title: Interaction of Bordetella pertussis adenylate cyclase with CD11b/CD18: Role of toxin acylation and identification of the main integrin interaction domain.
abstract: Adenylate cyclase toxin (CyaA) is one of the major virulence factors produced by Bordetella pertussis, the whooping cough agent. CyaA belongs to the repeat in toxin protein family and requires a post-translational fatty acylation to form cation-selective channels in target cell membranes and to penetrate into cytosol. We have demonstrated recently that CyaA uses the alphaMbeta2 integrin (CD11b/CD18) as a specific cellular receptor. Here we show that the acylation of CyaA is required for a productive and tight interaction of the toxin with cells expressing CD11b. In addition, we demonstrate that the catalytic domain is not required for binding of CyaA to CD11b and that the main integrin interacting domain of CyaA is located in its glycine/aspartate-rich repeat region. These data decipher, for the first time, the interaction of CyaA with CD11b-positive cells and open new prospects for understanding the interaction of Bordetella pertussis with innate and adaptive immune systems.
authors.affiliation: Unité de Biologie des Régulations Immunitaires, INSERM E 0352, Institut Pasteur, 75724 Paris, France.
authors.forename: Mohammed
authors.initials: M
authors.lastname: El-Azami-El-Idrissi
authors.forename: Cécile
authors.initials: C
authors.lastname: Bauche
authors.forename: Jirina
authors.initials: J
authors.lastname: Loucka
authors.forename: Radim
authors.initials: R
authors.lastname: Osicka
authors.forename: Peter
authors.initials: P
authors.lastname: Sebo
authors.forename: Daniel
authors.initials: D
authors.lastname: Ladant
authors.forename: Claude
authors.initials: C
authors.lastname: Leclerc
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D001224:Aspartic Acid / Q000737:chemistry; D001710:Biotin / Q000494:pharmacology; D001886:Bordetella pertussis / Q000201:enzymology*; D039481:CD11b Antigen / Q000378:metabolism*; D018821:CD18 Antigens / Q000378:metabolism*; D016466:CHO Cells; D002469:Cell Separation; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D005434:Flow Cytometry; D005822:Genetic Vectors; D005998:Glycine / Q000737:chemistry; D006801:Humans; D016023:Integrins / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D012756:Sheep; D014118:Toxins, Biological / Q000737:chemistry; D014162:Transfection
chemical_list: D000911:Antibodies, Monoclonal; D039481:CD11b Antigen; D018821:CD18 Antigens; D016023:Integrins; D011994:Recombinant Proteins; D014118:Toxins, Biological; D001224:Aspartic Acid; D001710:Biotin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D005998:Glycine