Journal article

Membrane rafts are involved in intracellular miconazole accumulation in yeast cells

  • François, Isabelle E. J. A. Centre of Microbial and Plant Genetics, Katholieke Universiteit Leuven, Belgium
  • Bink, Anna Centre of Microbial and Plant Genetics, Katholieke Universiteit Leuven, Belgium
  • Vandercappellen, Jo Centre of Microbial and Plant Genetics, Katholieke Universiteit Leuven, Belgium
  • Ayscough, Kathryn R. Department of Molecular Biology and Biotechnology, University of Sheffield, UK
  • Toulmay, Alexandre Division of Biochemistry, University of Fribourg, Switzerland
  • Schneiter, Roger Division of Biochemistry, University of Fribourg, Switzerland
  • Gyseghem, Elke van Laboratory of Pharmaceutical Technology and Biopharmacy, Katholieke Universiteit Leuven, Belgium
  • Mooter, Guy Van den Laboratory of Pharmaceutical Technology and Biopharmacy, Katholieke Universiteit Leuven, Belgium
  • Borgers, Marcel Barrier Therapeutics Geel, Belgium
  • Vandenbosch, Davy Laboratorium voor Farmaceutische Microbiologie, Universiteit Gent, Belgium
  • Coenye, Tom Laboratorium voor Farmaceutische Microbiologie, Universiteit Gent, Belgium
  • Cammue, Bruno P. A. Centre of Microbial and Plant Genetics, Katholieke Universiteit Leuven, Belgium
  • Thevissen, Karin Centre of Microbial and Plant Genetics, Katholieke Universiteit Leuven, Belgium
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    20.11.2009
Published in:
  • The Journal of Biological Chemistry. - 2009, vol. 284, p. 32680-32685
English Azoles inhibit ergosterol biosynthesis, resulting in ergosterol depletion and accumulation of toxic 14α-methylated sterols in membranes of susceptible yeast. We demonstrated previously that miconazole induces actin cytoskeleton stabilization in Saccharomyces cerevisiae prior to induction of reactive oxygen species, 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 miconazole-induced actin cytoskeleton stabilization and reactive oxygen species 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 in miconazole action consists of mediating intracellular accumulation of miconazole in yeast cells.
Faculty
Faculté des sciences et de médecine
Department
Département de Biologie
Language
  • English
Classification
Biology, life sciences
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/301370
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