Effect of different inhibitors of sterol biosynthesis on both fungal growth and aflatoxin production.
Azole antifungals are reported to interfere with fungal growth by selective impairment of the P-450 dependent 14 alpha-demethylase system key to biosynthesis of ergosterol (ERG), thus leading to the depletion of this sterol in fungal membranes and to the accumulation of methylated precursors. We have investigated whether azole antifungals ketoconazole, miconazole, econazole, or itraconazole were able to modify the sterol and fatty acid patterns of a toxigenic strain of Aspergillus parasiticus, inducing the growth of mycelium depleted of ergosterol (ERG) and rich in less oxidizable sterols. It had been demonstrated that oxidation of ERG is correlated to aflatoxin biosynthesis. However, in this study no alteration of sterol or fatty acid patterns was observed after 7, 14, and 21 days of incubation of A. parasiticus in the presence of sublethal doses of azole antifungals. Specific production of aflatoxin was unaffected. Among the four antifungals tested, itraconazole was the strongest inhibitor of fungal growth and aflatoxin production while ketoconazole was the least effective.
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Dipartimento di Biologia Vegetale, Università di Roma La Sapienza, Rome, Italy.
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D000348:Aflatoxins / Q000096:biosynthesis*; D000935:Antifungal Agents / Q000494:pharmacology*; D001230:Aspergillus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D003470:Culture Media; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004464:Econazole / Q000494:pharmacology; D004875:Ergosterol / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D017964:Itraconazole / Q000494:pharmacology; D007654:Ketoconazole / Q000494:pharmacology; D008825:Miconazole / Q000494:pharmacology
D000348:Aflatoxins; D000935:Antifungal Agents; D003470:Culture Media; D005227:Fatty Acids; D017964:Itraconazole; D004464:Econazole; D008825:Miconazole; D003577:Cytochrome P-450 Enzyme System; D007654:Ketoconazole; D004875:Ergosterol