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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 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.

Original publication

DOI

10.7554/eLife.42486

Type

Journal article

Journal

Elife

Publication Date

22/02/2019

Volume

8

Keywords

Cambodia, Staphylococcus aureus, genetics, genome-wide association study, genomics, infectious disease, microbiology, pyomyositis, Bacterial Toxins, Cambodia, Exotoxins, Genome-Wide Association Study, Humans, Leukocidins, Pyomyositis, Staphylococcal Infections, Staphylococcus aureus, Virulence Factors