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Glycolipid depletion in antimicrobial therapy

Svensson, Majlis LU ; Frendeus, B; Butters, T; Platt, F; Dwek, R and Svanborg, Catharina LU (2003) In Molecular Microbiology 47(2). p.453-461
Abstract
Mucosal 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... (More)
Mucosal 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Microbiology
volume
47
issue
2
pages
453 - 461
publisher
Wiley-Blackwell
external identifiers
  • wos:000180692100014
  • pmid:12519195
  • scopus:0037242037
ISSN
1365-2958
DOI
10.1046/j.1365-2958.2003.03306.x
language
English
LU publication?
yes
id
f816b7aa-9e10-4a0e-921c-7527509da576 (old id 319243)
date added to LUP
2007-09-23 09:42:04
date last changed
2017-01-15 03:42:54
@article{f816b7aa-9e10-4a0e-921c-7527509da576,
  abstract     = {Mucosal 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.},
  author       = {Svensson, Majlis and Frendeus, B and Butters, T and Platt, F and Dwek, R and Svanborg, Catharina},
  issn         = {1365-2958},
  language     = {eng},
  number       = {2},
  pages        = {453--461},
  publisher    = {Wiley-Blackwell},
  series       = {Molecular Microbiology},
  title        = {Glycolipid depletion in antimicrobial therapy},
  url          = {http://dx.doi.org/10.1046/j.1365-2958.2003.03306.x},
  volume       = {47},
  year         = {2003},
}