Modulatory effect of cAMP on fungal ergosterol level and inhibitory activity of azole drugs.
The functions and biosynthesis of sterols have been effective targets for fungal control in different areas, including pharmaceutical and agricultural applications. Fungi are among the organisms that synthesize sterols, principally ergosterol. In this paper, the effect of dibutyryl-cAMP (db-cAMP) on ergosterol level and the interaction of drugs that would change the concentration of cAMP with antifungal drugs have been investigated. Sterols were extracted from Candida albicans, and ergosterol was measured using the gas chromatography method. The interaction of different agents was measured by the broth dilution method. It was found that phosphodiesterase inhibitors reverse the inhibitory activity of azole antifungal drugs. Evaluating the ergosterol level of C. albicans incubated with db-cAMP revealed that it increased ergosterol level. Further experiments provided evidence attributing the observed interaction between azoles and phosphodiesterase inhibitors to the relationship between ergosterol and cAMP. The possible significance of this interaction includes potentiation of antifungal activity of drugs by manipulating the cAMP level.
Sardari
S
S
Biomedical Sciences, Fogarty Hall, 41 Lower College Road, University of Rhode Island, Kingston, RI 02881, USA. ssardari@hotmail.com
Mori
Y
Y
Kurosawa
T
T
Daneshtalab
M
M
D000666:Amphotericin B / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D002849:Chromatography, Gas; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D004357:Drug Synergism; D004875:Ergosterol / Q000096:biosynthesis / Q000378:metabolism*; D015725:Fluconazole / Q000494:pharmacology; D007654:Ketoconazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology
D000935:Antifungal Agents; D010726:Phosphodiesterase Inhibitors; D003994:Bucladesine; D001285:Atropine; D000666:Amphotericin B; D015725:Fluconazole; D000242:Cyclic AMP; D007654:Ketoconazole; D004875:Ergosterol