Abstract
We have previously reported that Cryptococcus neoformans strains are innately heteroresistant to fluconazole in vitro, producing minor, highly resistant subpopulations due to adaptive formation of disomic chromosomes. Using a mouse model, we assessed the emergence of heteroresistant clones in the brain during fluconazole treatment and found that the occurrence of heteroresistant clones in vivo with chromosomal disomy is strain dependent. Interestingly, emergence of heteroresistant clones in vivo was unrelated to the strain's MIC to fluconazole.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Animals
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Antifungal Agents / therapeutic use*
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Azoles / therapeutic use*
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Brain / metabolism*
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Chromosomes, Fungal / genetics
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Cryptococcosis / drug therapy
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Cryptococcosis / genetics
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Cryptococcus neoformans / drug effects*
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Cryptococcus neoformans / genetics
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Cryptococcus neoformans / metabolism
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Cryptococcus neoformans / pathogenicity*
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Drug Resistance, Fungal / genetics
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Female
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Fluconazole / therapeutic use*
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Fungal Proteins / genetics
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Fungal Proteins / metabolism
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Gene Dosage / genetics
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Mice
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Mice, Inbred BALB C
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Microbial Sensitivity Tests
Substances
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Antifungal Agents
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Azoles
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Fungal Proteins
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Fluconazole