1. Epidemiology and Global Health
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Improved characterisation of MRSA transmission using within-host bacterial sequence diversity

  1. Matthew D Hall  Is a corresponding author
  2. Matthew TG Holden
  3. Pramot Srisomang
  4. Weera Mahavanakul
  5. Vanaporn Wuthiekanun
  6. Direk Limmathurotsakul
  7. Kay Fountain
  8. Julian Parkhill
  9. Emma K Nickerson
  10. Sharon J Peacock
  11. Christophe Fraser
  1. University of Oxford, United Kingdom
  2. University of St Andrews, United Kingdom
  3. Sunpasitthiprasong Hospital, Thailand
  4. Mahidol University, Thailand
  5. University of Cambridge, United Kingdom
  6. Cambridge University Hospitals NHS Foundation Trust, United Kingdom
Research Article
  • Cited 2
  • Views 1,301
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Cite this article as: eLife 2019;8:e46402 doi: 10.7554/eLife.46402

Abstract

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 use 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 a wide range 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.

Article and author information

Author details

  1. Matthew D Hall

    Big Data Institute, University of Oxford, Oxford, United Kingdom
    For correspondence
    matthew.hall@bdi.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2671-3864
  2. Matthew TG Holden

    School of Medicine, University of St Andrews, St Andrews, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4958-2166
  3. Pramot Srisomang

    Department of Pediatrics, Sunpasitthiprasong Hospital, Ubon Ratchathani, Thailand
    Competing interests
    The authors declare that no competing interests exist.
  4. Weera Mahavanakul

    Department of Medicine, Sunpasitthiprasong Hospital, Ubon Ratchathani, Thailand
    Competing interests
    The authors declare that no competing interests exist.
  5. Vanaporn Wuthiekanun

    Mahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand
    Competing interests
    The authors declare that no competing interests exist.
  6. Direk Limmathurotsakul

    Mahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7240-5320
  7. Kay Fountain

    Mahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9984-5702
  8. Julian Parkhill

    Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Emma K Nickerson

    Department of Infectious Diseases, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. Sharon J Peacock

    Department of Medicine, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  11. Christophe Fraser

    Big Data Institute, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

Funding

Wellcome (098051)

  • Matthew TG Holden
  • Sharon J Peacock

Chief Scientist Office (SIRN10)

  • Matthew TG Holden

Wellcome (106698/Z/14/Z)

  • Vanaporn Wuthiekanun

Medical Research Council (G1000803)

  • Sharon J Peacock

European Research Council (PBDR-339251)

  • Matthew D Hall
  • Christophe Fraser

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: Ethical approval was obtained from the Ethical and Scientific Review subcommittee of the Royal Thai Government Ministry of Public Health (85/2550), and the Oxford Tropical Research Ethics Committee (024 07). All patients admitted to the two ICUs were eligible for inclusion and were enrolled after written informed consent, and consent to publish, was obtained.

Reviewing Editor

  1. Mark Jit, London School of Hygiene & Tropical Medicine, and Public Health England, United Kingdom

Publication history

  1. Received: February 26, 2019
  2. Accepted: October 1, 2019
  3. Accepted Manuscript published: October 8, 2019 (version 1)
  4. Accepted Manuscript updated: October 11, 2019 (version 2)
  5. Version of Record published: January 10, 2020 (version 3)
  6. Version of Record updated: January 14, 2020 (version 4)

Copyright

© 2019, Hall et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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