Design and Characterization of Myristoylated and Non-Myristoylated Peptides Effective against <i>Candida</i> spp. Clinical Isolates

oleh: Francesca Bugli, Federica Massaro, Francesco Buonocore, Paolo Roberto Saraceni, Stefano Borocci, Francesca Ceccacci, Cecilia Bombelli, Maura Di Vito, Rosalba Marchitiello, Melinda Mariotti, Riccardo Torelli, Maurizio Sanguinetti, Fernando Porcelli

Format: Article
Diterbitkan: MDPI AG 2022-02-01

Deskripsi

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 <i>Chionodracine</i>. 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 <i>Candida</i> spp., including the multidrug-resistant <i>C. auris</i>. The antifungal activity was also observed vs. biofilms of <i>C. albicans</i>, <i>C. tropicalis</i>, and <i>C. auris</i>. Finally, a pilot efficacy study was conducted on the in vivo model consisting of <i>Galleria mellonella</i> larvae. Treatment with the most-promising myristoylated peptide was effective in counteracting the infection from <i>C. auris</i> and <i>C. albicans</i> and the death of the larvae. Therefore, this myristoylated peptide is a potential candidate to develop antifungal agents against human fungal pathogens.