The global regulator Crc orchestrates the metabolic robustness underlying oxidative stress resistance in Pseudomonas aeruginosa

Abstract

Summary The remarkable metabolic versatility of bacteria of the genus Pseudomonas enable their survival across very diverse environmental conditions. P. aeruginosa, one of the most relevant opportunistic pathogens, is a prime example of this adaptability. The interplay between regulatory networks that mediate these metabolic and physiological features is just starting to be explored in detail. Carbon catabolite repression, governed by the Crc protein, controls the availability of several enzymes and transporters involved in the assimilation of secondary carbon sources. Yet, the regulation exerted by Crc on redox metabolism of P. aeruginosa (hence, on the overall physiology) had hitherto been unexplored. In this study, we address the intimate connection between carbon catabolite repression and metabolic robustness of P. aeruginosa PAO1. In particular, we explored the interplay between oxidative stress, metabolic rearrangements in central carbon metabolism and the cellular redox state. By adopting a combination of quantitative physiology experiments, multiomic analyses, transcriptional patterns of key genes, measurement of metabolic activities in vitro and direct quantification of redox balances both in the wild‐type strain and in an isogenic Δcrc derivative, we demonstrate that Crc orchestrates the overall response of P. aeruginosa to oxidative stress via reshaping of the core metabolic architecture in this bacterium.

Engineering Native and Synthetic Pathways in Pseudomonas putida for the Production of Tailored Polyhydroxyalkanoates

“…Other regulation mechanisms, apart from the carbon source used and the C/N ratio in the medium, are probably relevant. [ 91 ] For instance, under low C/N ratios—where PHA degradation is favored—Crc directly inhibits expression of the pha cluster, and this effect is suppressed when high C/N ratios are reached [ 82,92 ] (Figure 1). A subset of PTS proteins, i.e., PtsP, PtsO, and PtsN, has been proposed to be involved in regulating the C/N balance and controlling PHA production in P. putida .…”

Biochemistry, genetics and biotechnology of glycerol utilization in Pseudomonas species

“…Note the bimodal nature of the distribution of times of metabolic response in glycerol cultures. As indicated in the inset plots, the Bac Light ™ RedoxSensor ™ Green ( RSG ) reagent in combination with flow cytometry enables the identification of different bacterial populations by their level of metabolic activity (Corona et al., ). The grey rectangle in each histogram plot identifies the region considered negative for the RSG fluorescence signal.…”

Metabolic manipulation by Pseudomonas fluorescens: a powerful stratagem against oxidative and metal stress

“…To combat this situation, P. fluorescens elaborates a detoxification strategy reliant on the conversion of the divalent metal into calcite, a crystalline insoluble calcium carbonate. To achieve this metabolic feat, the microbe initially immobilizes the Ca in an epicellular organic matrix where the presence of the up-regulated carbonic anhydrase enables the controlled formation of calcite where the toxic divalent metal is locked [62][63][64][65].…”