Abstract
Hypersensitivity to the triazoles fluconazole and voriconazole associated with two-component signal transduction proteins has not been reported in Candida albicans. Herein, we show that strains of C. albicans lacking the response regulator Ssk1p or the Chk1p histidine kinase signal transduction proteins are hypersensitive to fluconazole and voriconazole compared to wild-type (wt) as well as gene-reconstituted strains, reflecting an increased hypersensitivity to these drugs of about 16- to 500-fold. In comparison to wt cells, both mutants had elevated levels of fluconazole accumulation and reduced viability upon incubation with either drug, suggesting that in the absence of Ssk1p or Chk1p, fluconazole and voriconazole have significantly increased fungicidal effects on C. albicans.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Antifungal Agents / metabolism
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Antifungal Agents / pharmacology*
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Candida albicans / drug effects
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Candida albicans / enzymology
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Candida albicans / genetics*
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Culture Media
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Drug Resistance, Fungal
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Fluconazole / metabolism
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Fluconazole / pharmacology*
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Histidine Kinase
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Microbial Sensitivity Tests
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Mutation / genetics
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Mutation / physiology*
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Phenotype
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Phosphorylation
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Protein Kinases / drug effects*
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Protein Kinases / genetics*
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Pyrimidines / metabolism
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Pyrimidines / pharmacology*
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Signal Transduction / drug effects
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Triazoles / metabolism
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Triazoles / pharmacology*
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Voriconazole
Substances
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Antifungal Agents
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Culture Media
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Pyrimidines
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Triazoles
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Fluconazole
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Protein Kinases
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Histidine Kinase
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Voriconazole