Dendritic Antifungal Peptides as Potent Agents against Drug-Resistant Candida albicans and Biofilm

Candida albicans infection is a major public health problem, exacerbated by the emergence of drug-resistant fungi with the widespread use of antifungal drugs. Therefore, the development of novel antifungal drugs for drug-resistant C. albicans infections is crucial. We constructed a series of dendritic antifungal peptides (AFPs) with different chain lengths of fatty acids as hydrophobic ends and 2 or 3 protease-stable repeats (Arg–Pro) as dendritic peptide branches. Among them, C4-3RP exhibited excellent antidrug-resistant fungal and biofilm activity (GMall = 5.04 μM) and was nontoxic. Furthermore, C4-3RP demonstrated high protease stability and salt ion tolerance, making it highly effective in murine skin infection mediated by C. albicans. In addition, C4-3RP uses multiple mechanisms of action to achieve excellent antifungal effects. In conclusion, the construction of dendritic peptides holds substantial potential in the treatment of fungal infections and provides a broader perspective on the design of peptide-based antifungal drugs.