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Membrane rafts are involved in intracellular miconazole accumulation in yeast cells

Isabelle E J A François1, Anna Bink, Jo Vandercappellen

  • 1Centre of Microbial and Plant Genetics, Katholieke Universiteit Leuven, 3001 Heverlee, Belgium.

The Journal of Biological Chemistry
|September 29, 2009
PubMed

Insights

Miconazole

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Mycology

Background:

  • Azoles disrupt ergosterol biosynthesis, depleting ergosterol and accumulating toxic sterols in yeast membranes.
  • Miconazole previously shown to stabilize actin cytoskeleton in Saccharomyces cerevisiae, suggesting a secondary mechanism.
  • Membrane rafts' role in miconazole's antifungal activity remains unclear.

Purpose of the Study:

  • To investigate the involvement of membrane rafts in miconazole's mode of action.
  • To identify yeast mutants with altered resistance to miconazole.
  • To elucidate the primary mechanism of miconazole's antifungal activity.

Main Methods:

  • Genome-wide agar-based screening of Saccharomyces cerevisiae mutants.
  • Assessment of miconazole resistance in deletion mutants (ipt1, sur1, skn1, erg3).
  • Evaluation of membrane raft-disturbing compounds' effects on miconazole activity.

Main Results:

  • Sphingolipid and ergosterol biosynthesis mutants (ipt1, sur1, skn1, erg3) exhibited miconazole resistance.
  • Membrane raft-disrupting compounds antagonized miconazole's antifungal activity.
  • These compounds also inhibited miconazole-induced actin stabilization and ROS accumulation.
  • Membrane rafts mediate the intracellular accumulation of miconazole in yeast cells.

Conclusions:

  • Membrane rafts play a primary role in miconazole's antifungal activity.
  • Miconazole's action is dependent on membrane raft integrity.
  • Intracellular miconazole accumulation via membrane rafts is a key aspect of its efficacy.

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