Bordetella extracytoplasmic adenylate cyclase: actions as a bacterial toxin

Virulent Bordetella organisms produce an adenylate cyclase which is extracytoplasmic in location, activated by the eukaryotic regulatory protein, calmodulin, and able to act as a toxin, promoting cyclic AMP accumulation in target mammalian cells. Initial steps in purification of this novel adenylate cyclase toxin reveal two forms: one which possesses only enzymatic adenylate cyclase activity, but has no effect on intact target cells; and the other which has both enzymatic and intoxicating activity. These data suggest that this toxin may conform to the A/B model for bacterial toxins. A variety of mammalian cell types can be affected by the adenylate cyclase toxin, including neutrophils, macrophages, monocytes, lymphocytes, lymphoma cells, and pituitary cells. Although the consequence of intoxication in many cells is inhibition of normal function, the enhancement of pituitary hormone secretion by this toxin suggests that its biological effects are the result of cAMP accumulation. These data confirm the hypothesis that Bordetella adenylate cyclase is, indeed, a toxin and illustrate its role as a novel research probe.