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 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.
| Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:etsu-works-11295 |
| Date | 01 February 2019 |
| Creators | Young, Bernadette C., Earle, Sarah G., Soeng, Sona, Sar, Poda, Kumar, Varun, Hor, Songly, Sar, Vuthy, Bousfield, Rachel, Sanderson, Nicholas D., Barker, Leanne, Stoesser, Nicole, Emary, Katherine R.W., Parry, Christopher M., Nickerson, Emma K., Turner, Paul, Bowden, Rory, Crook, Derrick, Wyllie, David, Day, Nicholas P.J., Wilson, Daniel J., Moore, Catrin E. |
| Publisher | Digital Commons @ East Tennessee State University |
| Source Sets | East Tennessee State University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | ETSU Faculty Works |
| Rights | http://creativecommons.org/licenses/by/4.0/ |
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