Carbon/nitrogen sensing and downstream metabolic regulation in Pseudomonas aeruginosa
Sakowitz, Sara R.
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The gram-negative, gamma proteobacterium Pseudomonas aeruginosa demonstrates substantial metabolic flexibility, allowing it to survive and thrive in diverse environments. Indeed, its ability to carefully maintain a buffered intracellular oxidoreduction state permits it to maintain structural and functional stability in the face of both nutrient-poor and nutrient-rich conditions. It is clear that metabolism is simply central to the existence of this microbe, yet knowledge of the genetics and biochemistry underlying this deeply intricate world of metabolic regulation is fundamentally incomplete. Two critical metabolites, alpha-ketoglutarate and glutamine, appear at the intersection of carbon and nitrogen metabolism, and may represent the status of Pseudomonas’ intracellular carbon or nitrogen pools. However, the coordination of carbon and nitrogen assimilation, whether through PII proteins, the Ntr regulatory cascade, the CbrAB regulatory system, or the PTS-NTR system, as well as these pathways’ cross-talk and ability to control downstream processes based on nutrient availability, still remain to be elucidated. Further, a more comprehensive understanding of P. aeruginosa’s metabolic regulation could be significant for the development of new therapies that specifically target critical biochemical pathways involved in the metabolism of this organism and offer new hope to patients suffering from P. aeruginosa infections in the clinic. Thus, this review considers how, when, and why carbon and nitrogen metabolism may be regulated in Pseudomonas aeruginosa, and proposes there may be more interaction and cross-regulation between these two seemingly divergent metabolic arms than originally thought.