The University of Southampton
University of Southampton Institutional Repository

Characterisation of the stringent response and polyphosphate biosynthesis in the intracellular pathogens Burkholderia pseudomallei, Francisella tularensis and Yersinia pestis

Characterisation of the stringent response and polyphosphate biosynthesis in the intracellular pathogens Burkholderia pseudomallei, Francisella tularensis and Yersinia pestis
Characterisation of the stringent response and polyphosphate biosynthesis in the intracellular pathogens Burkholderia pseudomallei, Francisella tularensis and Yersinia pestis
The paucity of novel antibiotics to treat intracellular pathogens has become a matter of intense concern for the scientific community. Similarly, innate, emerging and even engineered antibiotic resistance is of disquiet for pathogens of concern including those of interest in biodefence. Therefore there is a significant need to identify novel classes of antibiotics.
Under conditions of nutrient limitation, bacteria initiate the stringent response, co-ordinated by the signalling nucleotides guanosine tetra- and penta-phosphate, collectively termed (p)ppGpp. During starvation, (p)ppGpp accumulates and coordinates diverse transcriptional alterations. (p)ppGpp levels are controlled by two enzymes, RelA and SpoT, which are a monofunctional (p)ppGpp synthetase and a bifunctional (p)ppGpp synthetase/hydrolase, respectively.
#Inorganic polyphosphate, a global regulatory molecule, has also been linked to the stringent response. Levels of polyphosphate are controlled by a polyphosphate kinase (PPK) and an exopolyphosphatase (PPX). Mutation of the genes relA and spoT results not only in abrogation of (p)ppGpp production, but also results in lower levels of polyphosphate accumulation. However, the interaction of the stringent response with the polyphosphate regulon is not yet clearly understood.
The aim of this project is to inactivate the key genes involved in (p)ppGpp and polyphosphate metabolism in intracellular pathogens of interest to defence. The characterisation of these mutants in vitro and in vivo and the analysis of the global stringent response regulon are discussed in this thesis.
University of Southampton
Murch, Amber, Louise
23e3d7ca-bc11-4ddd-883d-92495b0ac434
Murch, Amber, Louise
23e3d7ca-bc11-4ddd-883d-92495b0ac434
Roach, Peter
ca94060c-4443-482b-af3e-979243488ba9

Murch, Amber, Louise (2016) Characterisation of the stringent response and polyphosphate biosynthesis in the intracellular pathogens Burkholderia pseudomallei, Francisella tularensis and Yersinia pestis. University of Southampton, Doctoral Thesis, 332pp.

Record type: Thesis (Doctoral)

Abstract

The paucity of novel antibiotics to treat intracellular pathogens has become a matter of intense concern for the scientific community. Similarly, innate, emerging and even engineered antibiotic resistance is of disquiet for pathogens of concern including those of interest in biodefence. Therefore there is a significant need to identify novel classes of antibiotics.
Under conditions of nutrient limitation, bacteria initiate the stringent response, co-ordinated by the signalling nucleotides guanosine tetra- and penta-phosphate, collectively termed (p)ppGpp. During starvation, (p)ppGpp accumulates and coordinates diverse transcriptional alterations. (p)ppGpp levels are controlled by two enzymes, RelA and SpoT, which are a monofunctional (p)ppGpp synthetase and a bifunctional (p)ppGpp synthetase/hydrolase, respectively.
#Inorganic polyphosphate, a global regulatory molecule, has also been linked to the stringent response. Levels of polyphosphate are controlled by a polyphosphate kinase (PPK) and an exopolyphosphatase (PPX). Mutation of the genes relA and spoT results not only in abrogation of (p)ppGpp production, but also results in lower levels of polyphosphate accumulation. However, the interaction of the stringent response with the polyphosphate regulon is not yet clearly understood.
The aim of this project is to inactivate the key genes involved in (p)ppGpp and polyphosphate metabolism in intracellular pathogens of interest to defence. The characterisation of these mutants in vitro and in vivo and the analysis of the global stringent response regulon are discussed in this thesis.

Text
Thesis_A.Murch_finalsubmission - Version of Record
Available under License University of Southampton Thesis Licence.
Download (6MB)

More information

Published date: September 2016
Organisations: University of Southampton, Chemistry

Identifiers

Local EPrints ID: 411869
URI: http://eprints.soton.ac.uk/id/eprint/411869
PURE UUID: b438502e-548b-45c3-b0df-b885f6b59208
ORCID for Peter Roach: ORCID iD orcid.org/0000-0001-9880-2877

Catalogue record

Date deposited: 27 Jun 2017 16:31
Last modified: 31 May 2020 04:01

Export record

Contributors

Author: Amber, Louise Murch
Thesis advisor: Peter Roach ORCID iD

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 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.

×