Salmonella produces sulfide to compete with Escherichia coli in the gut lumen

Hydrogen sulfide production is a characteristic that distinguishes Salmonella serovars from closely related species, such as Escherichia coli, but its biological significance remains obscure. Here, we show that PhsABC and AsrABC-mediated hydrogen sulfide production by Salmonella enterica serovar (S.) Typhimurium was linked to an increased abundance of Deltaproteobacteria and inhibition of cytochrome bd oxidase-mediated aerobic respiration of Escherichia coli in the murine large intestine. Functional phsABC and asrABC operons provided a growth benefit to S. Typhimurium in the cecum of Enterobacterales-free conventional mice only upon inoculation with commensal E. coli. In gnotobiotic mice engrafted with a defined community of 17 human Clostridia isolates, S. Typhimurium infection inhibited cytochrome bd oxidase-mediated aerobic respiration in E. coli only in the presence of Desulfovibrio piger, a sulfide-producing representative of the Deltaproteobacteria. A S. Typhimurium strain deficient for hydrogen sulfide production (phsA asrA mutant) did not inhibit cytochrome bd oxidase-mediated aerobic respiration in E. coli, even when D. piger was present. Collectively, these data suggest that the phsABC and asrABC operons of Salmonella serovars provide a benefit during competition with closely related bacteria, such as E. coli, by inhibiting cytochrome bd oxidase-mediated aerobic respiration of the commensal.