The transcriptional profile during deoxycholate-induced sporulation in a Clostridium 
perfringens isolate from foodborne illness.
The transcriptional profile during deoxycholate-induced sporulation in a Clostridium 
perfringens isolate from foodborne illness.
复制标题
梭状芽胞杆菌脱氧胆酸诱导孢子形成过程中的转录谱
DOI：
10.1128/aem.00252-16
复制
发表时间：
2016
影响因子：
4.4
通讯作者：
Miyake M.
中科院分区：
文献类型：
--
作者：
Yasugi M;Okuzaki D;Kuwana R;Takamatsu H;Fujita M;Sarker MR;Miyake M.
A型产气荚膜梭菌是人类食源性疾病（FBI）的常见来源。营养细胞在小肠中产生孢子，并产生主要致病因子产气荚膜原肠毒素。虽然产孢在FBI的发病机制中起关键作用，但诱导产孢的机制尚不清楚。胆汁盐曾被证实能诱导产孢，我们证实脱氧胆酸盐（DCA）能诱导产孢的产气荚膜荚膜菌NCTC8239与人肠上皮Caco-2细胞共培养。在本研究中，我们对菌株NCTC8239进行了转录组分析，以阐明dca诱导产孢的机制。在分析的2761个基因中，333个基因在dca诱导的产孢过程中上调或下调，包括细胞分裂、营养代谢、信号转导和防御机制的基因。相反，毒力相关的转录调控因子（VirR/VirS系统、agrsystem、codY和abrb）未被DCA激活。DCA显著增加了孢子形成过程的主要调控因子Spo0A控制的信号分子的表达，而在DCA存在或不存在的情况下，Spo0A本身的表达没有改变。在DCA的存在下，Spo0A的磷酸化增强。综上所述，这些结果表明，DCA至少部分地通过促进菌株NCTC8239中Spo0A的磷酸化和激活Spo0A调控基因来诱导产孢，同时改变各种基因的表达。由A型产气荚膜梭菌引起的疾病一直是发达国家人类最常见的细菌性食源性疾病之一。产气荚膜芽孢杆菌在小肠内的产孢是其发病的关键事件，但产气荚膜芽孢杆菌致病的因素和潜在机制目前尚不清楚。胆汁盐是胆汁的主要成分，由肝脏分泌用于脂质乳化，可诱导产孢。然而，胆盐诱导孢子形成的机制尚未明确。在本研究中，我们通过转录组分析证明脱氧胆酸盐（一种胆汁盐）通过促进Spo0A的磷酸化和激活Spo0A调节基因来诱导产孢。因此，本研究增强了我们对产气荚膜荚膜菌产孢机制的理解，特别是胆盐诱导的产孢机制。
Clostridium perfringens type A is a common source of foodborne illness (FBI) in humans. Vegetative cells sporulate in the small intestinal tract and produce the major pathogenic factor C. perfringens enterotoxin. Although sporulation plays a critical role in the pathogenesis of FBI, the mechanisms inducing sporulation remain unclear. Bile salts were shown previously to induce sporulation, and we confirmed deoxycholate (DCA)-induced sporulation in C. perfringens strain NCTC8239 cocultured with human intestinal epithelial Caco-2 cells. In the present study, we performed transcriptome analyses of strain NCTC8239 in order to elucidate the mechanism underlying DCA-induced sporulation. Of the 2,761 genes analyzed, 333 were up- or downregulated during DCA-induced sporulation and included genes for cell division, nutrient metabolism, signal transduction, and defense mechanisms. In contrast, the virulence-associated transcriptional regulators (the VirR/VirS system, theagrsystem,codY, andabrB) were not activated by DCA. DCA markedly increased the expression of signaling molecules controlled by Spo0A, the master regulator of the sporulation process, whereas the expression ofspo0Aitself was not altered in the presence or absence of DCA. The phosphorylation of Spo0A was enhanced in the presence of DCA. Collectively, these results demonstrated that DCA induced sporulation, at least partially, by facilitating the phosphorylation of Spo0A and activating Spo0A-regulated genes in strain NCTC8239 while altering the expression of various genes.IMPORTANCEDisease caused by Clostridium perfringens type A consistently ranks among the most common bacterial foodborne illnesses in humans in developed countries. The sporulation of C. perfringens in the small intestinal tract is a key event for its pathogenesis, but the factors and underlying mechanisms by which C. perfringens sporulatesin vivocurrently remain unclear. Bile salts, major components of bile, which is secreted from the liver for the emulsification of lipids, were shown to induce sporulation. However, the mechanisms underlying bile salt-induced sporulation have not yet been clarified. In the present study, we demonstrate that deoxycholate (one of the bile salts) induces sporulation by facilitating the phosphorylation of Spo0A and activating Spo0A-regulated genes using a transcriptome analysis. Thus, this study enhances our understanding of the mechanisms underlying sporulation, particularly that of bile salt-induced sporulation, in C. perfringens.