Resistance to fluconazole and cross-resistance to amphotericin B in Candida albicans from AIDS patients caused by defective sterol Delta(5,6)-desaturation
Resistance to fluconazole and cross-resistance to amphotericin B in Candida albicans from AIDS patients caused by defective sterol Delta(5,6)-desaturation
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DOI：
10.1016/s0014-5793(96)01360-9
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发表时间：
1997-01-02
期刊：
影响因子：
3.5
通讯作者：
Einsele, H
中科院分区：
文献类型：
--
作者：
Kelly, SL;Lamb, DC;Einsele, H
在艾滋病晚期的念珠菌病患者中，有10%对氟康唑耐药。我们在这里显示，在两个临床分离株中，耐药性是由甾醇Delta(5)、(6)-去饱和度缺陷引起的。这改变了在氟康唑处理下积累的类固醇的类型，从14α-甲基麦角-8，24(28)-二烯-3β，6α-二醇转变为能够支持生长的14α-甲基非甾醇。这种唑类耐药机制的结果是，缺乏麦角甾醇会导致对另一种主要抗真菌药物两性霉素B的交叉耐药。结果还表明，临床条件下氟康唑治疗后白色念珠菌的生长停滞是由14α(甲基麦角-8，24(28)-二烯-3β，6α-二醇蓄积引起的。
Fluconazole resistance occurs in > 10% of cases of candidosis during the late stages of AIDS. We show here in two clinical isolates that resistance was caused by defective sterol Delta(5),(6)-desaturation. This altered the type of sterol accumulating under fluconazole treatment from 14 alpha-methylergosta-8,24(28)-dien-3 beta,6 alpha-diol to 14 alpha-methylfecosterol which is capable of supporting growth. A consequence of this mechanism of azole resistance is that an absence of ergosterol causes cross-resistance to the other major antifungal agent available, amphotericin B. The results also show that growth arrest after fluconazole treatment of C. albicans in clinical conditions is caused by 14 alpha(methylergosta-8,24(28)-dien-3 beta,6 alpha-diol accumulation.