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Published on: February 14, 2018
Fisetin as a promising antifungal agent against Cryptocococcus neoformans species complex
M P C Reis1, C R C Carvalho1, F A Andrade1
1Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
Aims:
The aim of this study was to investigate the mechanisms of action of fisetin, a flavonol with antifungal activity previously evaluated against the Cryptococcus neoformans species complex.
Methods And Results:
Ergosterol content and flow cytometry analysis were determined for the C. neoformans species complex in the presence of fisetin and ultrastructural analysis of morphology was performed on Cryptococcus gattii and C. neoformans. Decrease in the total cellular ergosterol content after exposure to fisetin ranged from 25·4% after exposure to 128 μg ml(-1) to 21·6% after exposure to 64 μg ml(-1) of fisetin compared with the control (without fisetin). The fisetin effects obtained with flow cytometry showed metabolic impairment, and alterations in its normal morphology caused by fisetin in C. neoformans cells were verified using scanning electron microscopy.
Conclusions:
Fisetin is a compound that acts in the biosynthesis of ergosterol. Flow cytometry showed that fisetin reduced viability of the metabolically active cells of C. gattii, while morphological changes explain the action of fisetin in inhibiting growth of these fungi.
Significance And Impact Of The Study:
This study supports the idea that fisetin may represent a good starting point for the development of future therapeutic substances for cryptococcosis.
Insights
Fisetin, an antifungal flavonol, disrupts ergosterol biosynthesis and impairs cell metabolism in Cryptococcus neoformans and Cryptococcus gattii. This suggests fisetin
Area of Science:
- Mycology
- Pharmacology
- Biochemistry
Background:
- Cryptococcus neoformans and Cryptococcus gattii are pathogenic fungi causing cryptococcosis.
- Fisetin is a flavonol with demonstrated antifungal activity.
- Understanding the mechanisms of action of antifungal compounds is crucial for developing new therapies.
Purpose of the Study:
- To investigate the mechanisms by which fisetin exerts its antifungal effects against the Cryptococcus neoformans species complex.
- To evaluate the impact of fisetin on ergosterol biosynthesis and cellular morphology in Cryptococcus species.
Main Methods:
- Exposure of Cryptococcus neoformans and Cryptococcus gattii to fisetin.
- Measurement of total cellular ergosterol content.
- Flow cytometry analysis for metabolic activity and viability.
- Scanning electron microscopy for morphological analysis.
Main Results:
- Fisetin significantly decreased ergosterol content in Cryptococcus species.
- Flow cytometry revealed metabolic impairment in fisetin-treated cells.
- Morphological alterations, including changes in cell shape, were observed via electron microscopy.
Conclusions:
- Fisetin interferes with ergosterol biosynthesis, a key component of fungal cell membranes.
- Fisetin reduces the viability of metabolically active Cryptococcus cells.
- Morphological changes induced by fisetin contribute to its antifungal activity, supporting its potential as a therapeutic lead for cryptococcosis.
Related Concept Videos
Antifungal Agents
Anthelminthic Agents
Fungal Group Zygomycota
Fungal Phylum Microsporidia
Fungal Phylum Basidiomycota
Fungal Phylum Ascomycota

