Diorcinol D Exerts Fungicidal Action against Candida albicans through Cytoplasm Membrane Destruction and ROS Accumulation.
Diorcinol D Exerts Fungicidal Action against Candida albicans through Cytoplasm Membrane Destruction and ROS Accumulation.
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Diorcinol D 通过细胞质膜破坏和 ROS 积累对白色念珠菌发挥杀菌作用
DOI：
10.1371/journal.pone.0128693
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Lou H
中科院分区：
文献类型：
--
作者：
Li Y;Chang W;Zhang M;Li X;Jiao Y;Lou H
白色念珠菌是最常见的人类真菌病原体，在免疫功能低下的患者中引起高死亡率。抗真菌药物耐药性成为念珠菌感染管理的主要挑战。Diorcinol D （DD）是一种从内生真菌中分离得到的二苯醚衍生物，对念珠菌有一定的杀真菌作用。在本研究中，我们探讨了其抗真菌活性的可能机制。细胞膜动力学和通透性的变化表明，DD对细胞膜造成了破坏，细胞内甘油积累、细胞超微结构改变和细胞膜合成相关基因下调等证据进一步支持了这一观点。此外，用DD治疗白色念珠菌导致活性氧（ROS）升高，从而导致线粒体功能障碍。这些都表明，DD的抗真菌活性是通过破坏细胞质膜和积累活性氧来发挥的。这一发现有助于揭示二苯醚衍生物的潜在机制，并为抗临床真菌感染提供了潜在的应用。
Candida albicans, which is the most common human fungal pathogen, causes high mortality among immunocompromised patients. Antifungal drug resistance becomes a major challenge for the management of Candida infection. Diorcinol D (DD), a diphenyl ether derivative isolated from an endolichenic fungus, exerted fungicidal action against Candida species. In this study, we investigated the possible mechanism of its antifungal activity. The change of membrane dynamics and permeability suggested that the cell membrane was disrupted by the treatment of DD. This was further supported by the evidences of intracellular glycerol accumulation, alteration of cell ultrastructure, and down-regulation of genes involved in cell membrane synthesis. In addition, the treatment of C. albicans with DD resulted in the elevation of reactive oxygen species (ROS), which caused the dysfunction of mitochondria. These altogether suggested that DD exerted its antifungal activity through cytoplasmic membrane destruction and ROS accumulation. This finding is helpful to uncover the underlying mechanisms for the diphenyl ether derivatives and provides a potential application in fighting clinical fungal infections.
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