The role of interspecies recombination in the evolution of antibiotic-resistant pneumococci

Elife. 2021 Jul 14:10:e67113. doi: 10.7554/eLife.67113.

Abstract

Multidrug-resistant Streptococcus pneumoniae emerge through the modification of core genome loci by 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-type and Tn1207.1-type elements, 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-type 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.

Keywords: AMR; epidemiology; genetics; genomics; infectious disease; microbiology; recombination; streptococcus pneumoniae.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • DNA Transposable Elements
  • Drug Resistance, Bacterial / drug effects*
  • Drug Resistance, Bacterial / genetics*
  • Gene Transfer, Horizontal*
  • Genes, Bacterial / genetics
  • Germany
  • Humans
  • Macrolides / pharmacology
  • Phylogeny
  • Pneumococcal Vaccines
  • Serogroup
  • Serotyping
  • Streptococcus pneumoniae / drug effects
  • Streptococcus pneumoniae / genetics

Substances

  • Anti-Bacterial Agents
  • DNA Transposable Elements
  • Macrolides
  • Pneumococcal Vaccines

Associated data

  • figshare/10.6084/m9.figshare.c.5306462.v1