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Author Notes:

Email: tazarian@hsph.harvard.edu

Conceptualization: Taj Azarian, Maria Georgieva, Rebecca A. Gladstone, William P. Hanage.

Data curation: Taj Azarian, Maria Georgieva, Claudette M. Thompson, Bernard Beall.

Formal analysis: Taj Azarian, Maria Georgieva, Claudette M. Thompson, Amel Ghouila, Bernard Beall, Benjamin J. Metcalf

Funding acquisition: William P. Hanage.

Investigation: Patrick K. Mitchell, Maria Georgieva, Claudette M. Thompson, Anne von Gottberg, Mignon du Plessis, Martin Antonio, Brenda A. Kwambana-Adams, Stuart C. Clarke, Dean Everett, Jennifer Cornick, Ewa Sadowy, Waleria Hryniewicz, Anna Skoczynska, Jennifer C. Moïsi, Lesley McGee, Benjamin J. Metcalf, Robert F. Breiman, PL Ho, Raymond Reid, Katherine L. O’Brien, Rebecca A. Gladstone, Stephen D. Bentley.

Methodology: Taj Azarian, Maria Georgieva, Claudette M. Thompson, Andrew J. Pollard, Anne von Gottberg, Martin Antonio, Stuart C. Clarke, Jennifer Cornick, Ewa Sadowy, Bernard Beall, PL Ho, William P. Hanage.

Project administration: William P. Hanage.

Resources: Katherine L. O’Brien, Rebecca A. Gladstone, Stephen D. Bentley, William P. Hanage.

Software: Benjamin J. Metcalf, Stephen D. Bentley.

Supervision: Stephen D. Bentley, William P. Hanage.

Validation: Taj Azarian, William P. Hanage.

Visualization: Taj Azarian.

Writing – original draft: Taj Azarian, Maria Georgieva, Anna Skoczynska, William P. Hanage.

Writing – review & editing: Taj Azarian, Andrew J. Pollard, Anne von Gottberg, Mignon du Plessis, Brenda A. Kwambana-Adams, Stuart C. Clarke, Dean Everett, Jennifer Cornick, Ewa Sadowy, Waleria Hryniewicz, Anna Skoczynska, Jennifer C. Moïsi, Lesley McGee, Bernard Beall, Benjamin J. Metcalf, Robert F. Breiman, PL Ho, Raymond Reid, Katherine L. O’Brien, Rebecca A. Gladstone, Stephen D. Bentley, William P. Hanage.

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.

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.

The other authors have declared that no competing interests exist.

Subjects:

Research Funding:

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).

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Microbiology
  • Parasitology
  • Virology
  • COMMUNITY-ACQUIRED PNEUMONIA
  • STREPTOCOCCUS-PNEUMONIAE
  • ANTIBIOTIC-RESISTANCE
  • INVASIVE-DISEASE
  • CONJUGATE VACCINE
  • SEQUENCE TYPE
  • 13-VALENT
  • BACTERIAL
  • EVOLUTION
  • CLONES

Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci

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Journal Title:

PLoS Pathogens

Volume:

Volume 14, Number 11

Publisher:

, Pages e1007438-e1007438

Type of Work:

Article | Final Publisher PDF

Abstract:

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 Netherlands 3 –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.

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© 2018, Public Library of Science. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Universal : Public Domain Dedication License (http://creativecommons.org/publicdomain/zero/1.0/).

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