Responses of Clostridia to oxygen: from detoxification to adaptive strategies

Clostridia comprise bacteria of environmental, biotechnological and medical interest and many commensals of the gut microbiota. Because of their strictly anaerobic lifestyle, oxygen is a major stress for Clostridia. However, recent data showed that these bacteria can cope with O₂ better than expected for obligate anaerobes through their ability to scavenge, detoxify and consume O₂. Upon O₂ exposure, Clostridia redirect their central metabolism onto pathways less O₂-sensitive and induce the expression of genes encoding enzymes involved in O₂-reduction and in the repair of oxidized damaged molecules. While Faecalibacterium prausnitzii efficiently consumes O₂ through a specific extracellular electron shuttling system requiring riboflavin, enzymes such as rubrerythrins and flavodiiron proteins with NAD(P)H-dependent O₂- and/or H₂O₂-reductase activities are usually encoded in other Clostridia. These two classes of enzymes play indeed a pivotal role in O₂ tolerance in Clostridioides difficile and Clostridium acetobutylicum. Two main signalling pathways triggering O₂-induced responses have been described so far in Clostridia. PerR acts as a key regulator of the O₂- and/or reactive oxygen species–defence machinery while in C. difficile, σ^B, the sigma factor of the general stress response also plays a crucial role in O₂ tolerance by controlling the expression of genes involved in O₂ scavenging and repair systems.