A novel regulator controls Clostridium difficile sporulation, motility and toxin production.
A novel regulator controls Clostridium difficile sporulation, motility and toxin production.
复制标题
DOI：
10.1111/mmi.13361
复制
发表时间：
2016-06
影响因子：
3.6
通讯作者：
McBride SM
中科院分区：
文献类型：
--
作者：
Edwards AN;Tamayo R;McBride SM
艰难梭菌是一种厌氧病原体，它形成孢子，促进在环境中的生存并传播到新宿主。人们对艰难梭菌启动孢子形成的调控途径知之甚少。我们发现了两个与其他孢子形成细菌的 Rap 孢子形成蛋白相似性有限的因子。在这项研究中，我们发现基因 CD3668 的破坏会减少孢子形成并增加毒素的产生和运动。这种突变体的毒性更强，并且在仓鼠感染模型中表现出毒素基因表达增加。基于这些表型，我们将此基因座重命名为 rstA，用于孢子形成和毒素的调节器。我们的数据表明，RstA 是一种双功能蛋白，可通过未知途径上调孢子形成，并通过影响 sigD 转录来抑制运动性和毒素产生。保守的 RstA 直系同源物存在于其他致病性和工业梭菌属物种中，并且可能代表控制梭菌孢子形成的关键调节蛋白。
Clostridium difficile, is an anaerobic pathogen that forms spores which promote survival in the environment and transmission to new hosts. The regulatory pathways by which C. difficile initiates spore formation are poorly understood. We identified two factors with limited similarity to the Rap sporulation proteins of other spore-forming bacteria. In this study, we show that disruption of the gene CD3668 reduces sporulation and increases toxin production and motility. This mutant was more virulent and exhibited increased toxin gene expression in the hamster model of infection. Based on these phenotypes, we have renamed this locus rstA, for regulator of sporulation and toxins. Our data demonstrate that RstA is a bifunctional protein that upregulates sporulation through an unidentified pathway and represses motility and toxin production by influencing sigD transcription. Conserved RstA orthologs are present in other pathogenic and industrial Clostridium species and may represent a key regulatory protein controlling clostridial sporulation.