Diorcinol D Exerts Fungicidal Action against Candida albicans through Cytoplasm Membrane Destruction and ROS Accumulation.

Ying Li,Ming Zhang,Wenqiang Chang,Yang Jiao,Hongxiang Lou,Xiaobin Li,Joy Sturtevant

doi:10.1371/journal.pone.0128693

Ying Li, Ming Zhang + Show 5 more

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https://doi.org/10.1371/journal.pone.0128693

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Journal: PloS one	Publication Date: Jun 5, 2015
Citations: 59	License type: CC BY 4.0

Affiliation: Shandong University

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.

Highlights

Candida species are the fourth most common pathogenic fungus causing nosocomial bloodstream infections in the United States [1]
The time-killing kinetics profile showed that Diorcinol D (DD) (8 mg/L) reached its maximal fungicidal activity (84.0% ± 0.4%) within 30 min, more quickly than Amphotericin B (AMB) (3 h) (Fig 1C)
The data suggested that DD possessed a quick mode of fungicidal action against C. albicans

Summary

Introduction

Candida species are the fourth most common pathogenic fungus causing nosocomial bloodstream infections in the United States [1]. Albicans is the most frequently isolated Candida species, accounting for up to 63% of the infections [2,3]. Clinical used antifungal drugs often cause side effects, such as nephrotoxicity, hepatotoxicity, haemolytic anaemia, and life threatening arrhythmias due to lack of target specificity [4,5]. The formation of biofilms dramatically increases the resistance to antimicrobial drugs up to 10–1000 times [6]. The emergence of drug resistance leads to more nosocomial infections and costs [7], which highlights the need of novel and effective antifungal therapeutics.

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