Effects of the antifungal peptide Skh-AMP1 derived from Satureja khuzistanica on cell membrane permeability, ROS production, and cell morphology of conidia and hyphae of Aspergillus fumigatus

• Published in: Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2020-01, Vol.123, p.170195, Article 170195
• Main Authors: Khani, Soghra, Seyedjavadi, Sima Sadat, Hosseini, Hamideh Mahmoodzadeh, Goudarzi, Mehdi, Valadbeigi, Shirin, Khatami, Shohreh, Ajdary, Soheila, Eslamifar, Ali, Amani, Jafar, Imani Fooladi, Abbas Ali, Razzaghi-Abyaneh, Mehdi
• Format: Article
• Language: English
• Subjects: Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Antifungal peptide; Aspergillus fumigatus; Aspergillus fumigatus - growth & development; Cell Membrane Permeability - drug effects; Electron microscopy; Hyphae - growth & development; Mode of action; Plant Proteins - chemistry; Plant Proteins - pharmacology; Pore Forming Cytotoxic Proteins - chemistry; Pore Forming Cytotoxic Proteins - pharmacology; Reactive Oxygen Species - metabolism; ROS generation; Satureja - chemistry; Spores, Fungal - growth & development; Sporicidal activity
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2019.170195

•Skh-AMP1 showed sporicidal activity against nongerminated conidia of A. fumigatus.•Skh-AMP1 targeted fungal cell membrane integrity and permeability.•Skh-AMP1 induced ROS production which may cause apoptosis in fungal cells.•Skh-AMP1 destructed cell membrane and cellular compartments of conidia and hyphae. Skh-AMP1 (GRTSKQELCTWERGSVRQADKTIAG) is an antifungal peptide isolated from Satureja khuzistanica which has been shown to have strong antifungal activity against Aspergillus and Candida species, but no obvious hemolytic effects or cell cytotoxicity in vitro. In the present study, Skh-AMP1 was synthesized, and its mode of action on the plasma membrane, mitochondria, and morphological and ultrastructural changes against conidia and hyphae of Aspergillus fumigatus were evaluated. The results indicated that Skh-AMP1 had sporicidal activities against the non-germinated conidia of A. fumigatus at concentrations of 40 and 80 μM. Skh-AMP1 induced the release of K+ and the uptake of propidium iodide and enhanced reactive oxygen species (ROS) production in the conidia and hyphae of the fungus. Scanning and transmission electron microscopy showed deformation and shrinkage of the hyphae and conidia, cell membrane disruption and detachment from the cell wall, microvesicle formation, vacuolation and depletion of cytoplasm and organelles of the hyphae of A. fumigatus exposed to 40–80 μM of the peptide. The results further demonstrated that the antifungal activity of Skh-AMP1 may be related to its ability to disrupt fungal cell membrane permeabilization and induce enhanced ROS production. Therefore, Skh-AMP1 can be introduced as a novel antifungal candidate for developing new therapeutic agents.