Variable recombination dynamics during the emergence, transmission and 'disarming' of a multidrug-resistant pneumococcal clone.

• Published in: BMC Biology
• Main Authors: Croucher, Nicholas J, Hanage, William P, Harris, Simon R, McGee, Lesley, van der Linden, Mark, de Lencastre, Herminia, Sá-Leão, Raquel, Song, Jae-Hoon, Ko, Kwan Soo, Beall, Bernard, Klugman, Keith P, Parkhill, Julian, Tomasz, Alexander, Kristinsson, Karl G, Bentley, Stephen D
• Other Authors: Harvard Univ, Sch Publ Hlth, Ctr Communicable Dis Dynam, Dept Epidemiol, Boston, MA 02115 USA, Wellcome Trust Sanger Inst, Pathogen Genom, Cambridge CB10 1SA, England, Univ London Imperial Coll Sci Technol & Med, Dept Infect Dis Epidemiol, London W2 1NY, England, Ctr Dis Control & Prevent, Resp Dis Branch, Atlanta, GA USA, Rhein Westfal TH Aachen, Univ Hosp, Natl Reference Ctr Streptococci, Inst Med Microbiol, D-52062 Aachen, Germany, Univ Nova Lisboa, Inst Tecnol Quim & Biol, Genet Mol Lab, P-2780156 Oeiras, Portugal, Rockefeller Univ, Microbiol Lab, New York, NY 10021 USA, Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea, Asia Pacific Fdn Infect Dis, Seoul, South Korea, Sungkyunkwan Univ, Sch Med, Dept Mol Cell Biol, Suwon, South Korea, Emory Univ, Rollins Sch Publ Hlth, Hubert Dept Global Hlth, Atlanta, GA 30322 USA, Emory Univ, Sch Med, Div Infect Dis, Atlanta, GA USA, Natl Inst Communicable Dis, Ctr Resp Dis & Meningitis, Gauteng, South Africa, Landspitali Univ Hosp, Dept Clin Microbiol, Reykjavik, Iceland, Univ Iceland, Reykjavik, Iceland, Univ Cambridge, Addenbrookes Hosp, Dept Med, Cambridge CB2 0SP, England
• Format: Article in Journal/Newspaper
• Language: English
• Published: BioMed Central Ltd 2014
• Subjects: Lungnabólga; Lyfjagjöf; Bakteríusjúkdómar; Pneumococcal Infections/epidemiology*; Streptococcus pneumoniae/drug effects*; Streptococcus pneumoniae/immunology*; Drug Resistance; Bacterial; Streptococcus pneumoniae/genetics*; Anti-Bacterial Agents/pharmacology; Reykjavík; Iceland
• Online Access: http://hdl.handle.net/2336/325822; https://doi.org/10.1186/1741-7007-12-49

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access. Pneumococcal β-lactam resistance was first detected in Iceland in the late 1980s, and subsequently peaked at almost 25% of clinical isolates in the mid-1990s largely due to the spread of the internationally-disseminated multidrug-resistant PMEN2 (or Spain6B-2) clone of Streptococcus pneumoniae. Whole genome sequencing of an international collection of 189 isolates estimated that PMEN2 emerged around the late 1960s, developing resistance through multiple homologous recombinations and the acquisition of a Tn5253-type integrative and conjugative element (ICE). Two distinct clades entered Iceland in the 1980s, one of which had acquired a macrolide resistance cassette and was estimated to have risen sharply in its prevalence by coalescent analysis. Transmission within the island appeared to mainly emanate from Reykjavík and the Southern Peninsular, with evolution of the bacteria effectively clonal, mainly due to a prophage disrupting a gene necessary for genetic transformation in many isolates. A subsequent decline in PMEN2's prevalence in Iceland coincided with a nationwide campaign that reduced dispensing of antibiotics to children in an attempt to limit its spread. Specific mutations causing inactivation or loss of ICE-borne resistance genes were identified from the genome sequences of isolates that reverted to drug susceptible phenotypes around this time. Phylogenetic analysis revealed some of these occurred on multiple occasions in parallel, suggesting they may have been at least temporarily advantageous. However, alteration of 'core' sequences associated with resistance was precluded by the absence of any substantial homologous recombination events. PMEN2's clonal evolution was successful over the short-term in a limited geographical region, but its inability to alter major antigens or 'core' gene ...