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.