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Title: Membrane rafts are involved in intracellular miconazole accumulation in yeast cells
Authors: Francois, Isabelle *
Bink, Anna *
Vandercappellen, Jo
Ayscough, Kathryn
Toulmay, Alexandre
Schneiter, Roger
Van Gyseghem, Elke
Van den Mooter, Guy
Borgers, Marcel
Vandenbosch, Davy
Coenye, Tom
Cammue, Bruno ×
Thevissen, Karin #
Issue Date: Nov-2009
Publisher: American Society for Biochemistry and Molecular Biology
Series Title: Journal of Biological Chemistry vol:284 issue:47 pages:32680-32685
Abstract: Azoles inhibit ergosterol biosynthesis, resulting in ergosterol depletion and accumulation of toxic 14alpha-methylated sterols in membranes of susceptible yeasts. We previously demonstrated that miconazole induces actin cytoskeleton stabilization in Saccharomyces cerevisiae prior to induction of reactive oxygen species (ROS), pointing to an ancillary mode of action. Using a genome-wide agar-based screening, we demonstrate in this study that S. cerevisiae mutants affected in sphingolipid and ergosterol biosynthesis, namely ipt1-, sur1-, skn1- and erg3-deletion mutants, are miconazole resistant, suggesting an involvement of membrane rafts in its mode of action. This is supported by the antagonizing effect of membrane raft disturbing compounds on miconazole antifungal activity as well as on the miconazole-induced actin cytoskeleton stabilization and ROS accumulation. These antagonizing effects point to a primary role for membrane rafts in miconazole antifungal activity. We further show that this primary role of membrane rafts on miconazole action consists of mediating intracellular accumulation of miconazole in yeast cells.
ISSN: 0021-9258
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Drug Delivery and Disposition
Centre of Microbial and Plant Genetics
Laboratory of Molecular Immunology (Rega Institute)
* (joint) first author
× corresponding author
# (joint) last author

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