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To achieve the proposed research goals, a variety of experimental approaches are used which span the disciplines of microbiology, molecular biology, cellular biology, genetics and biochemistry.
By constructing isogenic knock-out mutants we have demonstrated that Clostridium perfringens enterotoxin (CPE) expression is necessary for the pathogenesis of both C. perfringens type A food poisoning and non-food-borne GI disease isolates. Recently, our spo0A knock-out mutant studies have provided some of the first direct genetic evidence supporting spore-formation is essential for production of CPE by cpe-positive C. perfringens. We have also demonstrated, by genotypic and phenotypic characterization of a large number of animal GI disease isolates, that the Beta2-toxigenic C. perfringens isolates are highly associated with GI diseases in domestic animals. Collectively, these findings provide a key part of the foundation for our future research plan outlined above.
The gram-positive, spore forming, anaerobic C. perfringens bacteria is an important cause of both histotoxic and GI disease in humans and domestic animals. C. perfringens type A food poisoning currently ranks as the third most commonly reported food-borne disease in the United States. In the U.S. alone C. perfringens type A food poisoning results in annual economic losses of more than million dollars. A vaccine is badly needed to prevent clostridial diseases, but vaccine development is complicated by the lack of an understanding of the molecular biology of the clostridia. We anticipate that our research will facilitate the designing and developing a vaccine against C. perfringens type A food poisoning.