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Analysis of the arrangement of the binding pocket of the MDR pump Cdr1p of the pathogenic yeast Candida albicans - a major contributor to clinical drug resistance.
Bartl, Tomáš ; Gášková, Dana (advisor) ; Krůšek, Jan (referee)
Title: Analysis of the arrangement of the binding pocket of the MDR pump Cdr1p of the pathogenic yeast Candida albicans - a major contributor to clinical drug resistance. Author: Tomáš Bartl Department: Institute of Physics of Charles University Supervisor: doc. RNDr. Dana Gášková, CSc., Institute of Physics of Charles University Abstract: Candida infections are becoming an increasing cause of death in hospitalized patients. The main reason for drug resistance in the most common yeast pathogen Candida albicans is an increased production of transport proteins, which are removing the drug from the cell cytosol and thus producing the phenomenon called multidrug resistance - MDR. The goal of this thesis was to verify the suitability of the yeast strain Saccharomyces cerevisiae with heterologously expressed MDR pumps from the pathogenic yeast Candida albicans and comparison to the results from C. albicans with homologous expression. The results that the azole drugs miconazole, bifonazole, and ketoconazole, together with potentiometric fluorescent probe diS-C3(3), are substrates of the CaCdr1p and CaCdr2p pumps, but not, or minimally, of the pump CaMdr1p, are consistent with the previously published work. The binding pocket of CaCdr1p was explored using the disc diffusion assay and the diS-C3(3) fluorescent probe...
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