Evidence for Soft Selective Sweeps in the Evolution of Pneumococcal Multidrug Resistance and Vaccine Escape

• Type of Material: Article
• Authors: Nicholas J. Croucher, Harvard University; Claire Chewapreecha, Wellcome Trust Sanger Institute; William P. Hanage, Harvard University; Simon R. Harris, Wellcome Trust Sanger Institute; Lesley McGee, Centers for Disease Control and Prevention; Mark van der Linden, Institute for Medical Microbiology; Jae-Hoon Song, Sungkyunkwan University; Kwan Soo Ko, Sungkyunkwan University; Herminia de Lencastre, Universidade Nova de Lisboa; Claudia Turner, Mahidol University; Fan Yang, Fudan University; Raque Sa-Leao, Universidade Nova de Lisboa; Bernard Beall, Centers for Disease Control and Prevention; Keith P Klugman, Emory University; Julian Parkhill, Wellcome Trust Sanger Institute; Paul Turner, Mahidol University; Stephen D. Bentley, Wellcome Trust Sanger Institute
• Language: English
• Date: 2014-07-01
• Publisher: Oxford University Press
• Publication Version: Final Published Version
• Copyright Statement: © 2014, Oxford University Press
• License: Creative Commons Attribution 3.0 IGO License
• Final Published Version (URL): http://dx.doi.org/10.1093/gbe/evu120
• Title of Journal or Parent Work: Genome Biology and Evolution
• ISSN: 1759-6653
• Volume: 6
• Issue: 7
• Start Page: 1589
• End Page: 1602
• Grant/Funding Information: This work was funded by Wellcome Trust grant number 098051. N.J.C. was funded by a postdoctoral fellowship from the AXA Foundation.; S.D.B. is partly funded by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre.; P.T. was funded by a Wellcome Trust Clinical Research Training Fellowship (083735/Z/07/Z).
• Keywords: MOLECULAR POPULATION-GENETICS; antibiotic resistance; vaccine escape; STREPTOCOCCUS-PNEUMONIAE; SEQUENCE; Science & Technology; selective sweeps; PNEUMONIAE SEROTYPE 19A; CHILDREN; recombination; bacterial evolution; CONJUGATE VACCINE; Life Sciences & Biomedicine; MAJOR CLONES; ALIGNMENT; phylogenomics; UNITED-STATES; MACROLIDE RESISTANCE; Evolutionary Biology; Genetics & Heredity
• Research Categories: Health Sciences, Immunology; Biology, Molecular

Abstract

The multidrug-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.