Oxygen Response and Tolerance Mechanisms in Clostridioides Difficile

While the gut is typically thought of as anoxic, there are two intersecting and decreasing oxygen gradients that are observed in the gut: oxygen decreases from the small to the large intestine and from the intestinal epithelium toward the colon lumen. Gut oxygen levels also increase following antibiotic induced-dysbiosis. While dysbiosis favors growth of Clostridioides difficile, the oxygen increase also causes stress to this anaerobic enteropathogen. To circumvent oxygen threat, C. difficile has developed efficient strategies: sporulation, biofilm formation, the rerouting of central metabolism and the production of oxygen detoxification enzymes. Especially, reverse rubrerythrins and flavodiiron proteins involved in oxygen reduction are crucial in C. difficile ability to tolerate and survive the oxygen concentrations encountered in the gastrointestinal tract. Two regulators, σ and PerR, play pivotal role in the mastering of these adaptive responses by controlling the various systems that protect cells from oxidative damages.