Fig. 3: C. albicans retains its virulence potential in a mouse model of systemic candidiasis even in the absence of hyphal elongation due to repression or deletion of EED1 accompanied by higher organ fungal loads.
Mice were intravenously infected with the following doses: a Low doses of 1 × 103 or 1 × 104 CFU/g body weight of WT (SC5314) or eed1Δ/Δ mutant. One experiment, n = 8 mice per group (except for WT 1 × 103, n = 7). b A high dose of 1.25 × 105 CFU/g body weight of WT (THE1-CIp10) or t-EED1 in the presence of doxycycline. One experiment, n = 10 mice per group. c An intermediate dose of 2.5 × 104 CFU/g body weight with WT (THE1-CIp10) or t-EED1 in the presence (+) or absence (−) of doxycycline. One experiment, n = 10 mice per group. a–c Survival was monitored over a course of 20 or 21 days and is shown as Kaplan–Meyer curve. Survival curves were compared using the two-sided Log-rank (Mantel–Cox) test, p-values are shown in the graph. d Representative images of PAS stained histological cross sections of kidneys from moribund mice infected with 2.5 × 104 CFU/g body weight with WT (THE1-CIp10) or t-EED1 in the presence (+) or absence (−) of doxycycline. Fungal cells are stained purple. Scale bar represents 20 µm and applies to all images. e Organ fungal loads of mice infected with 2.5 × 104 CFU/g body weight with WT (THE1-CIp10) or t-EED1 in the presence (+) or absence (−) of doxycycline. Shown is the number of CFU per gram organ from mice sacrificed 6, 24, 48 and 72 h post infection and from moribund mice (mor). Data are shown as median with interquartile range. Dashed gray lines indicate limit of detection. Moribund: one experiment, n = 10; Kidney: two independent experiments n = 10. Liver, spleen, brain: three independent experiments, n = 15. Two-sided Mann–Whitney test, asterisks indicate significant changes of t-EED1+ compared to WT+ groups at the indicated time points. *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001.
