This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Haynes, M P Articles by Pieringer, R A Search for Related Content PubMed PubMed Citation Articles by Haynes, M P Articles by Pieringer, R A

 Previous Article  |  Next Article 

Antimicrob Agents Chemother. 1994 July; 38(7): 1523-1529

Synergism between the antifungal agents amphotericin B and alkyl glycerol ethers.

M P Haynes, H R Buckley, M L Higgins and R A Pieringer

Department of Biochemistry, Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.

ABSTRACT

The alkyl glycerol ether rac-1-O-dodecylglycerol inhibited the growth of members of two genera of yeasts, Candida and Cryptococcus, and was strongly synergistic with amphotericin B. At one-half its MIC, dodecylglycerol decreased the MIC of amphotericin B by as much as 80-fold. This high degree of synergism between dodecylglycerol and amphotericin B was demonstrated against a number of species of yeasts including Candida albicans, Candida tropicalis, Candida parapsilosis, Cryptococcus neoformans, Cryptococcus albidus, and Cryptococcus laurentii. All fractional inhibitory concentrations (for all strains and species) were calculated to be less than 1, and most were less than 0.6, again demonstrating strong synergism. Other alkyl glycerol ethers with alkyl chain lengths ranging from 8 to 18 carbon atoms were also found to be synergistic with amphotericin B against C. neoformans and C. albicans. Electron microscopy experiments showed that C. neoformans grown in the presence of dodecylglycerol had severely abnormal, deformed capsules. Although the mechanism of action of dodecylglycerol is not known, dodecylglycerol was not simply acting as a detergent. The natural detergent sodium deoxycholate could not substitute for dodecylglycerol. At comparable and higher concentrations, sodium deoxycholate had no fungicidal effect on its own, nor did it potentiate the activity of amphotericin B. Dodecylglycerol did not interact synergistically with the water-soluble antifungal agent fluconazole. The lipid-soluble hydrophobic properties of amphotericin B appear to be important for this synergistic effect, in that alkyl glycerol ethers could promote synergism with amphotericin B by potentially increasing the interaction between membrane-bound ergosterol and amphotericin B.

---

Antimicrob Agents Chemother. 1994 July; 38(7): 1523-1529

This article has been cited by other articles:

• Sun, L., Sun, S., Cheng, A., Wu, X., Zhang, Y., Lou, H. (2009). In Vitro Activities of Retigeric Acid B Alone and in Combination with Azole Antifungal Agents against Candida albicans. Antimicrob. Agents Chemother. 53: 1586-1591 [Abstract] [Full Text]  
• Espuelas, S., Legrand, P., Loiseau, P. M., Bories, C., Barratt, G., Irache, J. M. (2000). In Vitro Reversion of Amphotericin B Resistance in Leishmania donovani by Poloxamer 188. Antimicrob. Agents Chemother. 44: 2190-2192 [Abstract] [Full Text]