Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci

Taj Azarian, Patrick K. Mitchell, Maria Georgieva, Claudette M. Thompson, Amel Ghouila, Andrew J. Pollard, 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, Bernard Beall, Benjamin J. MetcalfRobert F. Breiman, P. L. Ho, Raymond Reid, Katherine L O'Brien, Rebecca A. Gladstone, Stephen D. Bentley, William P. Hanage

Research output: Contribution to journalArticle

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 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.

Original languageEnglish (US)
Article numbere1007438
JournalPLoS Pathogens
Volume14
Issue number11
DOIs
StatePublished - Nov 1 2018

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Population Dynamics
Streptococcus pneumoniae
Endopeptidase Clp
Vaccines
Population
Antigenic Variation
Conjugate Vaccines
Bayes Theorem
Amino Acid Substitution
Operon
Microbial Drug Resistance
Population Density
Genomics
Serogroup
Mental Competency
Genetic Recombination
Capsules
Polysaccharides
Clone Cells
Adenosine Triphosphate

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Azarian, T., Mitchell, P. K., Georgieva, M., Thompson, C. M., Ghouila, A., Pollard, A. J., ... Hanage, W. P. (2018). Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci. PLoS Pathogens, 14(11), [e1007438]. https://doi.org/10.1371/journal.ppat.1007438

Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci. / Azarian, Taj; Mitchell, Patrick K.; Georgieva, Maria; Thompson, Claudette M.; Ghouila, Amel; Pollard, Andrew J.; von Gottberg, Anne; du Plessis, Mignon; Antonio, Martin; Kwambana-Adams, Brenda A.; Clarke, Stuart C.; Everett, Dean; Cornick, Jennifer; Sadowy, Ewa; Hryniewicz, Waleria; Skoczynska, Anna; Moïsi, Jennifer C.; McGee, Lesley; Beall, Bernard; Metcalf, Benjamin J.; Breiman, Robert F.; Ho, P. L.; Reid, Raymond; O'Brien, Katherine L; Gladstone, Rebecca A.; Bentley, Stephen D.; Hanage, William P.

In: PLoS Pathogens, Vol. 14, No. 11, e1007438, 01.11.2018.

Research output: Contribution to journalArticle

Azarian, T, Mitchell, PK, Georgieva, M, Thompson, CM, Ghouila, A, Pollard, AJ, von Gottberg, A, du Plessis, M, Antonio, M, Kwambana-Adams, BA, Clarke, SC, Everett, D, Cornick, J, Sadowy, E, Hryniewicz, W, Skoczynska, A, Moïsi, JC, McGee, L, Beall, B, Metcalf, BJ, Breiman, RF, Ho, PL, Reid, R, O'Brien, KL, Gladstone, RA, Bentley, SD & Hanage, WP 2018, 'Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci', PLoS Pathogens, vol. 14, no. 11, e1007438. https://doi.org/10.1371/journal.ppat.1007438
Azarian T, Mitchell PK, Georgieva M, Thompson CM, Ghouila A, Pollard AJ et al. Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci. PLoS Pathogens. 2018 Nov 1;14(11). e1007438. https://doi.org/10.1371/journal.ppat.1007438
Azarian, Taj ; Mitchell, Patrick K. ; Georgieva, Maria ; Thompson, Claudette M. ; Ghouila, Amel ; Pollard, Andrew J. ; von Gottberg, Anne ; du Plessis, Mignon ; Antonio, Martin ; Kwambana-Adams, Brenda A. ; Clarke, Stuart C. ; Everett, Dean ; Cornick, Jennifer ; Sadowy, Ewa ; Hryniewicz, Waleria ; Skoczynska, Anna ; Moïsi, Jennifer C. ; McGee, Lesley ; Beall, Bernard ; Metcalf, Benjamin J. ; Breiman, Robert F. ; Ho, P. L. ; Reid, Raymond ; O'Brien, Katherine L ; Gladstone, Rebecca A. ; Bentley, Stephen D. ; Hanage, William P. / Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci. In: PLoS Pathogens. 2018 ; Vol. 14, No. 11.
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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 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.",
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AU - Ho, P. L.

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