Dataset Information

Regulation of glycerol metabolism in Pseudomonas aeruginosa: characterization of the glpR repressor gene.

ABSTRACT: The operons of the glp regulon encoding the glycerol metabolic enzymes of Pseudomonas aeruginosa were hitherto believed to be positively regulated by the product of the glpR regulatory gene. During nucleotide sequence analysis of the region located upstream of the previously characterized glpD gene, encoding sn-glycerol-3-phosphate dehydrogenase, an open reading frame (glpR) was identified which encodes a protein of 251 amino acids that is 59% identical to the Glp repressor from Escherichia coli and could be expressed as a 28-kDa protein in a T7 expression system. Inactivation of chromosomal glpR by gene replacement resulted in constitutive expression of glycerol transport activity and glpD activity. These activities were strongly repressed after introduction of a multicopy plasmid containing the glpR gene; the same plasmid also efficiently repressed expression of a glpT-lacZ+ transcriptional fusion in an E. coli glpR mutant. Analysis of the glpD and glpF upstream region identified conserved palindromic sequences which were 70% identical to the E. coli glp operator consensus sequence. The results suggest that the operons of the glp regulon in P. aeruginosa are negatively regulated by the action of a glp repressor.

SUBMITTER: Schweizer HP

PROVIDER: S-EPMC178319 | biostudies-other | 1996 Sep

REPOSITORIES: biostudies-other

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Regulation of glycerol metabolism in Pseudomonas aeruginosa: characterization of the glpR repressor gene.

Schweizer H P HP Po C C

Journal of bacteriology 19960901 17

The operons of the glp regulon encoding the glycerol metabolic enzymes of Pseudomonas aeruginosa were hitherto believed to be positively regulated by the product of the glpR regulatory gene. During nucleotide sequence analysis of the region located upstream of the previously characterized glpD gene, encoding sn-glycerol-3-phosphate dehydrogenase, an open reading frame (glpR) was identified which encodes a protein of 251 amino acids that is 59% identical to the Glp repressor from Escherichia coli ...[more]

PMID: 8752340

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Project description:Pseudomonas aeruginosa is an important opportunistic pathogen that is lethal to cystic fibrosis (CF) patients. Glycerol generated during the degradation of phosphatidylcholine, the major lung surfactant in CF patients, could be utilized by P. aeruginosa. Previous studies have indicated that metabolism of glycerol by this bacterium contributes to its adaptation to and persistence in the CF lung environment. Here, we investigated the metabolic mechanisms of glycerol and its important metabolic intermediate glycerol 3-phosphate (G3P) in P. aeruginosa PAO1. We found that G3P homeostasis plays an important role in the growth and virulence factor production of P. aeruginosa PAO1. The G3P accumulation caused by the mutation of G3P dehydrogenase (GlpD) and exogenous glycerol led to impaired growth and reductions in pyocyanin synthesis, motilities, tolerance to oxidative stress, and resistance to kanamycin. Transcriptomic analysis indicates that the growth retardation caused by G3P stress is associated with reduced glycolysis and adenosine triphosphate (ATP) generation. Furthermore, two haloacid dehalogenase-like phosphatases (PA0562 and PA3172) that play roles in the dephosphorylation of G3P in strain PAO1 were identified, and their enzymatic properties were characterized. Our findings reveal the importance of G3P homeostasis and indicate that GlpD, the key enzyme for G3P catabolism, is a potential therapeutic target for the prevention and treatment of infections by this pathogen. IMPORTANCE In view of the intrinsic resistance of Pseudomonas aeruginosa to antibiotics and its potential to acquire resistance to current antibiotics, there is an urgent need to develop novel therapeutic options for the treatment of infections caused by this bacterium. Bacterial metabolic pathways have recently become a focus of interest as potential targets for the development of new antibiotics. In this study, we describe the mechanism of glycerol utilization in P. aeruginosa PAO1, which is an available carbon source in the lung environment. Our results reveal that the homeostasis of glycerol 3-phosphate (G3P), a pivotal intermediate in glycerol catabolism, is important for the growth and virulence factor production of P. aeruginosa PAO1. The mutation of G3P dehydrogenase (GlpD) and the addition of glycerol were found to reduce the tolerance of P. aeruginosa PAO1 to oxidative stress and to kanamycin. The findings highlight the importance of G3P homeostasis and suggest that GlpD is a potential drug target for the treatment of P. aeruginosa infections.

Dataset Information

Regulation of glycerol metabolism in Pseudomonas aeruginosa: characterization of the glpR repressor gene.

Publications

Regulation of glycerol metabolism in Pseudomonas aeruginosa: characterization of the glpR repressor gene.

Similar Datasets

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