Antifungal Activity and Mechanism of the Novel Antimicrobial Peptide Jelleine-Ic Against Candida albicans.

Candida albicans, an opportunistic fungus, is the most common cause of invasive candidiasis globally. Drug resistance and limited number of antifungal compounds highlight the necessity of new antifungal drugs to treat C. albicans infections. Antimicrobial peptides (AMPs) exhibit potential as antifungal agents. The novel AMP Jelleine-Ic designed by our group demonstrated superior antibacterial activity than its parent peptide Jelleine-I. This work investigated the antifungal activity, antibiofilm activity and mechanism of action of Jelleine-Ic against C. albicans. Jelleine-Ic showed stronger antifungal activity against C. albicans than Jelleine-I. It effectively inhibited biofilm formation and destructed the preformed biofilm of C. albicans. Notably, it exhibited synergistic effect when combined with Amphotericin B. At concentrations below 125 μg/mL, it was not hemolytic on rabbit red blood cells. Jelleine-Ic compromised cell wall integrity, increased the permeability of C. albicans cell membrane. Furthermore, upon entering the cell, Jelleine-Ic bound with DNA, altered the expression of genes involved in DNA replication and repair, and induced the production of intracellular reactive-oxygen species. Jelleine-Ic increased the survival of Galleria mellonella infected with C. albicans. Collectively, Jelleine-Ic effectively controlled C. albicans, and could be a potential replacement for antibiotics and other chemical fungicides in the treatment of fungal infections.