Sub-lethal concentrations of chlorhexidine inhibit Candida albicans growth by disrupting ROS and metal ion homeostasis

IF 3.7 2区医学 Q2 MICROBIOLOGY

Journal of Oral Microbiology Pub Date : 2023-11-09 DOI:10.1080/20002297.2023.2278937

Qian Jiang, Yuchen Deng, Shuaihu Li, Deqin Yang, Li Tao

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引用次数: 0

Abstract

Candida albicans is a normal resident of the human oral cavity. It is also the most common fungal pathogen, causing various oral diseases, particularly in immunocompromised individuals. Chlorhexidine digluconate (CHG) is a broad-spectrum antimicrobial agent widely used in dental practice and has been recommended to treat oral candidiasis. However, its action mechanism against the fungal pathogen C. albicans remains poorly understood. The aim of the present study was to investigate the effect of CHG at sub-lethal concentrations against C. albicans. CHG inhibited the growth of C. albicans in a dose- and time-dependent manner. Cells treated with CHG exhibited altered membrane permeability, reduced metabolic activity, and enhanced metal ion and reactive oxygen species (ROS) accumulation. Copper-sensing transcription factor Mac1, iron-sensing transcription factors Sfu1 and Sef2, and copper transporter Ctr1 regulated intracellular metal ion and ROS homeostasis in response to CHG. Deletion of MAC1, SFU1, or SEF2 increased intracellular ROS production and cell susceptibility to CHG. This study revealed a novel mechanism by which CHG induced apoptosis of C. albicans cells through the disruption of metal ion and ROS homeostasis, which may help to identify new targets for fungal infections.

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亚致死浓度的氯己定通过破坏活性氧和金属离子稳态来抑制白色念珠菌的生长

白色念珠菌是人类口腔的正常居民。它也是最常见的真菌病原体，引起各种口腔疾病，特别是在免疫功能低下的个体中。二光酸氯己定(CHG)是一种广泛应用于牙科实践的广谱抗菌药物，已被推荐用于治疗口腔念珠菌病。然而，其对真菌病原体白色念珠菌的作用机制尚不清楚。本研究的目的是探讨亚致死浓度的CHG对白色念珠菌的作用。CHG抑制白色念珠菌生长呈剂量和时间依赖性。经CHG处理的细胞表现出膜通透性改变，代谢活性降低，金属离子和活性氧(ROS)积累增强。铜敏感转录因子Mac1、铁敏感转录因子Sfu1和Sef2以及铜转运体Ctr1调节细胞内金属离子和ROS稳态响应CHG。MAC1、SFU1或SEF2的缺失增加了细胞内ROS的产生和细胞对CHG的易感性。本研究揭示了CHG通过破坏金属离子和ROS稳态诱导白色念珠菌细胞凋亡的新机制，这可能有助于发现真菌感染的新靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Oral Microbiology MICROBIOLOGY-

CiteScore

8.00

自引率

4.40%

发文量

审稿时长

12 weeks

期刊介绍： As the first Open Access journal in its field, the Journal of Oral Microbiology aims to be an influential source of knowledge on the aetiological agents behind oral infectious diseases. The journal is an international forum for original research on all aspects of ''oral health''. Articles which seek to understand ''oral health'' through exploration of the pathogenesis, virulence, host-parasite interactions, and immunology of oral infections are of particular interest. However, the journal also welcomes work that addresses the global agenda of oral infectious diseases and articles that present new strategies for treatment and prevention or improvements to existing strategies. Topics: ''oral health'', microbiome, genomics, host-pathogen interactions, oral infections, aetiologic agents, pathogenesis, molecular microbiology systemic diseases, ecology/environmental microbiology, treatment, diagnostics, epidemiology, basic oral microbiology, and taxonomy/systematics. Article types: original articles, notes, review articles, mini-reviews and commentaries