Young, BC;
Earle, SG;
Soeng, S;
Sar, P;
Kumar, V;
Hor, S;
Sar, V;
Bousfield, R;
Sanderson, ND;
Barker, L;
et al.
Young, BC; Earle, SG; Soeng, S; Sar, P; Kumar, V; Hor, S; Sar, V; Bousfield, R; Sanderson, ND; Barker, L; Stoesser, N; Emary, KR; Parry, CM; Nickerson, EK; Turner, P; Bowden, R; Crook, DW; Wyllie, DH; Day, NP; Wilson, DJ; Moore, CE
(2019)
Panton-Valentine leucocidin is the key determinant of Staphylococcus aureus pyomyositis in a bacterial GWAS.
Elife, 8.
ISSN 2050-084X
https://doi.org/10.7554/eLife.42486
SGUL Authors: Moore, Catrin Elisabeth
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Abstract
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.
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