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WMR Peptide as Antifungal and Antibiofilm against Albicans and Non-Albicans Candida Species: Shreds of Evidence on the Mechanism of Action
oleh: Angela Maione, Rosa Bellavita, Elisabetta de Alteriis, Stefania Galdiero, Luisa Albarano, Alessandra La Pietra, Marco Guida, Ermenegilda Parrilli, Caterina D’Angelo, Emilia Galdiero, Annarita Falanga
Format: | Article |
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Diterbitkan: | MDPI AG 2022-02-01 |
Deskripsi
<i>Candida</i> species are the most common fungal pathogens infecting humans and can cause severe illnesses in immunocompromised individuals. The increased resistance of <i>Candida</i> 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 <i>Candida albicans</i> and non-<i>albicans Candida</i> species in vitro and in vivo. Results showed a WMR antifungal activity on all <i>Candida</i> 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 <i>Candida</i> species when the peptide was administered before or after infection. Additional experiments to unravel the antifungal mechanism were performed on <i>C. albicans</i> and <i>C. parapsilosis</i>. 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 <i>CDR1</i>. 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 <i>Candida albicans</i> and non-<i>albicans</i>, providing fascinating scenarios for the identification of new potential antifungal targets.