Endogenous production and detoxification of a potent cytotoxin, nitric oxide, in Salmonella enterica serovar Typhimurium and Escherichia coli

Runkel, S (2014) Endogenous production and detoxification of a potent cytotoxin, nitric oxide, in Salmonella enterica serovar Typhimurium and Escherichia coli. Doctoral thesis, University of East Anglia.

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Abstract

Salmonella serovars are harmful enteric pathogens of economical and clinical
importance that possess sophisticated strategies to rapidly adapt to various
host (human and animal) and non-host (soil, water and industrial) environments.
Nitrosative stress, in the form of RNS such as the potent cytotoxin NO, is an
important stress in the Salmonella lifecycle. Salmonella is exposed to
exogenous NO, produced by activated macrophages as part of the host
immune response and to endogenous NO, produced during anaerobic nitrate
respiration. Salmonella employs three known enzymes (HmpA, NrfA and
NorVW) to detoxify NO to less toxic compounds, including the
neuropharmacological agent and greenhouse gas N2O. The production of
endogenous NO and N2O have been predominantly studied in denitrifying soil
bacteria and have been widely neglected in enteric bacteria.
Here, the physiological and molecular mechanisms involved in endogenous NO
production and detoxification were examined in the pathogenic Salmonella
enterica serovar Typhimurium and laboratory Escherichia coli (E. coli) strains.
Significant differences in N2O production were observed between the two
genera and between the tested E. coli strains, although they possess identical
nitrate respiration systems. The reason for this was found to be transcriptional,
with narG expression having the major impact. In addition, our results indicate
that a weak nitrous oxide reductase exists in Salmonella; a process that was
believed to be restricted to certain soil bacteria, archaea and fungi that possess
the enzyme NosZ. Furthermore, the contribution of selected NsrR regulon
genes, to endogenous N2O production of Salmonella was determined and
revealed that HmpA and the Hcp-Hcr operon are both crucial for high N2O
levels. These findings provide new insights into host-pathogen interactions,
which could potentially lead to new treatment strategies for Salmonella
infections, help to increase food safety and provide new mitigation strategies to
reduce global warming.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: Mia Reeves
Date Deposited: 09 Jul 2014 12:03
Last Modified: 09 Jul 2014 12:03
URI: https://ueaeprints.uea.ac.uk/id/eprint/49472
DOI:

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