Mechanisms of Bacterial Pathogenesis and Host Response
Pathogenic bacteria have evolved a diverse array of mechanisms for delivering toxins and other virulence factors into the interior of host cells. Studying the molecular structures of these virulence factors alone and in complex with host receptors and membranes can lend insight into how these delivery processes occur and how these processes can be exploited or prevented. To date, much of my research has centered on the three proteins that make up anthrax toxin. Of specific interest are the means by which these three proteins assemble on the host cell surface, the interaction of toxin with its host protein receptor, and the mechanism by which anthrax toxin traverses the endosomal membrane to gain access to the host cytosol. X-ray crystallography has been combined with a variety of biochemical and biophysical methods in an effort to understand anthrax intoxication at the molecular level. Current work involves a continuation of the effort on anthrax toxin as well as the expansion of these studies to include toxins and virulence factors from other organisms.