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

Title: Disruption of d-alanyl esterification of Staphylococcus aureus cell wall teichoic acid by the beta-lactam resistance modifier (-)-epicatechin gallate
Authors: Bernal, P
Zloh, M
Taylor, PW
Item Type: Journal Article
Abstract: 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.
Issue Date: 22-Mar-2009
Date of Acceptance: 24-Feb-2009
URI: http://hdl.handle.net/10044/1/42626
DOI: http://dx.doi.org/10.1093/jac/dkp094
ISSN: 1460-2091
Publisher: Oxford University Press
Start Page: 1156
End Page: 1162
Journal / Book Title: Journal of Antimicrobial Chemotherapy
Volume: 63
Issue: 6
Copyright Statement: Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org
Keywords: Science & Technology
Life Sciences & Biomedicine
Infectious Diseases
Microbiology
Pharmacology & Pharmacy
INFECTIOUS DISEASES
MICROBIOLOGY
PHARMACOLOGY & PHARMACY
epicatechin gallate
bacterial cell wall structure
beta-lactam resistance
MRSA
MOLECULAR MECHANICS
LIPOTEICHOIC ACID
LIPID BILAYERS
TEA CATECHINS
DLT OPERON
D-ALANINE
METHICILLIN
CHARGE
SUSCEPTIBILITY
SOLVATION
Alanine
Anti-Bacterial Agents
Catechin
Cell Wall
Enzyme Inhibitors
Magnetic Resonance Spectroscopy
Methicillin-Resistant Staphylococcus aureus
Models, Molecular
Oxacillin
Teichoic Acids
beta-Lactam Resistance
Cell Wall
Oxacillin
Catechin
Teichoic Acids
Alanine
Enzyme Inhibitors
Anti-Bacterial Agents
Magnetic Resonance Spectroscopy
beta-Lactam Resistance
Models, Molecular
Methicillin-Resistant Staphylococcus aureus
Microbiology
1115 Pharmacology And Pharmaceutical Sciences
0605 Microbiology
1108 Medical Microbiology
Publication Status: Published
Appears in Collections:Faculty of Natural Sciences



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