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Title: | Design and Characterization of Myristoylated and Non-Myristoylated Peptides Effective against Candida spp. Clinical Isolates | Authors: | Bugli, Francesca Massaro, Federica Buonocore, Francesco Saraceni, Paolo Roberto Borocci, Stefano Ceccacci, Francesca Bombelli, Cecilia Di Vito, Maura Marchitiello, Rosalba Mariotti, Melinda Torelli, Riccardo Sanguinetti, Maurizio Porcelli, Fernando |
Journal: | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | Issue Date: | 2022 | Abstract: | The increasing resistance of fungi to antibiotics is a severe challenge in public health, and newly effective drugs are required. Promising potential medications are lipopeptides, linear antimicrobial peptides (AMPs) conjugated to a lipid tail, usually at the N-terminus. In this paper, we investigated the in vitro and in vivo antifungal activity of three short myristoylated and nonmyristoylated peptides derived from a mutant of the AMP Chionodracine. We determined their interaction with anionic and zwitterionic membrane-mimicking vesicles and their structure during this interaction. We then investigated their cytotoxic and hemolytic activity against mammalian cells. Lipidated peptides showed a broad spectrum of activity against a relevant panel of pathogen fungi belonging to Candida spp., including the multidrug-resistant C. auris. The antifungal activity was also observed vs. biofilms of C. albicans, C. tropicalis, and C. auris. Finally, a pilot efficacy study was conducted on the in vivo model consisting of Galleria mellonella larvae. Treatment with the most-promising myristoylated peptide was effective in counteracting the infection from C. auris and C. albicans and the death of the larvae. Therefore, this myristoylated peptide is a potential candidate to develop antifungal agents against human fungal pathogens. |
URI: | http://hdl.handle.net/2067/46905 | ISSN: | 1422-0067 | DOI: | 10.3390/ijms23042164 | Rights: | Attribution-NonCommercial-NoDerivatives 4.0 International |
Appears in Collections: | A1. Articolo in rivista |
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