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

TitoloDesign and Characterization of Myristoylated and Non-Myristoylated Peptides Effective against Candida spp. Clinical Isolates
Tipo di pubblicazioneArticolo su Rivista peer-reviewed
Anno di Pubblicazione2022
AutoriBugli, F., Massaro F., Buonocore F., Saraceni P.R., Borocci S., Ceccacci F., Bombelli C., Di Vito M., Marchitiello R., Mariotti M., Torelli R., Sanguinetti M., and Porcelli F.
RivistaInternational Journal of Molecular Sciences
Volume23
ISSN16616596
Parole chiave1 palmitoyl 2 oleoyl sn glycero 3 phosphoglycerol sodium salt, 2 oleoyl 1 palmitoylphosphatidylcholine, acrylamide, animal, Animals, Antifungal activity, antifungal agent, Antifungal Agents, article, Bioassay, biofilm, biofilm demolition assay, Biofilms, blood culture, broadly neutralizing antibody, Candida, Candida albicans, Candida auris, Candida tropicalis, cell culture, cell viability, CFU counting, chemistry, Chionodracine, circular dichroism, complement hemolysis test, critical micellar concentration, Cytotoxicity, enzyme activity, FB789, fibroblast cell line, fungal cell culture, fungal strain, fungus isolation, Galleria mellonella, hemolysis, human, human cell, Humans, in vitro study, in vivo study, larva, lipid vesicle, lipopeptide, Lipopeptides, mammal, mammal cell, Mammals, MIC90, microbial sensitivity test, Microbial Sensitivity Tests, minimum inhibitory concentration, molecular dynamics, Mortality, mycosis, nonhuman, Parameters, peptide, physical chemistry, polypeptide antibiotic agent, Scanning electron microscopy, spectrofluorometry, unclassified drug
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. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Note

cited By 7

URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85124601700&doi=10.3390%2fijms23042164&partnerID=40&md5=67250859d0e4cd4235ebe1837a248886
DOI10.3390/ijms23042164
Citation KeyBugli2022