Adenylate cyclase toxin is a virulence factor produced by some members of the genus Bordetella.
Adenylate cyclase toxin from Bordetella pertussis is a 1706 amino acid residue long protein.
[5] This quick inactivation highlights the necessity of close contact between secreting bacterium and target cell.
[3] A feature of the RTX proteins is their ability to form pores in cell membranes, allowing ions to leak.
[5][2] The transiently opened pores do, however, contribute to AC domain function by potassium leakage and calcium influx into the target cell, which slows endocytosis of CR3/adenylate cyclase toxin clusters,[2] also, the CR3/toxin complex is mobilized by detachment from the cytoskeleton.
[7] cAMP is an important second messenger molecule and its massive overproduction affects many cellular processes.
Although phagocytic immune cells migrate to the site of infection in the lungs, they are not able to mount an effective response.
[5][7][3] The effect on neutrophils is most important in early infection with Bordetella, impairing most of their antimicrobial functions.
[7][3] cAMP accumulation after adenylate cyclase intoxication also interferes with IRF signalling in dendritic cells, which leads to lower IL-12 production.
Although cAMP induces dendritic cell migration into lymph nodes, it lowers their capacity to interact with T-cells and present antigen.
[4] Although not included in current vaccines, research shows that immunization with adenylate cyclase toxin elicits neutralizing antibodies.
Genetically detoxified adenylate cyclase toxin also serves in promoting the Th1/Th17 response, acting as an adjuvant.