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

J Antimicrob Chemother. 2009 Jun;63(6):1156-62. doi: 10.1093/jac/dkp094. Epub 2009 Mar 22.


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 beta-lactam antibiotics and account for other elements of the ECg-induced phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / antagonists & inhibitors*
  • Alanine / metabolism
  • Anti-Bacterial Agents / pharmacology
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Cell Wall / drug effects*
  • Cell Wall / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Models, Molecular
  • Oxacillin / pharmacology
  • Teichoic Acids / antagonists & inhibitors*
  • Teichoic Acids / chemistry
  • beta-Lactam Resistance / drug effects*


  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Teichoic Acids
  • Catechin
  • epicatechin gallate
  • Alanine
  • Oxacillin