Panton-Valentine leucocidin is the key determinant of <i>Staphylococcus aureus</i> pyomyositis in a bacterial GWAS

Young, Bernadette C, Earle, Sarah G, Soeng, Sona, Sar, Poda, Kumar, Varun, Hor, Songly, Sar, Vuthy, Bousfield, Rachel, Sanderson, Nicholas D, Barker, Leanne
et al (show 11 more authors) (2019) Panton-Valentine leucocidin is the key determinant of <i>Staphylococcus aureus</i> pyomyositis in a bacterial GWAS. ELIFE, 8. e42486-.

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Pyomyositis is a severe bacterial infection of skeletal muscle, commonly affecting children in tropical regions, predominantly caused by <i>Staphylococcus aureus</i>. To understand the contribution of bacterial genomic factors to pyomyositis, we conducted a genome-wide association study of <i>S. aureus</i> 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<sup>-17.9</sup>). The signal of association mapped both to the PVL-coding sequence and to 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.

Item Type: Article
Uncontrolled Keywords: Humans, Staphylococcus aureus, Staphylococcal Infections, Bacterial Toxins, Leukocidins, Exotoxins, Virulence Factors, Cambodia, Pyomyositis, Genome-Wide Association Study
Depositing User: Symplectic Admin
Date Deposited: 22 May 2019 15:24
Last Modified: 24 Jan 2024 20:24
DOI: 10.7554/eLife.42486
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