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

International Journal of Molecular Sciences

Annarita Falanga¹  Luisa Albarano²  Elisabetta de Alteriis²  Marco Guida²  Emilia Galdiero²  Angela Maione²  Alessandra La Pietra²  Ermenegilda Parrilli³  Caterina D’Angelo³  Stefania Galdiero⁴  Rosa Bellavita⁴ 

[1] Department of Agricultural Science, University of Naples ‘Federico II’, Via dell’Università 100, 80055 Portici, Italy;Department of Biology, University of Naples ‘Federico II’, Via Cinthia, 80126 Naples, Italy;Department of Chemical Sciences, University of Naples Federico II, 80125 Naples, Italy;Department of Pharmacy, School of Medicine, University of Naples ‘Federico II’, Via Domenico Montesano 49, 80131 Naples, Italy;

关键词: biofilm;    Candida species;    WMR;    Galleria mellonella;    oxidative damage;    CLSM;   

DOI  :  10.3390/ijms23042151

来源: DOAJ

【 摘 要 】

Candida species are the most common fungal pathogens infecting humans and can cause severe illnesses in immunocompromised individuals. The increased resistance of Candida 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 Candida albicans and non-albicans Candida species in vitro and in vivo. Results showed a WMR antifungal activity on all Candida 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 Candida species when the peptide was administered before or after infection. Additional experiments to unravel the antifungal mechanism were performed on C. albicans and C. parapsilosis. 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 CDR1. 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 Candida albicans and non-albicans, providing fascinating scenarios for the identification of new potential antifungal targets.

【 授权许可】

Unknown