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Antimicrobial Agents and Chemotherapy, October 2007, p. 3747-3751, Vol. 51, No. 10
0066-4804/07/$08.00+0     doi:10.1128/AAC.00929-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The Ssk1p Response Regulator and Chk1p Histidine Kinase Mutants of Candida albicans Are Hypersensitive to Fluconazole and Voriconazole

Department of Microbiology & Immunology, Georgetown University Medical Center, Washington, DC 20057

Received 18 July 2007/ Accepted 20 July 2007

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.

Published ahead of print on 30 July 2007.

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