Panton–Valentine leucocidin is the key determinant of Staphylococcus aureus pyomyositis in a bacterial GWAS
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 cultur...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
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eLife Sciences Publications Ltd
2019-02-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/42486 |
| _version_ | 1811201047923785728 |
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| author | Bernadette C Young Sarah G Earle Sona Soeng Poda Sar Varun Kumar Songly Hor Vuthy Sar Rachel Bousfield Nicholas D Sanderson Leanne Barker Nicole Stoesser Katherine RW Emary Christopher M Parry Emma K Nickerson Paul Turner Rory Bowden Derrick W Crook David H Wyllie Nicholas PJ Day Daniel J Wilson Catrin E Moore |
| author_facet | Bernadette C Young Sarah G Earle Sona Soeng Poda Sar Varun Kumar Songly Hor Vuthy Sar Rachel Bousfield Nicholas D Sanderson Leanne Barker Nicole Stoesser Katherine RW Emary Christopher M Parry Emma K Nickerson Paul Turner Rory Bowden Derrick W Crook David H Wyllie Nicholas PJ Day Daniel J Wilson Catrin E Moore |
| author_sort | Bernadette C Young |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T02:15:18Z |
| format | Article |
| id | doaj.art-196e44408db54cd89c458671036950d8 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:15:18Z |
| publishDate | 2019-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-196e44408db54cd89c458671036950d82022-12-22T03:52:16ZengeLife Sciences Publications LtdeLife2050-084X2019-02-01810.7554/eLife.42486Panton–Valentine leucocidin is the key determinant of Staphylococcus aureus pyomyositis in a bacterial GWASBernadette C Young0https://orcid.org/0000-0001-6071-6770Sarah G Earle1https://orcid.org/0000-0002-0738-7557Sona Soeng2Poda Sar3Varun Kumar4Songly Hor5Vuthy Sar6Rachel Bousfield7Nicholas D Sanderson8Leanne Barker9Nicole Stoesser10Katherine RW Emary11Christopher M Parry12https://orcid.org/0000-0001-7563-7282Emma K Nickerson13Paul Turner14https://orcid.org/0000-0002-1013-7815Rory Bowden15https://orcid.org/0000-0001-8596-0366Derrick W Crook16https://orcid.org/0000-0002-0590-2850David H Wyllie17Nicholas PJ Day18Daniel J Wilson19https://orcid.org/0000-0002-0940-3311Catrin E Moore20https://orcid.org/0000-0002-8639-9846Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; NIHR Oxford Biomedical Research Centre, Infection Theme, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, United KingdomNuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United KingdomCambodia Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, CambodiaCambodia Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, CambodiaDepartment of Pediatrics, East Tennessee State University Quillen College of Medicine, Johnson City, United StatesCambodia Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, CambodiaCambodia Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, CambodiaDepartment of Infectious Diseases, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United KingdomNuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United KingdomNuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United KingdomNuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; Public Health England Academic Collaborating Centre, John Radcliffe Hospital, Oxford, United KingdomNIHR Oxford Biomedical Research Centre, Infection Theme, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, United KingdomClinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, JapanDepartment of Infectious Diseases, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United KingdomCambodia Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United KingdomWellcome Centre for Human Genetics, University of Oxford, Oxford, United KingdomNuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; NIHR Oxford Biomedical Research Centre, Infection Theme, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, United Kingdom; Public Health England Academic Collaborating Centre, John Radcliffe Hospital, Oxford, United KingdomNuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; Public Health England Academic Collaborating Centre, John Radcliffe Hospital, Oxford, United Kingdom; The Jenner Institute Laboratories, University of Oxford, Oxford, United KingdomCentre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United KingdomNuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Institute for Emerging Infections, Oxford Martin School, University of Oxford, Oxford, United KingdomCentre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, ThailandPyomyositis 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.https://elifesciences.org/articles/42486Staphylococcus aureuspyomyositisCambodiagenome-wide association study |
| spellingShingle | Bernadette C Young Sarah G Earle Sona Soeng Poda Sar Varun Kumar Songly Hor Vuthy Sar Rachel Bousfield Nicholas D Sanderson Leanne Barker Nicole Stoesser Katherine RW Emary Christopher M Parry Emma K Nickerson Paul Turner Rory Bowden Derrick W Crook David H Wyllie Nicholas PJ Day Daniel J Wilson Catrin E Moore Panton–Valentine leucocidin is the key determinant of Staphylococcus aureus pyomyositis in a bacterial GWAS eLife Staphylococcus aureus pyomyositis Cambodia genome-wide association study |
| 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 |
| topic | Staphylococcus aureus pyomyositis Cambodia genome-wide association study |
| url | https://elifesciences.org/articles/42486 |
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