Unveiling the mechanism of action of acylated temporin L analogues against multidrug-resistant Candida albicans
The increasing resistance of fungi to conventional antifungal drugs has prompted worldwide the search for new compounds. In this work, we investigated the antifungal properties of acylated Temporin L derivatives, Pent-1B and Dec-1B, against Candida albicans, including the multidrug-resistant strains...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2022.2134359 |
| _version_ | 1827123327599116288 |
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| author | Rosa Bellavita Annarita Falanga Francesco Merlino Gabriella D’Auria Nicola Molfetta Anella Saviano Francesco Maione Umberto Galdiero Maria Rosaria Catania Stefania Galdiero Paolo Grieco Emanuela Roscetto Lucia Falcigno Elisabetta Buommino |
| author_facet | Rosa Bellavita Annarita Falanga Francesco Merlino Gabriella D’Auria Nicola Molfetta Anella Saviano Francesco Maione Umberto Galdiero Maria Rosaria Catania Stefania Galdiero Paolo Grieco Emanuela Roscetto Lucia Falcigno Elisabetta Buommino |
| author_sort | Rosa Bellavita |
| collection | DOAJ |
| description | The increasing resistance of fungi to conventional antifungal drugs has prompted worldwide the search for new compounds. In this work, we investigated the antifungal properties of acylated Temporin L derivatives, Pent-1B and Dec-1B, against Candida albicans, including the multidrug-resistant strains. Acylated peptides resulted to be active both on reference and clinical strains with MIC values ranging from 6.5 to 26 µM, and they did not show cytotoxicity on human keratinocytes. In addition, we also observed a synergistic or additive effect with voriconazole for peptides Dec-1B and Pent-1B through the checkerboard assay on voriconazole-resistant Candida strains. Moreover, fluorescence-based assays, NMR spectroscopy, and confocal microscopy elucidated a potential membrane-active mechanism, consisting of an initial electrostatic interaction of acylated peptides with fungal membrane, followed by aggregation and insertion into the lipid bilayer and causing membrane perturbation probably through a carpeting effect. |
| first_indexed | 2024-03-09T02:02:38Z |
| format | Article |
| id | doaj.art-39c43ad04aa145468deb70d283b01f6c |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2025-03-20T14:23:10Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-39c43ad04aa145468deb70d283b01f6c2024-09-09T17:23:19ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742023-12-01381365010.1080/14756366.2022.2134359Unveiling the mechanism of action of acylated temporin L analogues against multidrug-resistant Candida albicansRosa Bellavita0Annarita Falanga1Francesco Merlino2Gabriella D’Auria3Nicola Molfetta4Anella Saviano5Francesco Maione6Umberto Galdiero7Maria Rosaria Catania8Stefania Galdiero9Paolo Grieco10Emanuela Roscetto11Lucia Falcigno12Elisabetta Buommino13Department of Pharmacy, University of Naples “Federico II”, Naples, ItalyDepartment of Agricultural Science, University of Naples “Federico II”, Portici, ItalyDepartment of Pharmacy, University of Naples “Federico II”, Naples, ItalyDepartment of Pharmacy, University of Naples “Federico II”, Naples, ItalyDepartment of Pharmacy, University of Naples “Federico II”, Naples, ItalyDepartment of Pharmacy, University of Naples “Federico II”, Naples, ItalyDepartment of Pharmacy, University of Naples “Federico II”, Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, ItalyDepartment of Pharmacy, University of Naples “Federico II”, Naples, ItalyDepartment of Pharmacy, University of Naples “Federico II”, Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, ItalyDepartment of Pharmacy, University of Naples “Federico II”, Naples, ItalyDepartment of Pharmacy, University of Naples “Federico II”, Naples, ItalyThe increasing resistance of fungi to conventional antifungal drugs has prompted worldwide the search for new compounds. In this work, we investigated the antifungal properties of acylated Temporin L derivatives, Pent-1B and Dec-1B, against Candida albicans, including the multidrug-resistant strains. Acylated peptides resulted to be active both on reference and clinical strains with MIC values ranging from 6.5 to 26 µM, and they did not show cytotoxicity on human keratinocytes. In addition, we also observed a synergistic or additive effect with voriconazole for peptides Dec-1B and Pent-1B through the checkerboard assay on voriconazole-resistant Candida strains. Moreover, fluorescence-based assays, NMR spectroscopy, and confocal microscopy elucidated a potential membrane-active mechanism, consisting of an initial electrostatic interaction of acylated peptides with fungal membrane, followed by aggregation and insertion into the lipid bilayer and causing membrane perturbation probably through a carpeting effect.https://www.tandfonline.com/doi/10.1080/14756366.2022.2134359Acylated peptidestemporinsCandida albicansmembrane interaction |
| spellingShingle | Rosa Bellavita Annarita Falanga Francesco Merlino Gabriella D’Auria Nicola Molfetta Anella Saviano Francesco Maione Umberto Galdiero Maria Rosaria Catania Stefania Galdiero Paolo Grieco Emanuela Roscetto Lucia Falcigno Elisabetta Buommino Unveiling the mechanism of action of acylated temporin L analogues against multidrug-resistant Candida albicans Journal of Enzyme Inhibition and Medicinal Chemistry Acylated peptides temporins Candida albicans membrane interaction |
| title | Unveiling the mechanism of action of acylated temporin L analogues against multidrug-resistant Candida albicans |
| title_full | Unveiling the mechanism of action of acylated temporin L analogues against multidrug-resistant Candida albicans |
| title_fullStr | Unveiling the mechanism of action of acylated temporin L analogues against multidrug-resistant Candida albicans |
| title_full_unstemmed | Unveiling the mechanism of action of acylated temporin L analogues against multidrug-resistant Candida albicans |
| title_short | Unveiling the mechanism of action of acylated temporin L analogues against multidrug-resistant Candida albicans |
| title_sort | unveiling the mechanism of action of acylated temporin l analogues against multidrug resistant candida albicans |
| topic | Acylated peptides temporins Candida albicans membrane interaction |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2022.2134359 |
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