Drug induced proteome changes in Candida albicans: comparison of the effect of beta(1,3) glucan synthase inhibitors and two triazoles, fluconazole and itraconazole
| Autor: | Raymond Legrand, John Hodgson, Isabelle Maillet, Valérie Labas, Dominique Lecaque, Jean-Michel Bruneau, Claude Fudali, Eric Tagat, Françoise Supatto, Jean-Pierre Le Caer |
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| Rok vydání: | 2003 |
| Předmět: |
Antifungal Agents
Echinocandin Proteome Itraconazole Biology Biochemistry Peptides Cyclic Mass Spectrometry Microbiology Fungal Proteins chemistry.chemical_compound Echinocandins Lanosterol 14 alpha-demethylase Candida albicans medicine Image Processing Computer-Assisted Electrophoresis Gel Two-Dimensional Microscopy Phase-Contrast Molecular Biology Fluconazole chemistry.chemical_classification Ergosterol Dose-Response Relationship Drug Membrane Proteins Triazoles biology.organism_classification Corpus albicans Kinetics Glucose chemistry Glucosyltransferases Microscopy Electron Scanning Azole Schizosaccharomyces pombe Proteins medicine.drug |
| Zdroj: | Proteomics. 3(3) |
| ISSN: | 1615-9853 |
| Popis: | The dimorphic fungus Candida albicans is an opportunistic human pathogen. Candidiasis is usually treated with azole antifungal agents. However clinical treatments may fail due to the appearance of resistance to this class of antifungal agents in Candida. Echinocandin derivatives are an alternative for the treatment of these fungal infections and are active against azole resistant isolates of C. albicans. Azoles inhibit the lanosterol 14 alpha demethylase which is a key enzyme in the synthesis of ergosterol. In contrast, the echinocandin class of antibiotics inhibit noncompetitively beta-(1,3)-D-glucan synthesis in vitro. We have investigated the impact of mulundocandin on the proteome of C. albicans and compared it to those of a mulundocandin derivative, as well as to two azoles of different structure, fluconazole and itraconazole. The changes in gene expression underlying the antifungal responses were analyzed by comparative 2-D PAGE. Dose dependant responses were kinetically studied on C. albicans grown at 25 degrees C (yeast form) in synthetic dextrose medium. This study shows that antifungals with a common mechanism of action lead to comparable effects at the proteome level and that a proteomics approach can be used to distinguish different antifungals, with the promise to become a useful tool to study drugs of unknown mechanism of action. |
| Databáze: | OpenAIRE |
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