Aurein 1.2 analogues as promising agents against Candida parapsilosis: insights into mechanism and biofilm disruption.

INTRODUCTION: Candida parapsilosis has emerged among invasive fungal infections, boming an alarming problem for human health. Recent studies have focused on antimicrobial peptides and their derivatives, such as the Aurein family, as a new approach to developing cutting-edge antifungal agents. OBJECTIVE: This study aimed to evaluate the antifungal potential of Aurein 1.2 (Au) and two modified analogs, K-aurein (K-au) and D-aurein (D-au), containing an additional lysine or aspartic acid residue, respectively, at the N-terminal of the native peptide. MATERIALS & METHODS: To this, antifungal activity, time of action by time-kill curve, ergosterol-binding analysis in vitro and in silico, and antibiofilm assays were performed. Results: We found that K-au demonstrated the lowest cytotoxicity and the greatest antifungal activity compared to other tested peptides. K-au showed MIC values ranging from 62.5 to 125 μg/mL and time of action fungicide between 60 and 180 min. Molecular docking indicated strong interaction with ergosterol, particularly for K-au, supporting a membrane-targeting mechanism. Biofilm assays demonstrated that the peptides inhibited biofilm formation by up to 80% and were effective against mature biofilms, as confirmed by ultrastructural analysis. CONCLUSION: These findings highlight Au-derived peptides as promising molecules against C. parapsilosis.