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PMID: 9087482 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Fluconazole tolerance in clinical isolates of Cryptococcus neoformans.

Antimicrobial agents and chemotherapy ·Vol. 41 ·No. 4 ·1997-04-00 ·Pages 748-51

Venkateswarlu K, Taylor M, Manning NJ, Rinaldi MG, Kelly SL

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.

MeSH Terms
Amphotericin B/pharmacology Antifungal Agents/metabolism,pharmacology Cryptococcosis/microbiology Cryptococcus neoformans/drug effects,enzymology,metabolism Cytochrome P-450 Enzyme Inhibitors Drug Resistance Fluconazole/metabolism,pharmacology Microbial Sensitivity Tests Oxidoreductases/antagonists & inhibitors Sterol 14-Demethylase Sterols/biosynthesis,metabolism
Chemicals
Antifungal Agents Cytochrome P-450 Enzyme Inhibitors Sterols Amphotericin B Fluconazole Oxidoreductases Sterol 14-Demethylase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Venkateswarlu K
Department of Molecular Biology and Biotechnology, The University of Sheffield, United Kingdom.
Taylor M
Manning N J
Rinaldi M G
Kelly S L
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Article Info
Journal
Antimicrobial agents and chemotherapy
Abbr.
Antimicrob Agents Chemother
ISSN
0066-4804
DOI
10.1128/AAC.41.4.748
Published
1997-04-00
Pages
748-51
Language
English
Region
United States
NLM ID
0315061
PMCID
PMC163787
Subset
IM
External Links
PubMed source DOI: 10.1128/AAC.41.4.748 PMC Full Text View journal details
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