title: The glycopeptide vancomycin does not enhance toll-like receptor 2 (TLR2) activation by Streptococcus pneumoniae.
abstract: OBJECTIVE
  The exposure of Streptococcus pneumoniae to cell-wall-active antibiotics in vivo and in vitro results in the release of bacterial components that can induce proinflammatory activation of human cells via toll-like receptor 2 (TLR2). The aim of this study was to compare the activation of human TLR2 pathways after exposure of S. pneumoniae to faropenem, cefotaxime and vancomycin.
  
  
  METHODS
  Streptococcus pneumoniae D39 was exposed to cefotaxime, faropenem or vancomycin for 6 h during lag or early log phase growth. IL-8 promoter activity of HeLa cells was measured using a dual luciferase reporter plasmid system. HeLa cells were transfected with an expression vector containing TLR2/CD14, or empty vector/CD14 and IL-8 promoter activity was measured using luminescence. Cells were stimulated with antibiotic-treated bacteria, untreated bacteria or medium-only controls.
  
  
  RESULTS
  Lag phase S. pneumoniae treated at sub-MIC (1/8 MIC) cefotaxime or faropenem induced 11-fold and 8-fold increases, respectively, in TLR2-mediated IL-8 promoter activity when compared with untreated bacteria. Early log MIC cefotaxime or faropenem-treated bacteria also enhanced TLR2 activation by 3-fold and 4-fold, respectively, when compared with untreated bacteria. Vancomycin treatment had no effect on TLR2 induction at any growth stage or MIC ratio tested.
  
  
  CONCLUSIONS
  beta-Lactam antibiotics induce surface changes and release of cell wall structures from bacteria that are proinflammatory via TLR2, but the glycopeptide vancomycin does not.
authors.affiliation: Division of Genomic Medicine, University of Sheffield School of Medicine and Biomedical Sciences, Beech Hill Road, Sheffield S10 2RX, UK.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Moore
authors.forename: Alison C
authors.initials: AC
authors.lastname: Pridmore
authors.forename: Steven K
authors.initials: SK
authors.lastname: Dower
authors.forename: Robert C
authors.initials: RC
authors.lastname: Read
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002439:Cefotaxime / Q000494:pharmacology; D002473:Cell Wall / Q000187:drug effects; D002511:Cephalosporins / Q000494:pharmacology; D017930:Genes, Reporter / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D007769:Lactams / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis / Q000235:genetics; D008156:Luciferases / Q000235:genetics; D008562:Membrane Glycoproteins / Q000819:agonists*; D008826:Microbial Sensitivity Tests; D010957:Plasmids / Q000235:genetics; D011956:Receptors, Cell Surface / Q000819:agonists*; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014162:Transfection; D014640:Vancomycin / Q000494:pharmacology*; D047090:beta-Lactams
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D016209:Interleukin-8; D007769:Lactams; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D047090:beta-Lactams; D014640:Vancomycin; D008156:Luciferases; C107057:fropenem; D002439:Cefotaxime