Pneumococcal Capsular Switching: A Historical Perspective

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 isola tes were used to investigate capsular switching events. Results . We identi fi ed 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 penicil- lin-binding protein genes, predated both vaccine introducti on and widespread antibiotic use. This type of recombina- tion has likely been an intrinsic feature throughout the history of pneumococcal evolution.