title: Fluconazole tolerance in clinical isolates of Cryptococcus neoformans.
abstract: Eleven isolates of Cryptococcus neoformans were investigated to determine the biochemical basis of their tolerance to fluconazole. The MICs of fluconazole for three isolates with low-level resistance were 3- to 6-fold higher than those for sensitive isolates, while the MICs for four isolates with high-level resistance were 100- to 200-fold higher than those for sensitive isolates. The level of ergosterol present in the isolates varied, and those which had relatively low levels of ergosterol were resistant to amphotericin B. Changes in the affinity of the target enzyme (sterol 14alpha-demethylase) and decreases in the cellular content of fluconazole seemed to be responsible for the resistance in isolates with low-level and high-level resistance, respectively.
authors.affiliation: Department of Molecular Biology and Biotechnology, The University of Sheffield, United Kingdom.
authors.forename: K
authors.initials: K
authors.lastname: Venkateswarlu
authors.forename: M
authors.initials: M
authors.lastname: Taylor
authors.forename: N J
authors.initials: NJ
authors.lastname: Manning
authors.forename: M G
authors.initials: MG
authors.lastname: Rinaldi
authors.forename: S L
authors.initials: SL
authors.lastname: Kelly
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000378:metabolism / Q000494:pharmacology*; D003453:Cryptococcosis / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors; D004351:Drug Resistance; D015725:Fluconazole / Q000378:metabolism / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D058886:Sterol 14-Demethylase; D013261:Sterols / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D013261:Sterols; D000666:Amphotericin B; D015725:Fluconazole; D010088:Oxidoreductases; D058886:Sterol 14-Demethylase