Improved characterisation of MRSA transmission using within-host bacterial sequence diversity

Methicillin-resistant Staphylococcus aureus (MRSA) transmission in the hospital setting has been a frequent subject of investigation using bacterial genomes, but previous approaches have not yet fully utilised the extra deductive power provided when multiple pathogen samples are acquired from each h...

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Main Authors: Matthew D Hall, Matthew TG Holden, Pramot Srisomang, Weera Mahavanakul, Vanaporn Wuthiekanun, Direk Limmathurotsakul, Kay Fountain, Julian Parkhill, Emma K Nickerson, Sharon J Peacock, Christophe Fraser
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2019-10-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/46402
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spelling doaj-1d33e95379324f4d93e8ef4b57bf93252021-05-05T17:59:03ZengeLife Sciences Publications LtdeLife2050-084X2019-10-01810.7554/eLife.46402Improved characterisation of MRSA transmission using within-host bacterial sequence diversityMatthew D Hall0https://orcid.org/0000-0002-2671-3864Matthew TG Holden1https://orcid.org/0000-0002-4958-2166Pramot Srisomang2Weera Mahavanakul3Vanaporn Wuthiekanun4Direk Limmathurotsakul5https://orcid.org/0000-0001-7240-5320Kay Fountain6https://orcid.org/0000-0002-9984-5702Julian Parkhill7Emma K Nickerson8Sharon J Peacock9Christophe Fraser10Big Data Institute, University of Oxford, Oxford, United KingdomSchool of Medicine, University of St Andrews, St Andrews, United KingdomDepartment of Pediatrics, Sunpasitthiprasong Hospital, Ubon Ratchathani, ThailandDepartment of Medicine, Sunpasitthiprasong Hospital, Ubon Ratchathani, ThailandMahidol Oxford Tropical Medicine Research Unit, Mahidol University, Salaya, ThailandMahidol Oxford Tropical Medicine Research Unit, Mahidol University, Salaya, ThailandDepartment of Biology and Biochemistry, University of Bath, Bath, United KingdomDepartment of Veterinary Medicine, University of Cambridge, Cambridge, United KingdomDepartment of Infectious Diseases, Cambridge University Hospitals NHS Foundation, Cambridge, United KingdomDepartment of Medicine, University of Cambridge, Cambridge, United KingdomBig Data Institute, University of Oxford, Oxford, United KingdomMethicillin-resistant Staphylococcus aureus (MRSA) transmission in the hospital setting has been a frequent subject of investigation using bacterial genomes, but previous approaches have not yet fully utilised the extra deductive power provided when multiple pathogen samples are acquired from each host. Here, we used a large dataset of MRSA sequences from multiply-sampled patients to reconstruct colonisation of individuals in a high-transmission setting in a hospital in Thailand. We reconstructed transmission trees for MRSA. We also investigated transmission between anatomical sites on the same individual, finding that this either occurs repeatedly or involves a wide transmission bottleneck. We examined the between-subject bottleneck, finding considerable variation in the amount of diversity transmitted. Finally, we compared our approach to the simpler method of identifying transmission pairs using single nucleotide polymorphism (SNP) counts. This suggested that the optimum threshold for identifying a pair is 39 SNPs, if sensitivities and specificities are equally weighted.https://elifesciences.org/articles/46402molecular epidemiologyMRSAhospital infections
collection DOAJ
language English
format Article
sources DOAJ
author Matthew D Hall
Matthew TG Holden
Pramot Srisomang
Weera Mahavanakul
Vanaporn Wuthiekanun
Direk Limmathurotsakul
Kay Fountain
Julian Parkhill
Emma K Nickerson
Sharon J Peacock
Christophe Fraser
spellingShingle Matthew D Hall
Matthew TG Holden
Pramot Srisomang
Weera Mahavanakul
Vanaporn Wuthiekanun
Direk Limmathurotsakul
Kay Fountain
Julian Parkhill
Emma K Nickerson
Sharon J Peacock
Christophe Fraser
Improved characterisation of MRSA transmission using within-host bacterial sequence diversity
eLife
molecular epidemiology
MRSA
hospital infections
author_facet Matthew D Hall
Matthew TG Holden
Pramot Srisomang
Weera Mahavanakul
Vanaporn Wuthiekanun
Direk Limmathurotsakul
Kay Fountain
Julian Parkhill
Emma K Nickerson
Sharon J Peacock
Christophe Fraser
author_sort Matthew D Hall
title Improved characterisation of MRSA transmission using within-host bacterial sequence diversity
title_short Improved characterisation of MRSA transmission using within-host bacterial sequence diversity
title_full Improved characterisation of MRSA transmission using within-host bacterial sequence diversity
title_fullStr Improved characterisation of MRSA transmission using within-host bacterial sequence diversity
title_full_unstemmed Improved characterisation of MRSA transmission using within-host bacterial sequence diversity
title_sort improved characterisation of mrsa transmission using within-host bacterial sequence diversity
publisher eLife Sciences Publications Ltd
series eLife
issn 2050-084X
publishDate 2019-10-01
description Methicillin-resistant Staphylococcus aureus (MRSA) transmission in the hospital setting has been a frequent subject of investigation using bacterial genomes, but previous approaches have not yet fully utilised the extra deductive power provided when multiple pathogen samples are acquired from each host. Here, we used a large dataset of MRSA sequences from multiply-sampled patients to reconstruct colonisation of individuals in a high-transmission setting in a hospital in Thailand. We reconstructed transmission trees for MRSA. We also investigated transmission between anatomical sites on the same individual, finding that this either occurs repeatedly or involves a wide transmission bottleneck. We examined the between-subject bottleneck, finding considerable variation in the amount of diversity transmitted. Finally, we compared our approach to the simpler method of identifying transmission pairs using single nucleotide polymorphism (SNP) counts. This suggested that the optimum threshold for identifying a pair is 39 SNPs, if sensitivities and specificities are equally weighted.
topic molecular epidemiology
MRSA
hospital infections
url https://elifesciences.org/articles/46402
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