The role of interspecies recombination in the evolution of antibiotic-resistant pneumococci
Joshua C D'Aeth, Mark PG van der Linden, Lesley McGee, Hermı́nia de Lencastre, Paul Turner, Jae-Hoon Song, Stephanie W. Lo, Rebecca A. Gladstone, Raquel Sá‐Leão, Kwan Soo Ko, William P. Hanage, Robert F. Breiman, Bernard Beall, Stephen D. Bentley, Nicholas J. Croucher, Alejandra Corso, Diego Faccone, Paula Gagetti, Abdullah Brooks, Md Hasanuzzaman, Roly Malaker, Samir K. Saha, Alexander Davydov, Leonid Titov, Maria Cristina de Cunto Brandileone, Samanta Cristine Grassi Almeida, Margaret Ip, Pak‐Leung Ho, Pierra Y. Law, Chunjiang Zhao, Hui Wang, Jeremy D. Keenan, Eric Sampane-Donkor, Balaji Veeraraghavan, Geetha Nagaraj, KL Ravikumar, Noga Givon‐Lavi, Nurit Porat, Rachel Benisty, Ron Dagan, Godfrey Bigogo, Jennifer R. Verani, Anmol Kiran, Dean Everett, Jennifer Cornick, Maaike Alaerts, Shamala Devi Sekaran, Stuart C. Clarke, Houria Belabbès, Idrissa Diawara, Khalid Zerouali, Naima Elmdaghri, Benild Moiane, Betuel Sigaúque, Hélio Mucavele, Andrew J. Pollard, Rama Kandasamy, Philip E. Carter, Stephen Obaro, Sadia Shakoor, Deborah Lehmann, Rebecca Ford, Theresa J. Ochoa, Anna Skoczyńska, Ewa Sadowy, Waleria Hryniewicz, Sanjay Doiphode, Egorova Ea, Е. А. Воропаева, Yulia Urban, Metka Paragi, Tamara Kastrin, Anne von Gottberg, Kedibone Ndlangisa, Linda de Gouveia, Mignon du Plessis, Mushal Ali, Nicole Wolter, Shabir A. Madhi, Susan Nzenze, Somporn Srifuengfung, Brenda Kwambana-Adams, Ebenezer Foster-Nyarko, Ebrima Bojang, Martín Antonio, Peggy-Estelle Tientcheu, Jennifer C. Moïsi, Michele Nurse-Lucas, Patrick Eberechi Akpaka, Özgen Köseoğlu Eser, Alison J. Maguire, David M. Aanensen, Leon J. Bentley, Jyothish Bhai, Rafal Mostowy, John A. Lees, Keith P. Klugman, Paulina A. Hawkins, David Cleary
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 Tn 916 -type and Tn 1207.1 -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 Tn 1207.1 -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.