The Regulation of Glutamine Transport and Glutamine Synthetase in Salmonella typhimurium

Betteridge, P. R.; Ayling, P. D.

doi:10.1099/00221287-95-2-324

Cited by 19 publications

(13 citation statements)

References 20 publications

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“…Expression of glnHPQ requires nitrogen limitation but not glutamine (18,98,168). Nitrogen limitation increases the production of glnHPQ transcripts five-to ninefold (176).…”

Section: -Dependent Amino Acid Transport Systemsmentioning

confidence: 99%

Metabolic Context and Possible Physiological Themes of ς⁵⁴-Dependent Genes inEscherichia coli

Reitzer

Schneider

2001

Microbiol Mol Biol Rev

250

300

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SUMMARY ς54 has several features that distinguish it from other sigma factors in Escherichia coli: it is not homologous to other ς subunits, ς54-dependent expression absolutely requires an activator, and the activator binding sites can be far from the transcription start site. A rationale for these properties has not been readily apparent, in part because of an inability to assign a common physiological function for ς54-dependent genes. Surveys of ς54-dependent genes from a variety of organisms suggest that the products of these genes are often involved in nitrogen assimilation; however, many are not. Such broad surveys inevitably remove the ς54-dependent genes from a potentially coherent metabolic context. To address this concern, we consider the function and metabolic context of ς54-dependent genes primarily from a single organism, Escherichia coli, in which a reasonably complete list of ς54-dependent genes has been identified by computer analysis combined with a DNA microarray analysis of nitrogen limitation-induced genes. E. coli appears to have approximately 30 ς54-dependent operons, and about half are involved in nitrogen assimilation and metabolism. A possible physiological relationship between ς54-dependent genes may be based on the fact that nitrogen assimilation consumes energy and intermediates of central metabolism. The products of the ς54-dependent genes that are not involved in nitrogen metabolism may prevent depletion of metabolites and energy resources in certain environments or partially neutralize adverse conditions. Such a relationship may limit the number of physiological themes of ς54-dependent genes within a single organism and may partially account for the unique features of ς54 and ς54-dependent gene expression.

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“…Expression of glnHPQ requires nitrogen limitation but not glutamine (18,98,168). Nitrogen limitation increases the production of glnHPQ transcripts five-to ninefold (176).…”

Section: -Dependent Amino Acid Transport Systemsmentioning

confidence: 99%

Metabolic Context and Possible Physiological Themes of ς⁵⁴-Dependent Genes inEscherichia coli

Reitzer

Schneider

2001

Microbiol Mol Biol Rev

250

300

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“…tuberculosis appears to require substantially more L-glutamine than S. enterica serovar Typhimurium, as an S. enterica serovar Typhimurium glnA strain was able to grow normally with as little as 0.2 mM supplemental L-glutamine in minimal medium (24). S. enterica serovar Typhimurium possesses both a high-affinity glutamine transport system (K m ϭ 0.2 M, V max ϭ 2 nmol min Ϫ1 mg dry weight Ϫ1 ), encoded by glnHPQ, and a low-affinity transport system (K m ϭ 10 M, V max ϭ 3.5 nmol min Ϫ1 mg dry weight Ϫ1 ) (1,24). M. tuberculosis possesses glnH and glnQ homologs but lacks a glnP homolog (3).…”

Section: Vol 71 2003 Gs Is Essential For Growth Of M Tuberculosis mentioning

confidence: 99%

Glutamine Synthetase GlnA1 Is Essential for Growth of Mycobacterium tuberculosis in Human THP-1 Macrophages and Guinea Pigs

2003

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To assess the role of glutamine synthetase (GS), an enzyme of central importance in nitrogen metabolism, in the pathogenicity of Mycobacterium tuberculosis, we constructed a glnA1 mutant via allelic exchange. The mutant had no detectable GS protein or GS activity and was auxotrophic for L-glutamine. In addition, the mutant was attenuated for intracellular growth in human THP-1 macrophages and avirulent in the highly susceptible guinea pig model of pulmonary tuberculosis. Based on growth rates of the mutant in the presence of various concentrations of L-glutamine, the effective concentration of L-glutamine in the M. tuberculosis phagosome of THP-1 cells was ϳ10% of the level assayed in the cytoplasm of these cells (4.5 mM), indicating that the M. tuberculosis phagosome is impermeable to even very small molecules in the macrophage cytoplasm. When complemented by the M. tuberculosis glnA1 gene, the mutant exhibited a wild-type phenotype in broth culture and in human macrophages, and it was virulent in guinea pigs. When complemented by the Salmonella enterica serovar Typhimurium glnA gene, the mutant had only 1% of the GS activity of the M. tuberculosis wild-type strain because of poor expression of the S. enterica serovar Typhimurium GS in the heterologous M. tuberculosis host. Nevertheless, the strain complemented with S. enterica serovar Typhimurium GS grew as well as the wild-type strain in broth culture and in human macrophages. This strain was virulent in guinea pigs, although somewhat less so than the wild-type. These studies demonstrate that glnA1 is essential for M. tuberculosis virulence.Glutamine and glutamate are central molecules in nitrogen metabolism. Glutamine is used as the nitrogen donor for many nitrogen-containing molecules in the cell and is synthesized from L-glutamate, ammonia, and ATP by the enzyme glutamine synthetase (GS) (33). The internal L-glutamine pool has been shown to be a sensor of external nitrogen limitation for Salmonella enterica serovar Typhimurium (21). GS is the only known biosynthetic pathway for the synthesis of glutamine and along with glutamate synthetase is responsible for ammonia assimilation under nitrogen-limiting growth conditions. In enteric bacteria, glutamate dehydrogenase can assimilate ammonia directly into glutamate at high concentrations of ammonia. However, for bacteria such as Mycobacterium tuberculosis which lack glutamate dehydrogenase, GS and glutamate synthetase are the sole means of ammonia assimilation. Due to its central role in nitrogen metabolism, GS is subject to varied and complex forms of transcriptional and posttranslational regulation as well as feedback inhibition by several products of glutamine metabolism (7,33).There are at least four major forms of GS (25). In enteric bacteria, a single glnA gene encodes a GS type I (GSI) enzyme, and glnA null mutants are glutamine auxotrophs. Other bacteria have been shown to possess two or three different types of GS. In the case of Sinorhizobium meliloti (formerly Rhizobium meliloti), all three GS genes...

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“…The glutamine transport activity in E coli (Willis et al, 1975) and S typhimurium (Betteridge and Ayling, 1976) is very low in rich medium and is maximally derepressed only when the medium contains a poor source of nitrogen such as glutamate; glutamine does not cause repression, but free NH 4 + is an excellent repressor (Oxender et al, 1980). Similar observations have been made for yeast; eg the amino acid transport system of Saccharomyces cerevisiae is inhibited by NH 4 + (Grenson et al, 1970).…”

Section: Discussionmentioning

confidence: 81%

Extracellular proteinases from Micrococcus GF: I. Factors affecting growth and production

Fernando

Fox

1991

Lait

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Summary -Theoptimum temperature for growth of and extracellular proteinase production by Micrococcus GF was ses 30 oC. Growth was more rapid and proteoly1ic activity was enhanced by aeration. The microorganism grew and was able to produce extracellular proteinase on casaminoacids, gelatin, phytone peptone, glutamic acid and glutamine, but not on the other amino acids as the sole carbon/nitrogen source. Proteolytic activity decreased after the early exponential phase when Micrococcus GF was grown either on 1% casaminoacids or 1% gelatin, but not wh en grown on casarnlnoacids plus gelatin or phytone peptone. NH 4 CI had an inhibitory effect on growth rate, but it affected neither the proteoly1ic activity nor the final bacterial count when the microorganism grew on organic N plus NH 4 CI. When Micrococcus GF was grown at different phytone peptone concentrations, the shortest generation time was observed with 2% phytone peptone; proteoly1ic activity was constant in the range 1-2% phytone peptone. Glucose and maltose did not affect proteinase production, but the gene~ation time was increased by <': 1% glucose. Maltose had a slight inhibitory effect on growth as weill as on proteinase production. Addition of NaCI to the culture medium supressed proteinase production by Micrococcus GF. The shortest generation time was observed in 2% NaCI, and the microorganism was able to grow in phytone peptone broth (2%) containing 12%, but not 14% NaCI. Micrococcus

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The Regulation of Glutamine Transport and Glutamine Synthetase in Salmonella typhimurium

Cited by 19 publications

References 20 publications

Metabolic Context and Possible Physiological Themes of ς⁵⁴-Dependent Genes inEscherichia coli

Metabolic Context and Possible Physiological Themes of ς⁵⁴-Dependent Genes inEscherichia coli

Glutamine Synthetase GlnA1 Is Essential for Growth of Mycobacterium tuberculosis in Human THP-1 Macrophages and Guinea Pigs

Extracellular proteinases from Micrococcus GF: I. Factors affecting growth and production

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The Regulation of Glutamine Transport and Glutamine Synthetase in Salmonella typhimurium

Cited by 19 publications

References 20 publications

Metabolic Context and Possible Physiological Themes of ς54-Dependent Genes inEscherichia coli

Metabolic Context and Possible Physiological Themes of ς54-Dependent Genes inEscherichia coli

Glutamine Synthetase GlnA1 Is Essential for Growth of Mycobacterium tuberculosis in Human THP-1 Macrophages and Guinea Pigs

Extracellular proteinases from Micrococcus GF: I. Factors affecting growth and production

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Metabolic Context and Possible Physiological Themes of ς⁵⁴-Dependent Genes inEscherichia coli

Metabolic Context and Possible Physiological Themes of ς⁵⁴-Dependent Genes inEscherichia coli