Recent research regarding the structure and function of Bacillus anthracis lethal (LeTx) and
edema (ETx) toxins provides growing insights into the pathophysiology and treatment of
shock with this lethal bacteria. These are both binary-type toxins composed of protective
antigen necessary for their cellular uptake and either lethal or
edema factors, the toxigenic moieties. The primary cellular receptors for protective
antigen have been identified and constructed and key steps in the extracellular processing and internalization of the toxins clarified. Consistent with the lethal factor's primary action as an intracellular
endopeptidase targeting
mitogen-activated protein kinase kinases, growing evidence indicates that
shock with this toxin does not result from an excessive inflammatory response. In fact, the potent immunosuppressive effects of LeTx may actually contribute to the establishment and persistence of
infection. Instead,
shock with LeTx may be related to the direct injurious effects of lethal factor on endothelial cell function. Despite the importance of LeTx, very recent studies show that
edema factor, a potent
adenyl cyclase, has the ability to make a substantial contribution to
shock caused by B. anthracis and works additively with LeTx. Furthermore, ETx may contribute to the immunosuppressive effects of LeTx.
Therapies under development that target several different steps in the cellular uptake and function of these two toxins have been effective in in vitro and in vivo systems. Understanding how best to apply these agents clinically and how they interact with conventional treatments should be goals for future research.