| Modification Notes |
Bordetella pertussis, the causative agent of whooping cough, secretes several toxins implicated in this disease. One of these putative virulence factors is the adenylate cyclase toxin (Cya A or ACT), which elevates intracellular cAMP in eukaryotic cells to cytotoxic levels upon activation by endogenous calmodulin. The Bordetella pertussis Cya toxin-encoding locus (Cya) is composed of five genes. The Cya A gene encodes a virulence factor, Cya A, exhibiting adenylate cyclase, hemolytic and invasive activities. Cya A is related to the RTX (repeats in toxin) family of pore-forming toxins. Like all RTX toxins, Cya A is synthesized as a protoxin (proCya A) encoded by the cyaA gene. Activation to the mature cell-invasive toxin involves palmitoylation of Lysine 983 and is dependent on co-expression of Cya C. The Cya B, D and E gene products are necessary for Cya A transport, and the Cya C gene product is required to activate Cya A. Additionally, Cya A uses the åM∫2 Integrin (CD11b/CD18) as a cell receptor. Thus, the cellular distribution of CD11b, mostly on neutrophils, macrophages, and dendritic and natural killer cells, supports a role for Cya A in disrupting the early, innate antibacterial immune response. |
