Fig 1

Fig 1 Endogenous production of 3-HK by Kmo is required for defense against S. Typhimuriuminfection.

(A) The endogenous eukaryotic kynurenine pathway for tryptophan degradation that generates 3-HK (Ro61-8048 is a Kmo inhibitor). (B) Homozygous kmo mutant larvae infected 3 dpf with S. Typhimurium (CFU = 255 + /- 20) are sensitized to infection compared to their wildtype (WT) siblings. Sensitivity to infection is rescued by exogenous addition of 100µM 3-HK (N = 8 larvae/group; *p < 0.05, ***p < 0.001. Log rank test). (C) Larvae (3 dpf) infected with S. Typhimurium (CFU = 586 + /- 165) and treated with the Kmo inhibitor Ro61-8048 are impaired in their ability to control total organism bacterial burden as early as 4 hours post infection (HPI) compared to vehicle DMSO control. Data are representative of 3 experiments. CFU were quantified from individual larvae at indicated HPI; Unpaired t-test, *p < 0.05, **p < 0.01. dpf, days post fertilization; CFU, colony forming unit.