title: Pneumococcal capsular switching: a historical perspective.
abstract: BACKGROUND
  Changes in serotype prevalence among pneumococcal populations result from both serotype replacement and serotype (capsular) switching. Temporal changes in serotype distributions are well documented, but the contribution of capsular switching to such changes is unknown. Furthermore, it is unclear to what extent vaccine-induced selective pressures drive capsular switching.
  
  
  METHODS
  Serotype and multilocus sequence typing data for 426 pneumococci dated from 1937 through 2007 were analyzed. Whole-genome sequence data for a subset of isolates were used to investigate capsular switching events.
  
  
  RESULTS
  We identified 36 independent capsular switch events, 18 of which were explored in detail with whole-genome sequence data. Recombination fragment lengths were estimated for 11 events and ranged from approximately 19.0 kb to ≥ 58.2 kb. Two events took place no later than 1960, and the imported DNA included the capsular locus and the nearby penicillin-binding protein genes pbp2x and pbp1a.
  
  
  CONCLUSIONS
  Capsular switching has been a regular occurrence among pneumococcal populations throughout the past 7 decades. Recombination of large DNA fragments (>30 kb), sometimes including the capsular locus and penicillin-binding protein genes, predated both vaccine introduction and widespread antibiotic use. This type of recombination has likely been an intrinsic feature throughout the history of pneumococcal evolution.
authors.affiliation: Department of Zoology, University of Oxford, Oxford, United Kingdom.
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Wyres
authors.forename: Lotte M
authors.initials: LM
authors.lastname: Lambertsen
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Croucher
authors.forename: Lesley
authors.initials: L
authors.lastname: McGee
authors.forename: Anne
authors.initials: A
authors.lastname: von Gottberg
authors.forename: Josefina
authors.initials: J
authors.lastname: Liñares
authors.forename: Michael R
authors.initials: MR
authors.lastname: Jacobs
authors.forename: Karl G
authors.initials: KG
authors.lastname: Kristinsson
authors.forename: Bernard W
authors.initials: BW
authors.lastname: Beall
authors.forename: Keith P
authors.initials: KP
authors.lastname: Klugman
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.forename: Regine
authors.initials: R
authors.lastname: Hakenbeck
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bentley
authors.forename: Angela B
authors.initials: AB
authors.lastname: Brueggemann
mesh_terms: D016667:Bacterial Capsules / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D019143:Evolution, Molecular; D005798:Genes, Bacterial; D056426:Genetic Loci; D006801:Humans; D008969:Molecular Sequence Data; D058885:Multilocus Sequence Typing; D016415:Sequence Alignment; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000145:classification* / Q000235:genetics* / Q000276:immunology