DOI: 10.1046/j.1365-2958.2003.03306.x. Glycolipid depletion in antimicrobial therapy

Glycolipid depletion in antimicrobial therapy

10.1046/j.1365-2958.2003.03306.x

Crossref journal-article

Wiley

Molecular Microbiology (311)

Abstract

SummaryMucosal pathogens target sites of infection through specific adherence to host glycoconjugate receptors. As a consequence, depletion of such receptors from the cell surface may be expected to inhibit attachment, impair bacterial colonization and reduce the activation of mucosal inflammation. We have used the glucose analogue and glycosphingolipid (GSL) biosynthesis inhibitor N‐butyldeoxynojirimycin (NB‐DNJ) to deplete human uroepithelial cells and the murine urinary tract mucosa of receptors for P‐fimbriated Escherichia coli. NB‐DNJ blocks the ceramide‐specific glucosyltransferase, which catalyses the formation of glucosyl ceramide (GlcCer), the precursor for GSLs. The inhibitor was shown to decrease the GSL content in a dose‐dependent way, and depletion markedly inhibited P‐fimbriated bacterial attachment in vitro. NB‐DNJ‐fed C3H/HeN mice were depleted of GSLs in vivo and showed reduced susceptibility to experimental urinary tract infection with P‐fimbriated E. coli. The mucosal inflammatory response was impaired, as shown by reduced chemokine secretion and lower neutrophil recruitment, and the bacteria colonized the urinary tract less efficiently than in normal mice. These results confirmed the role of P fimbriae‐mediated adherence for colonization and inflammation and point to an interesting alternative to antibiotic treatment for urinary tract infection.

Bibliography

Svensson, M., Frendeus, B., Butters, T., Platt, F., Dwek, R., & Svanborg, C. (2003). Glycolipid depletion in antimicrobial therapy. Molecular Microbiology, 47(2), 453â461. Portico.

Authors 6

Majlis Svensson (first)
Björn Frendeus (additional)
Terry Butters (additional)
Frances Platt (additional)
Raymond Dwek (additional)
Catharina Svanborg (additional)

References 43 Referenced 33

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Dates

Type	When
Created	22 years, 5 months ago (March 12, 2003, 6:47 a.m.)
Deposited	1 year, 10 months ago (Oct. 14, 2023, 11:13 a.m.)
Indexed	2 months ago (July 1, 2025, 8:47 a.m.)
Issued	22 years, 8 months ago (Jan. 1, 2003)
Published	22 years, 8 months ago (Jan. 1, 2003)
Published Online	22 years, 7 months ago (Jan. 10, 2003)
Published Print	22 years, 8 months ago (Jan. 1, 2003)

Funders 0

None

BibTeX

@article{Svensson_2003, title={Glycolipid depletion in antimicrobial therapy}, volume={47}, ISSN={1365-2958}, url={http://dx.doi.org/10.1046/j.1365-2958.2003.03306.x}, DOI={10.1046/j.1365-2958.2003.03306.x}, number={2}, journal={Molecular Microbiology}, publisher={Wiley}, author={Svensson, Majlis and Frendeus, Björn and Butters, Terry and Platt, Frances and Dwek, Raymond and Svanborg, Catharina}, year={2003}, month=jan, pages={453–461} }

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