%0 Journal Article %T Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci %+ Harvard University %+ Laboratoire de Transmission, Contrôle et Immunobiologie des Infections - Laboratory of Transmission, Control and Immunobiology of Infection (LR11IPT02) %+ Oxford Vaccine Group %+ National Institute for Communicable Diseases [Johannesburg] (NICD) %+ Medical Research Council Unit The Gambia (MRC) %+ University of Southampton %+ University of Edinburgh %+ University of Liverpool %+ National Medicines Institute - Narodowy Instytut Leków [Warsaw] (NIL) %+ Pfizer France %+ Centers for Disease Control and Prevention [Atlanta] (CDC) %+ Emory Global Health Institute [Atlanta] (EGHI) %+ Department of Microbiology [HKU] %+ Johns Hopkins Bloomberg School of Public Health [Baltimore] %+ The Wellcome Trust Sanger Institute [Cambridge] %A Azarian, Taj %A Mitchell, Patrick %A Georgieva, Maria %A Thompson, Claudette, M %A Ghouila, Amel %A Pollard, Andrew, J %A von Gottberg, Anne %A Du Plessis, Mignon %A Antonio, Martin %A Kwambana-Adams, Brenda, A %A Clarke, Stuart, C %A Everett, Dean %A Cornick, Jennifer %A Sadowy, Ewa %A Hryniewicz, Waleria %A Skoczynska, Anna %A Moïsi, Jennifer, C %A Mcgee, Lesley %A Beall, Bernard %A Metcalf, Benjamin, J %A Breiman, Robert, F %A Ho, Pl, L %A Reid, Raymond %A O’brien, Katherine, L %A Gladstone, Rebecca, A %A Bentley, Stephen, D %A Hanage, William, P %Z The study was funded in part by National Institute of Allergy and Infectious Disease award to WPH (R01 AI106786). The Global Pneumococcal Sequencing project is funded by The Bill and Melinda Gates Foundation (Grant OPP1034556). %Z We acknowledge the Wellcome Trust Sanger Institute sequencing facility. We would also like to thank Richard Malley’s Laboratory for providing the antisera for the OPKA assays. %< avec comité de lecture %@ 1553-7366 %J PLoS Pathogens %I Public Library of Science %V 14 %N 11 %P e1007438 %8 2018-11-26 %D 2018 %R 10.1371/journal.ppat.1007438 %M 30475919 %Z Life Sciences [q-bio]Journal articles %X Streptococcus pneumoniae serotype 3 remains a significant cause of morbidity and mortality worldwide, despite inclusion in the 13-valent pneumococcal conjugate vaccine (PCV13). Serotype 3 increased in carriage since the implementation of PCV13 in the USA, while invasive disease rates remain unchanged. We investigated the persistence of serotype 3 in carriage and disease, through genomic analyses of a global sample of 301 serotype 3 isolates of the Netherlands3–31 (PMEN31) clone CC180, combined with associated patient data and PCV utilization among countries of isolate collection. We assessed phenotypic variation between dominant clades in capsule charge (zeta potential), capsular polysaccharide shedding, and susceptibility to opsonophagocytic killing, which have previously been associated with carriage duration, invasiveness, and vaccine escape. We identified a recent shift in the CC180 population attributed to a lineage termed Clade II, which was estimated by Bayesian coalescent analysis to have first appeared in 1968 [95% HPD: 1939–1989] and increased in prevalence and effective population size thereafter. Clade II isolates are divergent from the pre-PCV13 serotype 3 population in non-capsular antigenic composition, competence, and antibiotic susceptibility, the last of which resulting from the acquisition of a Tn916-like conjugative transposon. Differences in recombination rates among clades correlated with variations in the ATP-binding subunit of Clp protease, as well as amino acid substitutions in the comCDE operon. Opsonophagocytic killing assays elucidated the low observed efficacy of PCV13 against serotype 3. Variation in PCV13 use among sampled countries was not independently correlated with the CC180 population shift; therefore, genotypic and phenotypic differences in protein antigens and, in particular, antibiotic resistance may have contributed to the increase of Clade II. Our analysis emphasizes the need for routine, representative sampling of isolates from disperse geographic regions, including historically under-sampled areas. We also highlight the value of genomics in resolving antigenic and epidemiological variations within a serotype, which may have implications for future vaccine development. %G English %2 https://riip.hal.science/pasteur-02006050/document %2 https://riip.hal.science/pasteur-02006050/file/Global%20emergence%20and%20population%20dynamics%20of%20divergent%20serotype%203%20CC180%20pneumococci.pdf %L pasteur-02006050 %U https://riip.hal.science/pasteur-02006050 %~ RIIP %~ RIIP_TUNIS