The Ssk1p response regulator and Chk1p histidine kinase mutants of Candida albicans are hypersensitive to fluconazole and voriconazole.
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.
Department of Microbiology & Immunology, Georgetown University Medical Center, Washington, DC 20057, USA.
Neeraj
N
Chauhan
Michael
M
Kruppa
Richard
R
Calderone
D000935:Antifungal Agents / Q000378:metabolism / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D003470:Culture Media; D025141:Drug Resistance, Fungal; D015725:Fluconazole / Q000378:metabolism / Q000494:pharmacology*; D000071677:Histidine Kinase; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D010766:Phosphorylation; D011494:Protein Kinases / Q000187:drug effects* / Q000235:genetics*; D011743:Pyrimidines / Q000378:metabolism / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014230:Triazoles / Q000378:metabolism / Q000494:pharmacology*; D065819:Voriconazole
D000935:Antifungal Agents; D003470:Culture Media; D011743:Pyrimidines; D014230:Triazoles; D015725:Fluconazole; D011494:Protein Kinases; D000071677:Histidine Kinase; D065819:Voriconazole