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Disruption of d-alanyl esterification of Staphylococcus aureus cell wall teichoic acid by the β-lactam resistance modifier (−)-epicatechin gallate

OBJECTIVES: The naturally occurring polyphenol (−)-epicatechin gallate (ECg) increases oxacillin susceptibility in mecA-containing strains of Staphylococcus aureus. Decreased susceptibility to lysostaphin suggests alterations to the wall teichoic acid (WTA) content of ECg-grown bacteria. Changes in...

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Autores principales: Bernal, Patricia, Zloh, Mire, Taylor, Peter W.
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680342/
https://www.ncbi.nlm.nih.gov/pubmed/19307172
http://dx.doi.org/10.1093/jac/dkp094
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author Bernal, Patricia
Zloh, Mire
Taylor, Peter W.
author_facet Bernal, Patricia
Zloh, Mire
Taylor, Peter W.
author_sort Bernal, Patricia
collection PubMed
description OBJECTIVES: The naturally occurring polyphenol (−)-epicatechin gallate (ECg) increases oxacillin susceptibility in mecA-containing strains of Staphylococcus aureus. Decreased susceptibility to lysostaphin suggests alterations to the wall teichoic acid (WTA) content of ECg-grown bacteria. Changes in WTA structure in response to ECg were determined. METHODS: Nuclear magnetic resonance spectroscopy of purified monomers from S. aureus was used to elucidate WTA structures. Molecular modelling of WTA chains was employed to determine their spatial configuration. RESULTS: ECg-grown methicillin-resistant S. aureus (MRSA) strains BB568 and EMRSA-16 displayed markedly reduced resistance to oxacillin, had thickened cell walls and separated poorly. Growth in ECg-supplemented medium reduced the substitution of the WTA backbone by d-alanine (d-Ala); ratios of N-acetyl glucosamine to d-Ala were reduced from 0.6 and 0.49 (for BB568 and EMRSA-16) to 0.3 and 0.28, respectively. Molecular simulations indicated a decrease in the positive charge of the bacterial wall, confirmed by increased binding of cationized ferritin, and an increase in WTA chain flexibility to a random coil conformation. CONCLUSIONS: Structural elucidation and molecular modelling of WTA indicated that conformational changes associated with reduced d-Ala substitution may contribute to the increased susceptibility of MRSA to β-lactam antibiotics and account for other elements of the ECg-induced phenotype.
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spelling pubmed-26803422009-05-12 Disruption of d-alanyl esterification of Staphylococcus aureus cell wall teichoic acid by the β-lactam resistance modifier (−)-epicatechin gallate Bernal, Patricia Zloh, Mire Taylor, Peter W. J Antimicrob Chemother Original Research OBJECTIVES: The naturally occurring polyphenol (−)-epicatechin gallate (ECg) increases oxacillin susceptibility in mecA-containing strains of Staphylococcus aureus. Decreased susceptibility to lysostaphin suggests alterations to the wall teichoic acid (WTA) content of ECg-grown bacteria. Changes in WTA structure in response to ECg were determined. METHODS: Nuclear magnetic resonance spectroscopy of purified monomers from S. aureus was used to elucidate WTA structures. Molecular modelling of WTA chains was employed to determine their spatial configuration. RESULTS: ECg-grown methicillin-resistant S. aureus (MRSA) strains BB568 and EMRSA-16 displayed markedly reduced resistance to oxacillin, had thickened cell walls and separated poorly. Growth in ECg-supplemented medium reduced the substitution of the WTA backbone by d-alanine (d-Ala); ratios of N-acetyl glucosamine to d-Ala were reduced from 0.6 and 0.49 (for BB568 and EMRSA-16) to 0.3 and 0.28, respectively. Molecular simulations indicated a decrease in the positive charge of the bacterial wall, confirmed by increased binding of cationized ferritin, and an increase in WTA chain flexibility to a random coil conformation. CONCLUSIONS: Structural elucidation and molecular modelling of WTA indicated that conformational changes associated with reduced d-Ala substitution may contribute to the increased susceptibility of MRSA to β-lactam antibiotics and account for other elements of the ECg-induced phenotype. Oxford University Press 2009-06 2009-03-22 /pmc/articles/PMC2680342/ /pubmed/19307172 http://dx.doi.org/10.1093/jac/dkp094 Text en Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
spellingShingle Original Research
Bernal, Patricia
Zloh, Mire
Taylor, Peter W.
Disruption of d-alanyl esterification of Staphylococcus aureus cell wall teichoic acid by the β-lactam resistance modifier (−)-epicatechin gallate
title Disruption of d-alanyl esterification of Staphylococcus aureus cell wall teichoic acid by the β-lactam resistance modifier (−)-epicatechin gallate
title_full Disruption of d-alanyl esterification of Staphylococcus aureus cell wall teichoic acid by the β-lactam resistance modifier (−)-epicatechin gallate
title_fullStr Disruption of d-alanyl esterification of Staphylococcus aureus cell wall teichoic acid by the β-lactam resistance modifier (−)-epicatechin gallate
title_full_unstemmed Disruption of d-alanyl esterification of Staphylococcus aureus cell wall teichoic acid by the β-lactam resistance modifier (−)-epicatechin gallate
title_short Disruption of d-alanyl esterification of Staphylococcus aureus cell wall teichoic acid by the β-lactam resistance modifier (−)-epicatechin gallate
title_sort disruption of d-alanyl esterification of staphylococcus aureus cell wall teichoic acid by the β-lactam resistance modifier (−)-epicatechin gallate
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680342/
https://www.ncbi.nlm.nih.gov/pubmed/19307172
http://dx.doi.org/10.1093/jac/dkp094
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