Contextual Flexibility in Pseudomonas aeruginosa Central Carbon Metabolism during Growth in Single Carbon Sources.
American Society for Microbiology
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Dolan, S., Kohlstedt, M., Trigg, S., Vallejo Ramirez, P., Kaminski, C., Wittmann, C., & Welch, M. (2020). Contextual Flexibility in Pseudomonas aeruginosa Central Carbon Metabolism during Growth in Single Carbon Sources.. mBio, 11 (2)https://doi.org/10.1128/mbio.02684-19
Pseudomonas aeruginosa is an opportunistic human pathogen, particularly noted for causing infections in the lungs of people with cystic fibrosis (CF). Previous studies have shown that the gene expression profile of P. aeruginosa appears to converge towards a common metabolic program as the organism adapts to the CF airway environment. However, at a systems level, we still have only a limited understanding of how these transcriptional changes impact on metabolic flux. To address this, we analysed the transcriptome, proteome and fluxome of P. aeruginosa grown on glycerol or acetate. These carbon sources were chosen because they are the primary breakdown products of airway surfactant, phosphatidylcholine, which is known to be a major carbon source for P. aeruginosa in the CF airways. We show that the flux of carbon through central metabolism is radically different on each carbon source. For example, the newly-recognised EDEMP cycle plays an important role in supplying NADPH during growth on glycerol. By contrast, the EDEMP cycle is attenuated during growth on acetate, and instead, NADPH is primarily supplied by the isocitrate dehydrogenase(s)-catalyzed reaction. Perhaps more importantly, our proteomic and transcriptomic analyses reveal a global remodelling of gene expression during growth on the different carbon sources, with unanticipated impacts on aerobic denitrification, electron transport chain architecture, and the redox economy of the cell. Collectively, these data highlight the remarkable metabolic plasticity of P. aeruginosa; a plasticity which allows the organism to seamlessly segue between different carbon sources, maximising the energetic yield from each.
Pseudomonas aeruginosa, Carbon, Acetates, Glucose, Gene Expression Profiling, Proteomics, Adaptation, Physiological, Glycolysis, Pentose Phosphate Pathway
This work was funded by a grant (BB/M019411/1) awarded to MW from the BBSRC. ST was supported by a BBSRC DTP studentship. CFK acknowledges funding from the UK Engineering and Physical Sciences Research Council, EPSRC (grants EP/L015889/1 and EP/H018301/1), the Wellcome Trust (grants 3-3249/Z/16/Z and 089703/Z/09/Z) and the UK Medical Research. 678 Council, MRC (grants MR/K015850/1 and MR/K02292X/1).
Wellcome Trust (089703/Z/09/Z)
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External DOI: https://doi.org/10.1128/mbio.02684-19
This record's URL: https://www.repository.cam.ac.uk/handle/1810/302057
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