From In Silico Screening to Biofilm Disruption: Insect-Derived Peptides Against Candida spp.

Background: The global increase in antifungal resistance and spread of Candida spp. infections represent a growing clinical challenge and highlight the urgent need for alternative therapeutic strategies [1]. Natural compounds, such as insect-derived peptides, have been widely explored as potential antimicrobial agents, representing one of the most promising bioactive compounds [3,4]. Objective: In this perspective, our study aims to evaluate the antifungal potential of insect-derived peptides against Candida spp. using a combined in silico and in vitro experimental approach [2]. Methods: A total of 37 insect-derived peptides were screened through molecular docking analysis to evaluate their interactions with Candida albicans enzyme targets, including lanosterol 14-demethylase (LDM), secreted aspartic proteinase-5 (Sap-5), N-myristoyltransferase (NMT), and dihydrofolate reductase (DHFR). In vitro assays included Minimum Inhibitory Concentration (MIC), Minimum Fungicidal Concentration (MFC) in planktonic cells and biofilm structures of ATCC strains of C. albicans, C. tropicalis, C. glabrata and C. parapsilosis. Additionally, the three-dimensional structures of each biofilm were analyzed after treatment, via Confocal Laser Scanning Microscopy (CLSM). Results: In in silico assays, Blap-6 and Gomesin demonstrated to be good candidates for drug development. Following, in in vitro studies, Gomesin achieved complete biofilm eradication in three out of four Candida species, while Blap-6 showed moderate but consistent reduction across all species. However, C. tropicalis demonstrated resistance to complete eradication by both peptides [2]. In three-dimensional analysis, C. albicans demonstrated the highest loss of integrity in the biofilm matrix with absence of intact cells. C. glabrata showed some resistance in biofilm extracellular matrix disruption, without compromising cell disturbance [2]. Conclusions: These findings highlight insect-derived peptides as promising antifungal candidates and support their potential development as alternative therapeutic agents or templates for the design of novel peptide-based antifungal drugs targeting Candida infections.