title: Diorcinol D Exerts Fungicidal Action against Candida albicans through Cytoplasm Membrane Destruction and ROS Accumulation.
abstract: 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.
authors.affiliation: Department of Natural Product Chemistry, Key Lab of Chemical Biology of Ministry of Education, Shandong University, No. 44 West Wenhua Road, Jinan City, Shandong Province, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Natural Product Chemistry, Key Lab of Chemical Biology of Ministry of Education, Shandong University, No. 44 West Wenhua Road, Jinan City, Shandong Province, China.
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Chang
authors.affiliation: Department of Natural Product Chemistry, Key Lab of Chemical Biology of Ministry of Education, Shandong University, No. 44 West Wenhua Road, Jinan City, Shandong Province, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Natural Product Chemistry, Key Lab of Chemical Biology of Ministry of Education, Shandong University, No. 44 West Wenhua Road, Jinan City, Shandong Province, China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Natural Product Chemistry, Key Lab of Chemical Biology of Ministry of Education, Shandong University, No. 44 West Wenhua Road, Jinan City, Shandong Province, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Department of Natural Product Chemistry, Key Lab of Chemical Biology of Ministry of Education, Shandong University, No. 44 West Wenhua Road, Jinan City, Shandong Province, China.
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Lou
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D015536:Down-Regulation; D025141:Drug Resistance, Fungal; D006801:Humans; D010636:Phenols / Q000494:pharmacology*; D010647:Phenyl Ethers / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000935:Antifungal Agents; D010636:Phenols; D010647:Phenyl Ethers; D017382:Reactive Oxygen Species; C000606257:diorcinol D