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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.
ISSN: 2050084X
Appears in Collections:Scopus 2019

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