In Vitro Activity and Synergism of Amphotericin B and the Synthetic Bioinspired Peptide γ31-45PvD1++ Against Fungal Study Models Candida tropicalis and Saccharomyces cerevisiae.

Abstract

In recent years, following the COVID-19 pandemic, the emergence of antibiotic-resistant microorganisms has increased. This surge has prompted global research into new biologically active molecules, particularly those focused on combination therapies involving antifungal agents. Synthetic antimicrobial peptides have emerged as promising candidates to address this demand. Therefore, the objective of this study was to assess the synergistic therapeutic effects of the synthetic peptide γ_31-45PvD₁⁺⁺ combined with amphotericin B (AmB) on Candida tropicalis and Saccharomyces cerevisiae. This study aimed to identify the synergistic concentration that could facilitate advancement in the development of novel drugs. Here, we demonstrated that synergistic combinations of synthetic peptides and amphotericin B (AmB) effectively induce cell death in C. tropicalis and S. cerevisiae. The checkerboard test revealed synergistic concentrations of 0.048 µM for AmB, 0.39 µM for the synthetic peptide γ_31-45PvD₁⁺⁺ for C. tropicalis, 0.097 µM for AmB, and 0.78 µM for the synthetic peptide γ_31-45PvD₁⁺⁺ for S. cerevisiae. The mechanism of action underlying the death of these yeasts when exposed to these synergistic combinations involves several processes, including the loss of cell wall integrity, impairment of mitochondrial functionality, DNA condensation, and damage to cell morphology and ultrastructure. The data presented in this study will contribute significantly to the development of new therapies involving combinations of antifungal molecules.