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Updated: Jul 19, 2025
A Soluble Tetrazolium-Based Reduction Assay to Evaluate the Effect of Antibodies on Candida tropicalis Biofilms
Published on: September 16, 2022
Ssa1-targeted antibody prevents host invasion by Candida albicans
Xi-Ran Qiu1, Chen-Rui Shen1, Li-Wen Jiang1
1Department of Pharmacology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Introduction:
Candida 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.
Result:
Here 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.
Discussion:
These 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.
Insights
A new monoclonal antibody, mAb 13F4, targets Candida albicans Ssa1, inhibiting fungal invasion and improving survival in disseminated candidiasis models. This offers a promising new strategy against invasive fungal infections.
Area of Science:
- Mycology
- Immunology
- Infectious Diseases
Background:
- Candida albicans causes life-threatening invasive infections, especially in immunocompromised individuals.
- Increasing antifungal drug resistance and high mortality rates necessitate novel therapeutic strategies.
- Heat shock protein Ssa1 is a key invasin in C. albicans, mediating host cell interactions and disease pathogenesis.
Purpose of the Study:
- To investigate the therapeutic potential of targeting C. albicans Ssa1.
- To develop and characterize a monoclonal antibody against Ssa1.
- To evaluate the efficacy of the anti-Ssa1 antibody in vitro and in vivo models of candidiasis.
Main Methods:
- Discovery and characterization of a high-affinity monoclonal antibody (mAb 13F4) targeting C. albicans Ssa1.
- In vitro assays assessing mAb 13F4's ability to inhibit fungal adhesion and invasion of human epithelial cells.
- In vivo studies evaluating mAb 13F4's efficacy in a murine model of hematogenous disseminated candidiasis, including survival analysis.
- Homology modeling to determine the structural basis of mAb 13F4-Ssa1 interaction.
Main Results:
- mAb 13F4 demonstrated high affinity for C. albicans Ssa1 (EC50 = 39.78 ng/mL).
- The antibody effectively prevented fungal adherence and invasion of host cells and exhibited antifungal activity.
- mAb 13F4 synergized with fluconazole and significantly improved survival rates (to 75%) in a disseminated candidiasis mouse model.
- Structural analysis revealed that the antibody's antigen-binding fragment interacts with the Ssa1 N-terminus.
Conclusions:
- Blocking the cell surface function of Ssa1 is a viable strategy for controlling invasive C. albicans infections.
- mAb 13F4 represents a potential new therapeutic agent for invasive fungal infections.
- Targeting Ssa1 offers a promising avenue for developing novel antifungal treatments to combat drug resistance.
