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

ELife
Bernadette C YoungCatrin E Moore

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.

References

Oct 5, 1990·Journal of Molecular Biology·S F AltschulD J Lipman
Dec 11, 2002·The Journal of Bone and Joint Surgery. American Volume·J BickelsS Wientroub
May 20, 2003·Journal of Bacteriology·Edward J FeilNicholas P J Day
May 13, 2004·Postgraduate Medical Journal·S ChauhanS S Chauhan
Jun 24, 2004·Proceedings of the National Academy of Sciences of the United States of America·Matthew T G HoldenJulian Parkhill
Jul 3, 2004·Genome Research·Aaron C E DarlingNicole T Perna
Sep 20, 2006·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Pia S PannarajSheldon L Kaplan
Jan 20, 2007·Science·Maria Labandeira-ReyM Gabriela Bowden
Mar 20, 2008·Genome Research·Daniel R Zerbino, Ewan Birney
Dec 10, 2009·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Deborah LehmanGeorge Y Liu
Oct 29, 2010·Genome Research·Gerton Lunter, Martin Goodson
Feb 5, 2011·The American Journal of Tropical Medicine and Hygiene·Emma K NickersonSharon J Peacock
Feb 8, 2011·Nature Medicine·Michael Otto
Mar 6, 2012·Nature Methods·Ben Langmead, Steven L Salzberg
Mar 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Bernadette C YoungDaniel J Wilson
Jun 19, 2012·Nature Genetics·Xiang Zhou, Matthew Stephens
Jul 24, 2012·Transactions of the Royal Society of Tropical Medicine and Hygiene·Alvaro H D BorgesDavid G Lalloo
Aug 25, 2012·Frontiers in Cellular and Infection Microbiology·Alex J McCarthyJodi A Lindsay
Oct 30, 2012·The Lancet Infectious Diseases·Laura J ShallcrossAndrew C Hayward
Oct 30, 2012·The Lancet Infectious Diseases·Nicholas P J Day
Dec 25, 2012·Genome Biology·Xavier DidelotRosalind M Harding
Dec 25, 2012·Emerging Infectious Diseases·Coralith GarcíaJan Jacobs
Jan 18, 2013·Bioinformatics·Guillaume RizkRayan Chikhi
May 11, 2013·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Guoqing Xia, Christiane Wolz
May 21, 2013·Cell Host & Microbe·András N SpaanJos A G van Strijp
Jul 3, 2013·Proceedings of the National Academy of Sciences of the United States of America·Samuel K SheppardDaniel Falush
Feb 7, 2014·Journal of Clinical Microbiology·N C GordonT Golubchik
Jul 2, 2014·The Pediatric Infectious Disease Journal·Paul MoriartyClare Nourse
Feb 13, 2015·PLoS Computational Biology·Xavier Didelot, Daniel J Wilson
Feb 18, 2016·Current Infectious Disease Reports·Sanjay Verma
Aug 31, 2016·Nature Microbiology·Daniel Falush
Sep 17, 2016·Nature Communications·John A LeesJukka Corander
Nov 15, 2016·Nature Reviews. Genetics·Robert A PowerTulio de Oliveira

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Citations

Jan 9, 2020·Microbial Genomics·Stefano G GiulieriDeborah A Williamson
Mar 29, 2020·Tropical Medicine & International Health : TM & IH·Adebayo ShittuFrieder Schaumburg
Feb 23, 2020·Frontiers in Microbiology·James Emmanuel SanTulio de Oliveira
Jan 24, 2021·Anales de pediatría : publicación oficial de la Asociación Española de Pediatría (A.E.P.)·Leyre López FernándezLaura Cuadrado Piqueras
Jul 30, 2019·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·E JauneikaiteL E Lamb
Mar 4, 2021·The Pediatric Infectious Disease Journal·Deianira PedotoRoberto Della Casa
Jul 15, 2021·The Pediatric Infectious Disease Journal·Meltem Polat, Nuran Sabir
Aug 19, 2021·Tropical Medicine & International Health : TM & IH·Chamnab NgorCharles F Gilks
Aug 20, 2021·Journal of Pediatric Orthopedics·Neeraj VijMohan V Belthur

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Datasets Mentioned

BETA
CP000255.1
PRJNA418899

Methods Mentioned

BETA
Illumina sequencing

Software Mentioned

RAxML
R scripts
dsk
GEMMA
R package bugwas
bacterialGWAS
ClonalFrameML
Unicycler
BLAST
filtlong

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