Further characterisation of the envelope stress responses of Salmonella Typhimurium

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.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

University of East Anglia

Year dc:date.issued

2015

Author dc:creator

• Wells, Hannah

Language dc:language

en