Further characterisation of the envelope stress responses of Salmonella Typhimurium

Wells, Hannah (2015) Further characterisation of the envelope stress responses of Salmonella Typhimurium. Doctoral thesis, University of East Anglia.

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Salmonella serovars are enteric pathogens of economic and clinical
importance. The ability of Salmonella spp. to sense and adapt to exogenous
stresses contributes towards infection severity and prevalence. The envelope
stress responses promote survival within and between hosts by maintaining
envelope homeostasis and promoting the rapid response to environmental
insults. In this study, we present the first comprehensive analysis of the Cpx
regulated transcriptome in S. Typhimurium, identifying 116 genes as novel
members of the S. Typhimurium Cpx regulon. Transcriptomic analyses,
EMSAs and mutant screens further establish CpxAR as a major contributor
to S. Typhimurium virulence through regulation of SPI-1, and as a regulator
of post-transcriptional modification through the positive and negative
regulation of small regulatory RNAs (invR, omrA and omrB). Our data
confirm Cpx contribution to copper tolerance, a positive regulator of the heat
shock sigma factor rpoH and adds polyamine homeostasis and regulation of
host cell apoptosis to the growing list of Cpx regulated processes.
Furthermore, we present the first transcriptomic investigation into the ZraSR
two-component signal transduction system and characterisation of its
accessory protein, ZraP. We suggest ZraR mediated positive regulation of
the virulence factors MntH and GroEL, GroSL, DnaK and ClpB (the heat
shock chaperones). In addition, we show critical requirement of ZraSR for
maximal carbon-starvation induced cross-resistance to heat and polymyxin
B. The ZraR regulon described here includes functional groups required to
promote survival within the Salmonella containing vacuole and genes
contributing towards anaerobic metabolism. This work provides the
foundations for investigating the contribution of ZraSR to Salmonella hostpathogen
interactions and the potential this newly characterised ESR has as
a target for investigating Salmonella survival within host cells. Together these
investigations highlight the potential ESRs could hold as critical contributors
to Salmonella pathogenicity and as therapeutic targets for the treatment of
Salmonella infections.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: Jackie Webb
Date Deposited: 06 Jun 2016 14:54
Last Modified: 06 Jun 2016 14:54
URI: https://ueaeprints.uea.ac.uk/id/eprint/59224


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