Mark S. McClain, Ph.D.

We are interested in bacterial pathogenesis, with an emphasis in bacterial protein toxins. These proteins play critical roles in infectious diseases. Current studies focus on toxins produced by the human pathogens Helicobacter pylori and Clostridium perfringens. Through studying such toxins, we expect to better understand the molecular events that contribute to disease and to develop therapeutic inhibitors that will be used to treat disease. 

One focus of our studies is the Clostridium perfringens epsilon toxin. C. perfringens is a gram positive, anaerobic bacterium that causes a wide variety of illnesses, ranging from diarrhea to lethal toxemias, in humans and other animals. The epsilon toxin is an extremely potent pore-forming toxin responsible for an often fatal enterotoxemia in animals (particularly livestock, but also possibly in humans). A recent study suggests the toxin contributes to Multiple Sclerosis. Using a high-throughput screen and molecular biological, biochemical, and cell biological techniques, we seek to develop safe and effective inhibitors of the toxin. As we continue to develop inhibitors of the toxin, we also are working to understand the interaction between the toxin and mammalian cells and the cellular responses to the toxin.

A second focus of our studies is the gram negative bacterium Helicobacter pylori, an organism associated with peptic ulcers and gastric cancer in humans. Two proteins secreted by H. pylori are VacA and CagA. VacA is a secreted pore-forming toxin with a variety of effects on epithelial cells. CagA is a protein that is translocated directly from the bacterial cytoplasm into the cytoplasm of host epithelial cells through a specialized secretion apparatus. Using molecular biological, biochemical, and cell biological techniques, our current studies focus on structure-function relationships of the VacA toxin, the type IV secretion apparatus required for CagA secretion, and efforts to identify proteins other than CagA that are translocated by the H. pylori CagA secretion apparatus. As a result of these studies, we hope to better understand the contribution of H. pylori to peptic ulcers and gastric cancer.

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