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

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.