In Vivo Evaluation of Efficacy and Toxicity of Bioinspired Peptides With Antimicrobial Properties Against Fungal Infection in Galleria mellonella Larvae.

BACKGROUND

Fungal infections, particularly those caused by Candida species, represent a growing public health threat due to increasing resistance to conventional antifungal agents. Consequently, there is a need for the development of novel antifungals.

OBJECTIVE

This study evaluated the in vivo toxicity and efficacy of three peptides with antimicrobial properties, RR, D-RR, and WR that exhibit in vitro antifungal activity and are bioinspired from the Vigna unguiculata defensin γ-core.

METHODS

Using Galleria mellonella larvae, infections were established with a clinical strain of Candida tropicalis and Candida albicans over a 144-h period. Toxicity and efficacy were evaluated through survival assays, hemocyte density measurements, fungal load quantification, and health index monitoring. Peptides were administered in multiple doses over time.

RESULTS

Fungal lethal doses (FLD) in G. mellonella were 1 × 106 cells/mL for C. tropicalis and 0.5 × 106 cells/mL for C. albicans. Peptide lethal doses were 41 μM (RR) and 32 μM (D-RR) for C. tropicalis, and 60 μM (WR) for C. albicans. All treatments were nontoxic. Survival of infected larvae was 93.3% with RR and D-RR. Among peptides, WR showed the greatest efficacy, achieving 100% survival and outperforming fluconazole, while supporting continued larval development. The peptides exerted inhibitory effects within the in vivo tissue environment of G. mellonella.

CONCLUSIONS

These findings indicate that the peptides are promising safe antifungal candidates, warranting further investigation into their mechanisms of action and stability.