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<jats:title>Abstract</jats:title><jats:p>Pyomyositis is a severe bacterial infection of skeletal muscle, commonly affecting children in tropical regions and predominantly caused by <jats:italic>Staphylococcus aureus</jats:italic>. To understand the contribution of bacterial genomic factors to pyomyositis, we conducted a genome-wide association study of <jats:italic>S. aureus</jats:italic> cultured from 101 children with pyomyositis and 417 children with asymptomatic nasal carriage attending the Angkor Hospital for Children in 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 (<jats:italic>p</jats:italic> =10<jats:sup>-17.9</jats:sup>). The signal of association mapped both to the PVL-coding sequence and the sequence immediately upstream. Together these regions explained &gt; 99.9% of heritability. Our results establish staphylococcal pyomyositis, like tetanus and diphtheria, as critically dependent on expression of a single toxin and demonstrate the potential for association studies to identify specific bacterial genes promoting severe human disease.</jats:p>

Original publication

DOI

10.1101/430538

Type

Publisher

Cold Spring Harbor Laboratory

Publication Date

30/09/2018