title: Role of glycolipids in the pathogenesis of Enterococcus faecalis urinary tract infection.
abstract: BACKGROUND
  After uropathogenic Escherichia coli (UPEC), Enterococcus faecalis is the second most common pathogen causing urinary tract infections. Monoglucosyl-diacylglycerol (MGlcDAG) and diglucosyl-diacylglycerol (DGlcDAG) are the main glycolipids of the E. faecalis cell membrane. Examination of two mutants in genes bgsB and bgsA (both glycosyltransferases) showed that these genes are involved in cell membrane glycolipid biosynthesis, and that their inactivation leads to loss of glycolipids DGlcDAG (bgsA) or both MGlcDAG and DGlcDAG (bgsB). Here we investigate the function of bgsB and bgsA regarding their role in the pathogenesis in a mouse model of urinary tract infection and in bacterial adhesion to T24 bladder epithelial cells.
  
  
  RESULTS
  In a mouse model of urinary tract infection, we showed that E. faecalis 12030ΔbgsB and E. faecalis 12030ΔbgsA mutants, colonize uroepithelial surfaces more efficiently than wild-type bacteria. We also demonstrated that these mutants showed a more than three-fold increased binding to human bladder carcinoma cells line T24 compared to the wild-type strain. Bacterial binding could be specifically inhibited by purified glycolipids. Lipoteichoic acid (LTA), wall-teichoic acid (WTA), and glycosaminoglycans (GAGs) were not significantly involved in binding of E. faecalis to the bladder epithelial cell line.
  
  
  CONCLUSIONS
  Our data show that the deletion of bgsB and bgsA and the absence of the major glycolipid diglucosyl-diacylglycerol increases colonization and binding to uroepithelial cells. We hypothesize that secreted diglucosyl-diacylglycerol blocks host binding sites, thereby preventing bacterial adhesion. Further experiments will be needed to clarify the exact mechanism underlying the adhesion through glycolipids and their cognate receptors.
authors.affiliation: Division of Infectious Diseases, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Ann-Kristin
authors.initials: AK
authors.lastname: Diederich
authors.affiliation: Division of Infectious Diseases, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Dominique
authors.initials: D
authors.lastname: Wobser
authors.affiliation: Division of Infectious Diseases, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Meike
authors.initials: M
authors.lastname: Spiess
authors.affiliation: Nutrition and Immunology, Research Centre for Nutrition and Food Science, Technical University Munich, Munich, Germany.
authors.forename: Irina G
authors.initials: IG
authors.lastname: Sava
authors.affiliation: Division of Infectious Diseases, University Hospital Freiburg, Freiburg, Germany; Division of Pediatric Infectious Diseases, Dr. Von Hauner Children's Hospital, Ludwig Maximilian University Munich, Munich, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Huebner
authors.affiliation: Division of Infectious Diseases, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Türkân
authors.initials: T
authors.lastname: Sakιnç
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D013293:Enterococcus faecalis / Q000187:drug effects / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D005260:Female; D006017:Glycolipids / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D013682:Teichoic Acids / Q000494:pharmacology; D014552:Urinary Tract Infections / Q000382:microbiology*
chemical_list: D006017:Glycolipids; D006025:Glycosaminoglycans; D008070:Lipopolysaccharides; D013682:Teichoic Acids; C009900:lipoteichoic acid