Defense arsenal of the strict anaerobe against reactive oxygen species encountered during its infection cycle.

UNLABELLED

, a strict anaerobe, is the major cause of antibiotic-associated diarrhea. This enteropathogen must adapt to oxidative stress mediated by reactive oxygen species (ROS), notably those released by the neutrophils and macrophages recruited to the site of infection or those endogenously produced upon high oxygen (O) exposure. uses a superoxide reductase, Sor, and several peroxidases to detoxify ROS. We showed that Sor has a superoxide reductase activity and protects the bacterium from exposure to menadione, a superoxide donor. After confirming the peroxidase activity of the rubrerythrin, Rbr, we showed that this enzyme together with the peroxiredoxin, Bcp, plays a central role in the detoxification of HO and promotes the survival of in the presence of not only HO but also air or 4% O. Under high O concentrations encountered in the gastrointestinal tract, the bacterium generated endogenous HO. The two O reductases, RevRbr2 and FdpF, have also a peroxidase activity and participate in HO resistance. The gene, which also contributes to HO protection, forms an operon with , , and encoding a HO-sensing repressor. The expression of the genes encoding the ROS reductases and the CD0828 protein was induced upon exposure to either HO or air. We showed that the induction of the operon is mediated not only by PerR but also by OseR, a recently identified O-responsive regulator of , and indirectly by σ, the sigma factor of the stress response, whereas the expression of is only controlled by σ.

IMPORTANCE

ROS plays a fundamental role in intestinal homeostasis, limiting the proliferation of pathogenic bacteria. is an important enteropathogen that induces an intense immune response, characterized by the massive recruitment of immune cells responsible for secreting ROS, mainly HO and superoxide. We showed in this work that ROS exposure leads to the production of an armada of enzymes involved in ROS detoxification. This includes a superoxide reductase and four peroxidases, Rbr, Bcp, revRbr2, and FdpF. These enzymes likely contribute to the survival of vegetative cells of in the colon during the host immune response. Distinct regulations are also observed for the genes encoding the ROS detoxification enzymes allowing a fine tuning of the adaptive response to ROS exposure. Understanding the mechanisms of ROS protection during infection could shed light on how survives under conditions of an exacerbated inflammatory response.