Lv Quan-Zhen, Yan Lan, Jiang Yuan-Ying
a Center for New Drug Research, College of Pharmacy, Second Military Medical University , Shanghai , P.R. China.
Virulence. 2016 Aug 17;7(6):649-59. doi: 10.1080/21505594.2016.1188236. Epub 2016 May 24.
Sterols are the basal components of the membranes of the fungal pathogen Candida albicans, and these membranes determine the susceptibility of C. albicans cells to a variety of stresses, such as ionic, osmotic and oxidative pressures, and treatment with antifungal drugs. The common antifungal azoles in clinical use are targeted to the biosynthesis of ergosterol. In the past years, the synthesis, storage and metabolism of ergosterol in Saccharomyces cerevisiae has been characterized in some detail; however, these processes has not been as well investigated in the human opportunistic pathogen C. albicans. In this review, we summarize the genes involved in ergosterol synthesis and regulation in C. albicans. As well, genes in S. cerevisiae implicated in ergosterol storage and conversions with other lipids are noted, as these provide us clues and directions for the study of the homologous genes in C. albicans. In this report we have particularly focused on the essential roles of ergosterol in the dynamic process of cell biology and its fundamental status in the biological membrane system that includes lipid rafts, lipid droplets, vacuoles and mitochondria. We believe that a thorough understanding of this classic and essential pathway will give us new ideas about drug resistance and morphological switching in C. albicans.
甾醇是真菌病原体白色念珠菌细胞膜的基础成分,这些细胞膜决定了白色念珠菌细胞对各种应激的敏感性,如离子、渗透和氧化压力,以及抗真菌药物治疗。临床常用的抗真菌唑类药物作用于麦角甾醇的生物合成。在过去几年中,酿酒酵母中麦角甾醇的合成、储存和代谢已得到较为详细的表征;然而,在人类机会致病菌白色念珠菌中,这些过程尚未得到充分研究。在这篇综述中,我们总结了白色念珠菌中参与麦角甾醇合成和调控的基因。此外,还提到了酿酒酵母中与麦角甾醇储存以及与其他脂质转化相关的基因,因为这些为我们研究白色念珠菌中的同源基因提供了线索和方向。在本报告中,我们特别关注了麦角甾醇在细胞生物学动态过程中的重要作用及其在包括脂筏、脂滴、液泡和线粒体在内的生物膜系统中的基础地位。我们相信,深入了解这一经典且重要的途径将为我们提供有关白色念珠菌耐药性和形态转换的新思路。