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

Abstract The phagocyte immunometabolite itaconate, normally toxic to bacteria, functions as a signal to stimulate the adaptation of the pulmonary pathogen Pseudomonas aeruginos a to the lung. Itaconate is actively transported into P. aeruginosa where it induces σ 54 rp oN 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.