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Resistant P45051A1 activity in azole antifungal tolerant Cryptococcus neoformans from AIDS patients
Author(s) -
Lamb D.C.,
Corran A.,
Baldwin B.C.,
Kwon-Chung J.,
Kelly S.L.
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)00684-2
Subject(s) - azole , fluconazole , cryptococcus neoformans , microbiology and biotechnology , cryptococcosis , sterol , biology , drug resistance , demethylase , in vitro , microsome , pharmacology , antifungal , biochemistry , cholesterol , gene , epigenetics
Azole antifungal compounds are important in the treatment of Cryptococcosis, a major cause of mortality in AIDS patients. The target of the azole drugs is P450 mediated sterol 14α‐demethylase. We have investigated the P450 system of Cryptococcus neoformans with respect to azole tolerance observed in clinical isolates which were obtained following the failure of fluconazole therapy. The clinical failure was correlated with in vitro tolerance of azole antifungal when compared to wild‐type strains. The microsomal P450 system was typical of yeast and fungi and fluconazole tolerance was not associated with defective sterol biosynthesis. The strains had slightly elevated P450 content and slightly reduced azole levels in the cells, but a clear cause for resistance was the increased level of drug needed to inhibit the sterol 14α‐demethylase in vitro.