Panton–Valentine leucocidin is the key determinant of Staphylococcus aureus pyomyositis in a bacterial GWAS
Year: 2019
Type: article
Study design: Observational Study
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.
Source: eLife
DOI: 10.7554/elife.42486
Authors: Bernadette C Young, Sarah G Earle, Sona Soeng, Poda Sar, Varun Kumar, Songly Hor, Vuthy Sar, Rachel Bousfield, Nicholas D Sanderson, Leanne Barker, Nicole Stoesser, Katherine RW Emary, Christopher M Parry, Emma K Nickerson, Paul Turner, Rory Bowden, Derrick Crook, David Wyllie, Nicholas PJ Day, Daniel J Wilson, Catrin E Moore
Institutions: John Radcliffe Hospital, University of Oxford, NIHR Oxford Biomedical Research Centre, Angkor Hospital for Children, Cambodia-Oxford Medical Research Unit, East Tennessee State University, Cambridge University Hospitals NHS Foundation Trust, Public Health England, Liverpool School of Tropical Medicine, Nagasaki University, Centre for Human Genetics, Jenner Institute, Mahidol University, Mahidol Oxford Tropical Medicine Research Unit
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,500
Awards: G1198837610, G1205803525, Thailand Major Overseas Programme Core Grant Renewal 2010 to 2015., comBinig cELLular and humoral immunE RespOnses as a vaccine strategy against staPHhylOcoccus aureus pathogeN, G220799409, G2864667310, G3174266458, G3797955763, Investigating the natural variability in virulence of Staphylococcus aureus using whole genome sequencing, Thailand Major Overseas Programme Core Grant Renewal 2010 to 2015., G6217217735, G6723475937, Understanding the genetic basis of common human diseases: core funding for the Wellcome Trust Centre for Human Genetics., Thailand Major Overseas Programme Core Grant Renewal 2010 to 2015., G7888126997, Statistical Methods for Whole Genome Phenotype Mapping in Bacterial Populations.
OpenAlex ID: W2915215930