title: Bordetella pertussis adenylate cyclase inactivation by the host cell.
abstract: Bordetella pertussis produces a calmodulin-dependent adenylate cyclase (AC) which acts as a toxin capable of penetrating eukaryotic cells and generating high levels of intracellular cyclic AMP. Transfer of target cells into B. pertussis AC-free medium leads to a rapid decay in the intracellular AC activity, implying that the invasive enzyme is unstable in the host cytoplasm. We report here that treatment of human lymphocytes with a glycolysis inhibitor and an uncoupler of oxidative phosphorylation completely blocked the intracellular inactivation of B. pertussis AC. Lymphocyte lysates inactivated all forms of B. pertussis AC in the presence of exogenous ATP. This inactivation was associated with degradation of an 125I-labelled 200 kDa form of B. pertussis AC. It appears that ATP is required for the proteolytic pathway, but not as an energy source, since non-hydrolysable ATP analogues supported inactivation and complete degradation of the enzyme. The possibility that binding of ATP to B. pertussis AC renders it susceptible to degradation by the host cell protease is discussed.
authors.affiliation: Department of Hormone Research, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Gilboa-Ron
authors.forename: A
authors.initials: A
authors.lastname: Rogel
authors.forename: E
authors.initials: E
authors.lastname: Hanski
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000067956:Adenylyl Cyclase Inhibitors; D001770:Blood Bactericidal Activity; D001886:Bordetella pertussis / Q000201:enzymology*; D003847:Deoxyglucose / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology*; D009711:Nucleotides / Q000494:pharmacology; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D009711:Nucleotides; D014475:Uncoupling Agents; D000255:Adenosine Triphosphate; D003847:Deoxyglucose