AUTHOR=Qiu Xi-Ran , Shen Chen-Rui , Jiang Li-Wen , Ji Peng , Zhang Yu , Hou Wei-Tong , Zhang Wen , Shen Hui , An Mao-Mao 

TITLE=Ssa1-targeted antibody prevents host invasion by Candida albicans

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1182914

DOI=10.3389/fmicb.2023.1182914

ISSN=1664-302X

ABSTRACT=<sec><title>Introduction</title><p><italic>Candida albicans</italic> 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 <italic>C. albicans</italic> to cause maximal damage to host cells and induces disseminated and oropharyngeal disease.</p></sec><sec><title>Result</title><p>Here we discovered a mouse monoclonal antibody (mAb 13F4) that targeting <italic>C. albicans</italic> Ssa1 with high affinity (EC<sub>50</sub> = 39.78 ng/mL). mAb 13F4 prevented <italic>C. albicans</italic> from adhering to and invading human epithelial cells, displayed antifungal activity, and synergized with fluconazole in proof of concept <italic>in vivo</italic> 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.</p></sec><sec><title>Discussion</title><p>These results suggest that blocking Ssa1 cell surface function may effectively control invasive <italic>C. albicans</italic> infections and provide a potential new treatment strategy for invasive fungal infections.</p></sec>