The genus Pseudomonas is an important group of microorganisms that occupy a wide variety of habitats including soil , the rhizosphere , food  and mammalian hosts . Some species are important plant or human pathogens, whereas others are involved in processes such as bioremediation , biocontrol [6–8], nutrient cycling  or biotechnological processes . A key aspect of the lifestyle of Pseudomonads is their ability to adapt, grow and compete in a wide variety of habitats. Thus, Pseudomonads require great flexibility in controlling their diverse array of metabolic pathways and, like most microorganisms, have global regulatory systems that ensure that the best nutrient source is utilised and almost depleted before less favoured nutrient sources are exploited [11–13].
Pseudomonads favour the utilisation of organic acids, particularly tricarboxylic acid (TCA) cycle intermediates, and amino acids over various other carbon sources such as carbohydrates or hydrocarbons . This is in contrast to the majority of well-studied Enterobacteriaceae and Firmicutes, which favour glucose and use a system known as carbon catabolite repression (CCR) or catabolite repression control (CRC) to regulate carbon utilisation. The mechanism of CCR in Enterobacteriaceae and Firmicutes centres on a protein phosphorylation cascade and also involves transcriptional regulation mediated through cyclic AMP (cAMP) binding to the cAMP receptor protein (Crp) (for review see [11, 12]). Although Pseudomonads possess a Crp homolog, Vfr, this protein is not involved in carbon source regulation, at least in P. aeruginosa PAO1 . In fact, the CRC mechanism used by Pseudomonads to regulate carbon source utilisation is fundamentally different to CCR of Enterobacteriaceae and Firmicutes.
A central mediator of CRC is the Crc protein, which acts as a post-transcriptional regulator of target genes . The post-transcriptional action of Crc relies on the binding of Crc to an unpaired A-rich motif in the 5'-end of a target mRNA causing inhibition of the initiation of translation [17, 18]. It is still not fully understood how Crc activity is regulated in different Pseudomonas species, nor whether a common unified regulatory system is employed. In P. aeruginosa, activity is regulated by small RNA, CrcZ, which has five A-rich motifs, that binds to the Crc protein and sequesters it . Levels of the CrcZ sRNA, in turn, are regulated by a two-component system (CbrA/CbrB) and by RpoN. Interestingly, CbrAB and NtrBC form a network to control the C/N balance in both P. aeruginosa and P. fluorescens [19–21]. Furthermore, the presence of a readily available nitrogen source enhances the magnitude of CRC , two observations that are suggestive of a link between regulatory systems controlling C and N utilisation. Although the crcZ gene is present in other Pseudomonads, its role in regulating CRC outside of P. aeruginosa has not yet been demonstrated. Indeed, in P. putida, crc mRNA and Crc protein levels are higher under conditions where CRC is active, a phenomenon not observed in P. aeruginosa, suggesting that an alternative system of regulating CRC may be used in this species [23, 24].
Much of what is known about CRC comes from work on mutants lacking the Crc protein in P. aeruginosa and P. putida. Initially, the key work in identifying the CRC system came from the isolation and characterisation of a P. aeruginosa crc mutant . In this mutant, the succinate-mediated catabolite repression control (CRC) of glucose and mannitol transport and Entner-Doudoroff pathway enzymes was alleviated, thereby establishing the importance of Crc. More recently, the role of Crc has been examined on a global scale in P. putida  and P. aeruginosa  by carrying out transcriptome and proteome analyses of crc mutants. No less than 134 targets in P. putida and 65 targets in P. aeruginosa were differentially altered in expression in rich media as a result of a crc mutation. This indicates that crc is an important global regulator that superimposes an additional layer of regulation over many metabolic pathways that are otherwise regulated locally by specific regulatory elements that control only one or a few genes. The global analyses of the P. putida and P. aeruginosa crc mutants indicates that CRC is responsible for the hierarchical assimilation of amino acids from rich media, with pathways required for assimilation of valine, isoleucine, leucine, tyrosine, phenylalanine, threonine, glycine and serine inhibited by Crc [26, 27]. Additionally, the P. aeruginosa crc mutation was shown to alter the expression of targets with roles in anaerobic respiration, antibiotic resistance and virulence . Recent work on a crc mutant of P. putida DOT-T1E established that Crc is not involved in the induction of pathways for nutrient utilisation since the mutant grows on the same range of carbon and nitrogen sources as the wild type strain . This is in contrast to the E. coli CCR system where the cAMP-CRP complex is responsible for the induction of genes for utilisation of less favoured carbon sources such as lactose .
The role of CRC in regulating linear and aromatic hydrocarbon utilisation pathways in P. putida has received a lot of attention because of the potential implications of CRC on bioremediation processes. The utilisation of alkanes and a wide range of aromatic compounds including benzene and toluene are subject to CRC in P. putida [16, 30–34]. Indeed Crc mediated post-transcriptional control of the pheA and pheB toluene degradation genes , the benR activator of benzene degradation , the alkS activator of alkane degradation , the xylR activator of the TOL genes and xylB (benzyl alcohol dehydrogenase)  and the bkdR activator of branched-chain keto acid dehydrogenase  has been demonstrated. The Crc protein is known to bind in vitro to mRNAs of the PU, PM, PS1, PR1, promoters and mRNAs of the xylMABN (and weakly to xylL and xylQ) genes of the pWW0 toluene degradation plasmid in P. putida indicating that these targets may also be regulated by directly by Crc . Besides the role that CRC plays in the bioremediation activities of P. putida, little else is known about the control that CRC imposes on the ecological functions of Pseudomonads other than for virulence-associated functions in Pseudomonas aeruginosa. A crc mutant of P. aeruginosa PA14 was defective in biofilm formation and type IV pilus-mediated twitching motility . and a crc mutant of P. aeruginosa PAO1 displayed increased susceptibility to some antibiotics as well as defects in type III secretion, motility and expression of quorum sensing-regulated virulence factors . Given the range of ecological functions that Pseudomonas may perform there is great scope for Crc to be a significant regulator beyond the realm of primary metabolism. For instance, glucose metabolism is subject to CRC and gluconate is a product of glucose metabolism. Gluconate itself is linked to phosphate solubilisation  and biocontrol  and there is a link between the ability to produce gluconate and the levels of antimicrobial compounds produced such as 2,4-diacetylphloroglucinol and pyoluteorin . Additionally, recent evidence indicates that there is a link between primary metabolism and secondary metabolism controlled by the GacS/Rsm system . This suggests that there is great potential for CRC to interact with other regulatory networks, at least indirectly, and it is therefore a high priority to better understand the Crc regulon.
Based on the size of the Crc product and the proposed mechanism of action, it is thought that Crc binding must occur within -70 to +16 bp relative to the origin of translation . There remain, however, very few known direct targets of Crc: only benR , alkS , xylR and xylB  mRNAs from P. putida and amiE mRNA  (product of the amidase gene amiE), in P. aeruginosa have been demonstrated to bind Crc. To extend the number of direct targets known, we carried out a bioinformatic analysis using genome information from sequenced Pseudomonas strains. By identifying the specific targets in pathways that are known to be regulated by CRC, it will be possible to determine precisely how different Pseudomonads control nutrient uptake and utilisation. Furthermore, the analysis is expected to identify new pathways and processes, not previously known to be CRC-regulated. A better understanding of how Pseudomonas species use CRC will enhance knowledge of the ecology of these bacteria and will facilitate efforts to exploit the metabolic capacity of these bacteria in industrial and environmental microbiology.