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Determination of antifungal activity and action mechanism of the modified Aurein 1.2 peptide derivatives.
Madanchi, Hamid; Rahmati, Saman; Doaei, Yeganeh; Sardari, Soroush; Mousavi Maleki, Masoumeh Sadat; Rostamian, Mosayeb; Ebrahimi Kiasari, Ramin; Seyed Mousavi, Seyed Javad; Ghods, Elahe; Ardekanian, Maryam.
Afiliación
  • Madanchi H; Department and Research Center of Medical Biotechnology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran; Drug Design and Bioinformatics Unit, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran. Electronic address: hamidm
  • Rahmati S; Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
  • Doaei Y; Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran.
  • Sardari S; Drug Design and Bioinformatics Unit, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
  • Mousavi Maleki MS; Department and Research Center of Medical Biotechnology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
  • Rostamian M; Infectious Diseases Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
  • Ebrahimi Kiasari R; Drug Design and Bioinformatics Unit, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
  • Seyed Mousavi SJ; Drug Design and Bioinformatics Unit, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
  • Ghods E; Department and Research Center of Medical Biotechnology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
  • Ardekanian M; Department and Research Center of Medical Biotechnology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
Microb Pathog ; 173(Pt A): 105866, 2022 Dec.
Article en En | MEDLINE | ID: mdl-36336133
BACKGROUND: With the emergence of drug-resistant fungi and the increased population prone to fungal infections, more effective antifungal drugs are needed. Aurein 1.2 is a potent antimicrobial peptide. Here, we designed a novel derivative of Aurein 1.2, called Aurein N3, which is a modified form of Aurein N2 (another Aurein 1.2 derivative), in which Lys 8 residue was replaced with Leu 13, and was also modified by creating two other mutations. METHODS: Aurein N3 was designed using several algorithms and docking studies. All peptides were synthesized and some of their bio-activity indices such as antifungal properties on 11 fungi, cytotoxicity, hemolysis, and time of the killing were investigated. Electron microscopy, lived/dead staining, and ergosterol binding assay were performed to study their mechanism of action. RESULTS: In comparison to Aurein 1.2 and N2, the docking studies showed that Aurein N3 has reduced binding energy toward ergosterol. The antifungal assessments showed that both Aurein N2 and N3 had strong activity against many fungi. Aurein N3 had lower cytotoxicity and higher binding capability to ergosterol. The hemolytic activity of Aurein N2 and N3 was less than parental Aurein 1.2. All peptides were able to attack the cell wall/membrane and enter the fungi cells. CONCLUSION: Here we introduced a novel derivative of Aurein 1.2 which has lower cytotoxicity, higher ergosterol-binding capability, and comparable antifungal activity compared to the original peptides. It can bind to ergosterol and can also attack the cell wall/membrane of fungi, although more studies are required to find its accurate mechanism of action.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos Catiónicos Antimicrobianos / Antifúngicos Idioma: En Revista: Microb Pathog Asunto de la revista: DOENCAS TRANSMISSIVEIS / MICROBIOLOGIA Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos Catiónicos Antimicrobianos / Antifúngicos Idioma: En Revista: Microb Pathog Asunto de la revista: DOENCAS TRANSMISSIVEIS / MICROBIOLOGIA Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido