Abstract
In vitro activity of voriconazole against fluconazole-resistant Candida albicans clinical isolates with identified molecular basis of multidrug resistance (MDR) and recombinant Saccharomyces cerevisiae expressing C. albicans genes coding for major multidrug transporters, CaCdr1p, CaCdr2p or CaMdr1p, was compared with that of fluconazole, ketoconazole and clotrimazole. It was found that overexpression of the MDR genes made the yeast cells less susceptible to voriconazole. The voriconazole resistance indexes, defined as a ratio of minimum inhibitory concentrations (MICs) determined for MDR and sensitive cells, were comparable with those determined for fluconazole. Voriconazole effectively competed with rhodamine 6G for the active efflux mediated by CaCdr1p and CaCdr2p.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
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ATP-Binding Cassette Transporters / genetics
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ATP-Binding Cassette Transporters / metabolism
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Antifungal Agents / pharmacology*
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Candida albicans / drug effects*
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Candida albicans / metabolism
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Drug Resistance, Multiple, Fungal / genetics*
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Fluconazole / pharmacology
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Fungal Proteins / genetics
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Fungal Proteins / metabolism
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Genes, MDR / genetics
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Membrane Transport Proteins / genetics
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Membrane Transport Proteins / metabolism
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Microbial Sensitivity Tests
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Pyrimidines / pharmacology*
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Rhodamines / metabolism
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Saccharomyces cerevisiae / drug effects
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism
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Triazoles / pharmacology*
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Voriconazole
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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ATP-Binding Cassette Transporters
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Antifungal Agents
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CDR1 protein, Candida albicans
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Fungal Proteins
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Membrane Transport Proteins
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Pyrimidines
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Rhodamines
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Triazoles
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rhodamine 6G
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Fluconazole
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Voriconazole