Fungicidal Activity of AP10W, a Short Peptide Derived from AP-2 Complex Subunit mu-A, In Vitro and In Vivo

Abstract

With the increase in the incidence of fungal infections, and the restrictions of existing antifungal drugs, the development of novel antifungal agents is urgent. Here we prove that AP10W, a short peptide derived from AP-2 complex subunit mu-A, displays conspicuous antifungal activities against the main fungal pathogens of human infections Candida albicans and Aspergillus fumigatus. We also show that AP10W suppresses the fungal biofilm formation, and reduces the pre-established fungal biofilms. AP10W appears to exert its fungicidal activity through a mode of combined actions, including interaction with the fungal cell walls via laminarin, mannan and chitin, enhancement of cell wall permeabilization, induction of membrane depolarization, and increase in intracellular ROS generation. Importantly, we demonstrate that AP10W exhibits little toxicity towards mammalian fibroblasts, and effectively promotes the healing of wounded skins infected by C. albicans. These together indicate that AP10W is a new member of fungicidal agents. It also suggests that AP10W has a considerable potential for future development as a novel antifungal drug.