Modified Hevein-like Peptide from Amaranthus caudatus as a Promising Agent Against Pathogenic Candida Species

Background/Objectives: Currently, infections caused by fungi of the Candida genus remain a significant global health concern. The rising incidence of mycoses, coupled with the rapid emergence of fungal resistance, highlights the urgent need to search for new antifungal agents. Here, we obtained the recombinant hevein-like peptide from Amaranthus caudatus with two amino acid substitutions (F18W in the chitin-binding motif and M13A preventing the peptide from cleavage with cyanogen bromide during its biotechnological production). Methods: Antifungal potential of the modified hevein-like peptide, designated as mAc-AMP2, against susceptible and resistant strains of Candida albicans and non-albicans Candida species was studied. Results: We showed that mAc-AMP2 possessed anticandidal activities against all strains tested at nanomolar peptide concentrations. The presence of salts or serum affected the action of the peptide but its antifungal activity remained quite high. mAc-AMP2 exhibited anti-adherent properties and inhibited the formation of fungal biofilms. Using RP-HPLC, we demonstrated that degradation of the peptide in the presence of serum occurred rather slowly. mAc-AMP2 did not exhibit hemolytic and cytotoxic activities against the Caco-2 cell monolayer and peripheral blood mononuclear cells. Using flow cytometry, we demonstrated that the peptide at its high concentrations increased fungal membrane permeability. In resistance induction experiments, sensitivity of C. albicans toward mAc-AMP2 decreased over time, but restored after the peptide elimination. Conclusions: Taking into account all the data obtained, we suggest that the modified hevein-like peptide is a promising candidate for development of novel therapeutic agents to combat fungal infections caused by C. albicans and other Candida species.