Ssa1-targeted antibody prevents host invasion by Candida albicans

Frontiers in Microbiology

Microbiology

Hui Shen¹  Wei-Tong Hou²  Chen-Rui Shen²  Mao-Mao An²  Xi-Ran Qiu²  Li-Wen Jiang²  Peng Ji²  Wen Zhang²  Yu Zhang² 

[1] Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China;Department of Pharmacology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China;

关键词: antibody;    Ssa1;    Candida albicans;    systemic infection;    antifungal;   

DOI  :  10.3389/fmicb.2023.1182914

 received in 2023-03-09, accepted in 2023-06-20,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionCandida albicans is a commensal fungus that colonizes most healthy individuals’ skin and mucosal surfaces but can also cause life-threatening invasive infections, particularly in immunocompromised patients. Despite antifungal treatment availability, drug resistance is increasing, and mortality rates remain unacceptably high. Heat shock protein Ssa1, a conserved member of the Hsp70 family in yeast, is a novel invasin that binds to host cell cadherins, induces host cell endocytosis, and enables C. albicans to cause maximal damage to host cells and induces disseminated and oropharyngeal disease.ResultHere we discovered a mouse monoclonal antibody (mAb 13F4) that targeting C. albicans Ssa1 with high affinity (EC50 = 39.78 ng/mL). mAb 13F4 prevented C. albicans from adhering to and invading human epithelial cells, displayed antifungal activity, and synergized with fluconazole in proof of concept in vivo studies. mAb 13F4 significantly prolonged the survival rate of the hematogenous disseminated candidiasis mice to 75%. We constructed a mAb 13F4 three-dimensional structure using homology modeling methods and found that the antigen-binding fragment (Fab) interacts with the Ssa1 N-terminus.DiscussionThese results suggest that blocking Ssa1 cell surface function may effectively control invasive C. albicans infections and provide a potential new treatment strategy for invasive fungal infections.

【 授权许可】

Unknown   
Copyright © 2023 Qiu, Shen, Jiang, Ji, Zhang, Hou, Zhang, Shen and An.