WMR Peptide as Antifungal and Antibiofilm against Albicans and Non-Albicans Candida Species: Shreds of Evidence on the Mechanism of Action

• Published in: International journal of molecular sciences 2022-02, Vol.23 (4), p.2151
• Main Authors: Maione, Angela, Bellavita, Rosa, de Alteriis, Elisabetta, Galdiero, Stefania, Albarano, Luisa, La Pietra, Alessandra, Guida, Marco, Parrilli, Ermenegilda, D'Angelo, Caterina, Galdiero, Emilia, Falanga, Annarita
• Format: Article
• Language: English
• Subjects: Animals; Antifungal activity; Antifungal agents; Antifungal Agents - pharmacology; Antiinfectives and antibacterials; Antimicrobial agents; Antimicrobial peptides; Bacteria; Biofilms; Biofilms - drug effects; Candida; Candida - drug effects; Candida albicans; Candidiasis - drug therapy; Candidiasis - microbiology; Complementarity-determining region 1; Confocal microscopy; Drug resistance; Drug Resistance, Fungal - drug effects; Drug Synergism; Efflux; Fungicides; Genes; Gram-negative bacteria; Larva - microbiology; Larvae; Medical equipment; Microbial Sensitivity Tests - methods; Microscopy; Minimum inhibitory concentration; Mitochondria; Peptides; Peptides - pharmacology; Planktonic cells; Reactive oxygen species; Scanning microscopy
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23042151

species are the most common fungal pathogens infecting humans and can cause severe illnesses in immunocompromised individuals. The increased resistance of to traditional antifungal drugs represents a great challenge in clinical settings. Therefore, novel approaches to overcome antifungal resistance are desired. Here, we investigated the use of an antimicrobial peptide WMR against and non- species in vitro and in vivo. Results showed a WMR antifungal activity on all planktonic cells at concentrations between 25 μM to >50 μM and exhibited activity at sub-MIC concentrations to inhibit biofilm formation and eradicate mature biofilm. Furthermore, in vitro antifungal effects of WMR were confirmed in vivo as demonstrated by a prolonged survival rate of larvae infected by species when the peptide was administered before or after infection. Additional experiments to unravel the antifungal mechanism were performed on and . The time-killing curves showed their antifungal activity, which was further confirmed by the induced intracellular and mitochondrial reactive oxygen species accumulation; WMR significantly suppressed drug efflux, down-regulating the drug transporter encoding genes . Moreover, the ability of WMR to penetrate within the cells was demonstrated by confocal laser scanning microscopy. These findings provide novel insights for the antifungal mechanism of WMR against and non- , providing fascinating scenarios for the identification of new potential antifungal targets.