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. 1994 Jul;38(7):1523–1529. doi: 10.1128/aac.38.7.1523

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

M P Haynes 1, H R Buckley 1, M L Higgins 1, R A Pieringer 1
PMCID: PMC284587  PMID: 7979283

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.

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Selected References

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  1. Bozzette S. A., Larsen R. A., Chiu J., Leal M. A., Jacobsen J., Rothman P., Robinson P., Gilbert G., McCutchan J. A., Tilles J. A placebo-controlled trial of maintenance therapy with fluconazole after treatment of cryptococcal meningitis in the acquired immunodeficiency syndrome. California Collaborative Treatment Group. N Engl J Med. 1991 Feb 28;324(9):580–584. doi: 10.1056/NEJM199102283240902. [DOI] [PubMed] [Google Scholar]
  2. Brajtburg J., Powderly W. G., Kobayashi G. S., Medoff G. Amphotericin B: current understanding of mechanisms of action. Antimicrob Agents Chemother. 1990 Feb;34(2):183–188. doi: 10.1128/aac.34.2.183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brissette J. L., Cabacungan E. A., Pieringer R. A. Studies on the antibacterial activity of dodecylglycerol. Its limited metabolism and inhibition of glycerolipid and lipoteichoic acid biosynthesis in Streptococcus mutans BHT. J Biol Chem. 1986 May 15;261(14):6338–6345. [PubMed] [Google Scholar]
  4. Collins H. L., Bancroft G. J. Encapsulation of Cryptococcus neoformans impairs antigen-specific T-cell responses. Infect Immun. 1991 Nov;59(11):3883–3888. doi: 10.1128/iai.59.11.3883-3888.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Edelstein E. M., Rosenzweig M. S., Daneo-Moore L., Higgins M. L. Unit cell hypothesis for Streptococcus faecalis. J Bacteriol. 1980 Jul;143(1):499–505. doi: 10.1128/jb.143.1.499-505.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Koll B. S., Brown A. E. The changing epidemiology of infections at cancer hospitals. Clin Infect Dis. 1993 Nov;17 (Suppl 2):S322–S328. doi: 10.1093/clinids/17.supplement_2.s322. [DOI] [PubMed] [Google Scholar]
  7. Lee K. L., Buckley H. R., Campbell C. C. An amino acid liquid synthetic medium for the development of mycelial and yeast forms of Candida Albicans. Sabouraudia. 1975 Jul;13(2):148–153. doi: 10.1080/00362177585190271. [DOI] [PubMed] [Google Scholar]
  8. Lee K. L., Rega M. E., Campbell C. C. Amino acid synthetic media for fungal pathogens based on aminopeptidase specificities: Histoplasma capsulatum, Blastomyces dermititidis, Paracoccidioides brasiliensis and Cryptococcus neoformans. Sabouraudia. 1975 Jul;13(2):142–147. doi: 10.1080/00362177585190261. [DOI] [PubMed] [Google Scholar]
  9. Notario V., Gale E. F., Kerridge D., Wayman F. Phenotypic resistance to amphotericin B in Candida albicans: relationship to glucan metabolism. J Gen Microbiol. 1982 Apr;128(4):761–777. doi: 10.1099/00221287-128-4-761. [DOI] [PubMed] [Google Scholar]
  10. Odds F. C. Interactions among amphotericin B, 5-fluorocytosine, ketoconazole, and miconazole against pathogenic fungi in vitro. Antimicrob Agents Chemother. 1982 Nov;22(5):763–770. doi: 10.1128/aac.22.5.763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Vanden Bossche H., Willemsens G., Marichal P. Anti-Candida drugs--the biochemical basis for their activity. Crit Rev Microbiol. 1987;15(1):57–72. doi: 10.3109/10408418709104448. [DOI] [PubMed] [Google Scholar]
  12. Ved H. S., Gustow E., Mahadevan V., Pieringer R. A. Dodecylglycerol. A new type of antibacterial agent which stimulates autolysin activity in Streptococcus faecium ATCC 9790. J Biol Chem. 1984 Jul 10;259(13):8115–8121. [PubMed] [Google Scholar]
  13. Ved H. S., Gustow E., Pieringer R. A. Inhibition of peptidoglycan synthesis of Streptococcus faecium ATCC 9790 and Streptococcus mutans BHT by the antibacterial agent dodecyl glycerol. Biosci Rep. 1984 Aug;4(8):659–664. doi: 10.1007/BF01121019. [DOI] [PubMed] [Google Scholar]
  14. Ved H. S., Gustow E., Pieringer R. A. Synergism between penicillin G and the antimicrobial ether lipid, rac-1-dodecylglycerol, acting below its critical micelle concentration. Lipids. 1990 Feb;25(2):119–121. doi: 10.1007/BF02562216. [DOI] [PubMed] [Google Scholar]
  15. Ved H. S., Gustow E., Pieringer R. A. The involvement of the proteinase of Streptococcus faecium ATCC 9790 in the stimulation of its autolysin activity by dodecylglycerol. J Biol Chem. 1984 Jul 10;259(13):8122–8124. [PubMed] [Google Scholar]
  16. Weber N. Metabolism of orally administered rac-1-O-[1'-14C]dodecylglycerol and nutritional effects of dietary rac-1-O-dodecylglycerol in mice. J Lipid Res. 1985 Dec;26(12):1412–1420. [PubMed] [Google Scholar]
  17. White C. W., Cherniak R., Jacobson E. S. Side group addition by xylosyltransferase and glucuronyltransferase in biosynthesis of capsular polysaccharide in Cryptococcus neoformans. J Med Vet Mycol. 1990;28(4):289–301. doi: 10.1080/02681219080000381. [DOI] [PubMed] [Google Scholar]

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