Department of Microbiology/Immunology, Northeastern Ohio Universities College of Medicine, PO Box 95, State Route 44, Rootstown, OH 44272, USA
Sir,
Resveratrol (3,5,4'-trihydroxystilbene) is an antifungal agent found in grapes and other plants.1 Invasion of grapevines by fungi induces the production of resveratrol to ward off the potentially damaging microbes. Recently, resveratrol has also been shown to have antiviral properties.2 It is active against the herpes simplex virus. Because resveratrol has natural antifungal properties and has now been shown to have antiviral properties, we wished to determine its effect on bacteria and yeasts.
For this purpose microorganisms were obtained from clinical specimens except for Neisseria meningitidis (ATCC 13090; American Type Culture Collection, Rockville, MD, USA). The identification of all cultures was confirmed using standard microbiological methods.
The inhibitory concentration (IC) was determined on chocolate agar containing various concentrations of resveratrol or 0.5% ethanol (EtOH). Resveratrol (Sigma Chemical Co., St Louis, MO, USA) is insoluble in water so must first be dissolved in EtOH and diluted to the final test concentrations in the test media. The highest amount of residual EtOH in any sample was 0.5% and that concentration was therefore added to control plates that lacked resveratrol. Additional controls included chocolate agar plates that contained neither resveratrol nor EtOH.
Each bacterial culture tested was inoculated on to fresh plates and 24 h later a suspension was made from an isolated colony. Then 10 µL of this sample was spread evenly across the surface of the plates. All samples were incubated at 37°C with or without 5% CO2. After 24 h, the samples were read for growth, which was readily apparent, or no growth. The IC100 was defined as the lowest concentration of resveratrol that completely inhibited any visible growth and IC50 the concentration of resveratrol that reduced growth by 50%.
In the IC studies, the range of concentrations of resveratrol tested was 1200 mg/L. Resveratrol had no effect on Escherichia coli, Staphylococcus aureus, Streptococcus pyogenes, Pseudomonas aeruginosa or Candida albicans at the highest concentration tested. It was, however, active against Neisseria gonorrhoeae and N. meningitidis with IC50 values of 25 and 100 µg/mL and IC100 values of 75 and 125 µg/mL, respectively, at 24 h (Table).
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This lack of activity is consistent with the studies of others who also found that resveratrol had no effect on E. coli, S. aureus or P. aeruginosa.3 However, they did not test resveratrol against N. gonorrhoeae or N. meningitidis, which we have found to be the only bacteria sensitive in vitro to the action of resveratrol.
The mechanism by which resveratrol inhibits Neisseria spp. is unknown. It is reported to have a variety of physiological effects in vertebrates including anti-oxidant properties, which may reduce the risk of coronary artery disease by altering lipid synthesis and inhibition of platelet aggregation.4 It has also been described as a cancer chemopreventive.5 Resveratrol has been shown by other investigators to target numerous sites from protein kinases to DNA polymerase.6 However, the selectivity of resveratrol for Neisseria suggests a target that may be unique to these organisms, or that these organisms have a target that is particularly accessible to resveratrol.
Notes
J Antimicrob Chemother 2001; 47: 243244
* Corresponding author. Tel: +1-330-325-6133; E-mail: jjd{at}neoucom.edu
References
1 . Hain, R., Bieseler, B., Kindl, H., Schroeder, G. & Stoecker, R. (1990). Expression of a stilbene synthase gene in Nicotiana tabacum results in synthesis of the phytoalexin resveratrol. Plant Molecular Biology 15, 32536.[ISI][Medline]
2 . Docherty, J. J., Fu, M. M. H., Stiffler, B. S., Limperos, R. J., Pokabla, C. M. & DeLucia, A. L. (1999). Resveratrol inhibition of herpes simplex virus replication. Antiviral Research 43, 14555.[ISI][Medline]
3 . Ogungbamila, F. O., Onawunmi, G. O., Ibewuike, J. C. & Funmilayo, K. A. (1997). Antibacterial constituents of Ficus barteri fruits. International Journal of Pharmacognosy 35, 1859.
4 . Pace-Asciak, C. R., Rounova, O., Hahn, S. E., Diamandis, E. P. & Goldberg, D. M. (1996). Wines and grape juices as modulators of platelet aggregation in healthy human subjects. Clinical Chimia Acta 246, 16382.
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Jang, M., Cai, L., Udeani, G. O., Slowing, K. V., Thomas, C. F., Beecher, C. W. et al. (1997). Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 275, 21820.
6 . Sun, N. J., Woo, S. H., Cassaday, J. M. & Snapka, R. M. (1998). DNA polymerase and topoisomerase II inhibitors from Psoralea corylifolia. Journal of Natural Products 61, 3626.[ISI][Medline]