Figure 10.
Arg1 is essential for lung colonization and dissemination in a murine inhalation model of cryptococcosis. (A) arg1Δ is avirulent compared to WT and arg1Δ + ARG1. Mice (n = 10 per strain) were inoculated intranasally with 5× 105 cells/20 µL and monitored daily. Difference in survival between WT/arg1Δ + ARG1-infected mice and arg1Δ-infected mice is statistically significant (****P < 0.0001). (B) and (C) arg1Δ infection is rapidly cleared from mouse lung between 3 and 7 days post-infection. Mice (n = 3 per strain) were inoculated intranasally with 5× 105 cells/20 µL and sacrificed on the days indicated. Lung and brain were harvested for quantitative culture (CFUs) (B) or histopathological analysis for lung only by Periodic acid–Schiff (PAS) staining (C). In (B), the difference in lung CFUs for WT and arg1Δ-infected mice at day 3 is statistically significant (*P < 0.05). In (C), lung histopathology is shown at 3 days post-infection (PAS stain, 40x magnification). In WT-infected lung tissue, arrows indicate cryptococcomas where capsular material is represented by white halos surrounding the cell bodies (stained magenta). In arg1Δ-infected tissue, arrows indicate single acapsular cryptococcal cells.