Infectious particle identity determines dissemination and disease outcome for the inhaled human fungal pathogen Cryptococcus
Fig 2
Spores produced by avirulent yeast strains cause uniformly fatal cryptococcal meningoencephalitis in a mouse intranasal model of infection.
(A) Survival plot of mice (8 mice per group) infected intranasally with 2.5x105 B-3502 yeast (triangles) or 2.5x105 B-3501 yeast (circles), 2.5x105 yeast as a 1:1 mixture of B-3502 and B-3501 (B-3502 + B-3501; diamonds), or 2.5x105 spores derived from a cross between B-3502 and B-3501 (B-3502 x B-3501; squares). (B) Fungal burdens (as colony-forming units per gram of tissue plus 1) in the lung (dark gray bars), kidney (light gray bars), and brain (striped bars) at 3, 6, 14, 21, and 100 days after intranasal infection of mice with 2.5x105 yeast as a 1:1 mixture of B-3502 and B-3501. Circles represent individual mice (3 mice per time point). (C) Fungal burdens (as colony-forming units per gram of tissue plus 1) in the lung (dark gray bars), kidney (light gray bars) and brain (striped bars) at 3, 6, 14, 21 days and at endpoint after intranasal infection of mice with 2.5x105 spores derived from a cross between B-3502 and B-3501. Circles represent individual mice (3 mice per time-point). (D) Survival curves of 6 mice infected by intratracheal instillation with 1x105 spores derived from a B-3502 x B-3501 cross (squares) or 5 mice infected with 1x105 recombinant yeast (generated by germination of spores derived from a B-3502 x B-3501 cross into yeast; triangles). (E) Survival plots of mice infected by tail-vein injection with 1x106 yeast in a 1:1 mixture (B-3502 + B-3501; triangles) or 1x106 spores derived from a B-3502 x B-3501 cross (squares) (5 mice per group). Data in A, B, and C are representative of independent biological replicates (see Materials and Methods), and data in D and E are derived from single experiments.