Extracytoplasmic stress response systems in S. Typhimurium.
PhD thesis, University of Glasgow.
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Salmonella species can cause wide-ranging disease from mild food-poisoning enteritis
to a systemic, sometimes fatal typhoid infection.
These bacteria have evolved to survive in different environments within and outside
the host and do so through the regulation of differential gene expression following
activation of certain stress response systems.
In gram negative bacteria such as Salmonella, envelope stress responses (ESR) are
response systems that target stresses affecting components of the cell envelope such
as the periplasm and outer membrane proteins. The two best characterised ESRs are
the RpoE stress response system and the CpxAR two-component signal transduction
system. Two further ESRs, the BaeSR response and the phage shock response have
also recently been identified.
The intention of this thesis was to characterise the ESR systems of S. Typhimurium to
widen our current knowledge of genes involved in these systems and their role in the
pathogenesis of S. Typhimurium with the ultimate aim of identifying possible
candidate vaccine genes that may be used in future therapeutics against Salmonella
Firstly, extensive mutagenesis and phenotypic analysis studies were undertaken to
characterise genes thought to be members of the RpoE regulon.
Study of the phage shock response was initiated through mutagenesis, characterisation
and regulation studies.
A microarray experiment was designed in collaboration with colleagues at the Sanger
Centre to identify members of the S. Typhimurium CpxAR regulon, with several
members of this regulon being characterised further.
The structural components of HtrA, an important ESR protein in S. Typhimurium,
were analysed and finally work within this thesis was involved in the investigation of
potential overlaps between both the RpoE and CpxAR systems.
This led to the establishment of preliminary studies to investigate the vaccine
potential of the tol - pal genes in S. Typhimurium.
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