条件致病真菌烟曲霉麦角甾醇合成通路遗传调控机制研究进展

Advances on Genetic Regulation Mechanism of Ergosterol Synthesis Pathway in Opportunistic Pathogen Aspergillus fumigatus

环境中普遍存在的腐生性条件致病真菌--烟曲霉是引起人类侵袭性曲霉病的重要病原,因此,研究烟曲霉的致病机理,开发有效的治疗药物是全球关注的热点。麦角甾醇是真菌细胞膜的主要成分,参与细胞内许多生物学过程,麦角甾醇合成通路中的羊毛甾醇14-α-去甲基化酶Erg11A (Cyp51A同源蛋白)是抗曲霉病唑类药物的重要靶点,其受到转录因子Srb A与CCAAT结合复合物(CBC)的协同调控作用。文中阐述了主要的抗真菌药物以及抗真菌唑类药物的作用靶点-麦角甾醇及其合成途径的遗传调控机制的研究进展,同时分析了烟曲霉产生抗性的机制,期望为认识烟曲霉耐药产生和研发新型抗真菌药物提供帮助。

The opportunistic pathogen Aspergillus fumigatus( A. fumigatus),which is prevalent in the environment,is an important pathogen causing human invasive aspergillosis. Therefore,the research on the pathogenic mechanism of A. fumigatus and the development of effective therapeutic drugs are required against this pathogen. Ergosterol is a main component for fungal cell membrane and is involved in many biological processes in the cell. During process of ergosterol synthesis,the enzyme lanosterol 14-α-demethylase Erg11 A( Cyp51 A) is an important target by antiaspergillosis azole drugs,which is synergistically regulated by the transcription factor SrbA and CCAAT binding complex( CBC). In this review,we summarized the main categories of antifungal azole drugs which mainly target to ergosterol as well as related genetic regulation mechanism in this synthetic pathway. We proposed that it may provide a theoretical basis for understanding the mechanism of A. fumigatus resistance and developing new anti-fungi drugs.