title: Bordetella adenylate cyclase toxin: a unique combination of a pore-forming moiety with a cell-invading adenylate cyclase enzyme.
abstract: The adenylate cyclase toxin-hemolysin (CyaA, ACT or AC-Hly) is a key virulence factor of the whooping cough agent Bordetella pertussis. CyaA targets myeloid phagocytes expressing the complement receptor 3 (CR3, known as αMβ2 integrin CD11b/CD18 or Mac-1) and translocates by a poorly understood mechanism directly across the cytoplasmic membrane into cell cytosol of phagocytes an adenylyl cyclase(AC) enzyme. This binds intracellular calmodulin and catalyzes unregulated conversion of cytosolic ATP into cAMP. Among other effects, this yields activation of the tyrosine phosphatase SHP-1, BimEL accumulation and phagocyte apoptosis induction. In parallel, CyaA acts as a cytolysin that forms cation-selective pores in target membranes. Direct penetration of CyaA into the cytosol of professional antigen-presenting cells allows the use of an enzymatically inactive CyaA toxoid as a tool for delivery of passenger antigens into the cytosolic pathway of processing and MHC class I-restricted presentation, which can be exploited for induction of antigen-specific CD8(+) cytotoxic T-lymphocyte immune responses.
authors.affiliation: Laboratory of Molecular Biology of Bacterial Pathogens, Institute of Microbiology of the ASCR, v.v.i., Czech Academy of Sciences, 142 20, Prague 4, Czech Republic masin@biomed.cas.cz.
authors.forename: Jiri
authors.initials: J
authors.lastname: Masin
authors.affiliation: Laboratory of Molecular Biology of Bacterial Pathogens, Institute of Microbiology of the ASCR, v.v.i., Czech Academy of Sciences, 142 20, Prague 4, Czech Republic.
authors.forename: Radim
authors.initials: R
authors.lastname: Osicka
authors.affiliation: Laboratory of Molecular Biology of Bacterial Pathogens, Institute of Microbiology of the ASCR, v.v.i., Czech Academy of Sciences, 142 20, Prague 4, Czech Republic.
authors.forename: Ladislav
authors.initials: L
authors.lastname: Bumba
authors.affiliation: Laboratory of Molecular Biology of Bacterial Pathogens, Institute of Microbiology of the ASCR, v.v.i., Czech Academy of Sciences, 142 20, Prague 4, Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Sebo
mesh_terms: D037361:Adenylate Cyclase Toxin / Q000378:metabolism* / Q000633:toxicity*; D017209:Apoptosis; D001886:Bordetella pertussis / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002352:Carrier Proteins / Q000378:metabolism; D002470:Cell Survival; D004337:Drug Carriers / Q000378:metabolism; D010586:Phagocytes / Q000187:drug effects* / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014612:Vaccines / Q000276:immunology / Q000378:metabolism
chemical_list: D037361:Adenylate Cyclase Toxin; D002352:Carrier Proteins; D004337:Drug Carriers; D014612:Vaccines
keywords: adenylate cyclase toxin; antigen delivery tool; membrane penetration; pore-formation