FIG 4.

TBZ exposure causes antifungal resistance in vivo. The MICs of tebuconazole (TBZ), fluconazole (FLC), itraconazole (ITC), ravuconazole (RVC), and amphotericin B (AMB) were determined for colonies recovered from lungs of animals that had been infected with nonadapted (NA) and TBZ-adapted (A) cells of C. gattii R265 (A) or C. neoformans H99 (B) and treated (A + FCZ) or not treated (A) with FLC (10 mg/kg). After 15 days, the animals were euthanized and the lungs were collected for determination of the CFU level per gram. There were no statistical significant differences between the fungal loads in the lungs of animals that were infected with TBZ-adapted cells of C. gattii R265 (C) or C. neoformans H99 and (D) and treated or not treated with FLC. *, P < 0.05; **, P < 0.01; ***, P < 0.001.