       Document 0493
 DOCN  M9610493
 TI    Resistance to fluconazole in Candida albicans from AIDS patients
       correlated with reduced intracellular accumulation of drug.
 DT    9601
 AU    Venkateswarlu K; Denning DW; Manning NJ; Kelly SL; Krebs Institute for
       Biomolecular Research, Department of; Molecular Biology and
       Biotechnology, Sheffield University, UK.
 SO    FEMS Microbiol Lett. 1995 Sep 15;131(3):337-41. Unique Identifier :
       AIDSLINE MED/96013075
 AB    Mucosal candidosis is an almost inevitable consequence of AIDS.
       Resistance to fluconazole therapy associated with enhanced tolerance,
       detectable in microbiological estimation of sensitivity, occurs in up to
       10% of cases with late-stage AIDS. We report here our biochemical
       analysis of the basis of resistance in a study of two susceptible and
       two resistant isolates. Resistance was not associated with a change in
       the target enzyme sterol 14 alpha-demethylase, as indicated by
       equivalent levels of fluconazole inhibition of activity in extracts from
       all four isolates, or by mutations in sterol delta desaturase as
       previously observed in Saccharomyces cerevisiae and Ustilago maydis.
       Reduced cellular content of fluconazole in the resistant isolates of
       between six to ten-fold was observed which could account for their
       resistant phenotype.
 DE    Antifungal Agents/*PHARMACOKINETICS/THERAPEUTIC USE  AIDS-Related
       Opportunistic Infections/DRUG THERAPY/*MICROBIOLOGY  Candida
       albicans/*DRUG EFFECTS/ENZYMOLOGY  Candidiasis, Chronic
       Mucocutaneous/DRUG THERAPY/*MICROBIOLOGY  Cholestadienols/ANALYSIS
       Cytochrome P-450/METABOLISM  Drug Resistance, Microbial
       Ergosterol/ANALYSIS  Fluconazole/*PHARMACOKINETICS/THERAPEUTIC USE
       Human  Lanosterol/ANALOGS & DERIVATIVES/ANALYSIS  Microbial Sensitivity
       Tests  Oxidoreductases/METABOLISM  Support, Non-U.S. Gov't  JOURNAL
       ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

