Import of aspartate and malate by DcuABC drives H2/fumarate respiration to promote Salmonella initial gut-luminal colonization

Initial enteropathogen growth in the microbiota-colonized gut is poorly understood. Salmonella Typhimurium is metabolically plastic and can harvest energy by anaerobic respiration using hydrogen (H2), a product of microbiota metabolism, as an electron donor and fumarate as an electron acceptor. As fumarate is scarce in the gut, the source of this electron acceptor is unclear. Transposon sequencing analysis along the colonization-trajectory of S.Typhimurium implicated the C4-dicarboxylate exchanger DcuABC in murine gut colonization. In competitive colonization assays, DcuABC and enzymes converting the C4-dicarboxylates aspartate and malate into fumarate (AspA, FumABC), were required for fumarate/H2-dependent initial growth. Thus, S.Typhimurium obtains fumarate by DcuABC-mediated import and the subsequent conversion of L-malate and L-aspartate into fumarate. Fumarate reduction yields succinate, which is exported by DcuABC in exchange for L-aspartate and L-malate. This mechanism allows S.Typhimurium to harvest energy by H2/fumarate respiration in the microbiota-colonized gut. It might be relevant for other enteropathogens encoding the requisite genes.