Young, BC;
Earle, SG;
Soeng, S;
Sar, P;
Kumar, V;
Hor, S;
Sar, V;
Bousfield, R;
Sanderson, ND;
Barker, L;
et al.
Young, BC; Earle, SG; Soeng, S; Sar, P; Kumar, V; Hor, S; Sar, V; Bousfield, R; Sanderson, ND; Barker, L; Stoesser, N; Emary, KR; Parry, CM; Nickerson, EK; Turner, P; Bowden, R; Crook, DW; Wyllie, DH; Day, NP; Wilson, DJ; Moore, CE
(2019)
Panton-Valentine leucocidin is the key determinant of Staphylococcus aureus pyomyositis in a bacterial GWAS.
Elife, 8.
ISSN 2050-084X
https://doi.org/10.7554/eLife.42486
SGUL Authors: Moore, Catrin Elisabeth
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.
Item Type: |
Article
|
Additional Information: |
© 2019, Young et al.
This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited. |
Keywords: |
Cambodia, Staphylococcus aureus, genetics, genome-wide association study, genomics, infectious disease, microbiology, pyomyositis, Bacterial Toxins, Cambodia, Exotoxins, Genome-Wide Association Study, Humans, Leukocidins, Pyomyositis, Staphylococcal Infections, Staphylococcus aureus, Virulence Factors, Humans, Staphylococcus aureus, Staphylococcal Infections, Bacterial Toxins, Leukocidins, Exotoxins, Virulence Factors, Cambodia, Pyomyositis, Genome-Wide Association Study, 0601 Biochemistry and Cell Biology |
SGUL Research Institute / Research Centre: |
Academic Structure > Infection and Immunity Research Institute (INII) |
Journal or Publication Title: |
Elife |
ISSN: |
2050-084X |
Language: |
eng |
Dates: |
Date | Event |
---|
10 April 2019 | Published | 22 February 2019 | Published Online | 21 February 2019 | Accepted |
|
Publisher License: |
Publisher's own licence |
Projects: |
|
PubMed ID: |
30794157 |
Web of Science ID: |
WOS:000464106400001 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/114463 |
Publisher's version: |
https://doi.org/10.7554/eLife.42486 |
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