Gut inflammation provides a respiratory electron acceptor for Salmonella

Salmonella enterica serotype Typhimurium ( S . Typhimurium) causes acute gut inflammation by using its virulence factors to invade the intestinal epithelium and survive in mucosal macrophages. The inflammatory response enhances the transmission success of S . Typhimurium by promoting its outgrowth in the gut lumen through unknown mechanisms. Here we show that reactive oxygen species generated during inflammation react with endogenous, luminal sulphur compounds (thiosulphate) to form a new respiratory electron acceptor, tetrathionate. The genes conferring the ability to use tetrathionate as an electron acceptor produce a growth advantage for S . Typhimurium over the competing microbiota in the lumen of the inflamed gut. We conclude that S . Typhimurium virulence factors induce host-driven production of a new electron acceptor that allows the pathogen to use respiration to compete with fermenting gut microbes. Thus the ability to trigger intestinal inflammation is crucial for the biology of this diarrhoeal pathogen. A gut pathogen gains an edge The ability of the enteric pathogen Salmonella enterica serotype Typhimurium to use tetrathionate as a terminal electron acceptor has been used in the laboratory as a convenient means of enriching growth media containing this bacterium for many years. Tetrathionate respiration was thought to have little importance during infection, but to come into its own in free-living bacteria in environments containing tetrathionate, such as soil or decomposing carcasses. Now a possible role has been identified for this metabolism during intestinal infection. Acute intestinal inflammation induced by S. enterica Typhimurium virulence factors is shown to be accompanied by production of oxygen radicals in the gut lumen as part of the immune response. These oxygen radicals oxidize thiosulphate, the end product of hydrogen-sulphide detoxification by enterocytes, to tetrathionate. The pathogen can then use tetrathionate respiration during growth in the inflamed intestine, allowing it to out-compete other microbes that rely on anaerobic fermentation. Salmonella enterica serotype Typhimurium causes acute gut inflammation, which promotes the growth of the pathogen through unknown mechanisms. It is now shown that the reactive oxygen species generated during inflammation react with host-derived sulphur compounds to produce tetrathionate, which the pathogen uses as a terminal electron acceptor to support its growth. The ability to use tetrath