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Panton-valentine leucocidin is the key determinant of staphylococcus aureus pyomyositis in a bacterial GWAS

eLife, ISSN: 2050-084X, Vol: 8
2019
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Article Description

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- ). 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.

Bibliographic Details

Young, Bernadette C; Earle, Sarah G; Soeng, Sona; Sar, Poda; Kumar, Varun; Hor, Songly; Sar, Vuthy; Bousfield, Rachel; Sanderson, Nicholas D; Barker, Leanne; Stoesser, Nicole; Emary, Katherine Rw; Parry, Christopher M; Nickerson, Emma K; Turner, Paul; Bowden, Rory; Crook, Derrick W; Wyllie, David H; Day, Nicholas Pj; Wilson, Daniel J; Moore, Catrin E

eLife Sciences Publications, Ltd

Neuroscience; Biochemistry, Genetics and Molecular Biology; Immunology and Microbiology

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