Identification of target tissue glycosphingolipid receptors for uropathogenic, F1C-fimbriated Escherichia coli and its role in mucosal inflammation.
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.
Bäckhed
Fredrik
F
Microbiology and Tumorbiology Center, Karolinska Institute, SE 171 77 Stockholm, Sweden.
Alsén
Björn
B
Roche
Niamh
N
Angström
Jonas
J
von Euler
Anne
A
Breimer
Michael E
ME
Westerlund-Wikström
Benita
B
Teneberg
Susann
S
Richter-Dahlfors
Agneta
A
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*
D005699:Galactosylceramides; D006028:Glycosphingolipids; D016209:Interleukin-8; D011971:Receptors, Immunologic; D014281:Trihexosylceramides; C037872:pili, bacterial receptor; C018549:globotriaosylceramide; C012491:phytosphingosine; D013110:Sphingosine