Defects in intracellular trafficking of fungal cell wall synthases lead to aberrant host immune recognition
Fig 9
Mar1 is required for full virulence.
(A) The mar1Δ strain is attenuated in the C57BL/6 mouse background. For each strain, 9–10 C57BL/6 mice were inoculated with 1 x 105 cells, monitored daily for signs of infection, and sacrificed at predetermined clinical endpoints that predict mortality. Statistical significance was determined by log-rank test with Bonferroni correction: p < 0.0001, mar1Δ vs. WT; p < 0.001, mar1Δ vs. mar1Δ + MAR1; not significant. (B) There are minimal mar1Δ cells in the lungs of infected mice at early time points. Colony forming units (CFUs) were determined from lung homogenates from 5 mice per strain at days 1 and 4 post inoculation. *, p < 0.05 mar1Δ vs. WT; **, p < 0.01 mar1Δ vs. mar1Δ + MAR1 as determined by one-way ANOVA with Tukey’s multiple comparisons test. (C) The mar1Δ strain is avirulent in the BALB/c mouse background. For each strain, 9–10 BALB/c mice were inoculated with 1 x 105 cells, monitored daily, and sacrificed as described above. Statistical significance was determined by log-rank test with Bonferroni correction: p < 0.0001, mar1Δ vs. WT/mar1Δ + MAR1; not significant, WT vs. mar1Δ + MAR1. (D) The mar1Δ strain is not completely cleared from BALB/c mice despite mouse survival. CFUs were determined from lung and brain homogenates from mar1Δ infected mice post-mortem. Ratio indicates number of mice represented.