title: Uroplakin Ia is the urothelial receptor for uropathogenic Escherichia coli: evidence from in vitro FimH binding.
abstract: The binding of uropathogenic Escherichia coli to the urothelial surface is a crucial initial event for establishing urinary tract infection because it allows the bacteria to gain a foothold on the urothelial surface, thus preventing them from being removed by micturition. In addition, it triggers bacterial invasion as well as host urothelial defense. This binding is mediated by the FimH adhesin located at the tip of the bacterial type 1-fimbrium, a filamentous attachment apparatus, and its urothelial receptor. We have prepared a biotinylated, recombinant FimH-FimC adhesin:chaperone complex and used it to identify its mouse urothelial receptor. The FimH-FimC complex binds specifically to a single 24 kDa major mouse urothelial plaque protein, which we identified as uroplakin Ia by mass spectrometry, cDNA cloning and immunoreactivity. The terminal mannosyl moieties on Asn-169 of uroplakin Ia are responsible for FimH as well as concanavalin A binding. Although FimH binds to uroplakin Ia with only moderate strength (K(d) approximately 100 nM between pH 4 and 9), the binding between multiple fimbriae of a bacterium and the crystalline array of polymerized uroplakin receptors should achieve high avidity and stable bacterial attachment. The FimH-FimC complex binds preferentially to the mouse urothelial umbrella cells in a pattern similar to uroplakin staining. Our results indicate that the structurally related uroplakins Ia and Ib are glycosylated differently, that uroplakin Ia serves as the urothelial receptor for the type 1-fimbriated E. coli, and that the binding of uropathogenic bacteria to uroplakin Ia may play a key role in mediating the urothelial responses to bacterial attachment.
authors.affiliation: Skirball Institute of Biomolecular Medicine, Department of Biochemistry, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
authors.forename: G
authors.initials: G
authors.lastname: Zhou
authors.forename: W J
authors.initials: WJ
authors.lastname: Mo
authors.forename: P
authors.initials: P
authors.lastname: Sebbel
authors.forename: G
authors.initials: G
authors.lastname: Min
authors.forename: T A
authors.initials: TA
authors.lastname: Neubert
authors.forename: R
authors.initials: R
authors.lastname: Glockshuber
authors.forename: X R
authors.initials: XR
authors.lastname: Wu
authors.forename: T T
authors.initials: TT
authors.lastname: Sun
authors.forename: X P
authors.initials: XP
authors.lastname: Kong
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D018830:Adhesins, Escherichia coli; D000595:Amino Acid Sequence; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins; D002417:Cattle; D004926:Escherichia coli / Q000378:metabolism* / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000503:physiopathology; D029968:Escherichia coli Proteins; D036781:Fimbriae Proteins; D005690:Galactose / Q000378:metabolism; D006031:Glycosylation; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D037102:Lectins / Q000378:metabolism; D008358:Mannose / Q000378:metabolism; D013058:Mass Spectrometry; D008562:Membrane Glycoproteins / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D059470:Tetraspanins; D014552:Urinary Tract Infections / Q000378:metabolism / Q000382:microbiology; D060167:Uroplakin Ia; D019459:Urothelium / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology
chemical_list: D018829:Adhesins, Bacterial; D018830:Adhesins, Escherichia coli; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D037102:Lectins; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D059470:Tetraspanins; C490123:Upk1a protein, mouse; D060167:Uroplakin Ia; C489721:fimC protein, E coli; C058769:fimH protein, E coli; D036781:Fimbriae Proteins; D008358:Mannose; D005690:Galactose