title: Type 1 pilus-mediated bacterial invasion of bladder epithelial cells.
abstract: Most strains of uropathogenic Escherichia coli (UPEC) encode filamentous adhesive organelles called type 1 pili. We have determined that the type 1 pilus adhesin, FimH, mediates not only bacterial adherence, but also invasion of human bladder epithelial cells. In contrast, adherence mediated by another pilus adhesin, PapG, did not initiate bacterial internalization. FimH-mediated invasion required localized host actin reorganization, phosphoinositide 3-kinase (PI 3-kinase) activation and host protein tyrosine phosphorylation, but not activation of Src-family tyrosine kinases. Phosphorylation of focal adhesin kinase (FAK) at Tyr397 and the formation of complexes between FAK and PI 3-kinase and between alpha-actinin and vinculin were found to correlate with type 1 pilus-mediated bacterial invasion. Inhibitors that prevented bacterial invasion also blocked the formation of these complexes. Our results demonstrate that UPEC strains are not strictly extracellular pathogens and that the type 1 pilus adhesin FimH can directly trigger host cell signaling cascades that lead to bacterial internalization.
authors.affiliation: Department of Molecular Microbiology and Microbial Pathogenesis, Box 8230, Washington University School of Medicine, 660 S Euclid Avenue St Louis, MO 63110, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Martinez
authors.forename: M A
authors.initials: MA
authors.lastname: Mulvey
authors.forename: J D
authors.initials: JD
authors.lastname: Schilling
authors.forename: J S
authors.initials: JS
authors.lastname: Pinkner
authors.forename: S J
authors.initials: SJ
authors.lastname: Hultgren
mesh_terms: D000199:Actins / Q000378:metabolism; D018829:Adhesins, Bacterial; D018830:Adhesins, Escherichia coli; D001692:Biological Transport; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D004847:Epithelial Cells / Q000382:microbiology* / Q000648:ultrastructure; D004926:Escherichia coli / Q000472:pathogenicity* / Q000648:ultrastructure; D004927:Escherichia coli Infections / Q000209:etiology; D036781:Fimbriae Proteins; D010861:Fimbriae, Bacterial; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D001743:Urinary Bladder / Q000382:microbiology* / Q000648:ultrastructure; D014552:Urinary Tract Infections / Q000209:etiology
chemical_list: D000199:Actins; D018829:Adhesins, Bacterial; D018830:Adhesins, Escherichia coli; D036781:Fimbriae Proteins; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; C058769:fimH protein, E coli