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-.
Abstract
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 |
| Open Access URL: | https://doi.org/10.7554/eLife.42486 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3042499 |
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