Mechanism of action of novel synthetic dodecapeptides against Candida albicans.
Biochim Biophys Acta
; 1830(11): 5193-203, 2013 Nov.
Article
em En
| MEDLINE
| ID: mdl-23876294
ABSTRACT
BACKGROUND:
Three de novo designed low molecular weight cationic peptides (IJ2, IJ3 and IJ4) containing an unnatural amino acid α,ß-didehydrophenylalanine (∆Phe) exhibited potent antifungal activity against fluconazole (FLC) sensitive and resistant clinical isolates of Candida albicans as well as non-albicans and other yeast and filamentous pathogenic fungi. In the present study, their synthesis, susceptibility of different fungi and the mechanism of anti-candidal action have been elucidated.METHODS:
The antimicrobial peptides (AMPs) were synthesized by solid-phase method and checked for antifungal activity against different yeasts and fungi by broth microdilution method. Anti-candidal mode of action of the peptides was investigated through detecting membrane permeabilization by confocal microscopy, Reactive Oxygen Species (ROS) generation by fluorometry, apoptosis and necrosis by flow cytometry and cell wall damage using Scanning and Transmission Electron Microscopy. RESULTS ANDCONCLUSIONS:
The MIC of the peptides against C. albicans and other yeast and filamentous fungal pathogens ranged between 3.91 and 250µM. All three peptides exhibited effect on multiple targets in C. albicans including disruption of cell wall structures, compromised cell membrane permeability leading to their enhanced entry into the cells, accumulation of ROS and induction of apoptosis. The peptides also showed synergistic effect when used in combination with fluconazole (FLC) and caspofungin (CAS) against C. albicans. GENERALSIGNIFICANCE:
The study suggests that the AMPs alone or in combination with conventional antifungals hold promise for the control of fungal pathogens, and need to be further explored for treatment of fungal infections.Palavras-chave
ABC; ATP-Binding Cassette; Antifungal peptide; Antimicrobial peptide (AMP); Apoptosis; Candida albicans; FICI; Fraction Inhibitory Concentration Index; MDR; MFS; Major Facilitator Superfamily; Multidrug Resistance; ROS; Reactive Oxygen Species; Reactive Oxygen Species (ROS); SEM; Scanning Electron Microscopy; TEM; Transmission Electron Microscopy
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article