title: Voriconazole and multidrug resistance in Candida albicans.
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.
authors.affiliation: Department of Pharmaceutical Technology and Biochemistry, Gdańsk University of Technology, Gdańsk, Poland.
authors.forename: Roland
authors.initials: R
authors.lastname: Wakieć
authors.forename: Rajendra
authors.initials: R
authors.lastname: Prasad
authors.forename: Joachim
authors.initials: J
authors.lastname: Morschhäuser
authors.forename: Francesco
authors.initials: F
authors.lastname: Barchiesi
authors.forename: Edward
authors.initials: E
authors.lastname: Borowski
authors.forename: Sławomir
authors.initials: S
authors.lastname: Milewski
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000378:metabolism; D026141:Drug Resistance, Multiple, Fungal / Q000235:genetics*; D015725:Fluconazole / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D019450:Genes, MDR / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D011743:Pyrimidines / Q000494:pharmacology*; D012235:Rhodamines / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology*; D065819:Voriconazole
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D000935:Antifungal Agents; C094693:CDR1 protein, Candida albicans; D005656:Fungal Proteins; D026901:Membrane Transport Proteins; D011743:Pyrimidines; D012235:Rhodamines; D014230:Triazoles; C026188:rhodamine 6G; D015725:Fluconazole; D065819:Voriconazole