Regulation of carbohydrate degradation pathways in Pseudomonas involves a versatile set of transcriptional regulators

Abstract

Bacteria of the genus Pseudomonas are widespread in nature. In the last decades, members of this genus, especially Pseudomonas aeruginosa and Pseudomonas putida, have acquired great interest because of their interactions with higher organisms. Pseudomonas aeruginosa is an opportunistic pathogen that colonizes the lung of cystic fibrosis patients, while P. putida is a soil bacterium able to establish a positive interaction with the plant rhizosphere. Members of Pseudomonas genus have a robust metabolism for amino acids and organic acids as well as aromatic compounds; however, these microbes metabolize a very limited number of sugars. Interestingly, they have three-pronged metabolic system to generate 6-phosphogluconate from glucose suggesting an adaptation to efficiently consume this sugar. This review focuses on the description of the regulatory network of glucose utilization in Pseudomonas, highlighting the differences between P. putida and P. aeruginosa. Most interestingly, It is highlighted a functional link between glucose assimilation and exotoxin A production in P. aeruginosa. The physiological relevance of this connection remains unclear, and it needs to be established whether a similar relationship is also found in other bacteria.

Figure 1

Schematic representation of the glucose metabolism in Pseudomonas and Escherichia coli as deduced from gene annotations and functional analysis in the wild‐type strain. Genes whose expression is controlled by the regulators described in this review are boxed in different colours.

Figure 2

Genetic organization of genes encoding enzymes of carbohydrate degradation pathways and exotoxin A in different Pseudomonas strains. The genes that were found to be regulated are boxed, and the corresponding regulator y system is provided over each block of genes.

Figure 3

Schematic view of the concerted regulation of gene expression involved in glucose metabolism. A. Schematic view of the three internalization routes. B. The functional interconnectivity of the five regulatory mechanisms. C. Summary of information flow from effectors to regulated genes. The − and + symbols indicate repression or activation of gene expression respectively.

Figure 4

The mechanisms’ action of transcriptional regulators involved in the regulation of carbohydrate catabolism pathways. The − and + symbols indicate repression or activation of gene expression respectively. A. Effector‐mediated derepression (HexR and PtxS). B. Transcription activation by regulator binding to promotor (PtxR). C. Effector‐mediated dissolution PtxR/PtxS complex without binding (PtxR and PtxS). D. Effector‐mediated dissolution of PtxR/PtxS complex with binding (PtxR and PtxS). E. Effector‐mediated derepression of GntR. F. Effector‐mediated GltR/GtrS two component system.

Figure 5

Homology models of NH ₂ or COOH‐terminal extensions corresponding to the DNA‐binding domains of regulators involved in carbohydrate catabolism pathways. The amino acids involved in the interaction of the regulator with DNA are highlighted.

Figure 6

Homology model of the GltR regulator involved in the regulation of carbohydrate catabolism pathways and exotoxin A expression. The model has been generated using the I‐TASSER server software using the RegX3 from Mycobacterium tuberculosis structure as a template (PDB: 2OQR). The phosphoryl group accepting aspartate residue (D56) in the receiver domain is highlighted. The green part of the structure indicates the response regulator receiver domain, and the yellow part indicates the OMP/phoB type DNA‐binding domain.