title: Identification of target tissue glycosphingolipid receptors for uropathogenic, F1C-fimbriated Escherichia coli and its role in mucosal inflammation.
abstract: Bacterial adherence to mucosal cells is a key virulence trait of pathogenic bacteria. The type 1 fimbriae and the P-fimbriae of Escherichia coli have both been described to be important for the establishment of urinary tract infections. While P-fimbriae recognize kidney glycosphingolipids carrying the Galalpha4Gal determinant, type 1 fimbriae bind to the urothelial mannosylated glycoproteins uroplakin Ia and Ib. The F1C fimbriae are one additional type of fimbria correlated with uropathogenicity. Although it was identified 20 years ago its receptor has remained unidentified. Here we report that F1C-fimbriated bacteria selectively interact with two minor glycosphingolipids isolated from rat, canine, and human urinary tract. Binding-active compounds were isolated and characterized as galactosylceramide, and globotriaosylceramide, both with phytosphingosine and hydroxy fatty acids. Comparison with reference glycosphingolipids revealed that the receptor specificity is dependent on the ceramide composition. Galactosylceramide was present in the bladder, urethers, and kidney while globotriaosylceramide was present only in the kidney. Using a functional assay, we demonstrate that binding of F1C-fimbriated Escherichia coli to renal cells induces interleukin-8 production, thus suggesting a role for F1C-mediated attachment in mucosal defense against bacterial infections.
authors.affiliation: Microbiology and Tumorbiology Center, Karolinska Institute, SE 171 77 Stockholm, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Bäckhed
authors.forename: Björn
authors.initials: B
authors.lastname: Alsén
authors.forename: Niamh
authors.initials: N
authors.lastname: Roche
authors.forename: Jonas
authors.initials: J
authors.lastname: Angström
authors.forename: Anne
authors.initials: A
authors.lastname: von Euler
authors.forename: Michael E
authors.initials: ME
authors.lastname: Breimer
authors.forename: Benita
authors.initials: B
authors.lastname: Westerlund-Wikström
authors.forename: Susann
authors.initials: S
authors.lastname: Teneberg
authors.forename: Agneta
authors.initials: A
authors.lastname: Richter-Dahlfors
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D002855:Chromatography, Thin Layer; D004285:Dogs; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000473:pathology*; D005699:Galactosylceramides / Q000378:metabolism; D006028:Glycosphingolipids / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D009682:Magnetic Resonance Spectroscopy; D009092:Mucous Membrane / Q000473:pathology; D051381:Rats; D011971:Receptors, Immunologic / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D014281:Trihexosylceramides / Q000378:metabolism; D014551:Urinary Tract / Q000382:microbiology / Q000473:pathology*; D014552:Urinary Tract Infections / Q000382:microbiology / Q000473:pathology*
chemical_list: D005699:Galactosylceramides; D006028:Glycosphingolipids; D016209:Interleukin-8; D011971:Receptors, Immunologic; D014281:Trihexosylceramides; C037872:pili, bacterial receptor; C018549:globotriaosylceramide; C012491:phytosphingosine; D013110:Sphingosine