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Title: Evidence for soft selective sweeps in the evolution of pneumococcal multidrug resistance and vaccine escape
Authors: Nicholas J. Croucher
Claire Chewapreecha
William P. Hanage
Simon R. Harris
Lesley McGee
Mark Van Der Linden
Jae Hoon Song
Kwan Soo Ko
Herminia De Lencastre
Claudia Turner
Fan Yang
Raquel Sa-Leao
Bernard Beall
Keith P. Klugman
Julian Parkhill
Paul Turner
Stephen D. Bentley
Harvard School of Public Health
Wellcome Trust Sanger Institute
National Center for Immunization and Respiratory Diseases
Medizinische Fakultat und Universitats Klinikum Aachen
Sungkyunkwan University
Instituto de Tecnologia Quimica e Biologica - Univesidade Nova de Lisboa
Rockefeller University
Mahidol University
Nuffield Department of Clinical Medicine
Huashan Hospital
Emory University
National Institute for Communicable Diseases
University of Cambridge
Keywords: Agricultural and Biological Sciences;Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Jan-2014
Citation: Genome Biology and Evolution. Vol.6, No.7 (2014), 1589-1602
Abstract: Themultidrug-resistant Streptococcus pneumoniae Taiwan19F-14, orPMEN14, clone was first observed with a 19F serotype, which is targeted by the heptavalent polysaccharide conjugate vaccine (PCV7). However, "vaccine escape" PMEN14 isolates with a 19A serotype became an increasingly important cause of disease post-PCV7. Whole genome sequencing was used to characterize the recent evolution of 173 pneumococci of, or related to,PMEN14. This suggested that PMEN14is a single lineage that originated in the late 1980s in parallel with the acquisition of multiple resistances by close relatives. One of the four detected serotype switches to 19A generated representatives of the sequence type (ST) 320 isolates that have been highly successful post-PCV7. A second produced an ST236 19A genotype with reduced resistance to b-lactams owing to alteration of pbp1a and pbp2x sequences through the same recombination that caused the change in serotype.Athird, which generated amosaic capsule biosynthesis locus, resulted in serotype 19AST271 isolates. The rapid diversification through homologous recombination seen in the global collectionwas similarly observed in the absence of vaccination in a set of isolates from theMaela refugeecampin Thailand, a collection that also allowed variation to be observed within carriage through longitudinal sampling. This suggests that some pneumococcal genotypes generate a pool of standing variation that is sufficiently extensive to result in "soft" selective sweeps: The emergence of multiple mutants in parallel upon a change in selection pressure, such as vaccine introduction. The subsequent competition between thesemutants makes this phenomenon difficult to detect without deep sampling of individual lineages. © The Author(s) 2014.
ISSN: 17596653
Appears in Collections:Scopus 2011-2015

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