Abstract
The rise of antifungal drug resistance in Candida species responsible for life threatening candidiasis is considered as an increasing challenge for the public health. MCh-AMP1 has previously been reported as a natural peptide from Matricaria chamomilla L. flowers with broad-spectrum antifungal activity against human pathogenic molds and yeasts. In the current study, the mode of action of synthetic MCh-AMP1 was investigated against Candida albicans, the major etiologic agent of life-threatening nosocomial candidiasis at cellular and molecular levels. Candida albicans ATCC 10231 was cultured in presence of various concentrations of MCh-AMP1 (16–64 μg/mL) and its mode of action was investigated using plasma membrane permeabilization assays, reactive oxygen species (ROS) induction, potassium ion leakage and ultrastructural analyses by electron microscopy. MCh-AMP1 showed fungicidal activity against Candida albicans at the concentrations of 32 and 64 μg/mL. The peptide increased fungal cell membrane permeability as evidenced by elevating of PI uptake and induced potassium leakage from the yeast cells. ROS production was induced by the peptide inside the fungal cells to a maximum of 64.8% at the concentration of 64 μg/mL. Scanning electron microscopy observations showed cell deformation as shrinkage and folding of treated yeast cells. Transmission electron microscopy showed detachment of plasma membrane from the cell wall, cell depletion and massive destruction of intracellular organelles and cell membrane of the fungal cells. Our results demonstrated that MCh-AMP1 caused Candida albicans cell death via increasing cell membrane permeability and inducing ROS production. Therefore, MCh-AMP1 could be considered as a promising therapeutic agent to combat Candida albicans infections.
Highlights
Candida albicans is one of the most common nosocomial pathogens, which is responsible for various diseases that range from superficial to life-threatening systemic infections, especially in immunocompromised patients
Growth inhibition kinetic of MCh-AMP1 were evaluated against C. albicans ATCC10231, using different concentrations of the peptide (16, 32, 64 μg/mL) at various intervals (Figure 1A)
Growth inhibition results showed that the light absorbance rate at a wavelength of 600 nm (OD) in various concentration of MCh-AMP1 is decreased with increasing the concentration of the peptide
Summary
Candida albicans is one of the most common nosocomial pathogens, which is responsible for various diseases that range from superficial to life-threatening systemic infections, especially in immunocompromised patients. There seems to be a necessity to develop new antifungal agents Both experimental and clinical studies in past decade have revealed that antimicrobial peptides (AMPs) are appropriate templates as a potential new class of therapeutics (Teixeira et al, 2012). Natural AMPs are identified as small (12–50 amino acids), cationic, amphipathic, and with variable lengths, which commonly isolated from animals, plants, bacteria, or fungi (Zasloff, 2002; Hilpert et al, 2005). They are recognized as important components of the innate immune system against invasive pathogens (Li et al, 2012)
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