[The cAMP system and bacterial toxins]

The effects of cytotoxic proteinaceous bacterial toxins on the adenylate cyclase cyclic adenosine monophosphate (cAMP) system of host cells are reviewed. Bacterial exotoxins affecting intracellular cAMP levels of host cells can be classified into two subgroups: (1) adenosine diphosphate (ADP)-ribosyl-transferases and, (2) invasive adenylate cyclases. Among the ADP-ribosylating toxins are the enterotoxins of Vibrio cholerae, of Escherichia coli and one of the pertussis toxins termed "islet-activating protein". Toxins within this class share several structural and functional features. The three toxins consist of two functionally distinct parts: an A-component that is active enzymatically and a B-component that binds to surface receptors on cells or, if added in isolation blocks, the action of the complete toxin. The complete toxin shows little or no activity in broken cell preparations. When these toxins act on whole cells the contact is made initially through component B and then component A, but not B enters the cell and catalyzes the ADP-ribosylation of nucleotide regulatory components within the adenylate cyclase complex. The activities of the A-subunits of cholera toxin and heat-labile coli enterotoxin are directed against the stimulatory nucleotide-binding protein of adenylate cyclase whereas islet-activating protein probably alters the inhibitory coupling protein of host-cells. Only recently two bacterial adenylate cyclases from Bacillus anthracis and Bordetella pertussis were described which are capable of invading mammalian cells. These invasive adenylate cyclases, like ADP-ribosylating toxins, require the presence of specific proteins for binding and are activated by calmodulin which is not present in bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)