How the Anaerobic Enteropathogen Tolerates Low O Tensions.

is a major cause of diarrhea associated with antibiotherapy. After germination of spores in the small intestine, vegetative cells are exposed to low oxygen (O) tensions. While considered strictly anaerobic, is able to grow in nonstrict anaerobic conditions (1 to 3% O) and tolerates brief air exposure indicating that this bacterium harbors an arsenal of proteins involved in O detoxification and/or protection. Tolerance of to low O tensions requires the presence of the alternative sigma factor, σ, involved in the general stress response. Among the genes positively controlled by σ, four encode proteins likely involved in O detoxification: two flavodiiron proteins (FdpA and FdpF) and two reverse rubrerythrins (revRbr1 and revRbr2). As previously observed for FdpF, we showed that both purified revRbr1 and revRbr2 harbor NADH-linked O- and HO-reductase activities , while purified FdpA mainly acts as an O-reductase. The growth of a mutant is affected at 0.4% O, while inactivation of both revRbrs leads to a growth defect above 0.1% O O-reductase activities of these different proteins are additive since the quadruple mutant displays a stronger phenotype when exposed to low O tensions compared to the triple mutants. Our results demonstrate a key role for revRbrs, FdpF, and FdpA proteins in the ability of to grow in the presence of physiological O tensions such as those encountered in the colon. Although the gastrointestinal tract is regarded as mainly anoxic, low O tension is present in the gut and tends to increase following antibiotic-induced disruption of the host microbiota. Two decreasing O gradients are observed, a longitudinal one from the small to the large intestine and a second one from the intestinal epithelium toward the colon lumen. Thus, O concentration fluctuations within the gastrointestinal tract are a challenge for anaerobic bacteria such as This enteropathogen has developed efficient strategies to detoxify O In this work, we identified reverse rubrerythrins and flavodiiron proteins as key actors for O tolerance in These enzymes are responsible for the reduction of O protecting vegetative cells from associated damages. Original and complex detoxification pathways involving O-reductases are crucial in the ability of to tolerate O and survive to O concentrations encountered in the gastrointestinal tract.