Chenhao Suo,1,* Yiru Gao,2,* Sheng Yang,2 Wanli Zhang,2 Chao Li,3 Lanjing Ma,2 Yingchun Xu,4,5 Jianjun Lei,1 Chen Ding,2 Hailong Li,6 He Zhang,1 Tianshu Sun4,7 

1Laboratory Animal Department, Northern Theater General Hospital, Shenyang, Liaoning, 110000, People’s Republic of China; 2College of Life and Health Science, Northeastern University, Shenyang, Liaoning, 110000, People’s Republic of China; 3Department of Emergency Medicine, the Second Affiliated Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China; 4Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Beijing, 100730, People’s Republic of China; 5Medical Research Centre, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, 100730, People’s Republic of China; 6Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, 48109, USA; 7Clinical Biobank, Medical Research Center, National Science and Technology Key Infrastructure on Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Tianshu Sun; He Zhang, Email sun_tianshu@163.com; alwayszhh@163.com

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.

Keywords: endocytosis, Sla1, cell wall integrity, drug susceptibility, fungal pathogenicity