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

Elife. 2021 Jul 14;10:e67113. doi: 10.7554/eLife.67113. Online ahead of print.

Abstract

Multidrug-resistant Streptococcus pneumoniae emerge through the modification of core genome loci through short inter-species 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.

Keywords: genetics; genomics; infectious disease; microbiology.