The University of Southampton
University of Southampton Institutional Repository

Disruption of the cpsE and endA genes attenuates Streptococcus pneumoniae virulence: towards the development of a live attenuated vaccine candidate

Disruption of the cpsE and endA genes attenuates Streptococcus pneumoniae virulence: towards the development of a live attenuated vaccine candidate
Disruption of the cpsE and endA genes attenuates Streptococcus pneumoniae virulence: towards the development of a live attenuated vaccine candidate
The majority of deaths due to Streptococcus pneumoniae infections are in developing countries. Although polysaccharide-based pneumococcal vaccines are available, newer types of vaccines are needed to increase vaccine affordability, particularly in developing countries, and to provide broader protection across all pneumococcal serotypes. To attenuate pneumococcal virulence with the aim of engineering candidate live attenuated vaccines (LAVs), we constructed knockouts in S. pneumoniae D39 of one of the capsular biosynthetic genes, cpsE that encodes glycosyltransferase, and the endonuclease gene, endA, that had been implicated in the uptake of DNA from the environment as well as bacterial escape from neutrophil-mediated killing. The cpsE gene knockout significantly lowered peak bacterial density, BALB/c mice nasopharyngeal (NP) colonisation but increased biofilm formation when compared to the wild-type D39 strain as well as the endA gene knockout mutant. All constructed mutant strains were able to induce significantly high serum and mucosal antibody response in BALB/c mice. However, the cpsE-endA double mutant strain, designated SPEC, was able to protect mice from high dose mucosal challenge of the D39 wild-type. Furthermore, SPEC showed 23-fold attenuation of virulence compared to the wild-type. Thus, the cpsE-endA double-mutant strain could be a promising candidate for further development of a LAV for S. pneumoniae.
2076-393X
Amonov, Malik
8197b95e-e5c0-442f-a1c8-0a64d27e8498
Clarke, Stuart
f7d7f7a2-4b1f-4b36-883a-0f967e73fb17
Yeo, Chew Chieng
fdccc646-7c5d-4231-a9fa-ff01c39f4e5a
Amonov, Malik
8197b95e-e5c0-442f-a1c8-0a64d27e8498
Clarke, Stuart
f7d7f7a2-4b1f-4b36-883a-0f967e73fb17
Yeo, Chew Chieng
fdccc646-7c5d-4231-a9fa-ff01c39f4e5a

Amonov, Malik, Clarke, Stuart and Yeo, Chew Chieng (2020) Disruption of the cpsE and endA genes attenuates Streptococcus pneumoniae virulence: towards the development of a live attenuated vaccine candidate. Vaccines, 8 (2). (doi:10.3390/vaccines8020187).

Record type: Article

Abstract

The majority of deaths due to Streptococcus pneumoniae infections are in developing countries. Although polysaccharide-based pneumococcal vaccines are available, newer types of vaccines are needed to increase vaccine affordability, particularly in developing countries, and to provide broader protection across all pneumococcal serotypes. To attenuate pneumococcal virulence with the aim of engineering candidate live attenuated vaccines (LAVs), we constructed knockouts in S. pneumoniae D39 of one of the capsular biosynthetic genes, cpsE that encodes glycosyltransferase, and the endonuclease gene, endA, that had been implicated in the uptake of DNA from the environment as well as bacterial escape from neutrophil-mediated killing. The cpsE gene knockout significantly lowered peak bacterial density, BALB/c mice nasopharyngeal (NP) colonisation but increased biofilm formation when compared to the wild-type D39 strain as well as the endA gene knockout mutant. All constructed mutant strains were able to induce significantly high serum and mucosal antibody response in BALB/c mice. However, the cpsE-endA double mutant strain, designated SPEC, was able to protect mice from high dose mucosal challenge of the D39 wild-type. Furthermore, SPEC showed 23-fold attenuation of virulence compared to the wild-type. Thus, the cpsE-endA double-mutant strain could be a promising candidate for further development of a LAV for S. pneumoniae.

Text
Disruption of the cpsE - Version of Record
Available under License Creative Commons Attribution.
Download (4kB)

More information

Accepted/In Press date: 7 April 2020
Published date: 15 April 2020

Identifiers

Local EPrints ID: 447328
URI: http://eprints.soton.ac.uk/id/eprint/447328
ISSN: 2076-393X
PURE UUID: b1145410-64ca-4b20-8b1c-9556ef875086
ORCID for Stuart Clarke: ORCID iD orcid.org/0000-0002-7009-1548

Catalogue record

Date deposited: 09 Mar 2021 17:32
Last modified: 15 Sep 2021 01:51

Export record

Altmetrics

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 http://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.

×