Antifungal and antivirulence activity of antimicrobial peptide Oreoch-1 against Candida albicans

Objectives: The emergence of drug‑resistant fungal pathogens, such as Candida albicans (C. albicans), has intensified the global demand for antifungal agents with novel mechanisms of action. Conventional therapies, including azoles and polyenes, are increasingly limited by resistance and biofilm‑associated tolerance. Antimicrobial peptides (AMPs), naturally expressed in a variety of organisms as first-line defences against microbial infections, have emerged as promising alternatives due to their low propensity for resistance development, ability to disrupt microbial membranes, and inhibition of key virulence traits. While most current studies focus on peptides with antibacterial activity, relatively little is known about their antifungal properties. In this study, we investigated the antifungal and antivirulence activity of the AMP oreochromicin‑1 (oreoch-1), isolated from the gills of Nile tilapia (Oreochromis niloticus), against C. albicans.

Methods: An antifungal susceptibility assay was conducted to determine oreoch-1’s minimum inhibitory concentration (MIC), and its effect on growth kinetics was assessed. Hyphal formation was evaluated under filamentation-inducing conditions. Biofilm biomass reduction was quantified using crystal violet staining, and morphological changes were examined microscopically. The molecular responses to oreoch‑1 exposure were analysed by qRT-PCR for two virulence‑associated genes: HWP1 (adhesion) and ERG11 (ergosterol biosynthesis).

Results: Oreoch‑1 exhibited potent inhibitory activity with an MIC₉₀ of 25 μM, accompanied by reduced growth kinetics, a 67% reduction in biofilm formation, and an 85% reduction in hyphal formation. Microscopic analyses revealed pronounced morphological changes, including membrane disruption, surface deformation, and loss of structural integrity. Oreoch‑1 induced a clear dose‑dependent downregulation of both HWP1 and ERG11, with maximal suppression observed at MIC₉₀.

Conclusions: Collectively, these findings demonstrate that oreoch‑1 targets both structural and regulatory components of C. albicans pathogenicity. Its combined effects on growth inhibition, biofilm reduction, hyphal suppression, membrane disruption, and downregulation of virulence-associated genes highlight oreoch‑1 as a promising antifungal candidate for the management of C. albicans infections.