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.

Abstract

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.

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