Nitrate respiration by Salmonella during gut inflammation

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DESCRIPTION (provided by applicant): The recent emergence and spread of new bacterial pathogens has generated great interest into how infectious diseases can persist and spread within host populations. Although it is clear that antibiotic resistance can contribute to the expansion of a new pathogenic clone (e.g. multi-drug resistant Salmonella serovars), information on other factors that enhance persistence and spread of emerging pathogens remains sparse. The question of which molecular mechanisms are responsible for the emergence and transmission of a new pathogenic S. Typhimurium clone represents a high-impact topic that will be addressed in this application. Our central hypothesis is that the horizontally acquired type III secretion system effector SopE induces production of host-derived nitrate, an energetically highly valuable electron acceptor, thus fueling a bloom of Salmonella in the gut lumen through anaerobic nitrate respiration. We will test key aspects of our hypothesis by pursuing the following specific aims: 1.) Determine the role of SopE on transmission success and 2.) Determine the role of SopE in modulating expression of genes involved in anaerobic nitrate and tetrathionate respiration in the inflamed gut. Successful completion has a strong potential to have a high impact on gastroenteritis research by providing a novel concept, i.e. that the evolution of Salmonella may be driven by making new nutrients such as anaerobic respiratory electron acceptors available in the inflamed gut, thus boosting transmission success.