The role of interspecies recombinations in the evolution of antibiotic resistant pneumococci

  1. Joshua Charles D'Aeth  Is a corresponding author
  2. Mark P G van der Linden
  3. Lesley McGee
  4. Herminia De Lencastre
  5. Paul Turner
  6. Jae-Hoon Song
  7. Stephanie W Lo
  8. Rebecca A Gladstone
  9. Raquel Sa-Leao
  10. Kwan Soo Ko
  11. William P Hanage
  12. Robert F Breiman
  13. Bernard Beall
  14. Stephen D Bentley
  15. Nicholas J Croucher  Is a corresponding author
  16. The GPS Consortium
  1. Imperial College London, United Kingdom
  2. RWTH Aachen, Germany
  3. Centers for Disease Control and Prevention, United States
  4. Universidade Nova de Lisboa, Portugal
  5. Cambodia Oxford Medical Research Unit, Cambodia
  6. Sungkyunwan University School of Medicine, Republic of Korea
  7. Wellcome Trust Sanger Institute, United Kingdom
  8. Instituto de Tecnologia Química e Biológica, Portugal
  9. Sungkyunwan University School of Medicine, Korea (South), Republic of
  10. Harvard T.H Chan School of Public Health, United States
  11. Emory University, United States

Abstract

Multidrug-resistant Streptococcus pneumoniae emerge through the modification of core genome loci through short inter­species homologous recombinations and acquisition of gene cassettes. Both occurred in the otherwise contrasting histories of the antibiotic-resistant S. pneumoniae lineages PMEN3 and PMEN9. A single PMEN3 clade spread globally, evading vaccine-induced immunity through frequent serotype switching, whereas locally-circulating PMEN9 clades independently gained resistance. Both lineages repeatedly integrated Tn916 and Tn1207.1, conferring tetracycline and macrolide resistance respectively, through homologous recombination importing sequences originating in other species. A species-wide dataset found over 100 instances of such interspecific acquisitions of resistance cassettes and flanking homologous arms. Phylodynamic analysis of the most commonly-sampled Tn1207.1 insertion in PMEN9, originating from a commensal and disrupting a competence gene, suggested its expansion across Germany was driven by a high ratio of macrolide-to-β-lactam consumption. Hence selection from antibiotic consumption was sufficient for these atypically large recombinations to overcome species boundaries across the pneumococcal chromosome.

Data availability

All Sequencing data comes from publically available previously published datasets. All sequences used and their accession codes are available in the supporting S1 table.All figure source data has been deposited at Figshare, https://doi.org/10.6084/m9.figshare.c.5306462.v1

The following previously published data sets were used

Article and author information

Author details

  1. Joshua Charles D'Aeth

    Infectious disease epidemiology, Imperial College London, London, United Kingdom
    For correspondence
    j.daeth17@imperial.ac.uk
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9636-9886
  2. Mark P G van der Linden

    Institue for Medical Microbiology; National reference Center for Streptococci; University Hospital RWTH Aachen, RWTH Aachen, Aachen, Germany
    Competing interests
    No competing interests declared.
  3. Lesley McGee

    Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, United States
    Competing interests
    No competing interests declared.
  4. Herminia De Lencastre

    Laboratory of Molecular Genetics; Instituo de Tecnologia Quimica e Biologica, Universidade Nova de Lisboa, Oeiras, Portugal
    Competing interests
    No competing interests declared.
  5. Paul Turner

    Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Cambodia Oxford Medical Research Unit, Siem Reap, Cambodia
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1013-7815
  6. Jae-Hoon Song

    Department of Medicine, Sungkyunwan University School of Medicine, Suwon, Republic of Korea
    Competing interests
    No competing interests declared.
  7. Stephanie W Lo

    Infection Genomics, Wellcome Trust Sanger Institute, Hinxton, United Kingdom
    Competing interests
    No competing interests declared.
  8. Rebecca A Gladstone

    Infection Genomics, Wellcome Trust Sanger Institute, Hinxton, United Kingdom
    Competing interests
    No competing interests declared.
  9. Raquel Sa-Leao

    Instituto de Tecnologia Química e Biológica, Oeiras, Portugal
    Competing interests
    No competing interests declared.
  10. Kwan Soo Ko

    Department of Molecular Cell Biology, Sungkyunwan University School of Medicine, Suwon, Korea (South), Republic of
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0978-1937
  11. William P Hanage

    Center for Communicable Disease Dynamics, Harvard T.H Chan School of Public Health, Boston, United States
    Competing interests
    No competing interests declared.
  12. Robert F Breiman

    Emory University, Atlanta, United States
    Competing interests
    No competing interests declared.
  13. Bernard Beall

    Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, United States
    Competing interests
    No competing interests declared.
  14. Stephen D Bentley

    Infection Genomics, Wellcome Trust Sanger Institute, Hinxton, United Kingdom
    Competing interests
    No competing interests declared.
  15. Nicholas J Croucher

    Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom
    For correspondence
    n.croucher@imperial.ac.uk
    Competing interests
    Nicholas J Croucher, has consulted for Antigen Discovery Inc. Has received an investigator-initiated award from GlaxoSmithKline..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6303-8768
  16. The GPS Consortium

Funding

Wellcome Trust (102169/Z/13/Z)

  • Joshua Charles D'Aeth

Medical Research Council (MR/R015600/1)

  • Joshua Charles D'Aeth
  • Nicholas J Croucher

Department for International Development (MR/T016434/1)

  • Joshua Charles D'Aeth
  • Nicholas J Croucher

Wellcome Trust and Royal Society (104169/Z/14/A)

  • Nicholas J Croucher

Bill and Melinda Gates Foundation (OPP1034556)

  • Stephanie W Lo
  • Rebecca A Gladstone
  • Stephen D Bentley

Wellcome Trust (098051 and 206194)

  • Stephanie W Lo
  • Rebecca A Gladstone
  • Stephen D Bentley

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

Reviewing Editor

  1. Paul B Rainey, Max Planck Institute for Evolutionary Biology, Germany

Version history

  1. Received: February 1, 2021
  2. Accepted: April 16, 2021
  3. Accepted Manuscript published: July 14, 2021 (version 1)
  4. Version of Record published: July 29, 2021 (version 2)
  5. Version of Record updated: August 16, 2021 (version 3)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Joshua Charles D'Aeth
  2. Mark P G van der Linden
  3. Lesley McGee
  4. Herminia De Lencastre
  5. Paul Turner
  6. Jae-Hoon Song
  7. Stephanie W Lo
  8. Rebecca A Gladstone
  9. Raquel Sa-Leao
  10. Kwan Soo Ko
  11. William P Hanage
  12. Robert F Breiman
  13. Bernard Beall
  14. Stephen D Bentley
  15. Nicholas J Croucher
  16. The GPS Consortium
(2021)
The role of interspecies recombinations in the evolution of antibiotic resistant pneumococci
eLife 10:e67113.
https://doi.org/10.7554/eLife.67113

Share this article

https://doi.org/10.7554/eLife.67113

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