Antifungal Efficacy of Antimicrobial Peptide Octominin II against Candida albicans

Abstract

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 (1GWLIRGAIHAGKAIHGLI18) 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.

Pore-forming peptide C14R exhibits potent antifungal activity against clinical isolates of Candida albicans and Candida auris

“…The determination of ECVs per species allowed us to infer that C14R has a very good activity against C. albicans and C. auris, as populations, considering that the concentration of the peptide that is able to inhibit the growth of >95% of the isolates, was significantly lower than the MIC values reported in other studies evaluating AMPs against these pathogens (Vicente et al, 2019;Cheng et al, 2021;Gonzalez-Garcia et al, 2021;Jayasinghe et al, 2023; -Castano et al, 2023). The MIC mode of each species, which was the fourth (3.125 µg/ml) and fifth (6.25 µg/ml) lowest concentrations tested, showed us that an important proportion of isolates can be considered susceptible to C14R, suggesting its potential as a therapeutic option against infections caused by either Candida species.…”