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

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

Risultato della ricerca: Contributo in rivistaArticolo in rivista

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.
Lingua originaleEnglish
pagine (da-a)2164-N/A
RivistaInternational Journal of Molecular Sciences
Volume23
DOI
Stato di pubblicazionePubblicato - 2022

Keywords

  • Antifungal activity
  • Myristoylation
  • Lipopeptide
  • In vivo infection control

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