Genetic regulation by the environmental signals in Clostridium perfringens

革兰氏阳性芽孢形成细菌，产气荚膜梭菌是气性坏疽（梭菌性肌坏死）和人类食物中毒的病原体。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起致病性。许多毒素和酶的基因是由双组分VirR/VIrS系统调控的（VIrS和VirR分别是传感器激酶和反应调节因子），许多其他二级调节因子包括调控RNA分子（如VR-RNA和virX）也可能参与产气荚膜荚膜菌毒力基因的遗传调控。根据产气荚膜荚膜菌的基因组序列13，我们设计了DNA芯片，这些基因被用来比较野生型和各种特定调控基因突变体之间的基因表达谱。共获得bb100个微阵列数据，并使用各种生物信息学方法对其进行分析。许多操纵子和调控子被鉴定为包含在每次实验中总是以相同方式共同调节的基因。其中一个调控因子是VirR/VirS调控因子，包括37个由VirR/VirS系统直接调控的基因和大约100个由二级调控因子（VR-RNA）调控的基因，表明VirR/VirS系统调控的许多基因不仅涉及毒力（如磷脂酶C、气荚膜溶酶O、胶原酶），还涉及代谢（氨基酸合成、转运蛋白）和能量生产（糖利用）。

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).