Bernal, P., Zloh, M. and Taylor, P.W. (2009) Disruption of D-alanyl esterification of Staphylococcus aureus cell wall teichoic acid by the beta-lactam-resistance modifier(-)-epicatechin gallate. Journal of Antimicrobial Chemotherapy, 63 (6). pp. 1156-1162. 10.1093/jac/dkp094.
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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.
|Additional Information:||Full text available electronically.|
|Uncontrolled Keywords:||epicatechin gallate;;bacterial cell wall structure; β-lactam resistance; MRSA|
|Departments, units and centres:||Department of Pharmaceutics > Department of Pharmaceutics|
|Journal or Publication Title:||Journal of Antimicrobial Chemotherapy|
|Deposited By:||Library Staff|
|Deposited On:||04 Feb 2010 09:50|
|Last Modified:||21 Oct 2011 14:38|
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