Fig. 3

Azoles have differing efficacy in larvae lacking functional phagocytes. 2 dpf larvae were injected with A. fumigatus spores (TBK1.1), antifungal drugs or vehicle control were added to the larval water, and survival was tracked. Data represent three pooled replicates. P values and hazard ratios were calculated by Cox proportional hazard analysis. A. Neutrophil-defective mpx:rac2D57N or control mpx:rac2WT larvae were infected and treated with vehicle control, 2.5 µg/ml posaconazole, 1 µg/ml itraconazole, 0.5 µg/ml isavuconazole, or 1 µg/ml voriconazole. Average injection CFUs: mpx:rac2WT = 15, mpx:rac2D57N = 21. B. Wild-type or neutrophil-defective mpx:rac2D57N embryos were injected with Cas9 and gRNAs targeting irf8 or luciferase-targeting controls. After infection, larvae were treated with vehicle control, 2.5 µg/ml posaconazole, 0.5 µg/ml isavuconazole, or 1 µg/ml voriconazole. Average injection CFUs: WT+luc = 58, WT+irf8 = 117, mpx:rac2D57N+luc = 73, mpx:rac2D57N+irf8 = 80. C. Neutrophil-defective mpx:rac2D57N larvae homozygous for a stable irf8 loss of function mutation were infected and treated with vehicle control, 2.5 µg/ml posaconazole, 0.5 µg/ml isavuconazole, or 1 µg/ml voriconazole. Data from sibling larvae from this experiment are shown in Supp Fig S4. Average injection CFUs = 34.