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Originally published In Press as doi:10.1074/jbc.M111640200 on March 4, 2002
J. Biol. Chem., Vol. 277, Issue 20, 18198-18205, May 17, 2002
Identification of Target Tissue Glycosphingolipid Receptors for
Uropathogenic, F1C-fimbriated Escherichia coli and Its Role
in Mucosal Inflammation*
Fredrik
Bäckhed §¶,
Björn
Alsén§ ,
Niamh
Roche **,
Jonas
Ångström ,
Anne
von Euler ,
Michael E.
Breimer ,
Benita
Westerlund-Wikström§§,
Susann
Teneberg ¶¶, and
Agneta
Richter-Dahlfors 
From the Microbiology and Tumorbiology Center,
Karolinska Institute, SE 171 77 Stockholm, Sweden, the Institute
of Medical Biochemistry, Göteborg University, P. O. Box 440, SE
405 30 Göteborg, Sweden, the
 Department of Surgery, Sahlgrenska
University Hospital, SE 413 45 Göteborg, Sweden, and the
§§ Division of General Microbiology,
Department of Biosciences, P. O. Box 56, University of Helsinki,
Helsinki FIN-00014 Finland
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
Gal 4Gal 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.
*
This work was supported in part by the Swedish Medical
Research Council, the Swedish Cancer Foundation, and the Wallenberg Foundation.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
§
Both authors contributed equally to this work.
¶
Supported by grants from the program "Glycoconjugates in
Biological Systems" sponsored by the Swedish Foundation for Strategic Research.
**
Supported by grants from the program "Glycoconjugates in
Biological Systems" sponsored by the Swedish Foundation for Strategic Research.
¶¶
To whom correspondence should be addressed: Institute
of Medical Biochemistry, Göteborg University, P.O. Box 440, SE
405 30 Göteborg, Sweden. Tel.: 46-31-773-3492; Fax:
46-31-413-190; E-mail: Susann.Teneberg@medkem.gu.se.

Recipient of special grants from The Royal Swedish
Academy of Sciences and the Swedish Foundation for Strategic Research.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
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