Figure 1. Deletion of CFO1 increased susceptibility to azole antifungal drugs.

(A) The growth of the cfo1 mutant in media containing various azole antifungal drugs was monitored. Ten-fold serial dilutions of cells (starting at 104 5 cells) were spotted onto YPD plates with or without the antifungal drug at the concentrations indicated. Plates were incubated at 30°C for 2 days. (B) Tolerance to fluconazole was assayed with time kill curves in YPD liquid media with various concentrations of fluconazole, as indicated. No viable cells were observed for the cfo1 mutant cultured in the presence of fluconazole above 16 μg/ml while a small number of the wild-type cells grew in the presence of higher concentrations of the drug. Data are the averages of three separate measurements with the standard deviations. (C) Total cellular iron levels were determined using ICP analysis. Values indicate weight per cell and are averages from three independent experiments with standard deviations. (D) Combination treatment of an iron chelator and fluconazole or miconazole. The growth of the wildtype strain was tested in media containing azole drug with or without the iron chelator indicated. Tenfold serial dilutions of cells (starting at 104 15 cells) were spotted onto plates with subsequent incubation at 30°C for 2 days.