The healthy human gut contains a small number of sulfate-reducing bacteria of the genus Desulfovibrio. These bacteria gain energy by respiration and transfer electrons to sulfate as an electron acceptor, which leads to the production of toxic hydrogen sulfide. For thus far unknown reasons, there is a massive proliferation of Desulfovibrio bacteria in patients suffering from inflammatory bowel disease, bacteremia, Parkinson’s disease or autism.
Despite the importance of Desulfovibrio spp. little is known how these bacteria find a niche for colonization. We hypothesize that motile Desulfovibrio spp. uses chemotaxis to swim along chemical gradients into the deep layers of the mucus. This project aims to identify the key players in the perception and chemotactic response of Desulfovibro desulfuricans. We aim to elucidate the function of the 19 chemoreceptors that will be used as targets to inhibit the directed movement of this bacterium in niches and thereby prevent unhindered proliferation. To achieve this goal, we will (1) develop innovative genetic engineering tools for D. desulfuricans to generate deletion mutants, (2) study the chemotactic capabilities of D. desulfuricans by a combination of motility assays for wild type and mutants and biochemical protein-ligand binding assays, and (3) translate our findings into strategies to disturb chemotaxis.
The results of the project will not only contribute to a better understanding of the physiology of the intestinal commensals Desulfovibrio spp., which under certain conditions harm the host, but also open up a novel antimicrobial approach to restore a healthy human intestinal microbiota.