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Title: | Panton-valentine leucocidin is the key determinant of staphylococcus aureus pyomyositis in a bacterial GWAS |
Authors: | Bernadette C. Young Sarah G. Earle Sona Soeng Poda Sar Varun Kumar Songly Hor Vuthy Sar Rachel Bousfield Nicholas D. Sanderson Leanne Barker Nicole Stoesser Katherine R.W. Emary Christopher M. Parry Emma K. Nickerson Paul Turner Rory Bowden Derrick Crook David Wyllie Nicholas P.J. Day Daniel J. Wilson Catrin E. Moore Wellcome Trust Centre for Human Genetics University of Oxford Liverpool School of Tropical Medicine Cambridge University Hospitals NHS Foundation Trust Mahidol University Nagasaki University Nuffield Department of Clinical Medicine John Radcliffe Hospital East Tennessee State University Angkor Hospital for Children |
Keywords: | Biochemistry, Genetics and Molecular Biology;Immunology and Microbiology |
Issue Date: | 1-Feb-2019 |
Citation: | eLife. Vol.8, (2019) |
Abstract: | © 2019, eLife Sciences Publications Ltd. All rights reserved. Pyomyositis is a severe bacterial infection of skeletal muscle, commonly affecting children in tropical regions, predominantly caused by Staphylococcus aureus. To understand the contribution of bacterial genomic factors to pyomyositis, we conducted a genome-wide association study of S. aureus cultured from 101 children with pyomyositis and 417 children with asymptomatic nasal carriage attending the Angkor Hospital for Children, Cambodia. We found a strong relationship between bacterial genetic variation and pyomyositis, with estimated heritability 63.8% (95% CI 49.2-78.4%). The presence of the Panton-Valentine leucocidin (PVL) locus increased the odds of pyomyositis 130-fold (p=10- 17.9 ). The signal of association mapped both to the PVL-coding sequence and the sequence immediately upstream. Together these regions explained over 99.9% of heritability (95% CI 93.5-100%). Our results establish staphylococcal pyomyositis, like tetanus and diphtheria, as critically dependent on a single toxin and demonstrate the potential for association studies to identify specific bacterial genes promoting severe human disease. |
URI: | http://repository.li.mahidol.ac.th/dspace/handle/123456789/50280 |
metadata.dc.identifier.url: | https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85064197618&origin=inward |
ISSN: | 2050084X |
Appears in Collections: | Scopus 2019 |
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