Fanelli C, Fabbri A A, Brasini S, De Luca C, Passi S
Dipartimento di Biologia Vegetale, Università di Roma La Sapienza, Rome, Italy.
Nat Toxins. 1995;3(2):109-13. doi: 10.1002/nt.2620030209.
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.
据报道，唑类抗真菌药通过选择性损害对麦角固醇（ERG）生物合成至关重要的细胞色素P-450依赖性14α-脱甲基酶系统来干扰真菌生长，从而导致真菌细胞膜中这种固醇的消耗以及甲基化前体的积累。我们研究了唑类抗真菌药酮康唑、咪康唑、益康唑或伊曲康唑是否能够改变寄生曲霉产毒菌株的固醇和脂肪酸模式，诱导缺乏麦角固醇（ERG）且富含较难氧化固醇的菌丝体生长。已经证明，ERG的氧化与黄曲霉毒素的生物合成相关。然而，在本研究中，在亚致死剂量的唑类抗真菌药存在下，寄生曲霉培养7天、14天和21天后，未观察到固醇或脂肪酸模式的改变。黄曲霉毒素的特异性产生未受影响。在所测试的四种抗真菌药中，伊曲康唑是真菌生长和黄曲霉毒素产生的最强抑制剂，而酮康唑效果最差。
