HSP82 is required for full Histoplasma virulence in vivo. C57BL/6 mice were intranasally infected with HSP82(+) (strain OSU25), the hsp82 insertion mutant (hsp82::T-DNA; strain OSU74), or HSP82-complemented [hsp82::T-DNA/HSP82(+); strain OSU86] Histoplasma yeast. At 8 days postinfection, the fungal burdens in the lungs (A) and spleens (B) were determined. Data points represent CFU counts per organ for each mouse (n = 5). Data points on the x axis represent fungal burdens lower than the assay's limit of detection (100 CFU). Actual yeast cells delivered were determined by the enumeration of CFU counts in the inocula: 1.5 × 104 for HSP82(+), 1.2 × 104 for the hsp82 mutant, and 1.5 × 104 for the HSP82-complemented strain. Asterisks indicate statistically significant decreases (*, P < 0.05; **, P < 0.01) in CFU/organ compared to results of HSP82(+) infections as determined by the Wilcoxon rank-sum test.