Antagonism between Two Mechanisms of Antifungal Drug Resistance
| العنوان: | Antagonism between Two Mechanisms of Antifungal Drug Resistance |
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| المؤلفون: | Nicole Ricker, Caroline Sirjusingh, James B. Anderson |
| المصدر: | Eukaryotic Cell. 5:1243-1251 |
| بيانات النشر: | American Society for Microbiology, 2006. |
| سنة النشر: | 2006 |
| مصطلحات موضوعية: | Antifungal Agents, Saccharomyces cerevisiae Proteins, Population, Mutant, Antifungal drug, ATP-binding cassette transporter, Microbial Sensitivity Tests, Saccharomyces cerevisiae, Drug resistance, Biology, Microbiology, Drug Resistance, Fungal, Gene Expression Regulation, Fungal, Cycloheximide, education, Early Growth Response Protein 3, Fluconazole, Molecular Biology, Gene, Genetics, education.field_of_study, Rhodamines, Fungal genetics, Articles, General Medicine, Resistance mutation, DNA-Binding Proteins, Mutation, Trans-Activators, ATP-Binding Cassette Transporters, Directed Molecular Evolution, Transcription Factors |
| الوصف: | This study tested for interaction between two independently evolved mechanisms of fluconazole resistance in Saccharomyces cerevisiae . One set of strains was from a 400-generation evolution experiment, during which the concentration of fluconazole was increased from 16 to 256 μg/ml in four increments. At 100 generations, populations became fixed for resistance mutations in either of two transcriptional regulators, PDR1 or PDR3 . At 400 generations, replicate populations became fixed for another resistance mutation in UNK1 , an unmapped gene further increasing resistance. Another genotype used in this study came from a population placed initially in 128 μg/ml of fluconazole; this environment selects for resistance through loss of function at ERG3 , resulting in altered sterol metabolism. Mutant strains carrying PDR1 r or PDR3 r were crossed with the erg3 r mutant strain, and the doubly mutant, haploid offspring were identified. The double-mutant strains grew less well than the parent strains at all concentrations of fluconazole tested. In genome-wide assays of gene expression, several ABC transporter genes that were overexpressed in one parent and several ERG genes that were overexpressed in the other parent were also overexpressed in the double mutants. Of the 43 genes that were consistently overexpressed in the PDR1 r parents at generation 100, however, 31 were not consistently overexpressed in the double mutants. Of these 31 genes, 30 were also not consistently overexpressed after a further 300 generations of evolution in the PDR1 r parent populations. The two independently evolved mechanisms of fluconazole resistance are strongly antagonistic to one another. |
| تدمد: | 1535-9786 1535-9778 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5e9c207c9295e89d890f2fb0dd6e77daTest https://doi.org/10.1128/ec.00048-06Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5e9c207c9295e89d890f2fb0dd6e77da |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15359786 15359778 |
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