Laboratoire Pathogénese des Bactéries Anaérobies, Institut Pasteur, Paris, France.
Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
Environ Microbiol. 2017 May;19(5):1933-1958. doi: 10.1111/1462-2920.13696. Epub 2017 Mar 21.
Clostridium difficile is a major cause of diarrhoea associated with antibiotherapy. Exposed to stresses in the gut, C. difficile can survive by inducing protection, detoxification and repair systems. In several firmicutes, most of these systems are controlled by the general stress response involving σ . In this work, we studied the role of σ in the physiopathology of C. difficile. We showed that the survival of the sigB mutant during the stationary phase was reduced. Using a transcriptome analysis, we showed that σ controls the expression of ∼25% of genes including genes involved in sporulation, metabolism, cell surface biogenesis and the management of stresses. By contrast, σ does not control toxin gene expression. In agreement with the up-regulation of sporulation genes, the sporulation efficiency is higher in the sigB mutant than in the wild-type strain. sigB inactivation also led to increased sensitivity to acidification, cationic antimicrobial peptides, nitric oxide and ROS. In addition, we showed for the first time that σ also plays a crucial role in oxygen tolerance in this strict anaerobe. Finally, we demonstrated that the fitness of colonisation by the sigB mutant is greatly affected in a dixenic mouse model of colonisation when compared to the wild-type strain.
艰难梭菌是一种与抗生素治疗相关的腹泻的主要原因。暴露于肠道压力下，艰难梭菌可以通过诱导保护、解毒和修复系统来生存。在几种Firmicutes 中，这些系统中的大多数都受到涉及σ的一般应激反应的控制。在这项工作中，我们研究了σ在艰难梭菌生理病理中的作用。我们表明，σ突变体在静止期的存活率降低。通过转录组分析，我们表明σ控制着约 25%的基因的表达，包括与孢子形成、代谢、细胞表面生物发生和应激管理有关的基因。相比之下，σ不控制毒素基因的表达。与孢子形成基因的上调一致，σ突变体的孢子形成效率高于野生型菌株。σ失活也导致对酸化、阳离子抗菌肽、一氧化氮和 ROS 的敏感性增加。此外，我们首次表明，σ在这种严格厌氧菌的耐氧性中也起着至关重要的作用。最后，我们证明与野生型菌株相比，在艰难梭菌定植的二联小鼠模型中，σ突变体的定植适应性受到极大影响。
