title: Alkyl gallates, intensifiers of beta-lactam susceptibility in methicillin-resistant Staphylococcus aureus.
abstract: We found that ethyl gallate purified from a dried pod of tara (Caesalpinia spinosa) intensified beta-lactam susceptibility in methicillin-resistant and methicillin-sensitive strains of Staphylococcus aureus (MRSA and MSSA strains, respectively). This compound and several known alkyl gallates were tested with MRSA and MSSA strains to gain new insights into their structural functions in relation to antimicrobial and beta-lactam susceptibility-intensifying activities. The maximum activity of alkyl gallates against MRSA and MSSA strains occurred at 1-nonyl and 1-decyl gallate, with an MIC at which 90% of the isolates tested were inhibited of 15.6 microg/ml. At concentrations lower than the MIC, alkyl gallates synergistically elevated the susceptibility of MRSA and MSSA strains to beta-lactam antibiotics. Such a synergistic activity of the alkyl gallates appears to be specific for beta-lactam antibiotics, because no significant changes were observed in the MICs of other classes of antibiotics examined in this study. The length of the alkyl chain was also associated with the modifying activity of the alkyl gallates, and the optimum length was C5 to C6. The present work clearly demonstrates that the length of the alkyl chain has a key role in the elevation of susceptibility to beta-lactam antibiotics.
authors.affiliation: Department of Molecular Cell Biology, Institute of Health Biosciences, The University of Tokushima, Shomachi, Tokushima 770-8505, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Shibata
authors.forename: Kyoko
authors.initials: K
authors.lastname: Kondo
authors.forename: Ryo
authors.initials: R
authors.lastname: Katsuyama
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kawazoe
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sato
authors.forename: Kotaro
authors.initials: K
authors.lastname: Murakami
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Takaishi
authors.forename: Naokatu
authors.initials: N
authors.lastname: Arakaki
authors.forename: Tomihiko
authors.initials: T
authors.lastname: Higuti
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004357:Drug Synergism; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D010936:Plant Extracts / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013211:Staphylococcus aureus / Q000187:drug effects*; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D010936:Plant Extracts; D047090:beta-Lactams; D005707:Gallic Acid