title: Delivery of Bordetella pertussis adenylate cyclase toxin to target cells via outer membrane vesicles.
abstract: Bordetella pertussis adenylate cyclase toxin (ACT) intoxicates cells by producing intracellular cAMP. B. pertussis outer membrane vesicles (OMV) contain ACT on their surface (OMV-ACT), but the properties of OMV-ACT were previously unknown. We found that B. pertussis in the lung from a fatal pertussis case contains OMV, suggesting an involvement in pathogenesis. OMV-ACT and ACT intoxicate cells with and without the toxin's receptor CD11b/CD18. Intoxication by ACT is blocked by antitoxin and anti-CD11b antibodies, but not by cytochalasin-D; in contrast, OMV-ACT is unaffected by either antibody and blocked by cytochalasin-D. Thus OMV-ACT can deliver ACT by processes distinct from those of ACT alone.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Virginia School of Medicine, Charlottesville, VA 22908, USA. gmd2n@virginia.edu
authors.forename: Gina M
authors.initials: GM
authors.lastname: Donato
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Goldsmith
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Paddock
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Eby
authors.forename: Mary C
authors.initials: MC
authors.lastname: Gray
authors.forename: Erik L
authors.initials: EL
authors.lastname: Hewlett
mesh_terms: D037361:Adenylate Cyclase Toxin / Q000493:pharmacokinetics* / Q000633:toxicity*; D000818:Animals; D000907:Antibodies, Bacterial / Q000008:administration & dosage; D001886:Bordetella pertussis / Q000472:pathogenicity* / Q000648:ultrastructure; D016466:CHO Cells; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D006224:Cricetinae; D003412:Cricetulus; D015638:Cytochalasin D / Q000494:pharmacology; D006801:Humans; D051379:Mice; D046529:Microscopy, Electron, Transmission; D014357:Trypsin / Q000494:pharmacology; D014917:Whooping Cough / Q000209:etiology / Q000382:microbiology / Q000473:pathology
chemical_list: D037361:Adenylate Cyclase Toxin; D000907:Antibodies, Bacterial; D015638:Cytochalasin D; D014357:Trypsin