Florek, L. | bioRxiv Science

bioRxiv2025

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.

microbiology↗

bioRxiv2020

Interactions with stromal cells promote a more oxidized cancer cell redox state in pancreatic tumors

Access to electron acceptors supports oxidized biomass synthesis and can be limiting for cancer cell proliferation, but how cancer cells overcome this limitation in tumors is incompletely understood. Non-transformed cells in tumors can help cancer cells overcome metabolic limitations, particularly in pancreatic cancer, where pancreatic stellate cells (PSCs) promote cancer cell proliferation and tumor growth. However, whether PSCs affect the redox state of cancer cells is not known. By taking advantage of the endogenous fluorescence properties of reduced nicotinamide adenine dinucleotide cofactors and oxidized flavin adenine dinucleotide, we use optical imaging to assess the redox state of pancreatic cancer cells and PSCs and find that the redox state of cancer cells is more reduced while the redox state of PSCs is more oxidized. Direct interactions between PSCs and cancer cells promote a more oxidized state in cancer cells, suggesting that metabolic interactions between cancer cells and PSCs is a mechanism to overcome the redox limitations of cell proliferation in pancreatic cancer.

cancer biology↗