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Genome sequencing traces MRSA spread in high transmission setting

December 9, 2014 — Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of hospital-acquired infections, with the largest burden of infections occurring in under-resourced hospitals. While genome sequencing has previously been applied in well-resourced clinical settings to track the spread of MRSA, transmission dynamics in settings with more limited infection control is unknown. In a study published online today in Genome Research, researchers used genome sequencing to understand the spread of MRSA in a resource-limited hospital with high transmission rates.

Patients from two intensive care units (ICUs) in a hospital in northeast Thailand were tested over a three-month period for MRSA. During this time, 46 patients and 5 staff members tested positive at least once (16% adult and 34% pediatric patients). The genetic similarity of the MRSA isolates precluded the use of conventional low-resolution genotyping approaches for distinguishing transmission from one person to another. Therefore, whole genome sequencing was performed on a total of 76 patient isolates, including up to two repeat isolates from patients who tested positive for MRSA in the first screen. None of the patients or staff members that tested positive for MRSA had symptoms of an infection but rather were carriers.

“A striking feature of the phylogenetic tree based on S. aureus whole genome sequencing was the presence of multiple distinct clades,” said senior author Sharon Peacock from the University of Cambridge and Wellcome Trust Sanger Institute. “This suggested that multiple clades of the same lineage were circulating in the hospital at the same time.”



A scanning electron micrograph of methicillin-resistant Staphylococcus aureus (MRSA), magnified 2381x. Image courtesy of the CDC/Jeff Hageman, MHS.

Examining single base changes in the genomes of MRSA isolates allowed researchers to infer the most likely transmission routes between infected patients. Transmission events were observed between patients within the ICU, and also between patients and staff members. These results are in contrast to a previous study performed in the UK where patient-to-patient MRSA transmission in the ICU was rare.

“Our long term goal is to use such information to inform infection control practice,” said Peacock. “The degree of transmission we demonstrated in our study has directly led to the prioritization of improved hand hygiene practices at the study hospital.”

Genome sequencing also revealed that MRSA clades were dynamic in the ICU over the three-month period, with some clades more prevalent early in the study and others later.

Deep sequencing of isolates taken from a single patient carrying MRSA for the longest period revealed that although all isolates were of the same clade, there were small genetic differences between them, suggesting bacterial diversity within a single carrier. This lends further support to previous work suggesting that understanding transmission networks will require measures of within-host bacterial diversity as well as traditional ‘shoe-leather epidemiological’ data.

Scientists from the University of Cambridge, Wellcome Trust Sanger Institute, Menzies School of Health Research, Mahidol University, Public Health England, and Imperial College London contributed to this study.

This work was supported by the Medical Research Council, Wellcome Trust, and the Australian National Health and Medical Research Council.

Media contacts:

The authors are available for more information by contacting:

Craig Brierley, Office of External Affairs and Communications, University of Cambridge (Craig.Brierley@admin.cam.ac.uk, +44 (0)1223 766205)

Mary Clarke, Public Relations and Communications, Wellcome Trust Sanger Institute, (mc19@sanger.ac.uk, +44 (0)1223 492368)

Interested reporters may obtain copies of the manuscript via email from Peggy Calicchia, Administrative Assistant, Genome Research (calicchi@cshl.edu, +1-516-422-4012).

About the article:

The manuscript will be published online ahead of print on 9 December 2014. Its full citation is as follows:

Tong SYC, Holden MTG, Nickerson EK, Cooper BS, Köser CU, Cori A, Jombart T, Cauchemez S, Fraser C, Wuthiekanun V, Thaipadungpanit J, Hongsuwan M, Day NP, Limmathurotsakul D, Parkhill J, Peacock SJ. 2015. Genome sequencing defines phylogeny and spread of methicillin-resistant Staphylococcus aureus in a high transmission setting. Genome Res doi: 10.1101/gr.174730.114

About Genome Research:

Launched in 1995, Genome Research (www.genome.org) is an international, continuously published, peer-reviewed journal that focuses on research that provides novel insights into the genome biology of all organisms, including advances in genomic medicine. Among the topics considered by the journal are genome structure and function, comparative genomics, molecular evolution, genome-scale quantitative and population genetics, proteomics, epigenomics, and systems biology. The journal also features exciting gene discoveries and reports of cutting-edge computational biology and high-throughput methodologies.

About Cold Spring Harbor Laboratory Press:

Cold Spring Harbor Laboratory Press is an internationally renowned publisher of books, journals, and electronic media, located on Long Island, New York. Since 1933, it has furthered the advance and spread of scientific knowledge in all areas of genetics and molecular biology, including cancer biology, plant science, bioinformatics, and neurobiology. The Press is a division of Cold Spring Harbor Laboratory, an innovator in life science research and the education of scientists, students, and the public. For more information, visit our website at http://cshlpress.org/

Genome Research issues press releases to highlight significant research studies that are published in the journal.