The Multi-talented Bacterial Adenylate Cyclases

Bacterial pathogens produce a variety of toxins capable of altering the levels of cAMP in the cells of infected hosts. Moreover, cAMP is an important signaling molecule in many bacterial species, involved in regulation of gene expression in response to a variety of environmental stimuli. The genome of the opportunistic pathogen Pseudomonas aeruginosa encodes three adenylate cyclases. One of these is exoenzyme Y, which is translocated into the host cell via a type III secretion system (TTSS). The other two cyclases are CyaA and CyaB, that generate cAMP for intracellular signaling, and together with the cognate cAMP-binding protein Vfr, control the expression of the TTSS and several virulence factors. Using a mouse infection model, it was shown that CyaB, a membrane-bound class III adenylate cyclase plays a more prominent role in regulation of TTSS-encoding genes than CyaA. Given the wide distribution of the class III adenylate cyclases among bacteria, cAMP-dependent regulation of gene expression may have evolved as a conserved mechanism for sensing environmental signals ranging from nutritional content of the surrounding media to the presence of host tissues.