Salmonella Typhimurium expansion in the inflamed murine gut is dependent on aspartate derived from ROS-mediated microbiota lysis

Inflammation boosts the availability of electron acceptors in the intestinal lumen, creating a favorable niche for pathogenic Enterobacteriaceae. However, the mechanisms linking intestinal inflammation-mediated changes in luminal metabolites and pathogen expansion remain unclear. Here, we show that mucosal inflammation induced by Salmonella enterica serovar Typhimurium (S. Tm) infection increases intestinal levels of the amino acid aspartate. S. Tm used aspartate-ammonia lyase (aspA)-dependent fumarate respiration for growth in the murine gut only during inflammation. AspA-dependent growth advantage was abolished in the gut of germ-free mice and restored in gnotobiotic mice colonized with members of the classes Bacteroidia and Clostridia. Reactive oxygen species (ROS) produced during the host response caused lysis of commensal microbes, resulting in the release of microbiota-derived aspartate that was used by S. Tm, in concert with nitrate-dependent anaerobic respiration, to outcompete commensal Enterobacteriaceae. Our findings demonstrate the role of microbiota-derived amino acids in driving respiration-dependent S. Tm expansion during colitis. [Display omitted] •Salmonella Typhimurium (S. Tm) uses aspartate for growth during colitis in mice•Gut microbiota is the main source of aspartate during S. Tm intestinal infection•Aspartate supports S. Tm expansion by enabling anaerobic fumarate respiration•Host-derived ROS lyses commensal microbes to increase aspartate availability Yoo et al. describe how Salmonella Typhimurium (S. Tm)-induced gut inflammation increases aspartate levels, which fuels S. Tm growth during colitis in mice. Microbiota killing due to the host inflammatory response increases aspartate availability, and S. Tm uses this newly available aspartate to overcome competitors such as E. coli.