Antifungal Efficacy of Antimicrobial Peptide Octominin II against Candida albicans .

Most clinically isolated Candida albicans strains are drug-resistant, emphasizing the urgent need to discover alternative therapies. In this study, the previously characterized Octominin was modified into a shorter peptide with an 18 amino acid sequence ( 1 GWLIRGAIHAGKAIHGLI 18 ) and named Octominin II. The secondary structure of Octominin II is a random coil with a helical turn and a positive charge (+2.46) with a hydrophobic ratio of 0.46. Octominin II inhibited C. albicans , C. auris , and C. glabrata with minimum inhibitory and fungicidal concentrations against C. albicans of 80 and 120 µg/mL, respectively. Field emission scanning electron microscopy confirmed that Octominin II treatment caused ultra-structural changes in C. albicans cells. Furthermore, membrane permeability results for the fluorescent indicator propidium iodide revealed modifications in cell wall integrity in Octominin II-treated C. albicans . Octominin II treatment increases the production of reactive oxygen species (ROS) in C. albicans . Gene expression studies revealed that Octominin II suppresses virulence genes of C. albicans such as CDR1 , TUP1 , AGE3 , GSC1 , SAP2 , and SAP9 . In addition, a nucleic acid binding assay revealed that Octominin II degraded genomic DNA and total RNA in a concentration-dependent manner. Additionally, Octominin II inhibited and eradicated C. albicans biofilm formation. Octominin II showed relatively less cytotoxicity on raw 264.7 cells (0-200 µg/mL) and hemolysis activity on murine erythrocytes (6.25-100 µg/mL). In vivo studies confirmed that Octominin II reduced the pathogenicity of C. albicans . Overall, the data suggests that Octominin II inhibits C. albicans by employing different modes of action and can be a promising candidate for controlling multidrug-resistant Candida infections.