Abstract
It is difficult to identify new antifungal agents because of their eukaryotic nature. However, antimicrobial peptides can well differentiate among cell types owing to their variable amino acid content. This study aimed to investigate the antifungal effect of Hn-Mc, a chimeric peptide comprised of the N-terminus of HPA3NT3 and the C-terminus of melittin. We evaluated its potent antifungal activity at low minimal inhibitory concentrations (MICs) ranging from 1–16 μM against pathogenic yeast and molds. The cell-type specificity of Hn-Mc was mediated through the formation of a random α-helical structure to mimic the fungal membrane environment. Furthermore, Hn-Mc caused cell death in C. tropicalis and F. oxysporum by inducing apoptosis via the generation of reactive oxygen species (ROS) due to mitochondrial damage. The present results indicate that Hn-Mc has a high affinity for the fungal plasma membrane and induces apoptosis in fungal cells, and provide guidance for the development of new antifungal agents.
Highlights
In the last decade, the prevalence of fungal infections has increased among immunocompromised individuals, including infections of Candida and Aspergillus spp. [1]
The antifungal activity of Hn-Mc was tested against five yeast and six mold cells by determining the minimum inhibitory concentration (MIC)
Our results suggest that HPA3NT3 and ME peptides exert potent antifungal effects by targeting the fungal cell membrane; Hn-Mc inhibits fungal cells by inducing the generation of intracellular and a selective mitochondrial fluorescence probe, was used in C. tropicalis and F. oxysporum cells preMoreover, detect the Fluorescence induced mitochondrial
Summary
The prevalence of fungal infections has increased among immunocompromised individuals, including infections of Candida and Aspergillus spp. [1]. The prevalence of fungal infections has increased among immunocompromised individuals, including infections of Candida and Aspergillus spp. The prevalence of typical aspergillosis due to Aspergillus fumigatus has steadily increased [3] and numerous Fusarium spp. have caused severe diseases in animals, humans, and plants [4]. Global healthcare responses include several types of antifungal medicines agents that are administered orally or intravenously to infected individuals; such agents are classified as azoles, echinocandins, and polyenes [5,6]. Azoles interfere with ergosterol (Erg) biosynthesis, echinocandins inhibit β-(1,3)-D-glucan synthase activity, and polyenes bind to membrane Erg [7]. These molecules typically act on only one target in pathogens, which potentially induces rapid resistance. The emergence of fungal strains resistant to conventional treatments indicates the need to develop novel antifungal agents [8,9]
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