Penicillin enhances the toll-like receptor 2-mediated proinflammatory activity of Streptococcus pneumoniae
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.
Anti-Infective Agents, Aza Compounds, Choline, Colony Count, Microbial, Enzyme Inhibitors, Erythromycin, Ethanolamine, Fluoroquinolones, HeLa Cells, Humans, Interleukin-8, Membrane Glycoproteins, N-Acetylmuramoyl-L-alanine Amidase, Penicillins, Pneumococcal Infections, Quinolines, Receptors, Cell Surface, Streptococcus pneumoniae, Toll-Like Receptor 2, Toll-Like Receptors, Transfection, Journal Article, Research Support, Non-U.S. Gov't
1040-1048
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
1 October 2003
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.
(2003)
Penicillin enhances the toll-like receptor 2-mediated proinflammatory activity of Streptococcus pneumoniae.
The Journal of Infectious Diseases, 188 (7), .
(doi:10.1086/378238).
Abstract
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.
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Published date: 1 October 2003
Keywords:
Anti-Infective Agents, Aza Compounds, Choline, Colony Count, Microbial, Enzyme Inhibitors, Erythromycin, Ethanolamine, Fluoroquinolones, HeLa Cells, Humans, Interleukin-8, Membrane Glycoproteins, N-Acetylmuramoyl-L-alanine Amidase, Penicillins, Pneumococcal Infections, Quinolines, Receptors, Cell Surface, Streptococcus pneumoniae, Toll-Like Receptor 2, Toll-Like Receptors, Transfection, Journal Article, Research Support, Non-U.S. Gov't
Identifiers
Local EPrints ID: 416419
URI: http://eprints.soton.ac.uk/id/eprint/416419
ISSN: 0022-1899
PURE UUID: 41444eab-e9b7-4c83-be9d-08ede0a7bbb9
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Date deposited: 15 Dec 2017 17:30
Last modified: 10 Nov 2021 03:30
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Contributors
Author:
Lisa J. Moore
Author:
Alison C. Pridmore
Author:
Steven K. Dower
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