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JAC Advance Access originally published online on June 9, 2004
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Journal of Antimicrobial Chemotherapy 2004 54(1):76-78; doi:10.1093/jac/dkh301
JAC vol.54 no.1 © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved.

The glycopeptide vancomycin does not enhance toll-like receptor 2 (TLR2) activation by Streptococcus pneumoniae

Lisa J. Moore, Alison C. Pridmore, Steven K. Dower and Robert C. Read*

Division of Genomic Medicine, University of Sheffield School of Medicine and Biomedical Sciences, Beech Hill Road, Sheffield S10 2RX, UK

* Corresponding author. Tel: +44-114-271-2027; Fax: +44-114-275-3061; Email: r.c.read{at}shef.ac.uk

Objectives: 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.

Materials and 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: ß-Lactam antibiotics induce surface changes and release of cell wall structures from bacteria that are proinflammatory via TLR2, but the glycopeptide vancomycin does not.

Keywords: faropenem , cefotaxime , vancomycin , inflammation


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