Sequestration of the phagocyte metabolite itaconate by P. aeruginosa RpoN promotes successful pulmonary infection

AbstractThe phagocyte immunometabolite itaconate, normally toxic to bacteria, functions as a signal to stimulate the adaptation of the pulmonary pathogen Pseudomonas aeruginosa to the lung. Itaconate is actively transported into P. aeruginosa where it induces {sigma}54 rpoN expression and co-valently binds cysteine residues on RpoN. RpoN not only functions as a sink to limit itaconate toxicity but S- itaconated RpoN promotes increased utilization of the Entner Doudoroff pathway, optimizing bacterial metabolism in the setting of inflammation. S-itaconation of RpoN directs a global metabolic response that fuels pulmonary infection.