title: Disruption of D-alanyl esterification of Staphylococcus aureus cell wall teichoic acid by the {beta}-lactam resistance modifier (-)-epicatechin gallate.
abstract: OBJECTIVE
  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.
authors.affiliation: University of London, Brunswick Square, UK.
authors.forename: Patricia
authors.initials: P
authors.lastname: Bernal
authors.forename: Mire
authors.initials: M
authors.lastname: Zloh
authors.forename: Peter W
authors.initials: PW
authors.lastname: Taylor
mesh_terms: D000409:Alanine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002473:Cell Wall / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008958:Models, Molecular; D010068:Oxacillin / Q000494:pharmacology; D013682:Teichoic Acids / Q000037:antagonists & inhibitors* / Q000737:chemistry; D018440:beta-Lactam Resistance / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D013682:Teichoic Acids; D002392:Catechin; C062669:epicatechin gallate; D000409:Alanine; D010068:Oxacillin