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Antimicrobial Agents and Chemotherapy, February 2005, p. 549-555, Vol. 49, No. 2
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.2.549-555.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Alkyl Gallates, Intensifiers of ß-Lactam Susceptibility in Methicillin-Resistant Staphylococcus aureus

Hirofumi Shibata,1 Kyoko Kondo,2 Ryo Katsuyama,1 Kazuyoshi Kawazoe,2 Yoichi Sato,3 Kotaro Murakami,2 Yoshihisa Takaishi,2 Naokatu Arakaki,1 and Tomihiko Higuti1*

Department of Molecular Cell Biology and Medicine,1 Department of Natural Medicines,2 Department of Human Genetics and Public Health, Institute of Health Biosciences, The University of Tokushima, Shomachi, Tokushima, Japan3

Received 1 June 2004/ Returned for modification 25 August 2004/ Accepted 25 October 2004

We found that ethyl gallate purified from a dried pod of tara (Caesalpinia spinosa) intensified ß-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 ß-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 µg/ml. At concentrations lower than the MIC, alkyl gallates synergistically elevated the susceptibility of MRSA and MSSA strains to ß-lactam antibiotics. Such a synergistic activity of the alkyl gallates appears to be specific for ß-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 ß-lactam antibiotics.


* Corresponding author. Mailing address: Department of Natural Medicines, The University of Tokushima, Shomachi, Tokushima 770-8505, Japan. Phone: 81 88 633 7254. Fax: 81 88 633 9550. E-mail: thiguti{at}ph.tokushima-u.ac.jp.


Antimicrobial Agents and Chemotherapy, February 2005, p. 549-555, Vol. 49, No. 2
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.2.549-555.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Shibata, H., Nakano, T., Parvez, M. A. K., Furukawa, Y., Tomoishi, A., Niimi, S., Arakaki, N., Higuti, T. (2009). Triple Combinations of Lower and Longer Alkyl Gallates and Oxacillin Improve Antibiotic Synergy against Methicillin-Resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 53: 2218-2220 [Abstract] [Full Text]