CLEC3A-derived peptides exhibit broad-spectrum activity against Candida auris and clinically relevant pathogens

Introduction Antimicrobial resistance in bacterial and fungal pathogens poses a major threat to global health, with Candida auris recently classified by the WHO as a critical priority pathogen. Antimicrobial peptides (AMPs) have emerged as promising candidates due to their broad-spectrum activity and membrane-disruptive mechanisms. Methods In this study, the antibacterial and antifungal efficacy of two CLEC3A-derived peptides, HT-47 and WRK-30, was evaluated in comparison to the reference AMP LL-37 and the drugs amphotericin B and penicillin/streptomycin using viable count assays, biofilm assays, and scanning and transmission electron microscopy. Results HT-47 and WRK-30 showed antibacterial activity against the ESKAPE pathogens K. pneumoniae and A. baumannii , as well as antifungal effects against C. albicans , C. neoformans , and particularly C. auris , with MIC50 values comparable to or lower than amphotericin B. Both peptides significantly inhibited more potent C. auris biofilm formation, compared to amphotericin B. SEM and TEM revealed extensive membrane and subcellular damage in peptide-treated fungal cells. Conclusion CLEC3A-derived peptides HT-47 and WRK-30 exhibit potent and comparable antibacterial and antifungal activity, highlighting their potential as therapeutic candidates for combating multidrug-resistant pathogens, including C. auris .