Antifungal Potential of Peptide-Enriched Fractions Isolated from Capsicum frutescens Seeds Against Yeasts of the Genus Candida

Abstract The increasing emergence of drug-resistant fungal pathogens has heightened the search for new antimicrobial compounds with previously unexplored modes of action. Among candidate molecules for control of fungal diseases, plant antimicrobial peptides (AMPs) have attracted considerable interest because they are natural molecules with broad-spectrum inhibitory activities against microorganisms. In this study, peptide-enriched fractions obtained from Capsicum frutescens seeds were evaluated for antimicrobial activity and mechanisms of action against Candida species. Hemotoxicity was evaluated in vitro using sheep erythrocyte lysis, and inhibitory effects against serine protease and α-amylase enzymes were also determined. Initially, the protein-rich extract obtained was fractionated by reverse-phase chromatography on an HPLC system, resulting in five major fractions (F1–F5). Enzymatic assay revealed that all these fractions inhibited the activity of human salivary α-amylase, with F2 exhibiting 100% inhibition of activity. Fractions F2 and F3 exhibited the highest antifungal activity, inhibiting the growth of Candida albicans by 83% and 69% and Candida parapsilosis by 71% and 57%, respectively (200 µg mL − 1 ). These fractions reduced cell viability and increased membrane permeabilization. Additional mechanistic analyses suggested distinct cellular effects, with F2 associated with alterations in cell wall integrity and F3 associated with mitochondrial dysfunction. Partial sequence analysis indicated similarity to plant defense peptides, including heveins, defensins, and vicilin proteins. Importantly, both fractions exhibited low hemolytic activity, indicating selectivity toward fungal cells. Thus, the results highlight the potential of peptide-enriched fractions from C . frutescens seeds as multifunctional antifungal agents and support their relevance for the development of new strategies to control Candida infections.