Genetic regulation by the environmental signals in Clostridium perfringens

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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).