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Antimicrobial Agents and Chemotherapy, 07 1995, 1526-1529, Vol 39, No. 7
Copyright © 1995 by the American Society for Microbiology. All rights reserved.

Cross-resistance to polyene and azole drugs in Cryptococcus neoformans

T Joseph-Horne, D Hollomon, RS Loeffler and SL Kelly
Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, United Kingdom.

Fluconazole was observed to inhibit sterol 14 alpha-demethylase in the human pathogen Cryptococcus neoformans, and accumulation of a ketosteroid product was associated with growth arrest. A novel mechanism(s) of azole and amphotericin B cross-resistance was identified, unrelated to changes in sterol biosynthesis, as previously identified in Saccharomyces cerevisiae. Reduced cellular content of drug could account for the resistance phenotype, indicating the possible involvement of a mechanism similar to multidrug resistance observed in higher eukaryotes.


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