Panton-Valentine leukocidin is the key determinant of Staphylococcus aureus pyomyositis in a bacterial genome-wide association study
Young B., Earle S., Soeng S., Sar P., Kumar V., Hor S., Sar V., Bousfield R., Sanderson N., Barker L., Stoesser N., Emary KRW., Parry C., Nickerson E., Turner P., Bowden R., Crook D., Wyllie D., Day NPJ., Wilson DJ., Moore C.
Pyomyositis is a severe bacterial infection of skeletal muscle, commonly affecting children in tropical regions and 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 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 leukocidin (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 >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.