Salmonella Typhimurium: Mechanisms of nitric oxide detoxification and regulation of the periplasmic nitrate reductase

Addington, Emily (2016) Salmonella Typhimurium: Mechanisms of nitric oxide detoxification and regulation of the periplasmic nitrate reductase. Masters thesis, University of East Anglia.

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Abstract

The enteric pathogen Salmonella causes both severe systemic infection and
acute gastroenteritis, commonly known as food poisoning, in humans. It is
therefore responsible for millions of food and water born infections worldwide
each year and has a significant burden on global health. Typhoid fever is a
serious, life-threatening illness while gastroenteritis caused by Salmonella is
often fatal to at-risk individuals such as the immunocompromised, the elderly
and infants. The human innate immune system combats Salmonella infection
with both reactive oxygen and reactive nitrogen species (ROS and RNS)
largely produced by macrophages. Both ROS and RNS are capable of
damaging bacterial DNA, lipids and proteins, inhibiting Salmonella replication
and survival. Nitric Oxide (NO), a free radical and cytotoxin, is one such RNS
produced by the host immune system that acts as an antibacterial defence
against Salmonella. In order to survive in the host Salmonella must therefore
employ mechanisms to detoxify NO it encounters both endogenously and
exogenously. Currently three enzymes are well-characterised as mechanisms
by which Salmonella detoxifies NO, however Salmonella’s ability to survive
without these three enzymes suggests the existence of other, yet unidentified,
NO detoxification genes.
In this study, various Salmonella genes shown to be up-regulated under
nitrosative stress in preliminary data were further investigated and their role in
NO detoxification characterised. Single and combination deletion strains were
constructed and resultantly showed sensitivity to both nitrosative and
oxidative stress. This study also examined the regulation of the periplasmic
nitrate reductase of Salmonella, NapA, in relation to the SPI-1 transcriptional
activator HilA. Results of this research implicate a role for HilA as a negative
regulator of napA expression.

Item Type: Thesis (Masters)
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: Gillian Aldus
Date Deposited: 22 Feb 2017 12:10
Last Modified: 22 Feb 2017 12:16
URI: https://ueaeprints.uea.ac.uk/id/eprint/62681
DOI:

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