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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

Nyckelord

Animals

Bacterial Adhesion

Chromatography

Thin Layer

Dogs

Escherichia coli

Escherichia coli Infections/ pathology

Galactosylceramides/metabolism

Glycosphingolipids/ metabolism

Humans

Interleukin-8/biosynthesis

Magnetic Resonance Spectroscopy

Mucous Membrane/pathology

Rats

Receptors

Immunologic/metabolism

Sphingosine/ analogs & derivatives/metabolism

Trihexosylceramides/metabolism

Urinary Tract/microbiology/ pathology

Urinary Tract Infections/microbiology/ pathology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)