Abstract
Sulfoxide reductases in pathogenic bacteria have recently received increasing attention for their association with virulence and survival within the host. Here, we have re-investigated the physiological role of the molybdenum-containing DmsABC dimethyl sulfoxide (DMSO) reductase from Escherichia coli, which has a proposed role in anaerobic respiration with DMSO. Our investigation into potential physiological substrates revealed that DmsABC efficiently reduces pyrimidine N-oxide, nicotinamide N-oxide, and methionine sulfoxide, and exposure to host cell-produced stressors such as hypochlorite or hydrogen peroxide specifically increased expression of the E. coli dmsA gene. E. coli strains lacking dmsA showed increased lag times in the presence of hypochlorite, and these strains also showed up to a 90% reduction in adherence to human bladder cells. Interestingly, in the presence of hypochlorite, expression of multiple alternative S-/N-oxide reductases present in E. coli was elevated by 2- to 4-fold in a ∆dmsA strain compared to the wild-type strain, suggesting functional redundancy. The phenotypes of the E. coli ∆dmsA strains were strikingly similar to ∆dmsA strains of the respiratory pathogen Haemophilus influenzae, which confirms the role of both enzymes in supporting host-pathogen interactions. We propose that this function is conserved in enzymes closely related to E. coli DmsABC. Our study also uncovered that the expression of many E. coli Mo enzymes was induced by oxidative stressors, including metals such as copper, and further work should be directed at determining the connection of these enzymes to host-pathogen interactions.IMPORTANCEBacterial urinary tract infections are debilitating and frequently recurring in human populations worldwide, and Escherichia coli strains are a major cause of these infections. In this study, we have uncovered a new mechanism by which E. coli can avoid being killed by the human immune system. The bacteria use a set of seven related enzymes that can reverse damage to essential cell components such as amino acids, vitamins, and DNA building blocks. Antibacterial compounds produced by the human immune system specifically induced the production of these enzymes, confirming that they play a role in helping E. coli survive during infection and making these enzymes potential future drug targets.