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

<jats:p>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....

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Main Authors: Young, BC, Earle, SG, Soeng, S, Sar, P, Kumar, V, Hor, S, Sar, V, Bousfield, R, Sanderson, ND, Barker, L, Stoesser, N, Emary, KRW, Parry, CM, Nickerson, EK, Turner, P, Bowden, R, Crook, DW, Wyllie, DJ, Day, NPJ, Wilson, DJ, Moore, CE
Format: Journal article
Language:English
Published: eLife Sciences 2019
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author Young, BC
Earle, SG
Soeng, S
Sar, P
Kumar, V
Hor, S
Sar, V
Bousfield, R
Sanderson, ND
Barker, L
Stoesser, N
Emary, KRW
Parry, CM
Nickerson, EK
Turner, P
Bowden, R
Crook, DW
Wyllie, DJ
Day, NPJ
Wilson, DJ
Moore, CE
author_facet Young, BC
Earle, SG
Soeng, S
Sar, P
Kumar, V
Hor, S
Sar, V
Bousfield, R
Sanderson, ND
Barker, L
Stoesser, N
Emary, KRW
Parry, CM
Nickerson, EK
Turner, P
Bowden, R
Crook, DW
Wyllie, DJ
Day, NPJ
Wilson, DJ
Moore, CE
author_sort Young, BC
collection OXFORD
description <jats:p>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.</jats:p>
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spelling oxford-uuid:f733ecf5-f65f-4efc-99e0-28800c98f8672022-03-27T12:41:17ZPanton-Valentine leucocidin is the key determinant of Staphylococcus aureus pyomyositis in a bacterial GWASJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f733ecf5-f65f-4efc-99e0-28800c98f867EnglishSymplectic Elements at OxfordeLife Sciences2019Young, BCEarle, SGSoeng, SSar, PKumar, VHor, SSar, VBousfield, RSanderson, NDBarker, LStoesser, NEmary, KRWParry, CMNickerson, EKTurner, PBowden, RCrook, DWWyllie, DJDay, NPJWilson, DJMoore, CE<jats:p>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.</jats:p>
spellingShingle Young, BC
Earle, SG
Soeng, S
Sar, P
Kumar, V
Hor, S
Sar, V
Bousfield, R
Sanderson, ND
Barker, L
Stoesser, N
Emary, KRW
Parry, CM
Nickerson, EK
Turner, P
Bowden, R
Crook, DW
Wyllie, DJ
Day, NPJ
Wilson, DJ
Moore, CE
Panton-Valentine leucocidin is the key determinant of Staphylococcus aureus pyomyositis in a bacterial GWAS
title Panton-Valentine leucocidin is the key determinant of Staphylococcus aureus pyomyositis in a bacterial GWAS
title_full Panton-Valentine leucocidin is the key determinant of Staphylococcus aureus pyomyositis in a bacterial GWAS
title_fullStr Panton-Valentine leucocidin is the key determinant of Staphylococcus aureus pyomyositis in a bacterial GWAS
title_full_unstemmed Panton-Valentine leucocidin is the key determinant of Staphylococcus aureus pyomyositis in a bacterial GWAS
title_short Panton-Valentine leucocidin is the key determinant of Staphylococcus aureus pyomyositis in a bacterial GWAS
title_sort panton valentine leucocidin is the key determinant of staphylococcus aureus pyomyositis in a bacterial gwas
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