Hierarchical management of carbon sources is regulated similarly by the CbrA/B systems in Pseudomonas aeruginosa and Pseudomonas putida

Abstract

The CbrA/B system in pseudomonads is involved in the utilization of carbon sources and carbon catabolite repression (CCR) through the activation of the small RNAs crcZ in Pseudomonas aeruginosa, and crcZ and crcY in Pseudomonas putida. Interestingly, previous works reported that the CbrA/B system activity in P. aeruginosa PAO1 and P. putida KT2442 responded differently to the presence of different carbon sources, thus raising the question of the exact nature of the signal(s) detected by CbrA. Here, we demonstrated that the CbrA/B/CrcZ(Y) signal transduction pathway is similarly activated in the two Pseudomonas species. We show that the CbrA sensor kinase is fully interchangeable between the two species and, moreover, responds similarly to the presence of different carbon sources. In addition, a metabolomics analysis supported the hypothesis that CCR responds to the internal energy status of the cell, as the internal carbon/nitrogen ratio seems to determine CCR and non-CCR conditions. The strong difference found in the 2-oxoglutarate/glutamine ratio between CCR and non-CCR conditions points to the close relationship between carbon and nitrogen availability, or the relationship between the CbrA/B and NtrB/C systems, suggesting that both regulatory systems sense the same sort or interrelated signal.

Role of the Transporter-Like Sensor Kinase CbrA in Histidine Uptake and Signal Transduction

“…Given the weight of support for the hypothesis that CbrA is directly involved in the transport of histidine, combined with the fact that CbrA is a histidine kinase with a known role in signal transduction (26,27,30,31), the second part of our study explored the connection between signal transduction and transport. Several lines of evidence suggest that the two are coupled, as found in the Saccharomyces cerevisiae Gap1 amino acid transceptor (47).…”

“…Interestingly, bacterial genome sequencing has revealed the presence of a unique type of SK, which has a typical autokinase domain fused to a transporter-like polypeptide at the N terminus (8,25). A well-known example is the CbrA sensor kinase in Pseudomonas (26)(27)(28)(29)(30). The N-terminal portion is predicted to contain 14 transmembrane segments and shows a high degree of similarity with the Na ϩ /proline symporter PutP, which belongs to the sodium/solute symporter family (SSSF; Transporter Classification Database classification 2.A.21).…”

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

“…[Color figure can be viewed at wileyonlinelibrary.com] both at the level of mRNA and protein when comparing the Δcrc mutant against the wild-type strain. We gathered data both from RNA sequencing and isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics (Reales-Calderón et al, 2015b;Corona et al, 2018) in exponentially-growing LB medium cultures, in which the Crc-dependent catabolite repression is maximal (Valentini et al, 2014), for P. aeruginosa PAO1 and its Δcrc derivative (Fig. 5).…”

The Crc/CrcZ‐CrcY global regulatory system helps the integration of gluconeogenic and glycolytic metabolism in Pseudomonas putida

“…The transcription of crcZ and crcY occurs from RpoN-dependent promoters (PcrcZ and PcrcY respectively) that rely on the CbrA/CbrB two-component regulatory system, which in turn responds to an as yet unclear signal (Sonnleitner et al, 2009;Moreno et al, 2012;García-Mauriño et al, 2013). The activity of the promoters PcrcZ and PcrcY is greatest in cells growing at the expense of a poor carbon source such as oxaloacetate, and lowest when cells are cultivated in a complete medium such as LB; when succinate or glucose are provided, the activity of these promoters is intermediate (Valentini et al, 2014).…”

“…In P. aeruginosa, succinate elicits a strong CCR effect and is preferred over glucose (MacGregor et al, 1992;Hester et al, 2000). In fact, PcrcZ activity in cells using succinate is about half that seen in cells using glucose, suggesting that the Crc/Hfq-dependent CCR is higher in succinateusing cells (Valentini et al, 2014). In P. putida, however, succinate appears to be a weak repressor of nonpreferred substrates such as alkanes and branched-chain amino acids (Yuste et al, 1998;Hester et al, 2000), and the joint levels of CrcZ and CrcY in cells growing exponentially at the expense of succinate are rather high.…”