MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom
Mark PG van der Linden
Institute for Medical Microbiology, National Reference Center for Streptococci, University Hospital RWTH Aachen, Aachen, Germany
Lesley McGee
Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, United States
Herminia de Lencastre
Laboratory of Molecular Genetics, Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal; Laboratory of Microbiology and Infectious Diseases, The Rockefeller University, New York, United States
Cambodia Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
Jae-Hoon Song
Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
Stephanie W Lo
Parasites & Microbes, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom
Rebecca A Gladstone
Parasites & Microbes, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom
Raquel Sá-Leão
Laboratory of Molecular Microbiology of Human Pathogens, Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal
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.
