Serum repressing efflux pump CDR1 in Candida albicans
| Autor: | Ming-Yang Tsao, Yi-Hsuan Lin, Jen-Chung Fan, Hsin-I Shih, Yun-Liang Yang, Chia-Geun Chen, Jang-Shiun Wang, Hsiu-Jung Lo |
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| Rok vydání: | 2006 |
| Předmět: |
Serum
Antifungal Agents lcsh:QH426-470 Antifungal drug Germ tube Microbial Sensitivity Tests Drug resistance Biology Polymerase Chain Reaction Microbiology Fungal Proteins Drug Resistance Fungal In vivo Gene Expression Regulation Fungal Candida albicans medicine Animals lcsh:QH573-671 Promoter Regions Genetic Fluconazole Molecular Biology Luciferases Renilla lcsh:Cytology Membrane Transport Proteins biology.organism_classification Corpus albicans Culture Media DNA-Binding Proteins lcsh:Genetics Cattle Efflux Miconazole Research Article Transcription Factors medicine.drug |
| Zdroj: | BMC Molecular Biology BMC Molecular Biology, Vol 7, Iss 1, p 22 (2006) |
| ISSN: | 1471-2199 |
| DOI: | 10.1186/1471-2199-7-22 |
| Popis: | Background In the past decades, the prevalence of candidemia has increased significantly and drug resistance has also become a pressing problem. Overexpression of CDR1, an efflux pump, has been proposed as a major mechanism contributing to the drug resistance in Candida albicans. It has been demonstrated that biological fluids such as human serum can have profound effects on antifungal pharmacodynamics. The aim of this study is to understand the effects of serum in drug susceptibility via monitoring the activity of CDR1 promoter of C. albicans. Results The wild-type C. albicans cells (SC5314) but not the cdr1/cdr1 mutant cells became more susceptible to the antifungal drug when the medium contained serum. To understand the regulation of CDR1 in the presence of serum, we have constructed CDR1 promoter-Renilla luciferase (CDR1p-RLUC) reporter to monitor the activity of the CDR1 promoter in C. albicans. As expected, the expression of CDR1p-RLUC was induced by miconazole. Surprisingly, it was repressed by serum. Consistently, the level of CDR1 mRNA was also reduced in the presence of serum but not N-acetyl-D-glucosamine, a known inducer for germ tube formation. Conclusion Our finding that the expression of CDR1 is repressed by serum raises the question as to how does CDR1 contribute to the drug resistance in C. albicans causing candidemia. This also suggests that it is important to re-assess the prediction of in vivo therapeutic outcome of candidemia based on the results of standard in vitro antifungal susceptibility testing, conducted in the absence of serum. |
| Databáze: | OpenAIRE |
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