Disease relevance of csrA

• Pleiotropic regulation of central carbohydrate metabolism in Escherichia coli via the gene csrA [1].
• Regulation of Salmonella enterica serovar typhimurium invasion genes by csrA [2].
• Southern hybridization and nucleotide sequencing data have revealed apparent csrA homologs within several families of the alpha and gamma subdivisions of the proteobacteria (purple bacteria) and in the Gram-positive bacterium Bacillus subtilis [3].
• Global regulation in Erwinia species by Erwinia carotovora rsmA, a homologue of Escherichia coli csrA: repression of secondary metabolites, pathogenicity and hypersensitive reaction [4].
• Overexpresssion of a Legionella pneumophila homologue of the E. coli regulator csrA affects cell size, flagellation, and pigmentation [5].

High impact information on csrA

• Here, we performed comprehensive alanine-scanning mutagenesis on csrA of E. coli and tested the 58 resulting mutants for regulation of glycogen accumulation, motility, and biofilm formation [6].
• Thus, csrA exerts reciprocal effects on glycolysis versus gluconeogenesis and glycogen biosynthesis [1].
• Since the individual members of these isozyme pairs are allosterically regulated by different cellular metabolites, csrA is also capable of fine-tuning the allosteric regulation of glycolysis [1].
• Phosphoglucomutase and the gluconeogenic enzymes fructose-1,6-bisphosphatase and phosphoenolpyruvate synthetase were found to be under the negative control of csrA, and these enzyme activities were maximal during the early stationary phase of growth [1].
• In contrast, the expression of genes of the pentose phosphate pathway was weakly or negligibly affected by csrA [1].

Biological context of csrA

• The carbon storage regulator gene, csrA, encodes a factor which negatively modulates the expression of the glycogen biosynthetic gene glgC by enhancing the decay of its mRNA (M. Y. Liu, H. Yang, and T. Romeo, J. Bacteriol. 177:2663-2672, 1995) [7].
• Thus, csrA is now known to control all of the known glycogen biosynthetic genes (glg), which are located in three different operons [7].
• Genetic and physical mapping of the regulatory gene csrA on the Escherichia coli K-12 chromosome [8].
• Identification and molecular characterization of csrA, a pleiotropic gene from Escherichia coli that affects glycogen biosynthesis, gluconeogenesis, cell size, and surface properties [9].
• A plasmid clone of the native csrA gene strongly inhibited glycogen accumulation and affected the ability of cells to utilize certain carbon sources for growth [9].

Anatomical context of csrA

• We report here that epithelial cell invasion requires the serovar Typhimurium homologue of Escherichia coli csrA, which encodes a regulator that alters the stability of specific mRNA targets [2].
• These suppressed strains, however, did not recover the ability to invade cultured cells, indicating that the csrA-mediated loss of invasion cannot be attributed simply to poor growth and that the growth and invasion deficits of the csrA mutant arise from effects of CsrA on different targets [2].

Associations of csrA with chemical compounds

• Biofilm formation is not regulated by csrA, csrB or uvrY in a DeltapgaC mutant, which cannot synthesize PGA [10].
• Expression levels in the csrA mutant were approximately twofold higher when cells were grown in Luria broth (LB) and 5- to 10-fold higher when LB was supplemented with glucose [11].
• These effects of csrA were not mediated by increasing the regulatory enzymes of phenylalanine biosynthesis [12].
• A strain in which the aromatic (shikimate) pathway had been optimized produced twofold more phenylalanine when csrA was disrupted [12].

Other interactions of csrA

• The csrA gene did not affect glycogen debranching enzyme, which is now shown to be encoded by the gene glgX [7].
• Similarly, the expression of the degradative enzyme glycogen phosphorylase, which is encoded by glgY, was found to be negatively regulated via csrA in vivo [7].
• We investigated the influence of sigma(S) on cstA expression and found that a sigma(S) deficiency resulted in a threefold increase in cstA expression in wild-type and csrA mutant strains; however, CsrA-dependent regulation was retained [11].

References