Disruption of d-alanyl esterification of Staphylococcus aureus cell wall teichoic acid by the beta-lactam resistance modifier (-)-epicatechin gallate
Author(s)
Bernal, P
Zloh, M
Taylor, PW
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.
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.
Date Issued
2009-03-22
Date Acceptance
2009-02-24
Citation
Journal of Antimicrobial Chemotherapy, 2009, 63 (6), pp.1156-1162
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
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
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000266116100011&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
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
1115 Pharmacology And Pharmaceutical Sciences
0605 Microbiology
1108 Medical Microbiology
Publication Status
Published