Voriconazole and multidrug resistance in Candida albicans.
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.
Wakieć
Roland
R
Department of Pharmaceutical Technology and Biochemistry, Gdańsk University of Technology, Gdańsk, Poland.
Prasad
Rajendra
R
Morschhäuser
Joachim
J
Barchiesi
Francesco
F
Borowski
Edward
E
Milewski
Sławomir
S
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
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