Panton-Valentine leucocidin is the key determinant of Staphylococcus aureus pyomyositis in a bacterial GWAS
- University of Oxford, United Kingdom
- Cambodia Oxford Medical Research Unit, Cambodia
- East Tennessee State University, United States
- Cambridge University Hospitals NHS Foundation Trust, United Kingdom
- Oxford University Hospitals NHS Foundation Trust, United Kingdom
- Liverpool School of Tropical Medicine, United Kingdom
- Wellcome Trust Center Human Genetics, United Kingdom
- Mahidol University, Thailand
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 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.
Data availability
Sequence data has been submitted to Short Read Archive (Bioproject ID PRJNA418899).
Article and author information
Author details
Bernadette C Young
Funding
Wellcome (089275/H/09/Z)
- Nicholas PJ Day
University Of Oxford (MRF/MT2015/2180)
- Catrin E Moore
Royal Society (101237/Z/13/Z)
- Daniel J Wilson
National Institute for Health Research
- Daniel J Wilson
Seventh Framework Programme (601783)
- David J Wyllie
Wellcome (090532/Z/09/Z)
- Rory Bowden
Wellcome (089275/Z/09/Z)
- Nicholas PJ Day
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Julian Parkhill, The Wellcome Trust Sanger Institute, United Kingdom
Ethics
Human subjects: Approval for this study was provided by the AHC institutional review board and the Oxford Tropical Ethics Committee (507-12).
Version history
- Received: October 1, 2018
- Accepted: February 21, 2019
- Accepted Manuscript published: February 22, 2019 (version 1)
- Version of Record published: April 10, 2019 (version 2)
Copyright
© 2019, Young et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Panton-Valentine leucocidin is the key determinant of Staphylococcus aureus pyomyositis in a bacterial GWAS
eLife 8:e42486.
https://doi.org/10.7554/eLife.42486
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