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bioRxiv · 10.1101/2025.08.07.669126

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

Beg, A. Z.·Liu, Z.·Chen, Y. T.·Talat, A.·Gowdy, G.·Miller, J. W.·Florek, L.·Dietrich, L.·Wang, C.·Lewis, I.·Wong, T. F. L.·Riquelme, S.·Prince, A. S.
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Abstract

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.

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Beg, A. Z., Liu, Z., Chen, Y. T., Talat, A., Gowdy, G., Miller, J. W., Florek, L., Dietrich, L., Wang, C., Lewis, I., Wong, T. F. L., Riquelme, S., Prince, A. S.. 2025-08-07. Sequestration of the phagocyte metabolite itaconate by P. aeruginosa RpoN promotes successful pulmonary infection. https://doi.org/10.1101/2025.08.07.669126

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