Fig. 4.

Genetic compromise of C. albicans HSP90 renders FL more efficacious both in vitro and in a murine model of disseminated disease. (A) Compromising HSP90 expression in the tetO-HSP90/hsp90Δ strain results in FL-hypersensitivity, even in the absence of tetracycline. Fivefold dilutions of cells (from 1 × 10⁶/ml) were spotted on YPD with FL (1.5 μg/ml) (Top) and without FL (Bottom). (B) Compromising C. albicans HSP90 expression enhances the therapeutic efficacy of FL in a murine model of disseminated disease. CD1 mice were infected with an inoculum of 200 μl of 1 × 10⁶ CFU/ml of a strain expressing wild-type HSP90 levels. Inoculum for the strain with its only HSP90 allele regulated by tetO was 200 μl of 1 × 10⁷cells/ml, corresponding to ≈4-fold higher CFU/ml compared to the wild type (see Materials and Methods). FL was administered at 2-mg/kg i.p. at 1 h after infection and then daily, as indicated.