Figure 7. Crg2 regulates virulence in a murine inhalation model.

A) Female A/Jcr mice were intranasally inoculated with 10⁵ cells of the following strains: wild type (H99), crg2 mutant (CDX50), crg2 + CRG2 complemented strain (CDX112), and GPA1^Q284L overexpression strain (CDX156-2). Animals were monitored for clinical signs of cryptococcal infection and sacrificed at predetermined clinical end points that predict imminent mortality. The crg2 mutant and the GPA1^Q284L expression strain are both significantly reduced virulence compared to wild type strain H99 (P<0.001). The crg2 + CRG2 complemented strain is also significantly more virulent than the crg2 mutant (P<0.001). The virulence difference between the crg2 mutant and the GPA1^Q284L strain is not significant (P=0.0177). B–C) Progression of crg2 infection in vivo. Lungs from animals infected with crg2 mutant and wild type were isolated at 7, 14, and 21 days post-infection. H&E stained slides were prepared from lung cross sections and visualized by light microscopy. Colony forming units (CFU) were also measured in lung homogenates (C). Each data point and error bar indicates the standard error of the mean for values from three animals.