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PLoS Pathog. 2018 Nov 26;14(11):e1007438. doi: 10.1371/journal.ppat.1007438. eCollection 2018 Nov.

Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci.

Author information

Center for Communicable Disease Dynamics, Department of Epidemiology, T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts, United States of America.
Institut Pasteur de Tunis, LR11IPT02, Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Tunis-Belvédère, Tunisia.
Oxford Vaccine Group, Department of Paediatrics, University of Oxford; NIHR Oxford Biomedical Research Centre, Centre for Clinical Vaccinology and Tropical Medicine (CCVTM), Churchill Hospital, Oxford, United Kingdom.
Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
Medical Research Council Unit The Gambia, Fajara, The Gambia.
Faculty of Medicine and Institute for Life Sciences and Global Health Research Institute, University of Southampton, Southampton, United Kingdom.
NIHR Southampton Biomedical Research Centre, Southampton General Hospital, Southampton, United Kingdom.
Queens Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.
National Medicines Institute, Warsaw, Poland.
Pfizer Vaccines, Medical Development, Scientific and Clinical Affairs, Paris, France.
Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
Global Health Institute, Emory University, Atlanta, Georgia, United States of America.
Department of Microbiology, Queen Mary Hospital University of Hong Kong, Hong Kong, People's Republic of China.
Center for American Indian Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
Wellcome Trust, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.


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.

[Indexed for MEDLINE]
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Conflict of interest statement

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. AS has received assistance to attend scientific meetings and honoraria for lecturing funded from Pfizer and from GlaxoSmithKline, and Participated in Advisory Board of GlaxoSmithKline and Pfizer. WPH has consulted for Antigen Discovery Inc. JCM is employed by Pfizer, Inc. This does not alter our adherence to all PLOS Pathogens policies on sharing data and materials. The other authors have declared that no competing interests exist.

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