Saccharomyces cerevisiae has long been used as a model organism in the study of the ergosterol pathway and its inhibitors. The Pdr5 protein (Pdr5p), an ATP binding cassette transporter, plays an important role in active efflux of azole antifungals and therefore in azole sensitivity and resistance in S. cerevisiae. We have identified the Fluconazole Dominant Resistance-1 (FDR-1) mutant, which has a single dominant mutation conferring high-level resistance to fluconazole. FDR-1 has been found to be an activated allele of the Pleiotropic Drug Resistance-1 (PDR-1) gene (termed PDR1-100) and to upregulate PDR5 transcription. Resistance of PDR1-100 to fluconazole decreased in the background of mutations known to affect sterol homeostasis. Hence, the resistance to fluconazole of PDR1-100 was paradoxically decreased in an erg3 PDR1-100 double mutant. The erg3 mutants are resistant to azoles and accumulate 14-methyl-fecosterol instead of ergosterol in the presence of azoles. These results reinforce the emerging evidence in both S. cerevisiae and Candida albicans that sterols could serve as substrates for Pdr5p for transport across membranes.
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Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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Site | Modification | Modifier | Source | Reference |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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