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Bacterial nitrate metabolism in colonisation of the mammalian gastrointestinal tract

Main Researcher: Karen Prior

This project will provide the first integrated view of the importance of nitrate reduction on gut colonisation of enteric pathogens in order to develop new knowledge-based strategies for removing Salmonella from the food chain.

Little is know about how Salmonella adapts a to the biochemical environment of the GI tract during the early stages of infection. Given the anaerobic nature of the GI tract, the ability of nitrate to serve as a terminal electron acceptor during anaerobic bacterial growth, and the relatively high levels of nitrate, we hypothesise that there is a connection between the process of bacterial infection, colonisation of the GI tract and nitrate dissimilation by Salmonella. (Lundberg et al., 2004).

To establish the role that each of the nitrate reductase enzyme complex plays in the adaptation to the GI tract, Salmonella mutants lacking one of the three nitrate metabolism systems will be tested for their ability to dissimilate nitrate under aerobic or anaerobic conditions, and under varying levels of nitrate or nitrite. Culture in chemostats at the UEA Wolfson Fermentation Laboratory will help us assess the influence of the environment on Salmonella gene expression and enzyme activity. The ability of the mutants to invade epithelial cells in vitro and to colonise the mouse gut will also be assessed, providing the first evidence of the role of nitrate dissimilation in the early stages of the Salmonella infection process.

Funding is provided by the Norwich Research Park for this collaboration between the Hinton laboratory at IFR and David Richardson’s group at the University of East Anglia.

 

 

 

 

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