Metabolic reprogramming of macrophages exposed to Pseudomonas aeruginosa biofilm

To better understand the molecular processes by which P. aeruginosa biofilms interfere with human macrophage immune responses, we have undertaken NMR-based metabolomics studies of activated and resting macrophages. The studies aim to probe the metabolic reprogramming of these immune cells as result of exposure to secreted molecules produced by P. aeruginosa biofilms, using an in vitro host-pathogen co-culture model.   Herein, we present our most recent NMR-based metabolomics results demonstrating the presence of a significant metabolic shift between different macrophage phenotypes. This metabolic phenotyping is correlated with fluorescence-activated cell sorting (FACS) analysis which has been employed to characterize the relationship between metabolic profiles and macrophage immunomodulation (i.e. macrophage polarization into pro- or anti-inflammatory M1 or M2 subpopulations, respectively), resulting from macrophage exposure to secreted molecules from co-culture P. aeruginosa biofilms.

Biosketch

Dr. Copié is a Professor of Biochemistry and Director of Montana State University’s NMR center. Dr. Copié has received extensive experience and training in biological NMR, and has established a research program involving protein structural biology and the global profiling of small molecule metabolites (i.e. metabolomics). Our metabolomics research interests focus on understanding how bacterial pathogens manipulate host metabolism to evade host immune defenses, and how such metabolic reprogramming contributes to non-healing, chronic wounds in humans. Our lab is also interested in identifying specific metabolic strategies that enable hyperthermophilic microorganisms to grow and thrive in extreme environments including arsenic-contaminated soils.

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