Design and Characterization of Myristoylated and Non-Myristoylated Peptides Effective against Candida spp. Clinical Isolates

• Published in: International journal of molecular sciences Vol. 23; no. 4; p. 2164
• Main 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
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 16.02.2022; MDPI
• Subjects: Animals; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Antimicrobial agents; Bacteria; Biofilms; Candida; Candida albicans; Design; Fatty acids; Fungal infections; Fungi; Gram-positive bacteria; Humans; Larva; Lipopeptides - pharmacology; Mammals; Membranes; Microbial Sensitivity Tests; Multidrug resistant organisms; Pathogens; Peptides; Spectrum analysis; in vivo infection control; lipopeptide; myristoylation; antifungal activity
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23042164

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 non-myristoylated 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.