Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; NIHR Oxford Biomedical Research Centre, Infection Theme, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, United Kingdom
Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
Sona Soeng
Cambodia Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia
Poda Sar
Cambodia Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia
Varun Kumar
Department of Pediatrics, East Tennessee State University Quillen College of Medicine, Johnson City, United States
Songly Hor
Cambodia Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia
Vuthy Sar
Cambodia Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia
Rachel Bousfield
Department of Infectious Diseases, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
Nicholas D Sanderson
Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
Leanne Barker
Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
Nicole Stoesser
Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; Public Health England Academic Collaborating Centre, John Radcliffe Hospital, Oxford, United Kingdom
Katherine RW Emary
NIHR Oxford Biomedical Research Centre, Infection Theme, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, United Kingdom
Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan
Emma K Nickerson
Department of Infectious Diseases, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
Cambodia Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; NIHR Oxford Biomedical Research Centre, Infection Theme, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, United Kingdom; Public Health England Academic Collaborating Centre, John Radcliffe Hospital, Oxford, United Kingdom
David H Wyllie
Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; Public Health England Academic Collaborating Centre, John Radcliffe Hospital, Oxford, United Kingdom; The Jenner Institute Laboratories, University of Oxford, Oxford, United Kingdom
Nicholas PJ Day
Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Institute for Emerging Infections, Oxford Martin School, University of Oxford, Oxford, United Kingdom
Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
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.
