Genetic regulation by the environmental signals in Clostridium perfringens

革兰氏阳性芽胞形成菌产气荚膜梭菌是人类气性坏疽(梭状芽胞杆菌肌坏死)和食物中毒的病原体。产气荚膜梭菌产生大量毒素和酶，这些毒素和酶通过毒素和/或酶对组织中特定靶点的协同作用而导致致病性。许多毒素和酶的基因都受VirR/VIRS系统(VIRS和VirR分别是传感器、激酶和反应调节器)和许多其他二级调节因子的调节，包括调节性RNA分子(例如。Vr-RNA和virX)也可能参与产气荚膜梭菌毒力基因的遗传调控。根据产气荚膜梭菌13菌株的基因组序列，我们设计了DNA芯片，用于比较特定调控基因的野生型和不同突变体的基因表达谱。共获得了&gt；100个微阵列数据，并使用各种生物信息学方法对其进行了分析。许多操纵子和调节子被确定包含在每个实验中总是以相同的方式共同调节的基因。其中一个调控基因是VirR/VIRS系统，它包括由VirR/VIRS系统直接调控的37个基因和大约100个受二级调控基因(VR-RNA)调控的基因，这表明VirR/VIRS系统不仅调控许多与毒力有关的基因(例如，VIRS)，而且还调控许多与毒力有关的基因。不仅与代谢(氨基酸合成、转运)和能量产生(糖的利用)有关。

Gram-positive spore-forming bacteria, Clostridium perfringens is a causative agent for gas gangrene (clostridial myonecrosis) and food poisoning in humans. C. perfringens produces numerous toxins and enzymes, which are responsible for the pathogenicity through synergestic actions of toxins and/or enzymes on their specific targets in the tissue. Many genes for toxins and enzymes are regulated by the two-component VirR/VIrS system (VirS and VirR are sensor kinase and response regulator, respectively), and many other secondary regulators including regulatory RNA molecules (ex. VR-RNA and virX) might be also involved in the genetic regulation of the virulence genes in C. perfringensAccording to the genomic sequence of C. perfringens strain13, we have designed DNA microarrays, which were used to compare the gene expression profiles between wild-type and various mutants of specific regulatory genes. Total of >100 microarray data was obtained and they were analyzed using various bio-informatic methods. Numerous operons and regulons were identified to contain genes that were always co-regulated in the same manner in every experiment. One of the regulons was the VirR/VirS regulon including 37 genes directly regulated by the VirR/VirS system and approximately 100 genes that are regulated by the secondary regulator (VR-RNA), indicating that the VirR/VirS system regulates many genes involved not only in virulence (ex. phospholipase C, perfringolysin O, collagenase) but also in metabolism (amino acid synthesis, transporters) and energy production (sugar utilization).