Harnessing random peptide mixtures to combat multidrug-resistant fungal infections

. FK20 inhibited biofilm formation and displayed substantial activity against mature, pre-formed biofilms, both alone and synergistically in combination with caspofungin. Finally, FK20 showed significant therapeutic efficacy in a murine model of systemic candidiasis. Collectively, these findings establish RPMs as a versatile antifungal platform with broad-spectrum activity, biofilm efficacy, and a low resistance footprint, highlighting their promise as a novel therapeutic strategy against drug-resistant fungal infections. IMPORTANCE: species, impairs biofilm formation, and exhibits synergy with caspofungin. Importantly, FK20 limits the emergence of resistance and demonstrates therapeutic efficacy in a murine model of systemic candidiasis. These findings establish RPMs as a promising new class of antifungals with broad-spectrum activity and clinical potential against drug-resistant fungal infections.