Multidrug Resistance Genes in Candida albicans.
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概要
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Treatment failures in fungal infections have drawn attention recently to the problem of azole antifungal resistance and its underlying mechanisms. In most cases this failure is due to fluconazole- or azole-cross-resistant (fluconazole, ketoconazole and itraconazole) Candida albicans isolates. Energy-dependent drug efflux is emerging as an important mechanism of drug resistance in many organisms. A well-studied system is the human P-glycoprotein which is responsible for the multidrug resistance (MDR) of tumour cells to chemotherapeutic agents. There are several lines of evidence which indicate that proteins with structural similarities to drug pumps are involved in fluconazole resistance in C. albicans.In this review paper, fluconazole uptake by C. albicans strains, cloning of genes encoding predicted drug efflux proteins and comparative expression of multidrug resistance genes in azole-sensitive and -resistant strains are described. Transformation of an azole-sensitive strain with a plasmid containing a potential drug pump gene is also described. Drug efflux, mediated by membrane-associated drug efflux pumps, can protect cells from a range of toxic compounds and therefore may confer single-step multidrug resistance.
- 日本医真菌学会の論文
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