Interaction with CagF Is Required for Translocation of CagA into the Host via theHelicobacter pyloriType IV Secretion System

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Abstract
Development of severe gastric diseases is strongly associated with those strains ofHelicobacter pylorithat contain thecagpathogenicity island (PAI) inserted into the chromosome. ThecagPAI 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 nonpolarcagFmutant 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.