The role of interspecies recombination in the evolution of antibiotic-resistant pneumococci
Authors: D'Aeth Joshua C , van der Linden Mark PG , McGee Lesley , de Lencastre Herminia , Turner Paul , Song Jae-Hoon , Lo Stephanie W , Gladstone Rebecca A , Sá-Leão Raquel , Ko Kwan Soo , Hanage William P , Breiman Robert F , Beall Bernard , Bentley Stephen D , Croucher Nicholas J ,   The GPS Consortium, Corso Alejandra , Faccone Diego , Gagetti Paula , Brooks Abdullah W , Hasanuzzaman Md , Malaker Roly , Saha Samir K , Davydov Alexander , Titov Leonid , de Cunto Brandileone Maria Cristina , Almeida Samanta Cristine Grassi , Ip Margaret , Ho Pak Leung , Law Pierra , Zhao Chunjiang , Wang Hui , Keenan Jeremy , Sampane-Donkor Eric , Veeraraghavan Balaji , Nagaraj Geetha , Ravikumar KL , Givon-Lavi Noga , Porat Nurit , Benisty Rachel , Dagan Ron , Bigogo Godfrey , Verani Jennifer , Kiran Anmol , Everett Dean B , Cornick Jennifer , Alaerts Maaike , Sekaran Shamala Devi , Clarke Stuart C , Belabbès Houria , Diawara Idrissa , Zerouali Khalid , Elmdaghri Naima , Moiane Benild , Sigauque Betuel , Mucavele Helio , Pollard Andrew J , Kandasamy Rama , Carter Philip E , Obaro Stephen , Shakoor Sadia , Lehmann Deborah , Ford Rebecca , Ochoa Theresa J , Skoczynska Anna , Sadowy Ewa , Hryniewicz Waleria , Doiphode Sanjay , Egorova Ekaterina , Voropaeva Elena , Urban Yulia , Paragi Metka , Kastrin Tamara , Von Gottberg Anne , Ndlangisa Kedibone M , De Gouveia Linda , Du Plessis Mignon , Ali Mushal , Wolter Nicole , Madhi Shabir A , Nzenze Susan A , Srifuengfung Somporn , Kwambana-Adams Brenda , Foster-Nyarko Ebenezer , Bojang Ebrima , Antonio Martin , Tientcheu Peggy-Estelle , Moïsi Jennifer , Nurse-Lucas Michele , Akpaka Patrick E , Eser Özgen Köseoglu , Maguire Alison , Aanensen David , Bentley Leon , Bhai Jyothish N Nair Thulasee , Mostowy Rafal , Lees John A , Klugman Keith P , Hawkins Paulina , Cleary David 
Published: July 2021

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.