The University of Southampton
University of Southampton Institutional Repository

Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci

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

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.

1553-7366
1-26
Azarian, Taj
20fb8dfc-b435-43df-82ba-4cf3f82d04ac
Mitchell, Patrick K.
22ae9c96-a804-47d7-bab2-faed544b7cf7
Georgieva, Maria
02470825-9f78-4aeb-821a-e55e691d1ce3
Thompson, Claudette M.
794e8032-6fcc-48fd-b18c-9bff341840ca
Ghouila, Amel
c1ba8fbb-0f32-4386-929a-bcb73e454186
Pollard, Andrew J.
f54083f3-c730-4ecb-937e-6fb11fdd6a21
von Gottberg, Anne
2e435fdc-f9f3-4c37-b96a-f4d5184661f0
du Plessis, Mignon
22fdbb8a-0bcd-4e0d-8a32-520cb5e59e7f
Antonio, Martin
ac8a8442-881c-4d64-af8e-6ecf34f07c83
Kwambana-Adams, Brenda A.
b126d46e-f8c1-46e0-855e-ce8653e2a622
Clarke, Stuart C.
f7d7f7a2-4b1f-4b36-883a-0f967e73fb17
Everett, Dean
6518700c-7cda-4221-b0ff-e27bb84a4bf5
Cornick, Jennifer
6d915388-bfcd-458a-a9f5-3593b41019bc
Sadowy, Ewa
546bd161-37cc-4581-9690-367dc619ceda
Hryniewicz, Waleria
8df60ebb-ebc0-4e15-a267-d427983029fa
Skoczynska, Anna
d15b6176-9a9b-4955-a0c7-bd85de879395
Moïsi, Jennifer C.
41972c4b-fe47-43e0-b49c-120e9a281e39
McGee, Lesley
8b2b4ed5-fb63-4e8f-a9b1-ee14573daab0
Beall, Bernard
c9aa9f18-1f5e-438a-af62-c53d40443235
Metcalf, Benjamin J.
9e0aa2db-b894-43b8-add4-4d31ec09f3af
Breiman, Robert F.
38ff5868-bb32-43c3-97c4-d52ceba325d0
Ho, P.L.
78fd2483-d7c2-4244-8ffe-e3c8a2d27e32
Reid, Raymond
37c963dc-f1d2-4b71-b2f4-428713350d8b
O’Brien, Katherine L.
e4d7fb2b-2d0b-4ab7-b7df-8879358f4617
Gladstone, Rebecca A.
6a2011bf-2561-4956-9928-46e6b927ba6d
Bentley, Stephen D.
438443a4-8033-4a5d-a5a5-538dbd4e8d60
Hanage, William P.
23ab4323-a1d4-4cfb-943b-cd51a97bee77
Azarian, Taj
20fb8dfc-b435-43df-82ba-4cf3f82d04ac
Mitchell, Patrick K.
22ae9c96-a804-47d7-bab2-faed544b7cf7
Georgieva, Maria
02470825-9f78-4aeb-821a-e55e691d1ce3
Thompson, Claudette M.
794e8032-6fcc-48fd-b18c-9bff341840ca
Ghouila, Amel
c1ba8fbb-0f32-4386-929a-bcb73e454186
Pollard, Andrew J.
f54083f3-c730-4ecb-937e-6fb11fdd6a21
von Gottberg, Anne
2e435fdc-f9f3-4c37-b96a-f4d5184661f0
du Plessis, Mignon
22fdbb8a-0bcd-4e0d-8a32-520cb5e59e7f
Antonio, Martin
ac8a8442-881c-4d64-af8e-6ecf34f07c83
Kwambana-Adams, Brenda A.
b126d46e-f8c1-46e0-855e-ce8653e2a622
Clarke, Stuart C.
f7d7f7a2-4b1f-4b36-883a-0f967e73fb17
Everett, Dean
6518700c-7cda-4221-b0ff-e27bb84a4bf5
Cornick, Jennifer
6d915388-bfcd-458a-a9f5-3593b41019bc
Sadowy, Ewa
546bd161-37cc-4581-9690-367dc619ceda
Hryniewicz, Waleria
8df60ebb-ebc0-4e15-a267-d427983029fa
Skoczynska, Anna
d15b6176-9a9b-4955-a0c7-bd85de879395
Moïsi, Jennifer C.
41972c4b-fe47-43e0-b49c-120e9a281e39
McGee, Lesley
8b2b4ed5-fb63-4e8f-a9b1-ee14573daab0
Beall, Bernard
c9aa9f18-1f5e-438a-af62-c53d40443235
Metcalf, Benjamin J.
9e0aa2db-b894-43b8-add4-4d31ec09f3af
Breiman, Robert F.
38ff5868-bb32-43c3-97c4-d52ceba325d0
Ho, P.L.
78fd2483-d7c2-4244-8ffe-e3c8a2d27e32
Reid, Raymond
37c963dc-f1d2-4b71-b2f4-428713350d8b
O’Brien, Katherine L.
e4d7fb2b-2d0b-4ab7-b7df-8879358f4617
Gladstone, Rebecca A.
6a2011bf-2561-4956-9928-46e6b927ba6d
Bentley, Stephen D.
438443a4-8033-4a5d-a5a5-538dbd4e8d60
Hanage, William P.
23ab4323-a1d4-4cfb-943b-cd51a97bee77

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. and Hanage, William P. (2018) Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci. PLoS Pathogens, 14 (11), 1-26. (doi:10.1371/journal.ppat.1007438).

Record type: Article

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.

Text
Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci - Accepted Manuscript
Download (182kB)
Text
journal.ppat.1007438 - Version of Record
Download (3MB)

More information

Accepted/In Press date: 25 October 2018
e-pub ahead of print date: 26 November 2018
Published date: November 2018

Identifiers

Local EPrints ID: 426923
URI: https://eprints.soton.ac.uk/id/eprint/426923
ISSN: 1553-7366
PURE UUID: f569594d-66ab-41a5-904b-77c6f9c272fa
ORCID for Stuart C. Clarke: ORCID iD orcid.org/0000-0002-7009-1548

Catalogue record

Date deposited: 18 Dec 2018 17:30
Last modified: 14 Mar 2019 01:41

Export record

Altmetrics

Contributors

Author: Taj Azarian
Author: Patrick K. Mitchell
Author: Maria Georgieva
Author: Claudette M. Thompson
Author: Amel Ghouila
Author: Andrew J. Pollard
Author: Anne von Gottberg
Author: Mignon du Plessis
Author: Martin Antonio
Author: Brenda A. Kwambana-Adams
Author: Dean Everett
Author: Jennifer Cornick
Author: Ewa Sadowy
Author: Waleria Hryniewicz
Author: Anna Skoczynska
Author: Jennifer C. Moïsi
Author: Lesley McGee
Author: Bernard Beall
Author: Benjamin J. Metcalf
Author: Robert F. Breiman
Author: P.L. Ho
Author: Raymond Reid
Author: Katherine L. O’Brien
Author: Rebecca A. Gladstone
Author: Stephen D. Bentley
Author: William P. Hanage

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×