Penicillin enhances the toll-like receptor 2-mediated proinflammatory activity of Streptococcus pneumoniae.
The Streptococcus pneumoniae cell-wall components peptidoglycan and lipoteichoic acid activate Toll-like receptor 2 (TLR2), which transduces an inflammatory response. After exposure to penicillin, type 2 S. pneumoniae strain D39, but not the isogenic autolysin-deficient mutant AL2, induced significantly enhanced interleukin-8 promoter activity in TLR2-transfected HeLa cells. Lag-phase D39 exhibited enhanced TLR2 activation after exposure to penicillin at levels below the minimum inhibitory concentration (MIC); in contrast, early log-phase S. pneumoniae were most active when exposed to the MIC. This enhancement was not ablated by heat treatment but was attenuated by autolysin inhibitors. The antimicrobial activity of moxifloxacin and erythromycin was not associated with TLR2 activation by S. pneumoniae. These data show that penicillin treatment of S. pneumoniae releases proinflammatory cell-wall components that activate TLR2 and that this activity is dependent on autolysin, the growth phase of the organism, and the antibiotic concentration.
D000890:Anti-Infective Agents / Q000494:pharmacology; D001372:Aza Compounds; D002794:Choline / Q000494:pharmacology; D015169:Colony Count, Microbial; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004917:Erythromycin / Q000494:pharmacology; D019856:Ethanolamine / Q000494:pharmacology; D024841:Fluoroquinolones; D006367:HeLa Cells; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology*; D000077266:Moxifloxacin; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D010406:Penicillins / Q000494:pharmacology*; D011008:Pneumococcal Infections / Q000188:drug therapy / Q000276:immunology*; D011804:Quinolines; D011956:Receptors, Cell Surface / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000276:immunology*; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014162:Transfection
D000890:Anti-Infective Agents; D001372:Aza Compounds; D004791:Enzyme Inhibitors; D024841:Fluoroquinolones; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D010406:Penicillins; D011804:Quinolines; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D019856:Ethanolamine; D004917:Erythromycin; D009238:N-Acetylmuramoyl-L-alanine Amidase; D002794:Choline; D000077266:Moxifloxacin