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Panton-Valentine leucocidin is the key determinant of Staphylococcus aureus pyomyositis in a bacterial GWAS

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Young, Bernadette C, Earle, Sarah G, Soeng, Sona, Sar, Poda, Kumar, Varun, Hor, Songly, Sar, Vuthy, Bousfield, Rachel, Sanderson, Nicholas D, Barker, Leanne, Stoesser, Nicole, Emary, Katherine Rw, Parry, Christopher, Nickerson, Emma K, Turner, Paul, Bowden, Rory, Crook, Derrick W, Wyllie, David J, Day, Nicholas Pj, Wilson, Daniel J and Moore, Catrin E (2019) 'Panton-Valentine leucocidin is the key determinant of Staphylococcus aureus pyomyositis in a bacterial GWAS'. eLife, Vol 8, e42486.

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Abstract

Pyomyositis is a severe bacterial infection of skeletal muscle, commonly affecting children in tropical regions, predominantly caused by . To understand the contribution of bacterial genomic factors to pyomyositis, we conducted a genome-wide association study of 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 (=10). 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.

Item Type: Article
Subjects: QW Microbiology and Immunology > Bacteria > QW 142 Gram-positive bacteria (General)
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 680 Tropical diseases (General)
WE Musculoskeletal System > WE 140 Diseases (General)
WE Musculoskeletal System > WE 20 Research (General)
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.7554/eLife.42486.001
Depositing User: Stacy Murtagh
Date Deposited: 18 Mar 2019 11:10
Last Modified: 01 May 2019 09:23
URI: https://archive.lstmed.ac.uk/id/eprint/10397

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