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.

His-Ala-Phe-Lys peptide from Burkholderia arboris possesses antifungal activity

“…Additionally, some antifungal peptides can disrupt the fungal membrane, while others can pass through cell membranes to target intracellular DNA and RNA ( Han et al, 2019 ; Khani et al, 2020 ; Bansal et al, 2022 ; Ding et al, 2022 ). Moreover, accumulating evidence indicates that short peptides containing 2–10 amino acids also exhibit antifungal activity ( Velivelli et al, 2018 ; Gong et al, 2022 ). Compared to longer peptides, short antifungal peptides possess several advantages, including higher stability, lower toxicity to the host, and lower cost of synthesis ( Apostolopoulos et al, 2021 ).…”

Antimicrobial Peptides: Avant-Garde Antifungal Agents to Fight against Medically Important Candida Species

“…AP10W was evaluated in a mouse wound model, in which the back skin of each mouse bearing an 8 mm in diameter wound was infected with C. albicans ; one hour later, AP10W was applied to the wound. AP10W treatment promoted the closure and healing of skin wounds infected with the pathogenic yeast (up to 10% of the original size) and lowered yeast loads compared to the controls [ 56 ]. Protamine peptide is a 14-mer that comes from the arginine-rich protein protamine found in salmon spermatozoa.…”