Anti-fungal Effects and Mechanisms of Action of Wasp Venom-Derived Peptide Mastoparan-VT1 Against Candida albicans

Candida albicans, an opportunistic yeast pathogen, is equipped with a plethora of virulence attributes such as yeast-to-hyphae transition, secreted enzymes, tissue adhesion, and biofilm production. The dearth of effective anti-mycotics together with the emergence of drug-resistant C. albicans isolates underscore the need to explore novel anti-fungal agents. Anti-microbial peptides (AMPs) have recently awakened considerable interest as potential therapeutic agents. The intent of this study is to assess anti-fungal effects of Mastoparan VT-1 (MP-VT1), an AMP from the venom of social wasp Vespa tropica, against planktonic and biofilm-embedded cells of C. albicans. MP-VT1 had a tendency to adopt alpha-helical conformation based on peptide secondary structure prediction and circular dichroism spectroscopy (in 50% trifluoroethanol). The peptide showed MIC values ranging from 2 to 32 µg/mL against 10 clinical strains of C. albicans. Notably, a 6-h of exposure to 1 × MFC of MP-VT1 sufficed for total yeast clearance. At fungicidal concentrations, MP-VT1 exhibited slight cytotoxicity towards human dermal fibroblasts. Flow cytometric analysis and fluorescence microscopy revealed that MP-VT1 induced membrane disruption, leading to death of C. albicans mainly by necrosis. Interestingly, a significant inhibition of hyphal transition was noticed at 3 and 6 h post-contact with 32 µg/mL of MP-VT1. At sub-lethal concentrations, the peptide lessened not only candidal cell surface hydrophobicity but also the number of yeasts adhering to the polystyrene surfaces. Furthermore, C. albicans cells within biofilms were more vulnerable to MP-VT1 than to fluconazole. Overall, MP-VT1 has the potential to be used as a candidate for anti-fungal drug development.