Microbiota-derived aspartate drives pathogenic Enterobacteriaceae expansion in the inflamed gut

Abstract

SUMMARYInflammation 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 and chemical colitis results in increased intestinal levels of the amino acid aspartate. The S. Tm and E. coli genomes encode an aspartate ammonia-lyase (aspA) which converts aspartate into fumarate, an alternative electron acceptor. S. Tm and pathogenic E. coli used aspA-dependent fumarate respiration for growth in the murine gut only during inflammation. Such growth advantage was abolished in the gut of germ-free mice. However, mono-association of gnotobiotic mice with members of the classes Bacteroidia and Clostridia restored the benefit of aspartate utilization to the pathogens. Our findings demonstrate the role of microbiota-derived amino acids in driving respiration-dependent Enterobacteriaceae expansion during colitis.