Ergosterol biosynthesis in Aspergillus fumigatus: its relevance as an antifungal target and role in antifungal drug resistance.
Ergosterol biosynthesis in Aspergillus fumigatus: its relevance as an antifungal target and role in antifungal drug resistance.
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DOI：
10.3389/fmicb.2012.00439
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发表时间：
2012
影响因子：
5.2
通讯作者：
Mellado E
中科院分区：
文献类型：
--
作者：
Alcazar-Fuoli L;Mellado E
麦角甾醇是真菌膜的主要甾醇，对发育生长至关重要，也是目前用于治疗致命真菌感染的抗真菌药物的主要靶点。对现有抗真菌药物产生耐药性是当前的一个问题，在烟曲霉临床分离株中已经描述了几种继发耐药机制。因此，充分了解麦角甾醇生物合成控制似乎对提高抗真菌效果和防止抗真菌耐药性至关重要。烟曲霉（A. fumigatus）通过14种甾醇中间体合成麦角甾醇和另一种次级终产物C-24乙基甾醇，形成麦角甾醇生物合成途径。烟曲霉对宿主施加的胁迫或抗真菌药物反应的转录组学分析扩大了我们对甾醇生物合成和抗真菌药物作用方式的理解。最终，确定新药物设计的新靶点，或研究靶向甾醇生物合成与其他代谢途径的组合效应是有必要的。
Ergosterol, the major sterol of fungal membranes, is essential for developmental growth and the main target of antifungals that are currently used to treat fatal fungal infections. Emergence of resistance to existing antifungals is a current problem and several secondary resistance mechanisms have been described in Aspergillus fumigatus clinical isolates. A full understanding of ergosterol biosynthetic control therefore appears to be essential for improvement of antifungal efficacy and to prevent antifungal resistance. An ergosterol biosynthesis pathway in A. fumigatus has been proposed with 14 sterol intermediates resulting in ergosterol and another secondary final compound C-24 ethyl sterol. Transcriptomic analysis of the A. fumigatus response to host-imposed stresses or antifungal agents is expanding our understanding of both sterol biosynthesis and the modes of action of antifungal drugs. Ultimately, the identification of new targets for novel drug design, or the study of combinatorial effects of targeting sterol biosynthesis together with other metabolic pathways, is warranted.
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