Salmonella uses sulfate reductases with unique catalytic activity to promote gut colonization in mice

Abstract

<jats:title>Abstract</jats:title> <jats:p> Non-typhoidal <jats:italic>Salmonella</jats:italic> use molybdenum cofactor-containing MopB- or DMSO reductase-family members to respire chemically diverse substrates, including formate, nitrate and methionine sulfoxide, during infection. The DmsABC enzymatic complex encodes one such DMSO reductase to promote oxidative stress resistance. The <jats:italic>Salmonella</jats:italic> genome encodes several gene paralogues but their role in virulence is unclear. Here we characterize three <jats:italic>Salmonella</jats:italic> MopB-family extracytoplasmic sulfate reductases, which we call Xsr1A, Xsr2A and Xsr3A. Infection experiments in mice and macrophages show that these sulfate reductases support <jats:italic>Salmonella</jats:italic> growth and virulence in the gut and during systemic infection, countering the oxidative effects of host respiratory burst activity. Further experiments show that they are molybdenum cofactor-independent enzymes, and instead depend on the nearby redox-active [4Fe–4S] prosthetic group for catalytic activity. Orthologues of these sulfate reductases were found across distant evolutionary branches, suggesting that [4Fe–4S]-dependent catalysis may occur across the ubiquitous MopB superfamily. Our findings offer insights into the modular evolution of redox centres in the widespread MopB superfamily. </jats:p>