The incidence of Clostridium difficile infection has been steadily rising over the past decade. The increase in the rate of incidence is associated with the specific NAP1/BI/027 strains which are “hypervirulent” and have led to several large outbreaks since their emergence. However, the relation between these outbreaks and virulence regulation mechanisms remains unclear. It has been reported that the major virulence factor TcdA and TcdB in C. difficile could be repressed by cysteine. Here, we investigated the functional and virulence-associated regulation of C. difficile R20291 response to cysteine by using a time-resolved genome-wide transcriptome analysis. Dramatic changes of gene expression in C. difficile revealed functional processes related to transport, metabolism, and regulators in the presence of cysteine during different phases of growth. Flagellar and ribosomal genes were significantly down-regulated in long-term response to cysteine. Many NAP1/BI/027- specific genes were also modulated by cysteine. In addition, cdsB inactivation in C. difficile R20291 could remove the repression of toxin synthesis but could not remove the repression of butyrate production in the presence of cysteine. This suggests that toxin synthesis and butyrate production might have different regulatory controls in response to cysteine. Altogether, our research provides important insights into the regulatory mechanisms of C. difficile response to cysteine.

在过去的十年中，艰难梭菌感染的发生率一直在稳步上升。发病率的增加与特定的NAP1 / BI / 027菌株有关，这些菌株是“高毒力”的，自出现以来已导致数次大规模暴发。但是，这些爆发与毒力调节机制之间的关系仍不清楚。据报道，艰难梭菌中的主要毒力因子TcdA和TcdB可被半胱氨酸抑制。在这里，我们通过使用时间分辨的全基因组转录组分析来研究艰难梭菌R20291对半胱氨酸反应的功能和与毒力相关的调节。艰难梭菌基因表达的剧烈变化揭示了在生长的不同阶段中存在半胱氨酸的过程中与运输，代谢和调节剂有关的功能过程。鞭毛和核糖体基因在对半胱氨酸的长期反应中显着下调。半胱氨酸还调节了许多NAP1 / BI / 027特异性基因。此外，艰难梭菌R20291中的cdsB失活可以消除对毒素合成的抑制，但在半胱氨酸存在下不能消除对丁酸产生的抑制。这表明毒素合成和丁酸生产可能对半胱氨酸有不同的调节控制。总而言之，我们的研究为难辨梭状芽胞杆菌对半胱氨酸反应的调控机制提供了重要见解。