Bruce A McClane , PhD

Our laboratory studies the pathogenesis of Clostridium perfringens. This Gram-positive, sporeforming anaerobic bacterium causes histotoxic infections (such as gas gangrene), enteric infections and enterotoxemias in humans and domestic animals. Currently, we are studying the action of C. perfringens enterotoxin (CPE), which is responsible for the gastrointestinal symptoms of the second most common foodborne disease in the USA as well as many cases of antibiotic-associated diarrhea. This toxin binds to claudin receptors in tight junctions of epithelial cells and then oligomerizes to form a pore. We are currently studying how CPE forms this pore and how it damages the intestine. In addition, during food poisoning, CPE is only made when C. perfringens sporulates in the intestines, so we are analyzing the C. perfringens sporulation process and what intestinal factors trigger this effect. Besides studying CPE, we are also currently examining the contributions of sialidases to C. perfringens pathogenesis and growth. These studies have revealed that sialidases  potentiate CPE action, as well as strongly increasing C. perfringens intestinal adherence and growth. We are also beginning to study C. perfringens growth during gas gangrene, focusing on the role of branched-chain amino acid transporters in pathogenesis. We hypothesize that one or more of these transporters is important for virulence because C. perfringens cannot synthesize branched-chain amino acids by itself.