Erik L. Hewlett, MD, University of Virginia

The Hewlett lab is interested in bacterial toxins, as biomedical research tools, as well as virulence factors contributing to the pathogenesis of infectious diseases. Specifically, work in the laboratory is directed at the molecular mechanisms of action of anthrax toxins, edema toxin and lethal toxin, and two toxins from Bordetella pertussis: adenylate cyclase (AC) toxin and pertussis toxin. Edema toxin (ET), produced by Bacillus anthracis, is composed of a binding subunit, protective antigen (PA), and the enzymatically active adenylate cyclase, edema factor (EF). Although simplistically this toxin has a similar function to the bordetella AC toxin, namely producing supraphysiologic levels of cyclic AMP from host cell ATP, the functional and consequential differences between the two are just now becoming fully appreciated. For example, bordetella AC toxin elicits apoptotic cytotoxicity in multiple cell types, whereas ET does not, despite also increasing intracellular cAMP levels. Observations such as these are proving very useful in understanding physiologic processes in the biology of normal and cancer cells, quite apart from microbial pathogenesis.

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