ADENYLATE CYCLASE TOXIN AND ADENYLATE CYCLASE ANTIGEN
Adenylate cyclase toxin (ACT) is an important virulence factor secreted by Bordetella pertussis. When a lung infection is underway, ACT interacts with tracheal epithelial cells, inserting itself into cytoplasmic membranes, aiding the adhesion of bacteria to the airway lining. Host phagocytes responding to the site of infection are disabled by cAMP generated by ACT. Encoded by the Bordetella pertussis cyaA gene, adenylate cyclase toxin is single 1706 amino acid polypeptide, with an apparent molecular weight of 220 kDa. The N-terminal of this protein contains an adenylate cyclase domain which binds to host cell calmodulin and catalyzes unregulated conversion of cellular ATP to cAMP. The C-terminal, receptor binding domain, contains numerous repeat in toxin (RTX) motifs and is responsible for binding to the cellular receptor on the surface of immune cells, translocation to the cell cytosol and creating cation-selective pores in the host cell membrane.
Adenylate cyclase toxin both suppresses and modulates the host immune system contributing to pathogenesis of B. pertussis. This toxin is unusual in its ability to cross mammalian cell membranes and locate within the cytosol. As a cell biology tool, adenylate cyclase has been used to deliver immunogenic epitopes, targeting antigen presenting cells. ACT, product #188, and 188L are available from List Labs is an active enzyme, produced as a recombinant protein in E. coli. These two adenylate cyclase products differ in that #188 is freeze dried and #188L is liquid.
A non-enzymatic, genetically detoxified ACT toxoid (CyaA-AC-) has been produced. Although the catalytic activity in this toxoid is destroyed, it is still cell invasive and able to induce an immune response to co-administered pertussis antigens. This toxoid has been shown to be capable of delivering vaccine antigens into the cytosol of major histocompatibility complex (MHC) class I antigen-presenting cells. CyaA-AC- toxoid has been used as a tool to deliver antigens to T cells in anti-cancer immunotherapeutic vaccines. Samples are available of the genetically detoxified CyaA-AC- toxoid (Product #198L) and of an especially low endotoxin preparation of Adenylate Cyclase Toxin, Recombinant (Product #197L).
Bordetella pertussis virulence factors derived from native organisms and offered by List Labs, include Pertussis Toxin, Pertussis Toxin Subunits, Pertussis Toxin Mutant, Filamentous Hemagglutinin (FHA), Fimbriae 2/3, Pertactin (69 kDa protein), and B. pertussis Lipopolysaccharide (LPS). More information about each of these products may be obtained through the links on the Pertussis Toxins and Virulence Factors.