| Summary: | 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.
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