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

• Type of Material: Article
• Authors: Nicholas J Croucher, Harvard University; William P Hanage, Harvard University; Simon R Harris, Wellcome Trust Genome Campus; Lesley McGee, Emory University; Mark van der Linden, University Hospital, Aachen; Herminia de Lencastre, Universidade Nova de Lisboa; Raquel Sá-Leão, Universidade Nova de Lisboa; Jae-Hoon Song, Sungkyunkwan University; Kwan Soo Ko, Sungkyunkwan University; Bernard Beall, Emory University; Keith P Klugman, Emory University; Julian Parkhill, Wellcome Trust Genome Campus; Alexander Tomasz, The Rockefeller University; Karl G Kristinsson, Landspitali University Hospital; Stephen D Bentley, Wellcome Trust Genome Campus
• Language: English
• Date: 2014
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2014 Croucher et al.; licensee BioMed Central Ltd.
• License: Creative Commons Creative Commons CC0 1.0 Universal
• Final Published Version (URL): http://www.biomedcentral.com/1741-7007/12/49
• Title of Journal or Parent Work: BMC Biology
• ISSN: 1741-7007
• Volume: 12
• Issue: 49
• Grant/Funding Information: NJC was funded by an AXA Foundation postdoctoral fellowship.; The Global Strain Bank Project is a PATH-funded collaborative project between Emory University, the CDC and external contributors.; This work was funded by Wellcome Trust grant number 098051.; KGK has an investigator-initiated study sponsored by GlaxoSmithKline.
• Keywords: Recombination; Antibiotic resistance; Phylogeography; Bacterial evolution; Coalescent analysis; Mobile genetic elements
• Research Categories: Biology, Microbiology; Health Sciences, Public Health

Abstract

Background 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. Results 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. Conclusions 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 sequences associated with resistance may have prevented persistence over longer timespans.