Two-component regulatory systems involved in toxin production in Clostridium perfringens

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The bacterium studied in this project causes gas gangrene, a severe and often fatal infection of traumatic or surgical wounds. The project involves the detailed analysis of the process by which this bacterium controls the production of the toxic proteins that are required for disease to occur. The emphasis is to determine the mechanism by which this regulatory process is mediated. Research in this laboratory has identified two genes whose protein products are the key links in this regulatory network. The objectives of the project will be to determine which part of the regulatory protein interacts with the target toxin gene, to start to determine the structure of the regulatory protein so that the precise biochemical mechanism of action can be ascertained, to determine the components of the DNA target that are essential for binding activity, and to identify other genes that are involved in the regulation of both the toxin genes and other genes that may be implicated in the disease process. These studies will be facilitated by the availability of the complete genome sequence of this pathogenic bacterium. The project will make a major contribution to our knowledge of how bacteria that cause disease are able to control the production of the toxins that are critical to the disease process. If we are to learn how to more effectively control and treat bacterial infections then it is very important that we understand the complex regulatory networks that tell bacteria when to produce its disease-causing products.