Bacillus anthracis calmodulin-dependent adenylate cyclase: chemical and enzymatic properties and interactions with eucaryotic cells

Abstract

Studies on the mechanism of action of anthrax toxin have led to the discovery that the edema factor component is a calmodulin-dependent adenylate cyclase. This enzyme can be obtained in milligram amounts at high purity from culture supernatants of avirulent B. anthracis strains. The cyclase binds to and probably enters eucaryotic cells to cause large, unregulated increases in cyclic AMP concentrations, an effect that may decrease an animal's ability to limit B. anthracis infection. The similarity of this bacterial adenylate cyclase to calmodulin-dependent eucaryotic adenylate cyclases suggests that EF may have originated as a eucaryotic enzyme. Such a relationship may eventually be established through comparison of the antigenic and genetic properties of the enzymes or by demonstrating that the genes have related DNA sequences. Even if such a relationship is not found, the edema factor cyclase will be a useful model for study of the properties of calmodulin-dependent enzymes.