The role of interspecies recombinations in the evolution of antibiotic resistant pneumococci
- Imperial College London, United Kingdom
- RWTH Aachen, Germany
- Centers for Disease Control and Prevention, United States
- Universidade Nova de Lisboa, Portugal
- Cambodia Oxford Medical Research Unit, Cambodia
- Sungkyunwan University School of Medicine, Republic of Korea
- Wellcome Trust Sanger Institute, United Kingdom
- Instituto de Tecnologia Química e Biológica, Portugal
- Sungkyunwan University School of Medicine, Korea (South), Republic of
- Harvard T.H Chan School of Public Health, United States
- 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
Article and author information
Author details
Joshua Charles D'Aeth
Nicholas J Croucher
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
- Paul B Rainey, Max Planck Institute for Evolutionary Biology, Germany
Version history
- Received: February 1, 2021
- Accepted: April 16, 2021
- Accepted Manuscript published: July 14, 2021 (version 1)
- Version of Record published: July 29, 2021 (version 2)
- 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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The role of interspecies recombinations in the evolution of antibiotic resistant pneumococci
eLife 10:e67113.
https://doi.org/10.7554/eLife.67113
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