title: Anti-Staphylococcus aureus activity and oxacillin resistance modulating capacity of 3-O-acyl-catechins.
abstract: Epicatechin gallate (ECg), a component of green tea with weak activity against Staphylococcus aureus, reduces oxacillin resistance in methicillin-resistant S. aureus at concentrations below the MIC. Because catechins bind to artificial lipid bilayers, we investigated whether the anti-staphylococcal activity of catechins could be improved by increasing their capacity to interact with the cytoplasmic membrane. Substitution of the gallate group of ECg with 3-O-acyl chains of varying lengths (C(4)-C(18)) led to enhanced anti-staphylococcal activity with chain lengths of C(8) (octanoyl) and C(10) (decanoyl). 3-O-octanoyl catechin was bactericidal against MRSA as the result of membrane damage. 3-O-acyl catechins tested at a 1/4 MIC did not reduce the oxacillin MIC greater than two-fold. 3-O-acyl catechins warrant further investigation as anti-staphylococcal agents.
authors.affiliation: Microbiology Group, School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK. paul.stapleton@ulsop.ac.uk
authors.forename: Paul D
authors.initials: PD
authors.lastname: Stapleton
authors.forename: Saroj
authors.initials: S
authors.lastname: Shah
authors.forename: Jeremy M T
authors.initials: JM
authors.lastname: Hamilton-Miller
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Hara
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Nagaoka
authors.forename: Ayako
authors.initials: A
authors.lastname: Kumagai
authors.forename: Shinichi
authors.initials: S
authors.lastname: Uesato
authors.forename: Peter W
authors.initials: PW
authors.lastname: Taylor
mesh_terms: D000215:Acylation; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D018432:Drug Resistance, Multiple; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D010068:Oxacillin / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000166:cytology / Q000187:drug effects*
chemical_list: D002392:Catechin; D010068:Oxacillin