRARRGHAMSTLHKVKAYFGMAPMEDYDDEYYDDRAPSRGYARPRFDDDYGRYDGRDYDDARSDS (SEQ ID NO:510) RGDLRGEPADYPPPGYRGGYADEPRFRPREFDRAEMTRPRFGSWLRNSTRGALANDPRRMAMMFEDGHPLSKITTLRPKD YSEARTIGERFRDGSPVIMDLVSMDNADAKRLVDFAAGLAFALRGSFDKVATKVFLLSPADVDVSPEERRRIAETGFYAY Q >BL;Rv2164c, H37Rv2.tab 2427087:2428238 reverse MW:39647 MRAKREAPKSRSSDRRRRADSPAAATRRTTTNSAPSRRIRSRAGKTSAPGRQARVSRPGPQTSPMLSPFDRPAPAKNTSQ (SEQ ID NO:511) AKARAKARKAKAPKLVRPTPMERLAARLTSIDLRPRTLANKVPFVVLVIGSLGVGLGLTLWLSTDAAERSYQLSNARERT RMLQQHKEALERDVREAASAPALAEAARRQGMIPTRDTAHLVQDPDGNWVVVGTPKPADGVPPPPLNTKLPEDPPPPPKP AAVPLEVPVRVTPGPDDPAPPARSGPEVLVRTPDGTATLGGATHLPTQAGPQLPGPVPIPGAPGPMPAPPLGAVPSPAPA ENPVPLQVGAAPPACLPGPAPVAATPGLSGGSQPMVAPPAPVPANGEQFGPVTAPVPTAPGAPR >BL;Rv2169c, H37Rv2.tab 2431568:2431969 reverse MW:14571 MPLSDHEQRMLDQIESALYAEDPKFASSVRGGGFRAPTARRRLQGAALFIIGLGMLVSGVAFKETMIGSFPILSVFGFVV (SEQ ID NO:512) MFGGVVYAITGPRLSGRMDRGGSAAGASRQRRTKGAGGSFTSRMEDRFRRRFDE >BL;Rv2170, H37Rv2.tab 2432235:2432852 forward MW:22926 LAIFLIDLPPSDMERRLGDALTVYVDAMRYPRGTETLRAPMWLEHIRRRGWQAVAAVEVTAAEQAEAADTTALPSAAELS (SEQ ID NO:513) NAPMLGVAYGYPGAPGQWWQQQVVLGLQRSGFPRLAIARLMTSYFELTELHILPRAQGRGLGEALARRLLAGRDEDNVLL STPETNGEDNRAWRLYRRLGFTDIIRGYHFAGDPRAFAILGRTLPL >BL;Rv2172c, H37Rv2.tab 2433634:2434536 reverse MW:33007 VTLNTIALELVPPNLEGGKERAIEDARKVVQYSAASGLDGRIRHVMMPGMIAEDDDRPIPMQPKLDVLDFWSIIKPELAG (SEQ ID NO:514) VHGLCTQVTAFMDEPSLHRRLVDLSDAGMEGIVFVGVPRTMQDGEGSGVAPTDALSLYRQLVANRGVIVIPTRDGEQGRL NFKCSRGATYGMTQLLYSDAIVGFLREFARTTEHRPEILLSFGFVPKVETRIGLINWLIQDPGNAAVADEQAFVQKLAGS EPARRRRLMVDLYKRVLDGVADLGFPLSIHLEATYGVSAAAFETFAEMLAYWSPAEPGKPD >BL;Rv2175c, H37Rv2.tab 2437449:2437886 reverse MW:15743 MPGRAPGSTLARVGSIPAGDDVLDPDEPTYDLPRvAELLGVPVSKVAQQLREGHLVAVRRAGGVVIPQVFFTNSGQVVKS (SEQ ID NO:515) LPGLLTILHDGGYRDTEIMRWLFTPDPSLTITRDGSRDAVSNARPVDALHAHQAREVVRRAQAMAY >BL;Rv2179c, H37Rv2.tab 2441814:2442317 reverse MW:19488 VRYFYDTEFIEDGNTIELISIGVVAEDGREYYAVSTEFDPERAGSWVRTHVLPKLPPPASQLWRSRQQIRLDLEEFLRID (SEQ ID NO:516) GTDSIELWAWVGAYDHVALCQLWGPMTALPPTVPRFTRELRQLWEDRGCPRMPPRPRDVHDALVDARDQLRRFRLITSTD DAGRGAAR >BL;Rv2183c, H37Rv2.tab 2445418:2445810 reverse MW:13322 VSGAHTDVRPELRKLAQAILDGIDPAVRvAAAMASGGGPGTGKCQQVWCPLCALAALVTGEQHPLLTVIADHSLALLEVI (SEQ ID NO:517) RAIVDDIDRSAKPPPEGPPGGGQTGASGGENTNGEGSMKSHYQAIPVTIEE >BL;Rv2185c, H37Rv2.tab 2447069:2447500 reverse MW:16292 VADKTTQTIYIDADPGEVMKAIADIEAYPQWISEYKEVEILEADDEGYPKRARMLMDAAIFKDTLIMSYEWPEDRQSLSW (SEQ ID NO:518) TLESSSLLKSLEGTYRLAPKGSGTEVTYELAVDLAVPMIGMLKRKAERRLIDGALKDLKKRVEG >BL;Rv2186c, H37Rv2.tab 2447608:2447994 reverse MW:14573 MNSIQIADETYVAADAARvSAAVADRCSWRRWWPDLRLQVTEDRADKGIRWTVTGALTGTMEIWLEPSMDGVLLHYFLHA (SEQ ID NO:519) EPTGVAAWQLARMNLARMTHHRRVAGKKMAFEVKTVLERSRPIGVSPVT >BL;Rv2197C, N37Rv2.tab 2461507:2462148 reverse MW:22480 MVSRYSAYRRGPDVISPDVIDRILVGACAAVWLVFTGVSVAAAVALMDLGRGFHEMAGNPHTTWVLYAVIVVSALVIVGA (SEQ ID NO:520) IPVLLRARRMAEAEPATRPTGASVRGGRSIGSGHPAKRAVAESAPVQHADAFEVAAEWSSEAVDRIWLRGTVVLTSAIGI ALIAVAAATYLMAVGHDGPSWISYGLAGVVTAGMPVIEWLYARQLRRVVAPQSS >BL;Rv2199c, H37Rv2.tab 2463236:2463652 reverse MW:14865 MHIEARLFEFVAAFFVVTAVLYGVLTSMFATGGVEWAGTTALALTGGMALIVATFFRFVARRLDSRPEDYEGAEISDGAG (SEQ ID NO:521) ELGFFSPHSWWPIMVALSGSVAAVGIALWLPWLIAAGVAFILASAAGLVFEYYVGPEKH >BL;Rv2203, H37Rv2.tab 2468231:2468920 forward MW:24371 MPGPHSPNPGVGTNGPAPYPEPSSHEPQALDYPHDLGAAEPAFAPGPADDAALPPAAYPGVPPQVSYPKRRHKRLLIGIV (SEQ ID NO:522) VALALVSAMTAAIIYGVRTNGANTAGTFSEGPAKTAIQGYLNALENRDVDTIVRNALCGIHDGVRDKRSDQALAKLSSDA FRKQFSQVEVTSIDKIVYWSQYQAQVLFTMQVTPAAGGPPRGQVQGIAQLLFQRGQVLVCSYVLRTAGSY >BL;Rv2206, H37Rv2.tab 2470958:2471329 forward MW:13988 MMAGEEAYLLPRDRGPVRRYVRDVVDSRRNLLGLFMPSALTLLFVMFAVPQVQFYLSPAMLILLALMTIDAIILGRKVGR (SEQ ID NO:523) LVDTKFPSNTESRWRLGLYAAGRASQIRRLRAPRPQVERGGDVG >BL;Rv2219, H37Rv2.tab 2486235:2486984 forward MW:26864 MAKPRNAAESKAAKAQANAARKAAARQRRAQLWQAFTLQRKEDKRLLPYMIGAFLLIVGASVGVGVWAGGFTMFTMIPLG (SEQ ID NO:524) VLLGALVAFVIFGRRAQRTVYRKAEGQTGAAAWALDNLRGKWRVTPGVAATGNLDAVHRVIGRPGVIFVGEGSAARVKPL LAQEKKRTARLVGDVPIYDIIVGNGDGEVPLAKLERHLTRLPANITVKQMDTVESRLAALGSRAGAGVMPKGPLPTTAKM RSVQRTVRRK >BL;Rv2229c, H37Rv2.tab 2502738:2503472 reverse MW:26851 MKAGVAQQRSLLELAKLDAELTRIAHRATHLPQRAAYQQVQAEHNAANDRMAALRIAAEDLDGQVSRFESEIDAVRKRGD (SEQ ID NO:525) RDRSLLTSGATDAKQLADLQHELDSLQRRQASLEDALLEVLERREELQAQQTAESRALQALRADLAAAQQALDEALAEID QARHQHSSQRDMLTATLDPELAGLYERQRAGGGPGAGRLQGHRCGACRIEIGRGELAQISAAAEDEVVRCPECGAILLRL EGFEE >BL;Rv2235, H37Rv2.tab 2507637:2508449 forward MW:29762 MPRLAFLLRPGWLALALVVVAFTYLCFTVLAPWQLGKNAKTSRENQQIRYSLDTPPVPLKTLLPQQDSSAPDAQWRRVTA (SEQ ID NO:526) TGQYLPDVQVLARLRvVEGDQAFEVLAPFVVDGGPTVLVDRGYVRPQVGSHVPPIPRLPVQTVTITARLRDSEPSVAGKD PFVRDGFQQVYSINTGQVAALTGVQLAGSYLQLIEDQPGGLGVLGVPHLDPGPFLSYGIQWISFGILAPIGLGYFAYAEI RARRREKAGSPPPDKPMTVEQKLADRYGRRR >BL;Rv2239c, H37Rv2.tab 2511179:2511652 reverse MW:16962 MPIATVCTWPAETEGGSTVVAADHASNYARKLGIQRDQLIQEWGWDEDTDDDIRAAIEEACGGELLDEDTDEVIDVVLLW (SEQ ID NO:527) WRDGDGDLVDTLMDAIGPLAEDGVIWVVTPKTGQPGHVLPAEIAEAAPTAGLMPTSSVNLGNWSASRLVQPKSRAGKR >BL;Rv2242, H37Rv2.tab 2515304:2516545 forward MW:44606 VNDNQLAPVARPRSPLELLDTVPDSLLRRLKQYSGRLATEAVSAMQERLPFFADLEASQRASVALVVQTAVVNFVEWMHD (SEQ ID NO:528) PHSDVGYTAQAFELVPQDLTRRIALRQTVDMVRVTMEFFEEVVPLLARSEEQLTALTVGILKYSRDLAFTAATAYADAAE ARGTWDSRMEASVVDAVVRGDTGPELLSRAAALNWDTTAPATVLVGTPAPGPNGSNSDGDSERASQDVRDTAARHGRAAL TDVHGTWLVAIVSGQLSPTEKFLKDLLAAFADAPVVIGPTAPMLTAAHRSASEAISGMNAVAGWRGAPRPVLARELLPER ALMGDASAIVALHTDVMRPLADAGPTLIETLDAYLDCGGAIEACARKLFVHPNTVRYRLKRITDFTGRDPTQPRDAYVLR VAATVGQLNYPTPH >BL;Rv2256c, H37Rv2.tab 2529344:2529874 reverse MW:18896 VEPKEQQMRASNQFADVTSGVVYIHASPAAVCPHVEWALSSTLQAKANLVWTPQPALPPQLRAVTNWVGPVGTGARLANA (SEQ ID NO:529) LRSWSVLRFEVTEDPSPGVDGQRFSHTPQLGLWSGAMSANGDIMVGEMRLRAMMAQGADTLAAELDSVLGTAWDQALEVY RDGGDAGEVTWLSRGVG >BL;Rv2257c, H37Rv2.tab 2530007:2530822 reverse MW:28385 MTALEVLGGWPVPAAAAAVIGPAGVLATHGDTARvFALASVTKPLVARAAQVAVEEGVVNLDTPAGPPGSTVRHLLAHTS (SEQ ID NO:530) GLAMHSDQALARPGTRRMYSNYGFTVLAESVQRESGIEFGRYLTEAVCEPLGMVTTRLDGGPAAAGFGATSTVADLAVFA GDLLRPSTVSAQMHADATTVQFPGLDGVLPGYGVQRPNDWGLGFEIENSKSPHWTGECNSTRTFGHFGQSGGFIWVDPKA DLALVVLTARDFGDWALDLWPAISDAVLAEYT >BL;Rv2342, H37Rv2.tab 2620272:2620526 forward MW:9187 LIGYVAVLGLGYVLGAKAGRRRYEQIASTYRALTGSPVARSMIEGGRRKIANRISPDAGFVTLAEIDNQTAVVQRGVERQ (SEQ ID NO:531) PKTAR >BL;Rv2347c, H37Rv2.tab 2626226:2626519 reverse MW:10977 MATRFMTDPHAMRDMAGRFEVHAQTVEDEARRMWASAQNISGAGWSGMAEATSLDTMAQMNQAFRNIVNMLHGVRDGLVR (SEQ ID NO:532) DANNYEQQEQASQQILSS >BL;Rv2365c, H37Rv2.tab 2646750:2647088 reverse MW:11130 MMRRPITLAEQLDAEDAKLVVLARAAMARAEAGAGAAVRDVDGRTYAAAPVALSALELTGLQAAVAAAVSSGATGLQAAV (SEQ ID NO:533) LVAGSVDDPGIAAVRELAPTAAIIVTDRAGNPL >BL;Rv2376c, H37Rv2.tab 2655612:2656115 reverse MW:16635 MKMVKSIAAGLTAAAAIGAAAAGVTSIMAGGPVVYQMQPVVFGAPLPLDPASAPDVPTAAQLTSLLNSLADPNVSFANKG (SEQ ID NO:534) SLVEGGIGGTEARIADHKLKKAAEHGDLPLSFSVTNIQPAAAGSATADVSVSGPKLSSPVTQNVTFVNQGGWMLSRASAN ELLQAAGN >BL;Rv2413c, H37Rv2.tab 2710354:2711301 reverse MW:33113 LHLVLGDEELLVERAVADVLRSARQRAGTADVPVSRMRAGDVGAYELAELLSPSLFAEERIVVLGAAAEAGKDAAAVIES (SEQ ID NO:535) AAADLPAGTVLVVVHSGGGRAKSLANQLRSMGAQVHPCARITKVSERADFIRSEFASLRvKVDDETVTALLDAVGSDVRE LASACSQLVADTGGAVDAAAVRRYHSGKAEVRGFDIADKAVAGDVAGAAEALRWAMMRGEPLVVLADALAEAVHTIGRVG PQSGDPYRLAAQLGMPPWRvQKAQKQARRWSRDTVATAMRLVAELNANVKGAVADADYALESAVRQVAELVADRGR >BL;Rv2446c, H37Rv2.tab 2745770:2746138 reverse MW:13311 MTDRSREPADPWKGFSAVMAATLILEAIVVLLAIPVVDAVGGGLRPASLGYLVGLAVLLILLTGLQRRPWAIWVNLGAQP (SEQ ID NO:536) VLVAGFAVYPGVCFIGVLFAALWVLIAYLRAEVRRRRDYRVSQ >BL;Rv2466c, H37Rv2.tab 2768264:2768884 reverse MW:23035 MLEKAPQKSVADFWFDPLCPWCWITSRWILEVAKVRDIEVNFHVMSLAILNENRDDLPEQYREGMARAWGPVRVAIAAEQ (SEQ ID NO:537) AHGAKVLDPLYTAMGNRIHNQGNHELDEVITQSLADAGLPAELAKAATSDAYDNALRKSHHAGMDAVGEDVGTPTIHVNG VAFFGPVLSKIPRGEEAGKLWDASVTFASYPHFFELKRTRTEPPQFD >BL;Rv2468c, H37Rv2.tab 2771647:2772147 reverse MW:17288 MTHRSSRLEVGPVARGDVATIEHAELPPGWVLTTSGRISGVTEPGELSVHYPFPIADLVALDDALTYSSRACQVRFAIYL (SEQ ID NO:538) GDLGRDTAARAREILGKVPTPDNAVLLAVSPNQCAIEVVYGSQVRGRGAESAAPLGVAAASSAFEQGELVDGLISAIRVL SAGIAPG >BL;Rv2476c, H37Rv2.tab 2777391:2782262 reverse MW:176902 MTIDPGAKQDVEAWTTFTASADIPDWISKAYIDSYRGPRDDSSEATKAAEASWLPASLLTPAMLGAHYRLGRHRAAGESC (SEQ ID NO:539) VAVYRADDPAGFGPALQVVAEHGGMLMDSVTVLLHRLGIAYAAILTPVFDVHRSPTGELLRIEPKAEGTSPHLGEAWMHV ALSPAVDHKGLAEVERLLPKVLADVQRVATDATALIATLSELAGEVESNAGGRFSAPDRQDVGELLRWLGDGNFLLLGYQ RCRVADGMVYGEGSSGMGVLRGRTGSRPRLTDDDKLLVLAQARVGSYLRYGAYPYAIAVREYVDGSVVEHRFVGLFSVAA MNADVLEIPTISRRVREALAMAESDPSHPGQLLLDVIQTVPRPELFTLSAQRLLTMARAVVDLGSQRQALLFLRADRLQY FVSCLVYMPRDRYTTAVRMQFEDILVREFGGTRLEFTARVSESPWALMHFMVRLPEVGVAGEGAAAPPVDVSEANRIRIQ GLLTEAARTWADRLIGAAAAAGSVGQADAMHYAAAFSEAYKQAVTPADAIGDIAVITELTDDSVKLVFSERDEQGVAQLT WFLGGRTASLSQLLPMLQSMGVVVLEERPFSVTRPDGLPVWIYQFKISPHPTIPLAPTVAERAATANRFAEAVTAIWHGR VEIDRFNELVMRAGLTWQQVVLLRAYAKYLRQAGFPYSQSYIESVLNEHPATVRSLVDLFEALFVPVPSGSASNRDAQAA AAAVAADIDALVSLDTDRILRAFASLVQATLRTNYFVTRQGSARCRDVLALKLNAQLIDELPLPRPRYEIFVYSPRVEGV HLRFGPVARGGLRWSDRRDDFRTEILGLVKAQAVKNAVIVPVGAKGGFVVKRPPLPTGDPAADRDATRAEGVACYQLFIS GLLDVTDNVDHATASVNPPPEVVRRDGDDAYLVVAADKGTATFSDIANDVAKSYGFWLGDAFASGGSVGYDHKAMGITAR GAWEAVKRHFREIGIDTQTQDFTVVGIGDMSGDVFGNGMLLSKHIRLIAAFDHRHIFLDPNPDAAVSWAERRRMFELPRS SWSDYDRSLISEGGGVYSREQKAIPLSAQVRAVLGIDGSVDGGAAEMAPPNLIRAILRAPVDLLFNGGIGTYIKAESESD ADVGDRANDPVRVNANQVRAKVIGEGGNLGVTALGRVEFDLSGGRINTDALDNSAGVDCSDHEVNIKILIDSLVSAGTVK ADERTQLLESMTDEVAQLVLADNEDQNDLMGTSRANAASLLPVHAMQIKYLVAERGVNRELEALPSEKEIARRSEAGIGL TSPELATLMAHVKLGLKEEVLATELPDQDVFASRLPRYFPTALRERFTPEIRSHQLRREIVTTMLINDLVDTAGITYAFR IAEDVGVTPIDAVRTYVATDAIFGVGHIWRRIRAANLPIALSDRLTLDTRRLIDRAGRWLLNYRPQPLAVGAEINRFAAM VKALTPRMSEWLRGDDKAIVEKTAAEFASQGVPEDLAYRVSTGLYRYSLLDIIDIADIADIDAAEVADTYFALMDRLGTD GLLTAVSQLPRHDRWHSLARLAIRDDIYGALRSLCFDVLAVGEPGESSEQKIAEWEHLSASRVARARRTLDDIRASGQKD LATLSVAARQIRRMTRTSGRGISG >BL;Rv2484c, H37Rv2.tab 2791022:2792494 reverse MW:52309 MAESGESPRLSDELGPVDYLMHRGEANPRTRSGIMALELLDGTPDWDRFRTRFENASRRVLRLRQKVVVPTLPTAAPRWV (SEQ ID NO:540) VDPDFNLDFHVRRVRVSGPATLREVLDLAEVILQSPLDISRPLWTATLVEGMADGRAAMLLHVSHAVTDGVGGVEMFAQI YDLERDPPPRSTPPQPIPEDLSPNDLMRRGINHLPIAVVGGVLDALSGAVSMAGRAVLEPVSTVSGILGYARSGIRVLNR AAEPSPLLRRRSLTTRTEAIDIRLADLHKAAKAGGGSINDAYLAGLCGALRRYHEALGVPISTLPMAVPVNLRAEGDAAG GNQFTGVNLAAPVGTIDPVARMKKIRAQMTQRRDEPAMNIIGSIAPVLSVLPTAVLEGITGSVIGSDVQASNVPVYPGDT YLAGAKILRQYGIGPLPGVAMMVVLISRGGWCTVTVRYDRASVRNDELFAQCLQAGFDEILALAGGPAPRVLPASFDTQG AGSVPRSVSGS >BL;Rv2507, H37Rv2.tab 2822438:2823256 forward MW:28520 MNDPRRPQRFGPPLSGYGPTGPQVPPNPPTADPAYADQSPYASTYGGYVSPPWSPGGPPPRPPQWPPGPHEASPTQQLPQ (SEQ ID NO:541) YWQYDQPPPGGFPPDGLTPPPPQGPRTPRWLWFAAGSAVLLVVALVIALVIANGSVKKQTAIEPLPPMPGPSPTRPTTTT PTPPSPSAAPAPTTTTGTPSETVAGAMQTVVYDVTGEGRAISITYMDSGNVIQTEFNVALPWRKEVSLSKSSLHPASVTI VNIGHNVTCSVTVAGVQVRQRTGAGLTICDAPS >BL;Rv2520c, H37Rv2.tab 2837391:2837615 reverse MW:8341 VVDRDPNTIKQEIDQTRDQLAATIDSLAERANPRRLADDAKTRVIAFLRKPIVTVSLVGIGSVVVVVVIHKIRNR (SEQ ID NO:542) >BL;Rv2525c, H37Rv2.tab 2849855:2850574 reverse MW:25369 MSVSRRDVLKFAAATPGVLGLGVVASSLRAAPASAGSLGTLLDYAAGVIPASQIRAAGAVGAIRYVSDRRPGGAWMLGKP (SEQ ID NO:543) IQLSEARDLSGNGLKIVSCYQYGKGSTADWLGGASAGVQHARRGSELHAAAGGPTSAPIYASIDDNPSYEQYKNQIVPYL RSWESVIGHQRTGVYANSKTIDWAVNDGLGSYFWQHNWGSPKGYTHPAAHLHQVEIDKRKVGGVGVDVNQILKPQFGQWA >BL;Rv2536, H37Rv2.tab 2860452:2861141 forward MW:24626 MTNWMLRGLAFAAAMVVLRLFQGALINAWQMLSGLISLVLLLLFAIGGVVWGVMDGRADAKASPDPDRRQDLAMTWLLAG (SEQ ID NO:544) LVAGALSGAVAWLISLFYKAIYTGGPINELTTFAAFTALIVFLVGIVGVAVGRWLVDRQLAKAPVRHHGLAAEHERAADT DVFSAVRADDSPTGEMQVAQPEAQTAAVATVEREAPTEVIRTTESDTPTEVIRTDTEADQTKPGDEPKKD >BL;Rv2588C, H37Rv2.tab 2915849:2916193 reverse MW:12966 MESFVLFLPFLLIMGGFMYFASRRQRRAMQATIDLHDSLQPGERVHTTSGLEATIVAIADDTIDLEIAPGVVTTWMKLAI (SEQ ID NO:545) RDRILPDDDIDEELNEDLDKDVDDVAGERRVTNDS >BL;Rv2609c, H37Rv2.tab 2936813:2937865 reverse MW:38096 MTWLVLAGAVLLVVLVAFGAWGYQTANRLNRLNVRYDLSWQSLDSALARRAVVARAVAIDAYGGAPQGSRLAALADAAEG (SEQ ID NO:546) APRHARENAENELSAALANVNPASLPAALIAELADAEARVLLARRFHNDAVRDTLALGERRLVRLLRLGGTAVLPTYFEI VERPHALVNGDQGASGRRTSARVVLLDDSGAVLLLCGSDPANPAFRDGAAPKWWFTVGGQVRPGERLAQAAARELAEETG LRVAPADMIGPIWRRDEVFEFNGSLIDSEEFYLVHRTRRFEPAVQGRTELERRYIRDARWCDANDIAQLVAAGERWPLQ LGELLPAANRLVDVALDNGAARDAGVPQPIR >BL;Rv2673, H37Rv2.tab 2989290:2990588 forward MW:48883 VYGALVTAADSIRTGLGASLLAGFRPRTGAPSTATILRSALWPAAVLSVLHRSIVLTTNGNITDDFKPVYRAVLNFRRGW (SEQ ID NO:547) DIYNEHFDYVDPHYLYPPGGTLLMAPFGYLPFAPSRYLFISINTAAILVAAYLLLRMFNFTLTSVAAPALILAMFATETV TNTLVFTNINGCILLLEVLFLRWLLDGRASRQWCGGLAIGLTLVLKPLLGPLLLLPLLNRQWRALVAAVVVPVVVNVAAL PLVSDPMSFFTRTLPYILGTRDYFNSSILGNGVYFGLPTWLILFLRILFTAITFGALWLLYRYYRTGDPLFWFTTSSGVL LLWSWLVMSLAQGYYSMMLFPFLMTVVLPNSVIRNWPAWLGVYGFMTLDRWLLFNWMRWGRALEYLKITYGWSLLLIVTF TVLYFRYLDAKADNRLDGGIDPAWLTPEREGQR >BL;Rv2680, H37Rv2.tab 2996104:2996733 forward MW:22555 LTSAGDDAERSDEEERRLTSAEPALFREAVAANNAVTVRPEIELGPIRPPQRLAPYSYALGAEIKHPELDVIPERSEGDA (SEQ ID NO:548) FGRLIMLYDPDGSDAWDGTIRLVAYVQADLDSSEAVDPLLPEVAWSWLVDALTARTDQVRALGGTVTATTSVRYGDISGP PRAHQLELRASWTATTPDLGAHVQAFCDVLEHAAGLPPAGVTDLGSRSRA >BL;Rv2683, H37Rv2.tab 3000111:3000605 forward MW:17729 MKVNIDPTAPTFATYRRDMRAEQMAEDYPVVSIDSDALDAARMLAEHRLPGLLVTAGAGKQYAVLPASQVVRFIVPRYVQ (SEQ ID NO:549) DDPLLAGVLNESTADRCAERLSGKKVRDVLPDHLVEVPPANADDTIIEVAAVMARLRSPLLAVVKDGSLLGVVTASRLLA AALKT >BL;Rv2695, H37Rv2.tab 3011915:3012619 forward MW:24154 MAVDLDGVTTVLLPGTGSDNDYVRRAFSAPLRRAGAVLVTPVPHPGRLIDGYRAALDDAARDGPVVVGGVSLGAAVAAAW (SEQ ID NO:550) ALEHPDRAVAVLAALPAWTGEPELAPAAQAARYTAARLRCDGLAATTTRMRASSPVWLAEELTRSWRVQWPELPDAMEEA AAYVAPSRAELARLVAPLAVAAAVDDPIHPLQVAADWVSVAPHAALRTVTLDEIGADAAALGSACLAALAEVSGA >BL;Rv2696c, H37Rv2.tab 3012831:3013607 reverse MW:27216 MAFGRRTGKDGGKRKAGHAPVQPADEHVRPEDTVVASAAAASGVEDQEELQGPFDIDDFDDPSVAVLARLDLGSVLIPMP (SEQ ID NO:551) AAGQVQVELTESGVPSAVWVITPNGRYSIAAYAAPKTGGLWREVAGELADSLRKDSAKVSIKDGPWGREVIGIAAGVVRF IGVDGYRWNIRCVVNGPQETVDALTEEAREALADTVVRRGDTPLPVRTPLPVHLPEPMAAQLREAAAAQADTQRQAAAGV ARRGAQGSAMQQLRSTTGG >BL;Rv2698, H37Rv2.tab 3014172:3014654 forward MW:17530 VSGTRLAPHSVRYRERLWVPWWWWPLAFALAALIAFEVNLGVAALPDWVPFATLFTVAAGTLLWLGRVEIRVTAGSADGA (SEQ ID NO:552) GVKLWAGPAHLPVAVIARSAEIPATAKSAALGRQLDPAAYVLHRAWVGPMVLVVLDDPNDPTPYWLVSCRHPERVLSALR S >BL;Rv2699c, H37Rv2.tab 3014665:3014964 reverse MW:10915 MPTDYDAPRRTETDDVSEDSLEELKARRNEAASAVVDVDESESAESFELPGADLSGEELSVRVVPKQADEFTCSSCFLVQ (SEQ ID NO:553) HRSRLASEKNGVMICTDCAA >BL;Rv2700, H37Rv2.tab 3015202:3015849 forward MW:22627 VVAQITEGTAFDKHGRPFRRRNPRPAIVVVAFLVVVTCVMWTLALTRPPDVREAAVCNPPPQPAGSAPTNLGEQVSRTDM (SEQ ID NO:554) TDVAPAKLSDTKVHVLNASGRGGQAADIAGALQDLGFAQPTAANDPIYAGTRLDCQGQIRFGTAGQATAAALWLVAPCTE LYHDSRADDSVDLALGTDFTTLAHNDDIDAVLANLRPGATEPSDPALLAKIHANSC >BL;Rv2708c, H37Rv2.tab 3021550:3021795 reverse MW:8962 MSGMQTQTIERTDADERVDDGTGSDTPKYFHYVKKDKIAESAVMGSHVVALCGEVFPVTRAPKPGSPVCPDCKRIYDTLK (SEQ ID NO:555) KG >BL;Rv2709, H37Rv2.tab 3021838:3022281 forward MW:16810 MWDSRVNKHGLRLGFNGQFDDFDDFDDKGRPVLITAAAPSYEVEHRTRVRKYLTLMAFRVPALILAAIAYGAWHNGLISL (SEQ ID NO:556) LIVAASVPLPWMAVLIANDRPPRRADEPRRFDVARRRIPLFPTAERPALEPRRQPAERSAPRGFADHG >BL;Rv2714, H37Rv2.tab 3027064:3028035 forward MW:35520 MARDQGADEAREYEPGQPGMYELEFPAPQLSSSDGRGPVLVHALEGFSDAGHAIRLAAAHLKAALDTELVASFAIDELLD (SEQ ID NO:557) YRSRRPLMTFKTDHFTHSDDPELSLYALRDSIGTPFLLLAGLEPDLKWERFITAVRLLAERLGVRQTIGLGTVPMAVPHT RPITMTAHSNNRELISDFQPSISEIQVPGSASNLLEYRMAQHGHEVVGFTVHVPHYLTQTDYPAAAQALLEQVAKTGSLQ LPLAVLAEAAAEVQAKIDEQVQASAEVAQVVAALERQYDAFIDAQENRSLLTRDEDLPSGDELGAEFERFLAQQAEKKSD DDPT >BL;Rv2715c, H37Rv2.tab 3031042:3031536 reverse MW:17324 MTPVRPPHTPDPLNLRGPLDGPRWRRAEPAQSRRPGRSRPGGAPLRYHRTGVGMSRTGHGSRPVPPATTVGLALLAAAIT (SEQ ID NO:558) LWLGLVAQFGQMITGGSADGSADSTGRvPDRLAVVRvETGESLYDVAVRvAPNAPTRQVADRIRELNGLQTPALAVGQTL IAPVG >BL;Rv2722, H37Rv2.tab 3034634:3034879 forward MW:9077 MPCLARQPVDLPPWAGPRCGPYCPRARITLLQRTTIAKSNRKYYENGYPADVKLMPGHAAVVSNRAAARAGFALPCRKRQ (SEQ ID NO:559) PD >BL;Rv2728c, H37Rv2.tab 3040768:3041460 reverse MW:23455 VLSAIGIVPSAPVLVPELAGAAAAELADLGAAVIAAASLLPKSWIAVGTGRADDVVRPTDVGTFAGFGADVRVGLAPQDG (SEQ ID NO:560) DGVAVPVELPLCALLTAWVRGQARPEARAQVHVYASDHGSDAAVARGRQLRADIDREPDPIGVLVVADGLNTLTPRAPGG YDPDGAGMQRALDDALASGDLAVLTRLPAQVLGRvAFQVLAGLAEPGPRSAKEFYRGAPHGVGYFAGVWQP >BL;Rv2732c, H37Rv2.tab 3044377:3044988 reverse MW:21989 MMSHEHDAGDLDALRAEIEAAERRvAREIEPGARALVVAILVFVLLGSFILFHTGSVRGWDVLFSSHGAGRAAVALPSRV (SEQ ID NO:561) FAWLALVFGVGFSMLALLTRRWALAWVALAGSANASGTGLLAVWSRQTVAAGHPGPGIGLIVAWITAIVLTFXWAQVVWS RTIVQLAAEERRRRVVAQQQCKTLLDHVQTDSEAGTTPDRGTDR >BL;Rv2738c, H37Rv2.tab 3051808:3052011 reverse MW:7551 MLAGVRLTEFHERVALHFGAAYGSSVLLDHVLTGFDGRSAAQAIEDGVEPRDVWRALCADFDVPHDRW (SEQ ID NO:562) >BL;Rv2740, H37Rv2.tab 3053232:3053678 forward MW:16593 MAELTETSPETPETTEAIRAVEAFLNALQNEDFDTVDAALGDDLVYENVGFSRIRGGRRTATLLRRMQGRVGFEVKIHRI (SEQ ID NO:563) GADGAAVLTERTDALIIGPLRvQFWVCGVFEVDDGRITLWRDYFDVYDMFKGLLRGLVALVVPSLKATL >BL;Rv2771c, H37Rv2.tab 3080583:3081032 reverse MW:16000 VRRLLIVHHTPSPHMQEMFEAVVSGATDPEIEGVEVVRRPALTVSPIEMLEADGYLLGTPANLGYISGALKHAFDVCYYL (SEQ ID NO:564) CLDTTRGRSFGAYIHGNEGTEGAERAVDAITTGLGWVQAAETVVVMGKPSKADIEACWNLGATVAAQLMG >BL;Rv2772c, H37Rv2.tab 3081121:3081591 reverse MW:17326 MTRRTLYVQLIIAFMCVAMVAYLVMLGRvAVAMIGSGRAAAAGLGLALLILPVIGLWANIATLRAGFAYQRLARLIAEDG (SEQ ID NO:565) LDIDASALPRRASGRIQRDAADALFAAVRTELEDDADDWRRWYRLARAYDYAGDRRRAREANKTALQLEGRARPGAR >BL;Rv2795c, H37Rv2.tab 3103939:3104910 reverse MW:37568 VTWKGSGQETVGAEPTLWAISDLHTGHLGNKPVAESLYPSSPDDWLIVAGDVAERTDEIRWSLDLLRRRFAKVIWVPGNH (SEQ ID NO:566) ELWTTNRDPMQIFGRARYDYLVNMCDEMGVVTPEHPFPVWTERGGPATIVPMFLLYDYSFLPEGANSKAEGVAIAKERNV VATDEFLLSPEPYPTRDAWCHERVAATRARLEQLDWMQPTVLVNHFPLLRQPCDALFYPEFSLWCGTTKTADWHTRYNAV CSVYGHLHIPRTTWYDGVRFEEVSVGYPREWRRRKPYSWLRQVLPDPQYAPGYLNDFGGHFVITPEMRTQAAQFRERLRQ RQSR >BL;Rv2840c, H37Rv2.tab 3147961:3148257 reverse MW:10601 VRTCVGCRKRGLAVELLRvVAVSTGNGNYAVIVDTATSLPGRGAWLHPLRQCAQQAIRRAFARALRIAGSPDTSAVVEY (SEQ ID NO:567) LESLGELEPPGNRTGSNRT >BL;2V2843, H37Rv2.tab 3150170:3150712 forward MW:17735 VLPAAPVINRLTNRPISRRGVLAGGAALAALGVVSACGESAPKAPAVEELRSPLDQARHDGALAAAAATAIGIPPQVAAA (SEQ ID NO:568) LTVVATQRTSHARALATEIARAAGKLVSATSETSSSSPSPTDPAAPPPAVSDVIDSLRTSAGEASRLVATTSGYRAGLLA SIAASCTASYTVALVPSGPSI >BL;Rv2844, H37Rv2.tab 3150712:3151197 forward MW:16940 MTSSEPAHGATPKRSPSEGSADNAALCDALAVEHATIYGYGIVSALSPPGVNFLVADALKQHRHRRDDVIVMLSARGVTA (SEQ ID NO:569) PIAAAGYQLPMQVSSAANAARLAVRMENDGATAWRAVVEHAETADDRvFASTALTESAVMATRWNRvLGAWPITAAFPGG DE >BL;Rv2876, H37Rv2.tab 3187662:3187973 forward MW:11805 MFGQWEFDVSPTGGIAVASTEVEHFAGSQHEVDTAEVPSAAWGWSRIDHRTWHIVGLCIFGFLLAMLRGNHVGHVEDWFL (SEQ ID NO:570) ITFAAVVLFVLARDLWGRRRGWIR >BL;Rv2898c, H37Rv2.tab 3207944:3208327 reverse MW:14223 MTTLKTMTRVQLGAMGEALAVDYLTSMGLRILNRNWRCRYGELDVIACDAATRTVVFVEVKTRTGDGYGGLAHAVTERKV (SEQ ID NO:571) RRLRRLAGLWLADQEERWAAVRIDVIGVRVGPKNSGRTPELTHLQGIG >BL;Rv2901C, H37Rv2.tab 3211805:3212107 reverse MW:12225 MSAEDLEKYETEMELSLYREYKDIVGQFSYVVETERRFYLANSVEMVPRNTDGEVYFELRLADAWVWDMYRPARFVKQVR (SEQ ID NO:572) VVTFKDVNIEEVEKPELRLPE >BL;Rv2917, H37Rv2.tab 3226362:3228239 forward MW:68334 VRVTRLVDAESTRCDVGPAPKSVANLHFTAATSRFRLGRERANSVRSDGGWGVLQPVSATFNPPLRGWQRRALVQYLGTQ (SEQ ID NO:573) PRDFLAVATPGSGKTSFALRIAAELLRYHTVEQVTVVVPTEHLKVQWAHAAAAHGLSLDPKFANSNPQTSPEYHGVMVTY AQVASHPTLHRVRTEARKTLVVFDEIHNGGDAKTWGDAIREAFGDATRRLALTGTPFRSDDSPIPFVSYQPDADGVLRSQ ADHTYGYAEALADGVVRPVVFLAYSGQARWRDSAGEEYEARLGEPLSAEQTARAWRTALDPEGEWMPAVITAADRRLRQL RAHVPDAGGMIIASDRTTARAYARLLTTMTAEEPTVVLSDDPGSSARITEFAQGTSRWLVAVRMVSEGVDVPRLSVGVYA TNASTPLFFAQAIGRFVRSRRPGETASIFVPSVPNLLQLASALEVQRNHVLGRPHRESAHDPLDGDPATRTQTERGGAER GFTALGADAELDQVIFDGSSFGTATPTGSDEEADYLGIPGLLDAEQMRALLHRRQDEQLRKRAQLQKGATQPATSGASAS VHGQLRDLRRELHTLVSIAHHRTGKPHGWIHDERRRRCGGPPIAAATRAQIKARIDALRQLNSERS >BL;Rv2926c, H37Rv2.tab 3240550:3241170 reverse MW:22378 VDLGGVRRRISLMARQHGPTAQRHVASPMTVDIARLGRRPGAMFELHDTVHSPARIGLELIAIDQGALLDLDLRVESVSE (SEQ ID NO:574) GVLVTGTVAAPTVGECARCLSPVRGRVQVALTELFAYPDSATDETTEEDEVGRVVDETIDLEQPIIDAVGLELPFSPVCR PDCPGLCPQCGVPLASEPGHRHEQIDPRWAKLVEMLGPESDTLRGER >BL;Rv2949c, H37Rv2.tab 3299973:3300569 reverse MW:22587 MTECFLSDQEIRKLNRDLRILIAANGTLTRVLNIVADDEVIVQIVKQRIHOVSPKLSEFEQLGQVGVGRVLQRYIILKGR (SEQ ID NO:575) NSEHLFVAAESLIAIDRLPAAIITRLTQTNDPLGEVMAASHIETFKEEAKVWVGDLPGWLALHGYQNSRKRAVARRYRVI SGGQPIMVVTEHFLRSVFRDAPHEEPDRWQFSNAITLAR >BL;Rv2968c, H37Rv2.tab 3323073:3323702 reverse MW:23100 VVAARPAERSGDPAAVRVPVPSAWWVLIGGVIGLFASMTLTVEKVRILLDPIYVPSCNVNPIVSCGSVMTTPQASLLGFP (SEQ ID NO:576) NPLLGIAGFTVVVVTGVLAVAKVPLPRWYWIGLAVGILVGVAFVHWLIPQSLYRIGALCPYCMVVWAVIATLLVVVASIV FGPMRENRGSQERvGARLLYQWRWSLATLWFTTVFLLIMVRFWDYWSTLI >BL;Rv2980, H37Rv2.tab 3335959:3336501 forward MW:18752 VTGESDGPPRAVLIAAAALAAAVIGVILVVAANRQPPERPVVIPAVPAPQATGPGCKALLAALPQRLGEYPRAPVAEPTT (SEQ ID NO:577) AGATAWRTGPNSTPVILRCGLDRPAEFVVGSAIQVVDRVQWFQVAAQNPDEPGRSTWYTVDRPVYVALTLPSGSGPTAIQ ELSDVIDHTIPAVPIOPAPAR >BL;Rv3005c, H37Rv2.tab 3363695:3364531 reverse MW:28827 VTSSNDSHWQRPDDSPGPMPGRPVSASLVDPEDDLTPARYAGDFGSGTTTVIPPYDAASSGVGNSGYSLIEAAEPLPYVQ (SEQ ID NO:578) PQPGRQVPAGSAGIDMDDDERVRAAGRRGTQNLGLLILRVGLGAVLIAHGLQKLFGWWDGQGLAGFQNSLSDIGYQHAEI LAYVSAGGEIVAGVLLVLGLFTPLAAAGALAFLINGLLAGISAQHSRPVAYFLQDGHEYQITLVVMAVAVILSGPGRYGL DAARGWAHRPFIGSFVALLGGIAAGIAVWVLLNGANPLA >BL;Rv3013, H37Rv2.tab 3371814:3372467 forward MW:22967 VRSYLLRIELADRPGSLGSLAVALGSVGADILSLDVVERGNGYAIDDLVVELPPGAMPDTLITAAEALNGVRVDSVRPHT (SEQ ID NO:579) GLLEAHRELELLDHVAAAEGATARLQVLVNEAPRVLRVSWCTVLRSSGGELHRLAGSPGAPETRANSAPWLPIERAAALD GGADWVPQAWRDMDTTMVAAPLGDTHTAVVLGRPGPEFRPSEVARLGYLAGIVATMLR >BL;Rv3015c, H37Rv2.tab 3374653:3375663 reverse MW:34212 VSVFATATGIGSWPGTAAREAAQVVVGELAGALAYLTELPARGVGADMLGRAGGLLVDVAIDTVPRGYRIAARPGAVTRR (SEQ ID NO:580) AASLLDEDMDALEEAWETAGLRGCGRAVKVQAPGPVTLVAGLELANGHRAITDPGAVRDLAASLAEGVAAHRAALARRLD TPVVVQFDEPSLPAALGGRLTGVTALSPVAPLDETVAEALLDTCIAAVDADVALHSCSPDLPWDLLQRSRISAVSVDAST LQAADLDAVAAFVESGRTVVLGLVPVTAPERAPSMEEVAAAAVAVTDRLGVPRSALRDRLGVSPACGLANATGQWARTAV GLARDVAEAFARDPEAI >BL;Rv3035, H37Rv2.tab 3395378:3396457 forward MW:37305 LAAGPALSARGYLALNGQTPAGCSLMEWQNDNNGRQRWCVRLVQGGGFAGPLFDGFDNLYVGQPGAIISFPPTQWTRWRQ (SEQ ID NO:581) PVIGMPSTPRFLGHGRLLVSTHLGQLLVFDTRRGMVVGSPVDLVDGIDPTDATRGLADCAPARPGCPVAAAPAFSSVNGT VVVSVWQPGEPAAKLVGLKYHAEQLVREWTSDAVSAGVLASPVLSADGSTVYVNGRDHRLWALNAADGKAKWSAPLGFLA QTPPALTPHGLIVSGGGPDTALAAFRDAGDHAEGAWRRDDVTALSTASLAGTGVGYTVISGPNHDGTPGLSLLVFDPANG HTVNSYPLPGATGYPVGVSVGNDRRvVTATSDGQVYSFAP >BL;Rv3038c, H37Rv2.tab 3398427:3399407 reverse MW:36049 MTRSSNIPADATPNPHATAEQVAAARHDSKLAQVLYHDWEAENYDEKWSISYDQRCVDYARGRFDAIVPDEVIAQLPYDR (SEQ ID NO:582) ALELGCGTGFFLLNLIQAGVARRGSVTDLSPGMVKVATRNGQALGLDIDGRvADAEGIPYDDDAFDLVVGHAVLHHIPDV ELSLREVVRVLKPGGRFVFAGEPTTVGDGYARTLSTLTWRVVTNATKLPGLRGWRRPQGELDESSRAAALEALVDLHTFT PQDLQRIAHNAGAVEVQTATEEFTAANLGWPLRTFECTVPPGRLGWGWARFAFTSWKTLGWVDANVWRHVVPKGWFYNVM ITGVKPS >BL;Rv3195, H37Rv2.tab 3564363:3565778 forward MW:49325 VSTGEVMGDLPFGFSSGDDPPEDPSGRDKRGKDGADSGSGANPLGAFGIGGEFNMADLGQIFTRLGEMFGGVGTAMAAGK (SEQ ID NO:583) TSGPVNYDLARQVASSSIGFIAPIPAATNSAIADAVHLADTWLDGATSLPAGATKAVGWSPTDWVDNTLATWKRLCDPMA QQISTVWASSLPEEAKSMAGPLLSIMSQMGGIAFGSQLGQALGRLSREVLTSTDIGLPLGPKGVAAILPGAVESFAAGLE QPRSEILTFLATREAAHHRLFSHVPWLASQLLGAVEAYAMGMKIDMTGIEELARDINPTSLADPAAMEQLLSQGVFEPKA TPAQTQALERLETLLALIEGWVQTVVTAALGERIPGEAALSETLRRRRASGGPAEQTFATLVGLELRPRKLREAGALWER LTRAVGMDARDAVWQHPDLLPATDDLDDPAAFIDRvIGGDTSGIDEAIAELERDQQARGADDSGHDGGPVDN >BL;Rv3205c, H37Rv2.tab 3581629:3582504 reverse MW:31352 MGSTRLTGVNVEPPPEHVLVAFGLAGAQPILLGAGWEGGWRCGEVVLSMVADNARAAWSARvRETLFVDGVRLARPVRST (SEQ ID NO:584) DGRYVVSGWRADTFVAGAPEPRHDEVVSAAVRLHEATGKLERPRFLTQGPAAPWAEIDVFVAADRAGWEERPLQSVPPGV PTAPPAADPQRSIDLINQLAGLRKPTKSPNQLVUGDLYGTVLFAGTAPPGITDITPYWRPASWAAGVAVVDALSWGAADD GLIERWNALPEWPQMLLRALMFRLAVYALHPRSTAEAFPGLAHTAALVRLVL >BL;2V3207c, H37Rv2.tab 3583803:3584657 reverse MW:31034 VSTYGWRAYALPVLMVLTTVVVYQTVTGTSTPRPAAAQTVRDSPAIGVVGTAILDAPPRGLAVFDANLPAGTLPDGGPFT (SEQ ID NO:585) EAGDKTWRvVPGTTPQVGQGTVKVFRYTVEIENGLDPTMYGGDNAFAQMVDQTLTNPKGWTHNPQFAFVRIDSGKPDFRI SLVSPTTVRGGCGYEFRLETSCYNPSFGGMDRQSRVFINEARWVRGAVPFEGDVGSYRQYVINHEVGHAIGYLRHEPCDQ QGGLAPVMMQQTFSTSNDDAAKFDPDFVKADGKTCRFNPWPYPIP >BL;Rv3208c, H37Rv2.tab 3585679:3585948 reverse MW:9400 VEVKIGITDSPRELVFSSAQTPSEVEELVSNALRDDSGLLTLTDERGRRFLIHTARIAYVEIGVADARRvGFGVGVDAAA (SEQ ID NO:586) GSAGKVATSG >BL;Rv3209, H37Rv2.tab 3586273:3586830 forward MW:19118 VALGAVATAVIINSGDSTSTKAIVGAPAPRTVISTSPRPTAPTSTSPHPSPSTLRPQLPPETVTTVAPPGTGPTTVPTRT (SEQ ID NO:587) PTAAPPQTAVPPPAPLNPRTVVYRvTGTKQLFDLVNVVYTDARGFPVTDFNVSLPWTKMVVLNPGVQTESVVATSLYSRL NCSIVNTGAQTVVASTNNAIIATCTR >BL;Rv3212, H37Rv2.tab 3589393:3590613 forward MW:42506 MVKPERRTKTDIAAAATIAVVVAVAASLIWWTSDARATISRPAAVAVPTPAPAREVPTSLKQLWTAASPATRVPVVVGGT (SEQ ID NO:588) VATGDGRQVDGRDPATGESLWSYARDTDLCGVTWVYHYAVAVYRYDRGCGQVSTIDGSTGRRGAARSGYADPRVRLPSDG TTVLSAGDTRLELWRSDMVRMLAYGEIDARVKPSNRGLQSGCTLESAAASSAAVSVLEACTNQADLRLVLLRPGKEDDEP IQRIVPEPGVRPGSGARVLVVSQNNTAVYLPARSGAQPRVDVIDETGATVSSTLLAKPPSTSAVASRTGNLVTWWTGDAL LVFDAGNLTQRYTIAAGETTAPVGPGVMMAGQLLVPVTGGIGVYDPVSGANNRYIPVTRPPSTSAVIPAVSGSRVIEQRG DTLVALG >BL;Rv3217C, H37Rv2.tab 3593806:3594234 reverse MW:14260 VPVRAPAAVRGAGLIVAVQGGAALVVAAALLVRGLAGADQHIVNGLGTAGWFVLVGGAVLAAGCRLAVGKLWGRGLAVFA (SEQ ID NO:589) QLLLLPVAWYLIVGSHQPAIGIPVGIIALGVLVLLFSPPSIRWAAGRDQRGAASAANRGPDSR >BL;Rv3242C, H37Rv2.tab 3621572:3622210 reverse MW:22481 VLDLVLPLECGGCGAPATRWCAACAAELSVAAGEPHVVSPRVDPQVPVFALGRYAGVRRQAILAMKEHGRRDLVAPLACA (SEQ ID NO:590) LIVGVDHLLSWGMLENPLTMVPAPTRRWAARRRGGDPVSRMARIAGATLGRHHDVTVVPALRMRALARDSVGLGASARER NITGRVLLRGQRPRNEVVLVDDIITTGATARESVRVLQAAGVRVGAVLAVAAA >BL;Rv3256c, H37Rv2.tab 3636277:3637314 reverse MW:35277 VNVARAIDLEDTEGLIAADRGALLRAASMAGAQVRAIAAAADEGELDLLRGSDRPRSVIWVTGRGTAETAGTILASTLGA (SEQ ID NO:591) GAAEPIVLASAAPPWVGPLDVLIVAGDDPGDPALVGAAAIGVRRGARVVVVAPYEGPLRDSTAGRVAVLEPRLRVPDEFG LSRYLAAGLAALQTVDPKLRIDLASLADELDAEALRNSAGREVFTNPAKALAARVSGCQLALAGDNAATLALARHGSSVM LRIANQVVAATRLSDAVVALRAGTPPDALFHDEEIDGPAPQRLRvLALALAGERTVVAARVAGLDDAYLVAAEDVPELLD APVGSGGAVLAVRLEMAAVYLRLVRG >BL;2V3258c, H37Rv2.tab 3638813:3639301 reverse MW:16810 MRVSGASAALVHDSLSVVNVPRRCCRPGCPHYAVATLTFVYSDSTAVIGPLATAREPHSWDLCVGHAGRITAPRGWELVR (SEQ ID NO:592) HAGPLPSHPDEDDLVALADAVREGGPSAGRRHHPGGNGAPLHGFDDFPAAATGAPTGGGVLAPPEPGAGRRRGHLRVLPD PAD >BL;Rv3259, H37Rv2.tab 3639424:3639840 forward MW:15649 MRGPLLPPTVPGWRSRAERFDMAVLEAYEPIERRWQERVSQLDIAVDEIPRIAAKDPESVQWPPEVIADGPIALARLIPA (SEQ ID NO:593) GVDVRGNATRARIVLFRKPIERRAKDTEELGELLHEILVAQVAIYLDVDPSVIDPTIDD >BL;Rv3269, H37Rv2.tab 3650233:3650511 forward MW:9750 MAIQVFLAKATTTVITGLAGVTAYEILKKAAAKAPLRQTAVSAAALGLRGTRKAEEAAESARLKVADVMAEARERIGEES (SEQ ID NO:594) PTPAISDLHDHDH >BL;Rv3277, H37Rv2.tab 3659877:3660692 forward MW:30079 MNEVTAGVRELATAIMVSRHLTGVLAGHGSQTVTYHFASILCSSVHSLVVSFADATIARLPGVVQPYAQRHHELIKFAIV (SEQ ID NO:595) GGTTFIIDTAIFYTLKLTVLEPKPVTAKVIAGIVAVIASYVLNREWSFRDRGGRERHHEALLFFAFSGVGVLLSMAPLWF SSYILQLRVPTVSLTMENIADFISAYIIGNLLQMAFRFWAFRRWVFPDEFARNPDKALESALTAGGIAEVFEDVLEGGFE DGNVTLLRAWRNRANRFAQLGDSSEPRvSKTS >BL;Rv3278C, H37Rv2.tab 3660653:3661168 reverse MW:19820 MSYPENVLAAGEQVVLHRHPHWNRLIWPVVVLVLLTGLAAFGSGFVNSTPWQQIAKNVIHAVIWGIWLVIVGWLTLWPFL (SEQ ID NO:596) SWLTTHPVVTNRRvMFRHGVLTRSGIDIPLARINSVEFRDRIFERIFRTGTLIIESASQDPLEFYNIPRLREVHALLYHE VFDTLGSDESPS >BL;Rv3281, H37Rv2.tab 3663688:3664218 forward MW:19013 MGTCPCESSERNEPVSRVSGTNEVSDGNETNNPAEVSDGNETNNPAEVSDGNETNNPAPVSRVSGTNEVSDGNETNNPAP (SEQ ID NO:597) VSRvSGTNEVSDGNETNNPAPVTEKPLHPHEPHIEILRGQPTDQELAALIAVLGSISGSTPPAQPEPTRWGLPVDQLRYP VFSWQRITLQEMTHMRR >BL;Rv3311, H37Rv2tab 3698120:3699379 forward MW:45732 MVADLVPIRLSLSAGDRYTLWAPRWRDAGDEWEAFLGKDDDLYGFESVSDLVAFVRTDTENDLVDHPAWQDLTGAHAHNL (SEQ ID NO:598) NPAEDNQFDLVVVEELLAEKPTAESVAALAASLAIVSAIGSVCELAAVSKFFNGNPILGTVSGGLEHFTGKAGNKRWNSI AEVIGRSWDDVLAAIDEIISTPEVDAELSEKVAEELAEEPEGAEEVAAEVEATQDTQEAAESDDEEADAPGDSVVLGGDR DFWLQVGIDPIQIMTGTATFYTLRCYLDDRPIFLGRNGRISVFGSERALARYLADEHDHDLSDLSTYDDIRTAATDGSLA VAVTDDNVYVLSGLVDDFADGPDAVDREQLDLAVELLRDIGDYSEDSAVDKALETTRPLGQLVAYVLDPHSVGKPTAPYA AAVREWEKLERFVESRLRRE >BL;Rv33S4, H37Rv2.tab 3769110:3769496 forward MW:12987 MNLRRHQTLTLRLLAASAGILSAAAFAAPAQANPVDDAFIAALNNAGVNYGDPVDAKALGQSVCPILAEPGGSFNTAVAS (SEQ ID NO:599) VVARAQGMSQDMAQTFTSIAISMYCPSVMADVASGNLPALPDMPGLPGS >BL;Rv3368c, H37Rv2.tab 3780337:3780978 reverse MW:23733 MTLNLSVDEVLTTTRSVRKRLDFDKPVPRDVLMECLELALQAPTGSNSQGWQWVFVEDAAKKKAIADVYLANARGYLSGP (SEQ ID NO:600) APEYPDGDTRGERMGRVRDSATYLAEHMHRAPVLLIPCLKGREDESAVGGVSFWASLFPAVWSFCLALRSRGLGSCWTTL IILLDNGEHKVADVLGIPYDEYSQGGLLPIAYTQGIDFRPAKRLPAESVTHWNGW >BL;Rv3412, H37Rv2.tab 3831725:3832132 forward MW:15269 VRDHLPPGLPPDPFADDPCDPSAALEAVEPGQPLDQQERMAVEADLADLAVYEALLAHKGIRGLVVCCDECQQDHYHDWD (SEQ ID NO:601) MLRSNLLQLLIDGTVRPHEPAYDPEPDSYVTWDYCRGYADASLNEAAPDADRFRRR >BL;Rv3415c, H37Rv2.tab 3833696:3834520 reverse MW:28627 VNETPHAPVVEQVLVAAAFGNQPGSWPLPTAITPHHLWLRAVAAGGQGRYAHAYGDLSVLRRLVPAGPLASLAHSTQGSL (SEQ ID NO:602) LRQLGWHTLARGWDGRALALAGADREAGADALIGLAADALGVGRFAAAGALLDRADPLVVSPLVADRLAVRRRWVAAELA MATGDGATAVRHAEEAVELTQAMAVASARHRvKSDVVLAAALCSAGAVARARAVGEEALDATARFGLLPLRWALACLLID IGTVTFSAQQLRELTKIRNICAGQVRRAGGCWRTA >BL;Rv3438, H37Rv2.tab 3857396:3858235 forward MW:29209 VPRIRKLVAALHRRGPHRVLRGDLAFAGLPGVVYTPEAGLHLPGVAFGHDWLTGTSRYSGLLEHLASWGIVAAAPDSERG (SEQ ID NO:603) LAPSVLNLAFDLGVALDIVAGVRLGPGKISVHPAKLGLVGHGFGGSAAVFAAAGLTGTHVKSVAAIFPTVTNPAAEQPAA TLDVPGLILTAPGDPKTLTSNALGLSRAWDKATLRIVSKARAGGLVEGRRLTKVLGLPGPHRRTQRSVRALLTGYLLYTL GGDKTYRRFADPDLQLPKTDPIDPEAPPITPGEKIVTLLK >BL;Rv3587c, H37Rv2.tab 4028971:4029762 reverse MW:27067 VLDLEPRGPLPTEIYWRRRGLALGIAVVVVGIAVAIVIAFVDSSAGAKPVSADKPASAQSHPGSPAPQAPQPAGQTEGNA (SEQ ID NO:604) AAAPPQGQNPETPTPTAAVQPPPVLKEGDDCPDSTLAVKGLTNAPQYYVGDQPKFTMVVTNIGLVSCKRDVGAAVLAAYV YSLDNKRLWSNLDCAPSNETLVKTFSPGEQVTTAVTWTGMGSAPRCPLPRPAIGPGTYNLVVQLGNLRSLPVPFILNQPP PPPGPVPAPGPAQAPPPESPAQGG >BL;Rv3603c, H37Rv2.tab 4045210:4046118 reverse MW:31104 MERFDGLRPARLKVGIISAGRVGTALGVALQRADHVVVACSAISHASRRRAQRRLPDTPVLPPLDVAASAELLLLAVTDS (SEQ ID NO:605) ELAGLVSGLAATSAVRPQTIVAHTSGANGIGILAPLAQQGCIPLAIHPAMTFTGSDEDISRLPDTCFGITAADDVGYAIG QSLVLEMGGEPFCVREDARILYHAALAHASNHIVTVLADALEALRAALSGGELLGQQTVDDQPGGIVERIVGPLARAALE NTLQRGQAALTGPVARGDAAAVADHLAALADVDAALAQAYRINALRTAQRAHAPADVVEVLTA >BL;Rv3604c, H37Rv2.tab 4046306:4047691 reverse MW:49862 VPRAASAMAEPAMGVGRRRCWPGGRPGMRGCLRGEFGRTAYPAKPCGNRRTGATRGLTSPGYSQAMTVLSRGARVRRGGR (SEQ ID NO:606) RPGWVLLTALLVLAIGASSALVFTDRVELLKLAVLLALWAAVAGAFVSVLYRRQSDVDQARVRDLKLVYDLQLDREISAR REYELTLESQLRRELASELRAPAADEVAALRAELAALRTSLEILFDADLEHRPALGTVEKEARAARALDGESPPADWVSS DRVMAVRGGDGASRTDEASIIDVPEVGVPPVSGGPRHYEAPPPPQPEPLFEPRHRPPPLPPQQERPVWQPVTSHGQWLPA ETPGSQWASVEPETTPAAPPPGRRRRARHASPADQAYNPPAYVELAAQYGESGRRSRHSAEHRDHDIGGSGAGTGERPPS PPMAPPPPAEPTRRHRTADTPPDDSGGLHARDPLTGGQSVADLMARLQVESTGGGRRRRRGE >BL;Rv3605c, H37Rv2.tab 4047708:4048181 reverse MW:16789 MGPTRKRDLTAAVVGAAAVGYLLVAVLYRWFPPITVWTGLSLLAVAVAEALWARYVRVKISDGEIGDGPGWLHPLVVARS (SEQ ID NO:607) LMVAKASAWVGALVTGWWIGVLAYFLPRRSWLRAAAEDTTGTVVAAGSALALVVAALWLQHCCKSPQDPTEHADGAES >BL;Rv3614c, H37Rv2.tab 4054145:4054696 reverse MW:19802 VDLPGNDFDSNDFDAVDLWGADGAEGWTADPIIGVGSAATPDTGPDLDNAHGQAETDTEQEIALFTVTNPPRTVSVSTLM (SEQ ID NO:608) DGRIDHVELSARvAWMSESQLASEILVIADLARQKAQSAQYAFILDRMSQQVDADEHRvALLRKTVGETWGLPSPEEAAA AEAEVFATRYSDDCPAPDDESDPW >BL;Rv3615c, H37Rv2.tab 4054815:4055123 reverse MW:10795 MTENLTVQPERLGVLASHHDNAAVDASSGVEAAAGLGESVAITHGPYCSQFNDTLNVYLTAHNALGSSLHTAGVDLAKSL (SEQ ID NO:609) RIAAKIYSEADEAWRKAIDGLFT >BL;Rv3616c, H372V2.tab 4055200:4056375 reverse MW:39888 MSRAFIIDPTISAIDGLYDLLGIGIPNQGGILYSSLEYFEKALEELAAAFPGDGWLGSAADKYAGKNRNHVNFFQELADL (SEQ ID NO:610) DRQLISLIHDQANAVQTTRDILEGAKKGLEFVRPVAVDLTYIPVVGHALSAAFQAPFCAGAMAVVGGALAYLVVKTLINA TQLLKLLAKLAELVAAAIADIISDVADIIKGTLGEVWEFITNALNGLKELWDKLTGWVTGLFSRGWSNLESFFAGVPGLT GATSGLSQVTGLFGAAGLSASSGLAHADSLASSASLPALAGIGGGSGFGGLPSLAWVHAASTRQALRPRADGPVGAAAEQ VGGQSQLVSAQGSQGMGGPVGMGGMHPSSGASKGTTTKKYSEGAAAGTEDAERAPVEADAGGGQKVLVRNVV >BL;Rv3619c, H37Rv2.tab 4059987:4060268 reverse MW:9832 MTINYQFGDVDAHGAMIRAQAGSLEAEHQAIISDVLTASDFWGGAGSAACQGFITQLGRNFQVIYEQANAHGQKVQAAGN (SEQ ID NO:611) NMAQTDSAVGSSWA >BL;Rv3632, H37Rv2.tab 4071236:4071577 forward MW:13068 MNWIQVLLIASIIGLLFYLLRSRRSARSRAWVKVGYVLFVLAGIYAVLRPDDTTVVANWFGVRRGTDLMLYALVIVIAFSFT (SEQ ID NO:612) TLSTYMRFKDLELRYARIARALALEGAQAPEQCR >BL;Rv3647c, H37Rv2.tab 4087613:4088188 reverse MW:20314 VSQLSFFAAESVPPAVADLSGVLAGPGQIVLVGCGARLSVVVAESWRASALAEMIQEAGLVPEVARTDENTPLVRTAVDP (SEQ ID NO:613) LLCGIAAEWTRGAVKTVPPRWLPGPRELRAWTLAAGSPEADRYLLGLDPHAPDTHS PLASALMRvGIAPTLIGTRGTRPA LRISGRRRLSRLVENVGEPPDGAEAWVQWPRT >BL;Rv3662c, H37Rv2.tab 4101268:4102035 reverse MW:26338 VTVDPLAPLMELPGVAAASDRVRDALSRvHRHRANLRGWPVAAAEASLRAARASSVLDGGPARLHDAGAPTSGKPALSDP (SEQ ID NO:614) VFAGALRVGQALEGGAGPVVGVWRRAPLQALARLHMLAAADQVDDDRLGRPRSDADVGPRLELLALVVTHPTLASAPVVA AVAHGELLTLRPFGCADGVVARAVSRLVTIATGLDPHGLGVPEVIWMRQPAEYHDAARRFAGGTPDGVAGWLLLCCGAML DGAREALSIAESLSPG >BL;Rv3668c, H37Rv2.tab 4109786:4110481 reverse MW:23102 LQTAHRRFAAAFAAVLLAVVCLPANTAAADDKLPLGGGAGIVVNGDTMCTLTTIGHDKNGDLIGFTSAHCGGPGAQIAAE (SEQ ID NO:615) GAENAGPVGIMVAGNDGLDYAVIKFDPAKVTPVAVFNGFAINGIGPDPSFGQIACKQGRTTGNSCGVTWGPGESPGTLVM QVCGGPGDSGAPVTVDNLLVGMIHGAFSDNLPSCITKYIPLHTPAVVMSINADLADINAKNRPGAGFVPVPA >BL;Rv3669, H37Rv2.tab 4110827:4111342 forward MW:18887 VSKIDRKNGVPSTLTTIPLADPHAGPAEPSIGDLIKDATTQMSTLVRAEVELARAEITRDVKKGLTGSVFFISSLVVGFY (SEQ ID NO:616) STFFFFFFVAELLDTWIWRWVAFLLVFAIMVVVTAVLALLGFLKVRRIRGPRQTIASVKETRTALTPGHDKTPVTPKPVT SDRATPVDPSGW >BL;Rv3680, H37Rv2.tab 4119795:4120952 forward MW:41405 MSVTPKTLDMGAILADTSNRVVVCCGAGGVGKTTTAAALALRAAEYGRTVVVLTIDPAKRLAQALGINDLGNTPQRVPLA (SEQ ID NO:617) PEVPGELHAMMLDMRRTFDEMVMQYSGPERAQSILDNQFYQTVATSLAGTQEYMAMEKLGQLLSQDRWDLIVVDTPPSRN ALDFLDAPKRLGSFMDSRLWRLLLAPGRGIGRLITGVMGLAMKALSTVLGSQMLADAAAFVQSLDATFGGFREKADRTYA LLKRRGTQFVVVSAAEPDALREASFFVDRLSQESMPLAGLVFNRTHPMLCALPIERAIDAAETLDAETTDSDATSLAAAV LRIHAERGQTAKREIRLLSRFTGANPTVPVVGVPSLPFDVSDLEALRALADQLTTVGNDAGRAAGR >BL;Rv37OSc, H37Rv2.tab 4148321:4148962 reverse MW:22359 MRIAAAVVSIGLAVIAGFAVPVADAHPSEPGVVSYAVLGKGSVGNIVGAPMGWEAVFTRPFQAFWVELPACNNWVDIGLP (SEQ ID NO:618) EVYDDPDLASFNGATTQTSATDQTHLVKQAVGVFASNDAADRAFHRvVDRTVGCSGQTTAIHLDDGTTQVWSFAGGPSTG TDEAWTKQEAGTDRRCFVQTRLRENVLLQAKVCQSGNAGPAVNVLAGAMQNTLG >BL;Rv3716c, H37Rv2.tab 4160515:4160913 reverse MW:13357 MQPGGDMSALLAQAQQMQQKLLEAQQQLANSEVHGQAGGGLVKVVVKGSGEVIGVTIDPKVVDPDDIETLQDLIVGAMRD (SEQ ID NO:619) ASQQVTKMAQERLGALAGANRPPAPPAAPPGAPGMPGMPGMPGAPGAPPVPGI >BL;Rv3718c, H37Rv2.tab 4161818:4162258 reverse MW:15661 MGQVSAASTILINAEPTATLDALADYETVRPKILSPHYSEYQVLEGGKGRGTVAKWRLQATQSRVRDVQVNVDVAGHTVI (SEQ ID NO:620) EKDMNSSMVTNWTVAPAGPGSSVTVKTTWTGAGGVKGFFEKTFAPLGLKKIQAEVLSNLKTELEGDA >BL;Rv3723, H37Rv2.tab 4168536:4169297 forward MW:27367 MGRKVAVLWHASFSIGAGVLYFYFVLPRWPELMGDTGHSLGTGLRIATGALVGLAALPVVFTLLRTRKPELGTPQLALSM (SEQ ID NO:621) RIWSIMAHVLAGALIVGTAISEVWLSLDAAGQWLFGIYGAAAAIAVLGFFGFYLSFVAELPPPPPKPLKPKKPKQRRLRR KKTAKGDEAEPEAAEEAENTELAAQEDEEAVEAPPESIESPGGEPESATREAPAAETATAEEPRGGLRNRRPTGKTSHRR RRTRSGVQVAKVDE >BL;Rv3753c, H37Rv2.tab 4199724:4200221 reverse MW:17917 MQRPAADTPDGFGVAVVREEGRWRCSPMGPKALTSLRAAETELRELRSAGAVFGLLDVDDEFFVIVRPAPSGTRLLLSDA (SEQ ID NO:622) TAALDYDIAAEVLDNLDAEIDPEDLEDADPFEEGDLGLLSDIGLPEAVLGVILDETDLYADEQLGRIAREMGFADQLSAV IDRLGR >BL;Rv3760, H37Rv2.tab 4205538:4205837 forward MW:10533 VPGSVPGKAPEEPPVKFTRAAAVWSALIVGFLILILLLIFIAQNTASAQFAFFGWRWSLPLGVAILLAAVGGGLITVFAG (SEQ ID NO:623) TARILQLRRAAKKTHAAALR >BL;Rv3779, H37Rv2.tab 4224985:4226982 forward MW:71763 VGLWFGTLIALILLIAPGAMVARIAQLRWPVAIAVGPALTYGVVALAIIPYGALGIPWNGWTALAALAVTCAVATGLQLL (SEQ ID NO:624) LARFRDLDAEALAVSRWPAVTVAAGVLLGALLIGWAAYRGIPHWQSIPSTWDAVWHANTVRFILDTGQASSTHMGELRNV ETHAPLYYPSVFHGLVAVFCQLTGAAPTTGYTLSSLAASVWLFPVSAAVLTWRAVRSHPGALWSASCASAEWRAAGAAGT AAALSASFTAVPYVEFDTAAMPNLAAYGIAVPTMVLITSTLRHRDRIPVAVLALVGVFSLHITGGIVVALLVSAWWLFEA LRHPVRSRLADLLTLAGVAAMAGLVMLPQFLSVRQQEDIIAGHAFPTYLSKKRGLFDAVFQHSRHLNDFPVQYALIVLAA IGGLILLVKKIWWPLAVWLLLIVMNVDAGTPLGGPIGGVAGALGEFFYHDPRRIAAATTLLLMLMAGVALFATVNLLVAA AKRLTDRFRPQPVSVWASATATLLIGATLVSAWHYFPRHRFLFGDKYDSVMIDQKDLDANAYLASLPGARDTLIGNANTD GTAWMYAVAGLHPLWTHYDYPLQQGPGYHRFIFWAYGRNGESDPRvLEAIQVLRIRYILTSTPTVRGFAVPDGLVSLETS RSWAKIYDNGEARIYEWRGTAAATHS >BL;Rv3780, H37Rv2.tab 4226989:4227522 forward MW:19484 VRKRMVIGLSTGSDDDDVEVIGGVDPRLIAVQENDSDESSLTDLVEQPAKVMRIGTMIKQLLEEVRAAPLDEASRNRLRD (SEQ ID NO:625) IHATSIRELEDGLAPELREELDRLTLPFNEDAVPSDAELRIAQAQLVGWLEGLFHGIQTALFAQQMAARAQLQQMRQGAL PPGVGKSGQHGHGTGQYL >BL;Rv3792, H37Rv2.tab 4237932:4239860 forward MW:69516 MPSRRKSPQFGHEMGAFTSARAREVLVALGQLAAAVVVAVGVAVVSLLAIARVEWPAFPSSNQLHALTTVGQVGCLAGLV (SEQ ID NO:626) GIGWLWRHGRFRRLARLGGLVLVSAFTVVTLGMPLGATKLYLFGISVDQQFRTEYLTRLTDTAALRDMTYIGLPPFYPPG WFWIGGRAAALTGTPAWEMFKPWAITSMAIAVAVALVLWWRMIRFEYALLVTVATAAVMLAYSSPEPYAAMITVLLPPML VLTWSGLGARDRQGWAAVVGAGVFLGFAATWYTLLVAYGAFTVVLMALLLAGSRLQSGIKAAVDPLCRLAVVGAIAAAIG STTWLPYLLRAARDPVSDTGSAQHYLPADGAALTFPMLQFSLLGAICLLGTLWLVMRARSSAPAGALAIGVLAVYLWSLL SMLATLARTTLLSFRLQPTLSVLLVAAGAFGFVEAVQALGKRGRGVIPMAAAIGLAGAIAFSQDIPDVLRPDLTIAYTDT DGYGQRGDRRPPGSEKYYPAIDAAIRRVTGKRRDRTVVLTADYSFLSYYPYWGFQGLTPHYANPLAQFDKRATQIDSWSG LSTADEFIAALDKLPWQPPTVFLMRHGAHNSYTLRLAQDVYPNQPNVRRYTVDLRTALFADPRFVVEDIGPFVLAIRKPQ ESA >BL;Rv38O2c, H37Rv2.tab 4263358:4264365 reverse MW:35448 MAKNSRRKRHRILAWIAAGAMASVVALVIVAVVIMLRGAESPPSAVPPGVLPPGPTPAHPHKPRPAFQDASCPDVQMISV (SEQ ID NO:627) PGTWESSPQQNPLNPVQFPKALLLKVTGPIAQQFAPARVQTYTVAYTAQFHNPLTTDNQMSYNDSRAEGTRAMVAAMTDM NNRCPLTSYVLIGFSQGAVIAGDVASDIGNGRGPVDEDLVLGVTLIADGRRQQGVGNQVPPSPRGEGAEITLHEVPVLSG LGLTMTGPRPGGFGALDGRTNEICAQGDLICAAPAQAFSPANLPTTLNTLAGGAGQPVHAMYATPEFWNSDGEPATEWTL NWAHQLIENAPHPKHR >BL;Rv3805c, H37Rv2.tab 4266956:4268836 reverse MW:68710 MVRVSLWLSVTAVAVLFGWGSWQRRWIADDGLIVLRTVRNLLAGNGPVFNQGERVEANTSTAWTYLLYVGGWVGGPMRLE (SEQ ID NO:628) YVALALAMVLSLLGMVLLMLGTGRLYAPSLRGRRAIMLPAGALVYIAVPPARDFATSGLESGLVLAYLGLLWWMMVCWSQ PLRARPDSQMFLGALAFVAGCSVLVRPEFALIGGLALIMMLIAARTWRRRVLIVLAGGFLPVAYQIFRMGYYGLLVPSTA LAKDAAGDKWSQGMIYVSNFNRPYALWVPLVLSVPLGLLLMTARRRPSFLRPVLAPDYGRvARAVQSPPAVVAFIVGSGV LQALYWIRQGGDFMHGRvLLAPLFCLLAPVGVIPILLPDGKDFSRETGRWLVGALSGLWLGIAGWSLWAANSPGMGDDAT RVTYSGIVDERRFYAQATGHAHPLTAADYLDYPRMAAVLTALNNTPEGALLLPSGNYNQWDLVPMIRPSSGTAPGGKPAP KPQHAVFFTNMGMLGMNVGLDVRVIDQIGLVNPLAAHTERLKHARIGHDKNLFPDWVIADGPWVKWYPGIPGYIDQQWVT QAEAALQCPATRAVLNSVRAPITLHRFLSNVLHSYEFTRYRIDRVPRYELVRCGLDVPDGPGPPPRE >BL;Rv3807c, H37Rv2.tab 4269843:4270337 reverse MW:17218 MVAVQSALVDRPGMLATARGLSHFGEHCIGWLILALLGAIALPRRRREWLVAGAGAFVAHAIAVLIKRLVRRQRPDHPAI (SEQ ID NO:629) AVNVDTPSQLSFPSAHATSTTAAALLMGRATGLPLPVVLVPPMALSRILLGVHYPSDVAVGVALGATVGAIVDSVGGGRQ RARKR >BL;Rv3808c, H37Rv2.tab 4270369:4272279 reverse MW:71507 MSELAASLLSRVILPRPGEPLDVRKLYLEESTTNARRAHAPTRTSLQIGAESEVSFATYFNAFPASYWRRWTTCKSVVLR (SEQ ID NO:630) VQVTGAGRVDVYRTKATGARIFVEGHDFTGTEDQPAAVETEVVLQPFEDGGWVWFDITTDTAVTLHSGGWYATSPAPGTA NIAVOIPTFNRPADCVNALRELTADPLVDQVIGAVIVPDQGERKVRDHPDFPAAAARLGSRLSIHDQPNLGGSGGYSRVM YEALKNTDCQQILFMDDDIRLEPDSILRvLAMHRFAKAPMLVGGQMLNLQEPSHLNIMGEVVDRSIFMWTAAPHAEYDHD FAEYPLNDNNSRSKLLHRRIDVDYNGWWTCMIPRQVAEELGQPLPLFIKWDDADYGLRAAEHGYPTVTLPGAAIWHMAWS DKDDAIDWQAYFHLRNRLVVAAMHWDGPKAQVIGLVRSHLKATLKHLACLEYSTVAIQNKAIDDFLAGPEHIFSILESAL PQVHRIRKSYPDAVVLPAASELPPPLHKNKAMKPPVNPLVIGYRLARGIMHNLTAANPQHHRRPEFNVPTQDARWFLLCT VDGATVTTADGCGVVYRQRDRAKNFALLWQSLRRQRQLLKRFEEMRRIYRDALPTLSSKQKWETALLPAANQEPEHG >BL;Rv3821, H37Rv2.tab 4285973:4286683 forward MW:24627 MWSTVLVLALSVICEPVRIGLVVLMLNRRRPLLHLLTFLCGGYTMAGGVANVTLVVLGATPLAGHFSVAEVQIGTGLIAL (SEQ ID NO:631) LIAFALTTNVIGKHVRRATHARVGDDGGRVLRESVPPSGAHKLAVRARCFLQGDSLYVAGVSGLGAALPSANYMGAMAAI LASGATPATQALAVVTFNVVAFTVAEVPLVSYLAAPRKTRAFMAALQSWLRSRSRRDAALLVAAGGCLMLTLGLSNL >BL;Rv3835, H37Rv2.tab 4309047:4310393 forward MW:47043 MLDAPEQDPVDPGDPASPPHGEAEQPLPGPRWPRALRASATRRALLLTALGGLLIAGLVTAIPAVGRAPERLAGYIASNP (SEQ ID NO:632) VPSTGAKINASFNRVASGDCLMWPDGTPESAAIVSCADEHRFEVAESIDMRTFPGMEYGQNAAPPSPARIQQISEEQCEA AVRRYLGTKFDPNSKFTISMLWPGDRAWRQAGERRMLCGLQSPGPNNQQLAFKGKVADIDQSKVWPAGTCLGIDATTNQP IDVPVDCAAPHAMEVSGTVNLAERFPDALPSEPEQDGFIKDACTRMTDAYLAPLKLRTTTLTLIYPTLTLPSWSAGSRVV ACSIGATLGNGGWATLVNSAKGALLINGQPPVPPPDIPEERLNLPPIPLQLPTPRPAPPAQQLPSTPPGTQHLPAQQPVV TPTRPPESHAPASAAPAETQPPPPDAGAPPATQSPEATPPGPAEPAPAG >BL;Rv3843c, H37Rv2.tab 4315571:4316596 reverse MW:37353 VIQVCSQCGTGWNVRERQRvWCPRCRGMLLAPLADMPAEARWRTPARPQVPTASDTRRTPPRLPPGFRWIAVRPGAAPPP (SEQ ID NO:633) RHGPRLRGPTPRYAGIPRWGLTDHVDQAPVPASAKAGPSPAAVRTTLLVSLLVFSIAVVVFVVRYVLLVINRNTLLNSVV ASASVWLGVLVSLAAIAAAGTTIVLLVRWLVARRAAAFMHQGLPERRSARELWAGCLLPMVNLLWAPLYVIELALVEDRY TRLRRPIVVWWIVWIVSNAISMFAFATSWVTDAQGIANNTTMMVLAYLCAAAAVAAAARVFEGFEQKPVERPAHRWVVVN TDGRSAPASSVAVELDGQEPAA >BL;Rv3847, H37Rv2.tab 4321538:4322068 forward MW:18278 MGTGSGGPIGVSPFHSRGALKGFVISGRWPDSTKEWAQLLMVAVRvASLPGLLSTTTVFGAREELPDEPEPGTVGLVLAE (SEQ ID NO:634) GTVFGESAIQPGYFADHQPPALLMLHPPSETTPSLPECTGAASGCVLLPGLPYLGLEHRAAWVEAEADGTITSMVSRVGV DPISHPDTAILAMLLAA >BL;2V3849, H37Rv2.tab 4323499:4323894 forward MW:14708 MSTTFAARLNRLFDTVYPPGRGPHTSAEVIAALKAEGITMSAPYLSQLRSGNRTNPSGATMAALANFERIKAAYFTDDEY (SEQ ID NO:635) YEKLDKELQWLCTMRDDGVRRIAQRAHGLPSAAQQKVLDRIDELRRAEGIDA >BL;Rv3850, M37Rv2.tab 4324015:4324668 forward MW:23811 MGLFGKRKSRATRRAEARAIKARAKLEAKLSAKNEARRIKAAQRAESKALKAQLKARRDSDRAALKVAEAELKVAREGKL (SEQ ID NO:636) LSPTRIRRLLTVSRLLAPILTPVIYRAANAARGLIDQRRADQLGVPLAQIGRFSGHGARLSARvGGAERSLRMVQEKKPK DVETKQFVSAVTNRLTDLSAIWAAAEHMPAKRRRTAHSAISSQLDGIEADLMARLGLT >BL;Rv3867, H37Rv2.tab 4342770:4343318 forward MW:19945 MVDPPGNDDDHGDLDALDFSAAHTNEASPLDALDDYAPVQTDDAEGDLDALHALTERDEEPELELFTVTNPQGSVSVSTL (SEQ ID NO:637) MDGRIQHVELTDKATSMSEAQLADEIFVIADLARQKARASQYTFMVENIGELTDEDAEGSALLREFVGMTLNLPTPEEAA AAEAEVFATRYDVDYTSRYKADD >BL;Rv3869, H37Rv2.tab 4345039:4346478 forward MW:51093 MGLRLTTKVQVSGWRFLLRRLEHAIVRRDTRMFDDPLQFYsRSIALGIVVAVLILAGAALLAYFKPQGKLGGTSLFTDRA (SEQ ID NO:638) TNQLYVLLSGQLHPVYNLTSARLVLGNPANPATVKSSELSKLPMGQTVGIPGAPYATPVSAGSTSIWTLCDTVARADSTS PVVQTAVIANPLEIDASIDPLQSHEAVLVSYQGETWIVTTKGRHAIDLTDRALTSSMGIPVTARPTPISEGMFNALPDMG PWQLPPIPAAGAPNSLGLPDDLVIGSVFQIHTDKGPQYYVVLPDGIAQVNATTAAALRATQAHGLVAPPAMVPSLVVRIA ERvYPSPLPDEPLKIVSRPQDPALCWSWQRSAGDQSPQSTVLSGRHLPISPSAMNMGIKQIHGTATVYLDGGKFVALQSP DPRYTESMYYIDPQGVRYGVPNAETAKSLGLSSPQNAPWEIVRLLVDGPVLSKDAALLEHDTLPADPSPRKVPAGASGAP >DL;Rv3874, H37Rv2.tab 4352274:4352573 forward MW:10793 MAEMKTDAATLAQEAGNFERISGDLKTQIDQVESTAGSLQGQWRGAAGTAAQAAVVRFQEAANKQKQELDEISTNIRQAG (SEQ ID NO:639) VQYSRADEEQQQALSSQMGF >BL;Rv3876, H37Rv2.tab 4353010:4355007 forward MW:70645 MAADYDKLFRPHEGMEAPDDMAAQPFFDPSASFPPAPASANLPKPNGQTPPPTSDDLSERFVSAPPPPPPPPPPPPPTPM (SEQ ID NO:640) PIAAGEPPSPEPAASKPPTPPMPIAGPEPAPPKPPTPPMPIAGPEPAPPKPPTPPMPIAGPAPTPTESQLAPPRPPTPQT PTGAPQQPESPAPHVPSHGPHQPRRTAPAPPWAKMPIGEPPPAPSRPSASPAEPPTRPAPQHSRRARRGHRYRTDTERNV GKVATGPSIQARLRAEEASGAQLAPGTEPSPAPLGQPRSYLAPPTRPAPTEPPPSPSPQRNSGRRAERRVHPDLAAQNAA AQPDSITAATTGGRRRKRAAPDLDATQKSLRPAAKGPKVKKVKPQKPKATKPPKVVSQRGWRHWVHALTRINLGLSPDEK YELDLHARVRRNPRGSYQIAVVGLKGGAGKTTLTAALGSTLAQVRADRILALDADPGAGNLADRVGRQSGATIADVLAEK ELSHYNDIRAHTSVNAVNLEVLPAPEYSSAQRALSDADWHFIADPASRFYNLVLADCGAGFFDPLTRGVLSTVSGVVVVA SVSIDGAQQASVALDWLRNNGYQDLASRACVVINHIMPGEPNVAVKDLVRHFEQQVQPGRVVVMPWDRHIAAGTEISLDL LDPIYKRKVLELAAALSDDFERAGRR >BL;Rv3877, H37Rv2.tab 4355007:4356539 forward MW:53981 LSAPAVAAGPTAAGATAARPATTRVTILTGRRMTDLVLPAAVPMETYIDDTVAVLSEVLEDTPADVLGGFDFTAQGVWAF (SEQ ID NO:641) ARPGSPPLKLDQSLDDAGVVDGSLLTLVSVSRTERYRPLVEDVIDAIAVLDESPEFDRTALNRFVGAAIPLLTAPVIGMA MRAWWETGRSLWWPLAIGILGIAVLVGSFVANRFYQSGHLAECLLVTTYLLIATAAALAVPLPRGVNSLGAPQVAGAATA VLFLTLMTRGGPRKRHELASFAVITAIAVIAAAAAFGYGYQDWVPAGGIAFGLFIVTNAAKLTVAVARIALPPIPVPGET VDNEELLDPVATPEATSEETPTWQAIIASVPASAVRLTERSKLAKQLLIGYVTSGTLILAAGAIAVVVRGHFFVHSLVVA GLITTVCGFRSRLYAERWCAWALLAATVAIPTGLTAKLIIWYPHYAWLLLSVYLTVALVALVVVGSMAHVRRvSPVVKRT LELIDGAMIAAIIPMLLWITGVYDTVRNIRF >BL;Rv3880c, H37Rv2.tab 4360202:4360546 reverse MW:12167 VSMDELDPHVARALTLAARFQSALDGTLNQMNNGSFRATDEAETVEVTINGHQWLTGLRIEDGLLKKLGAEAVAQRVNEA (SEQ ID NO:642) LHNAQAASAYNDAAGEQLTAALSAMSRANNEGMA >BL;Rv3882c, H37Rv2.tab 4362035:4363420 reverse MW:50397 MRNPLGLRFSTGHALLASALAPPCIIAFLETRYWWAGIALASLGVIVATVTFYGRRITGWVAAVYAWLRRRRRPPDSSSE (SEQ ID NO:643) PVVGATVKPGDHVAVRWQGEFLVAVIELIPRPFTPTVIVDGQAHTDDMLDTGLVEELLSVHCPDLEADIVSAGYRVGNTA APDVVSLYQQVIGTDPAPANRRTWIVLRADPERTRKSAQRRDEGVAGLARYLVASATRIADRLASHGVDAVCGRSFDDYD HATDIGFVREKWSMIKGRDAYTAAYAAPGGPDVWWSARADHTITRVRVAPGMAPQSTVLLTTADKPKTPRGFARLFGGQR PALQGQHLVANRHCQLPIGSAGVLVGETVNRCPVYMPFDDVDIALNLGDAQTFTQFVVRAAAAGAMVTVGPQFEEFARLI GAHIGQEVKVAWPNATTYLGPHPGIDRVILRHNVIGTPRHRQLPIRRvSPPEESRYQMALPK >BL;Rv3909, H37Rv2.tab 4394192:4396597 forward MW:83878 VTALQLGWAALARVTSAIGVVAGLGMALTVPSAAPHHALAGEPSPTPFVQVRIDQVTPDVVTTSSEPHVTVSGTVTNTGDR (SEQ ID NO:644) PVRDVMVRLEHAAAVTSSTALRTSLDGGTDQYQPAADFLTVAPELDRGQEAGFTLSAPLRSLTRPSLAVNQPGIYPVLLVN VNGTPDYGAPARLDNARFLLPVVGVPPDQATDFGSAVAPETTAPVWITMLWPLADRPRLAPGAPGGTVPVRLVDDDLANS VNGTPDYGAPARLDNARFLLPVVGVPPDQATDFGSAVAPETTAPVWITMLWPLADRPRLAPGAPGGTVPVRLVDDDLANS LANGGRLDILLSAAEFATNREVDPDGAVGRALCLAIDPDLLITVNAMTGGYVVSDSPDGAAQLPGTPTHPGTGQAAASSW LDRLRTLVHRTCVTPLPFAQADLDALQRVNDPRLSAIATISPADIVDRILDVSSTRGATVLPDGPLTGRAINLLSTHGNT VAVAAADFSPEEQQGSSQIGSALLPATAPRRLSPRVVAAPFDPAVGAALAAAGTNPTVPTYLDPSLFVRIAHESITARRQ DALGAMLWRSLEPNAAPRTQILVPPASWSLASDDAQVILTALATAIRSGLAVPRPLPAVIADAAARTEPPEPPGAYSAAR GRFNDDITTQIGGQVARLWKLTSALTIDDRTGLTGVQYTAPLREDMLRALSQSLPPDTRNGLAQQRLAVVGKTIDDLFGA VTIVNPGGSYTLATEHSPLPLALHNGLAVPIRVRLQVDAPPGMTVADVGQIELPPGYLPLRVPIEVNFTQRVAVDVSLRT PDGVALGEPVRLSVHSNAYGKVLFAITLSAAAVLVTLAGRRLWHRFRGQPDRADLDRPDLPTGKHAPQRRAVASRDDEKH RV -
Claims (74)
1. A method for identification and the selection of essential genes for the survival or the virulence of mycobacterium species which comprises:
a. Aligning the genomic sequence of a first mycobacterium species on a genomic sequence of the genomic sequence of a second mycobacterium species,
b. Selecting a polypolynucleotide sequence highly conserved in both genomes with no counterparts in other bacterial genomic sequences and which corresponds to an essential gene for the survival or the virulence of mycobacterium species, and
c. Optionally, testing the polypolynucleotide selected in step b) for its capacity of virulence or involved in the survival of a mycobacterium species said testing being based on the activation or inactivation of said polypolynucleotide in a bacterial host or said testing being based on the activity of the product of expression of said polynucleotide in vivo or in vitro.
2. A method according to claim 1 , wherein the first genomic sequence of mycobacterium belongs to Mycobacterium tuberculosis.
3. A method according to claim 1 , wherein the second genomic sequence of mycobacterium belongs to Mycobacterium leprae.
4. A method according to any one of claims 1 to 3 , wherein the complete genomic sequence of said mycobacterium species is analysed.
5. A method for the identification and the selection in silico of essential genes for the survival or the virulence of mycobacterium species according to any one of claims 1 to 4 .
6. Purified polynucleotide molecule obtained by the method according to any one of claims 1 to 5 .
7. A purified polynucleotide molecule of claim 6 which encodes essential proteins or fragments of proteins of Mycobacteium species.
8. A purified polynucleotide molecule of a formula selected from the group consisting of polynucleotidic sequences, which encode for polypeptides and regulatory sequences essential for the virulence and/or the survival of mycobacterium which are, in one hand, specific to Mycobacterium tuberculosis and, in the other hand, specific to Mycobacterium leprae, that is to say, said polynucleotidic sequences are not found in publicly accessible banks of non-Mycobacterium tuberculosis and non-Mycobacterium leprae genome.
9. A purified polynucleotide molecule according to claim 8 obtained by the method according to any one of claims 1 to 5 .
10. A purified polynucleotide molecule that hybridizes to either strand of a denratured, double-stranded DNA comprising the purified polynucleotide sequence according to claims 6 to 9 under conditions of moderate stringency in 50% formamide and 6× SSC at 42° C. with washing conditions of 60° C., 0.5×SSC, 0.1% of SDS.
11. The purified polynucleotide molecule as claimed in claim 10 , wherein said purified polynucleotide molecule is derived by mutagenesis.
12. A purified polynucleotide molecule degenerate from the purified polynucleotide molecule according to any one of claims 6 to 9 as a result of the genetic code.
13. A purified polynucleotide according to any one of claims 6 to 9 which encodes M. tuberculosis or M. leprae marker polypeptide.
14. A purified polynucleotide molecule according to any one of claims 6 to 9 which encodes an allelic variant of M. tuberculosis or M. leprae marker polypeptide according to claim 13 .
15. A purified polynucleotide molecule according to any one of claims 6 to 9 which encodes a similar sequence of M. tuberculosis or M. leprae marker polypeptide DNA according to claim 13 .
16. A purified polypeptide encoded by a polynucleotide molecule according to claim 8 .
17. A purified polypeptide of a formula selected from the group consisting of SEQ ID NO: X to SEQ ID NO: Y.
18. A purified polypeptide according to claim 17 encoded by a polynucleotide molecule according to claims 6 or 9.
19. A purified polypeptide according to claim 16 in non-glycosylated form.
20. A purified polypeptide according to claim 16 in glycosylated form.
21. A purified polypeptide according to claim 17 in non-glycosylated form.
22. A purified polypeptide according to claim 17 in glycosylated form.
23. A purified polypeptide according to claim 18 in non-glycosylated form.
24. A purified polypeptide according to claim 18 in non-glycosylated form.
25. Process of screening of active molecules comprising:
a. Preparation of at least one purified polynucleotidic molecule or fragment thereof according to claims 6 to 9 in an acceptable medium,
b. Contacting the purified polynucleotide sequence or a fragment thereof corresponding to said essential gene of interest with an active molecule to be tested, and
c. Selecting the active molecule by inhibition or activation of the activity of the purified polynucleotide compared to the standard activity of the essential gene in absence of said active molecule.
26. Process of screening of an active molecule comprising:
a. Preparation of at least one purified polypeptide according to claims 16 to 24 or fragment thereof to be used as a target in an acceptable medium,
b. Contacting said purified polypeptide or fragment thereof obtained in step a) with an active molecule to be tested, and
c. Selecting the active molecule by inhibition or activation of the activity of the purified polypeptide obtainable after expression of the essential gene selected according to claim 1 and compared to the standard activity of said polypeptide.
27. A recombinant BAC containing a fragment of M. tuberculosis genome deposited on Feb. 20, 2001 at the C.N.C.M. under the accession number I-2625.
28. A recombinant BAC containing a fragment of M. tuberculosis genome deposited on Feb. 20, 2001 at the C.N.C.M. under the accession number I-2626.
29. A recombinant BAC containing a fragment of M. tuberculosis genome deposited on Feb. 20, 2001 at the C.N.C.M. under the accession number I-2627.
30. A recombinant BAC containing a fragment of M. tuberculosis genome deposited on Feb. 20, 2001 at the C.N.C.M. under the accession number I-2628.
31. A recombinant BAC containing a fragment of M. tuberculosis genome deposited on Feb. 20, 2001 at the C.N.C.M. under the accession number I-2629.
32. A recombinant cosmid containing a fragment of M. leprae genome deposited on Feb. 21, 2001 at the C.N.C.M. under the accession number I-2632.
33. A recombinant cosmid containing a fragment of M. leprae genome deposited on Feb. 21, 2001 at the C.N.C.M. under the accession number I-2633.
34. A recombinant purified vector that directs the expression of a polynucleotide molecule selected from the group consisting of purified polynucleotide molecule selected according to claims 1 or 6, 7, 8, 9, 13, 14 and 15.
35. A recombinant purified vector that directs the expression of a purified polynucleotide molecule according to claims 10 or 11.
36. A recombinant purified vector that directs the expression of a purified polynucleotide molecule according to claim 12 .
37. A recombinant purified vector containing a part of the polynucleotide insert of claims 27 to 32 or claims 33 to 35 which is a plasmid.
38. A host cell transfected or transduced with the vector of claim 34 .
39. A host cell transfected or transduced with the vector of claim 35 .
40. A host cell transfected or transduced with the vector of claim 36 .
41. A host cell transfected or transduced with the plasmid of claim 37 .
42. A method for the production of mycobacterium purified marker polypeptide comprising culturing a host cell of claim 38 under conditions promoting expression, and recovering the polypeptide from the culture medium.
43. A method for the production of mycobacterium purified marker polypeptide comprising culturing a host cell of claim 39 under conditions promoting expression, and recovering the polypeptide from the culture medium.
44. A method for the production of mycobacterium purified marker polypeptide comprising culturing a host cell of claim 40 under conditions promoting expression, and recovering the polypeptide from the culture medium.
45. A method for the production of mycobacterium purified marker polypeptide comprising culturing a host cell of claim 41 under conditions promoting expression, and recovering the polypeptide from the culture medium.
46. The method according to any one of claims 42 to 45 , wherein the host cell is selected from the group consisting of bacterial cells, yeast cells, plant cells, and mammalian cells.
47. An immunological complex comprising a Mycobacterium purified marker polypeptide produced by a method according to any one of claims 42 to 45 and an antibody that specifically recognizes said polypeptide.
48. A composition comprising at least a mycobacterium purified polypeptide marker produced by a method according to any one of claims 42 to 45 .
49. A method for detecting infection by mycobacteria, said method comprises:
a. Providing a composition according to claim 48 with a biological sample suspected to be infected with a mycobacterium,
b. Assaying for the presence of said mycobacterium, and
c. Optionally, detecting the presence of mycobacteria in said biological sample if infected.
50. The method of claim 49 , which in step b) the assay is performed by electrophoresis or by immunoassay with antibodies that are immunologically reactive with M. tuberculosis and/or M. leprae.
51. An in vitro diagnostic method for the detection of the presence or the absence of antibodies which bind to an antigen or fragment of antigen comprising a mycobacterium purified polypeptide molecule according to any one of claims 16 to 24 , wherein the method comprises contacting the antigen or fragment of antigen with a biological fluid for a time and under conditions sufficient for the antigen and antibodies in the biological fluid to form an immunological complex, detecting the formation of the complex, and optionally measuring the formation of the immunologicalcomplex.
52. The method as claimed in claim 51 , wherein the formation of the immunological complex is detected by immunoassay method based on western blot technique, ELISA, indirect immuno-fluorescense assay, or immunoprecipitation assay.
53. An in vitro diagnostic method for the detection of the presence or the absence of antibodies which bind to an antigen or fragment of antigen comprising a mycobacterium purified polypeptide molecule obtained by a method according to any one of claims 42 to 45 , wherein the method comprises contacting the antigen or fragment of antigen with a biological fluid for a time and under conditions sufficient for the antigen and antibodies in the biological fluid to form an immunological complex, detecting the formation of the complex, and optionally measuring the formation of the immunological complex.
54. The method as claimed in claim 53 , wherein the formation of the immunological complex is detected by immunoassay method based on western blot technique, ELISA, indirect immuno-fluorescence assay, or immunoprecipitation assay.
55. A kit for the in vitro diagnostics of mycobacterium infections comprising:
a. A mycobacterium purified polypeptide molecule according to any one of claims 16 to 24 or mixture thereof,
b. Antibodies capable of forming an immunological complex with said polypeptides, and
c. Acceptable medium to permit the detection of the formation of the complex thereof.
56. A kit as claimed in claim 55 useful for the detection of M. tuberculosis infections.
57. A kit as claimed in claim 55 useful for the detection of M. leprae infections.
58. An immunogenic composition comprising at least a purified polypeptide according to any one of claims 16 to 24 in an amount sufficient to induce an immunogenic or protective response in vivo, and a pharmaceutically acceptable carrier therefor.
59. A polynucleotidic probe comprising a purified polynucleotide molecule or fragment thereof according to any one of claims 6 to 15 .
60. A polynucleotidic probe which is complementary to the full length sequence of a purified nucleic acid that hybridizes under conditions of moderate stringency in 50% formamide and 6× SSC at 42° C. with washing conditions of 60° C., 0.5×SSC, 0.1% SDS with a nucleic acid encoding a purified polypeptide according to any one of claims 6 to 24 .
61. A method for the detection of the presence or the absence of mycobacteria in a sample comprising:
a. contacting a sample suspected to contain genetic material of mycobacteria with at least one probe according to claims 59 or 60,
b. Detecting the hybridization under conditions of moderate stringency in 50% formamide and 6× SSC at 42° C. with washing conditions of 60° C., 0.5×SSC, 0.1% SDS.
62. A method for the detection of the presence or the absence of mycobacteria according to claim 61 , wherein said method is specific for the detection of M. tuberculosis infections.
63. A method for the detection of the presence or the absence of mycobacteria according to claim 61 , wherein said method is specific for the detection of M. leprae infections.
64. A method for the detection of the presence or the absence of mycobacteria according to any one of claims 61 to 63 , wherein the sample contains nucleic acids of at least one microorganism other than the mycobacteria.
65. A method of selection according to claim 1 , wherein the comparison of the genetic informations of different types of organisms, wherein the method comprises:
a. Providing a database including sequence libraries for a plurality of types of organism, said libraries having multiple genomic sequences,
b. Providing one or more probe sequences according to claims 59 or 60,
c. Determining homologous matches between one or more of said probe sequences and one or more sequences of said sequences in said genomic libraries; and
d. Displaying the results of said determination.
66. A method according to claims 1 to 4 , wherein the genomic sequence of a first mycobacterium species is the recombinant BAC deposited at the C.N.C.M. according to claim 27 .
67. A method according to claims 1 to 4 , wherein the genomic sequence of a first mycobacterium species is the recombinant BAC deposited at the C.N.C.M. according to claim 28 .
68. A method according to claims 1 to 4 , wherein the genomic sequence of a first mycobaterium species is the recombinant BAC deposited at the C.N.C.M. according to claim 29 .
69. A method according to claims 1 to 4 , wherein the genomic sequence of a first mycobacterium species is the recombinant BAC deposited at the C.N.C.M. according to claim 30 .
70. A method according to claims 1 to 4 , wherein the genomic sequence of a first mycobacterium species is the recombinant BAC deposited at the C.N.C.M. according to claim 31 .
71. A method according to claims 1 to 4 , wherein the genomic sequence of the second mycobacterium species is the recombinant BAC deposited at the C.N.C.M. according to claim 32 .
72. A method according to claims 1 to 4 , wherein the genomic sequence of the second mycobacterium species is the recombinant BAC deposited at the C.N.C.M. according to claim 33 .
73. An in vitro diagnostic method for the detection of the presence or the absence of essential nucleotidic sequences for the survival or the virulence in mycobacterium by hybridization or amplification of said specific sequence comprising:
a. Providing a composition comprising a probe according to claims 59 or 60 with a sequence library of interest to be tested in an acceptable medium and in sufficient time to obtain an hybridization and/or an amplification of said sequence,
b. Purifying the sequence which hybridizes with said probe; and
c. Optionally, quantifying said sequence.
74. A method according to claim 1 , wherein the first genomic sequence of mycobacterium belongs to Mycobacterium microti.
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US20040197896A1 (en) | 2004-10-07 |
EP1401866A2 (en) | 2004-03-31 |
WO2002074903A3 (en) | 2003-11-13 |
WO2002074903A2 (en) | 2002-09-26 |
US7538206B2 (en) | 2009-05-26 |
US20040121322A9 (en) | 2004-06-24 |
CA2438279A1 (en) | 2002-09-26 |
CN1599751A (en) | 2005-03-23 |
AU2002302919A1 (en) | 2002-10-03 |
CN1277843C (en) | 2006-10-04 |
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