Clostridioides difficile is a major cause of diarrhea associated with antibiotherapy. After germination of C. difficile spores in the small intestine, vegetative cells are exposed to low oxygen (O₂) tensions. While considered strictly anaerobic, C. difficile is able to grow in nonstrict anaerobic conditions (1 to 3% O₂) and tolerates brief air exposure indicating that this bacterium harbors an arsenal of proteins involved in O₂ detoxification and/or protection. Tolerance of C. difficile to low O₂ tensions requires the presence of the alternative sigma factor, σ^B, involved in the general stress response. Among the genes positively controlled by σ^B, four encode proteins likely involved in O₂ 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 O₂- and H₂O₂-reductase activities in vitro, while purified FdpA mainly acts as an O₂-reductase. The growth of a fdpA mutant is affected at 0.4% O₂, while inactivation of both revRbrs leads to a growth defect above 0.1% O₂. O₂-reductase activities of these different proteins are additive since the quadruple mutant displays a stronger phenotype when exposed to low O₂ tensions compared to the triple mutants. Our results demonstrate a key role for revRbrs, FdpF, and FdpA proteins in the ability of C. difficile to grow in the presence of physiological O₂ tensions such as those encountered in the colon.

中文翻译：

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厌氧性肠病梭状芽孢杆菌如何耐受低氧张力。

艰难梭菌是与抗生物疗法有关的腹泻的主要原因。在小肠中的艰难梭菌孢子萌发后，植物细胞暴露于低氧（O ₂）张力下。虽然艰难梭菌被认为是严格厌氧的，但它能够在非严格的厌氧条件下生长（1-3％O ₂），并能承受短暂的空气暴露，表明该细菌具有与O ₂解毒和/或保护有关的蛋白质库。的耐受性艰难梭菌到低Ò ₂张力需要替代σ因子的存在下，σ^乙，参与一般的压力反应。在由σ强制控制的基因^乙四个编码的蛋白质可能参与为O ₂解毒：二flavodiiron蛋白（FdpA和FdpF）和两个反向rubrerythrins（revRbr1和revRbr2）。如以前对FdpF的观察，我们显示纯化的revRbr1和revRbr2均在体外具有NADH连接的O ₂和H ₂ O ₂还原酶活性，而纯化的FdpA主要充当O ₂还原酶。fdpA突变体的生长在0.4％O ₂时受到影响，而两个revRbrs的失活都会导致在0.1％O ₂以上的生长缺陷。Ø ₂这些不同蛋白质的β-还原酶活性是累加的，因为与三重突变体相比，当暴露于低O ₂张力时，四重突变体表现出更强的表型。我们的结果证明了revRbrs，FdpF和FdpA蛋白在艰难梭菌在生理O ₂张力（例如在结肠中遇到的张力）存在下生长的能力中的关键作用。