Clostridium difficile toxin expression is inhibited by the novel regulator TcdC
Clostridium difficile toxin expression is inhibited by the novel regulator TcdC
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DOI：
10.1111/j.1365-2958.2007.05739.x
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发表时间：
2007-06-01
影响因子：
3.6
通讯作者：
Dupuy, Bruno
中科院分区：
文献类型：
--
作者：
Matamouros, Susana;England, Patrick;Dupuy, Bruno
艰难梭菌是一种临床意义日益增加的新出现的医院病原体，它产生两种大的蛋白质毒素，这两种毒素是与疾病相关的细胞损伤的原因。毒素合成受环境变化调节的确切机制尚未发现。毒素基因（tcdA和tcdB）与tcdR和tcdC一起位于致病性基因座（PaLoc）中。TcdR是直接激活毒素基因表达的替代RNA聚合酶σ因子，而一方面tcdR、tcdA和tcdB基因的表达与另一方面tcdC的表达之间的反向关系导致TcdC以某种方式干扰毒素基因表达的建议。这一观点进一步得到了许多最近的C。其中毒素产生增加的艰难梭菌流行株携带常见的tcdC缺失突变。在这份报告中，我们表明，TcdC负调节毒素合成在体内和体外。TcdC在开放复合物形成之前使含TcdR的全酶不稳定，显然是通过与TcdR或含TcdR的RNA聚合酶全酶或两者的相互作用。此外，我们发现C. difficile流行株不是由于它们在tcdC中常见的18 bp框内缺失。
Clostridium difficile, an emerging nosocomial pathogen of increasing clinical significance, produces two large protein toxins that are responsible for the cellular damage associated with the disease. The precise mechanisms by which toxin synthesis is regulated in response to environmental change have yet to be discovered. The toxin genes (tcdA and tcdB) are located in a pathogenicity locus (PaLoc), along with tcdR and tcdC. TcdR is an alternative RNA polymerase sigma factor that directly activates toxin gene expression, while the inverse relationship between expression of tcdR, tcdA and tcdB genes on the one hand and tcdC on the other has led to the suggestion that TcdC somehow interferes with toxin gene expression. This idea is further supported by the finding that many recent C. difficile epidemic strains in which toxin production is increased carry a common tcdC deletion mutation. In this report we demonstrate that TcdC negatively regulates toxin synthesis both in vivo and in vitro. TcdC destabilizes the TcdR-containing holoenzyme before open complex formation, apparently by interaction with TcdR or TcdR-containing RNA polymerase holoenzyme or both. In addition, we show that the hypertoxigenicity phenotype of C. difficile epidemic strains is not due to their common 18 bp in-frame deletion in tcdC.