title: Interaction with CagF is required for translocation of CagA into the host via the Helicobacter pylori type IV secretion system.
abstract: Development of severe gastric diseases is strongly associated with those strains of Helicobacter pylori that contain the cag pathogenicity island (PAI) inserted into the chromosome. The cag PAI encodes a type IV secretion system that translocates the major disease-associated virulence protein, CagA, into the host epithelial cell. CagA then affects host signaling pathways, leading to cell elongations and inflammation. Since the precise mechanism by which the CagA toxin is translocated by the type IV secretion system remained elusive, we used fusion proteins and immunoprecipitation studies to identify CagA-interacting secretion components. Here we demonstrate that CagA, in addition to other yet-unidentified proteins, interacts with CagF, presumably at the inner bacterial membrane. This interaction is required for CagA translocation, since an isogenic nonpolar cagF mutant was translocation deficient. Our results suggest that CagF may be a protein with unique chaperone-like function that is involved in the early steps of CagA recognition and delivery into the type IV secretion channel.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Alberta, 1-17 Medical Sciences Building, Edmonton, Alberta T6G 2R3, Canada.
authors.forename: Marc Roger
authors.initials: MR
authors.lastname: Couturier
authors.forename: Elizabetta
authors.initials: E
authors.lastname: Tasca
authors.forename: Cesare
authors.initials: C
authors.lastname: Montecucco
authors.forename: Markus
authors.initials: M
authors.lastname: Stein
mesh_terms: D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D002460:Cell Line; D005753:Gastric Mucosa / Q000382:microbiology; D016481:Helicobacter Infections / Q000382:microbiology*; D016480:Helicobacter pylori / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology*; D006801:Humans; D021381:Protein Transport / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C080866:cagA protein, Helicobacter pylori; C507457:cagF protein, Helicobacter pylori