Author:
Parada-Kusz Margarita,Clatworthy Anne E.,Goering Emily R.,Blackwood Stephanie M.,Salm Elizabeth J.,Choi Catherine,Combs Senya,Lee Jenny S. W.,Rodriguez-Osorio Carlos,Tomita Susumu,Hung Deborah T.
Abstract
SUMMARYBacterial infection involves a complex interaction between the pathogen and host where the outcome of infection is not solely determined by pathogen eradication. To identify small molecules that promote host survival by altering the host-pathogen dynamic, we conducted anin vivochemical screen using zebrafish embryos and found that treatment with 3-hydroxy-kynurenine protects from lethal gram-negative bacterial infection. 3-hydroxy-kynurenine, a metabolite produced through host tryptophan metabolism, has no direct antibacterial activity but enhances host survival by restricting bacterial expansion in macrophages by targeting kainate-sensitive glutamate receptors. These findings reveal new mechanisms by which tryptophan metabolism and kainate-sensitive glutamate receptors function and interact to modulate immunity, with significant implications for the coordination between the immune and nervous systems in pathological conditions.
Publisher
Cold Spring Harbor Laboratory