The Endocytosis Adaptor Sla1 Facilitates Drug Susceptibility and Fungal Pathogenesis Through Sla1-Efg1 Regulating System in Candida albicans.

IF 2.9 3区医学 Q2 INFECTIOUS DISEASES

Infection and Drug Resistance Pub Date : 2024-10-22 eCollection Date: 2024-01-01 DOI:10.2147/IDR.S483623

Chenhao Suo, Yiru Gao, Sheng Yang, Wanli Zhang, Chao Li, Lanjing Ma, Yingchun Xu, Jianjun Lei, Chen Ding, Hailong Li, He Zhang, Tianshu Sun

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Abstract

Introduction: The role of endocytosis in Candida albicans drug-resistance and pathogenicity remains poorly understood, despite its importance as a fundamental component of intracellular trafficking.

Objective: In order to understand the role of endocytosis in Candida albicans cell wall integrity, drug resistance, and virulence.

Methods: Detection of intracellular endocytosis by FM4-64 staining; Scanning electron microscopy is used to detect cell wall components; Spot assay for detecting drug sensitivity; Co-ip is used to detect protein interactions.

Results: In this study, we found the functions of Sla1 in regulating endocytosis is conserved among pathogenic fungi. Our results also revealed that the deletion of the SLA1 gene altered cell wall properties, composition, and gene expression. In addition, we showed that C. albicans Sla1 was responsible for hyphal development in vitro and for fungal pathogenicity in a murine infection model. Intriguingly, sla1∆/∆ mutant demonstrated enhanced drug resistance, and Sla1 was found to interact with the transcription factor Efg1; the relationship between Sla1 and Efg1 impacts the expression of genes encoding components of the ergosterol biosynthesis pathway, including ERG1, EGR11, and ERG25.

Discussion: These findings have expanded our knowledge of the capabilities of Sla1 beyond its role as an endocytosis adapter and provided insights into a potential new therapeutic target for the treatment of fungal infections.

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内吞适配体 Sla1 通过 Sla1-Efg1 调节系统促进白色念珠菌的药物敏感性和真菌致病机理

简介：内吞作用在白色念珠菌耐药性和致病性中的作用仍然鲜为人知：尽管内吞作用是细胞内运输的基本组成部分，但人们对其在白色念珠菌耐药性和致病性中的作用仍然知之甚少：目的：了解内吞作用在白色念珠菌细胞壁完整性、耐药性和致病性中的作用：方法：通过FM4-64染色检测细胞内吞作用；扫描电镜检测细胞壁成分；斑点试验检测药物敏感性；Co-ip检测蛋白质相互作用：结果：我们发现Sla1在病原真菌中调节内吞的功能是保守的。我们的研究结果还发现，SLA1基因的缺失会改变细胞壁的性质、组成和基因表达。此外，我们还发现，白僵菌 Sla1 在体外负责菌丝发育，在小鼠感染模型中负责真菌致病性。耐人寻味的是，Sla1∆/∆ 突变体表现出更强的抗药性，而且发现 Sla1 与转录因子 Efg1 相互作用；Sla1 和 Efg1 之间的关系影响麦角甾醇生物合成途径中编码成分的基因的表达，包括 ERG1、EGR11 和 ERG25：这些发现拓展了我们对 Sla1 功能的认识，使其超越了其作为内吞适配器的作用，并为治疗真菌感染提供了一个潜在的新治疗靶点。

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

Infection and Drug Resistance Medicine-Pharmacology (medical)

CiteScore

5.60

自引率

7.70%

发文量

826

审稿时长

16 weeks

期刊介绍： About Journal Editors Peer Reviewers Articles Article Publishing Charges Aims and Scope Call For Papers ISSN: 1178-6973 Editor-in-Chief: Professor Suresh Antony An international, peer-reviewed, open access journal that focuses on the optimal treatment of infection (bacterial, fungal and viral) and the development and institution of preventative strategies to minimize the development and spread of resistance.