Bordetella Adenylate Cyclase Toxin

A major virulence factor of the genus Bordetella is a unique toxin, a secreted adenylate cyclase, which penetrates membranes of mammalian cells resulting in unregulated generation of adenosine 3′:5′-monophosphate (CAMP). In human infections caused by Bordetella pertussis, this toxin, Bordetella Adenylate Cyclase Toxin (BACT), and a second. Pertussis Toxin, apparently cause an unprecedented disruption of cellular transmembrane signaling processes. In Vitro, virtually all mammalian hematologic cells are susceptible to the action of BACT. Following brief exposure, intracellular cAMP in such cells increases several hundred-fold. Numerous other organ cells and established cell lines are similarly affected. Multiple aberrations in cellular function and proliferation accompany the production of intracellular cAMP induced by BACT. Although this toxin has not been purified, it, like Pertussis Toxin, appears to conform to the A/B model of protein toxins. The BACT holotoxin is labile and this has confounded efforts to identify the component(s) responsible for target cell binding and internalization of the catalytic moiety. In contrast, the latter, the adenylate cyclase, is rather well characterized. Unique features of the enzyme are its small molecular weight, an extraordinarily high specific activity, a lack of regulation by usual effectors of adenylate cyclase activity and a remarkable sensitivity to activation by eukaryotic calmodulin.