The glycopeptide vancomycin does not enhance toll-like receptor 2 (TLR2) activation by Streptococcus pneumoniae
The glycopeptide vancomycin does not enhance toll-like receptor 2 (TLR2) activation by Streptococcus pneumoniae
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: 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.
Anti-Bacterial Agents, Cefotaxime, Cell Wall, Cephalosporins, Genes, Reporter, HeLa Cells, Humans, Interleukin-8, Lactams, Lipopolysaccharide Receptors, Luciferases, Membrane Glycoproteins, Microbial Sensitivity Tests, Plasmids, Receptors, Cell Surface, Streptococcus pneumoniae, Toll-Like Receptor 2, Toll-Like Receptors, Transfection, Vancomycin, beta-Lactams, Journal Article, Research Support, Non-U.S. Gov't
76-78
Moore, Lisa J.
13095db5-12ee-47f4-ae09-b1deca4881d3
Pridmore, Alison C.
b704c202-afcc-4fde-9169-48e51f9fa0b0
Dower, Steven K.
c59b6ed1-57d4-49cb-815c-038a96601ecc
Read, Robert C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51
July 2004
Moore, Lisa J.
13095db5-12ee-47f4-ae09-b1deca4881d3
Pridmore, Alison C.
b704c202-afcc-4fde-9169-48e51f9fa0b0
Dower, Steven K.
c59b6ed1-57d4-49cb-815c-038a96601ecc
Read, Robert C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Moore, Lisa J., Pridmore, Alison C., Dower, Steven K. and Read, Robert C.
(2004)
The glycopeptide vancomycin does not enhance toll-like receptor 2 (TLR2) activation by Streptococcus pneumoniae.
Journal of Antimicrobial Chemotherapy, 54 (1), .
(doi:10.1093/jac/dkh301).
Abstract
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: 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.
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More information
Published date: July 2004
Keywords:
Anti-Bacterial Agents, Cefotaxime, Cell Wall, Cephalosporins, Genes, Reporter, HeLa Cells, Humans, Interleukin-8, Lactams, Lipopolysaccharide Receptors, Luciferases, Membrane Glycoproteins, Microbial Sensitivity Tests, Plasmids, Receptors, Cell Surface, Streptococcus pneumoniae, Toll-Like Receptor 2, Toll-Like Receptors, Transfection, Vancomycin, beta-Lactams, Journal Article, Research Support, Non-U.S. Gov't
Identifiers
Local EPrints ID: 416421
URI: http://eprints.soton.ac.uk/id/eprint/416421
ISSN: 0305-7453
PURE UUID: 16bf030d-bc70-44b3-8fdf-163b375ab4ab
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Date deposited: 15 Dec 2017 17:30
Last modified: 16 Mar 2024 04:10
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Contributors
Author:
Lisa J. Moore
Author:
Alison C. Pridmore
Author:
Steven K. Dower
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