Interdependence of K+ and glutamate accumulation during osmotic adaptation of Escherichia coli.

McLaggan, Debbie; Náprstek, J.; Buurman, Ed T.; Epstein, Wolfgang

doi:10.1016/s0021-9258(17)42113-2

Cited by 208 publications

(34 citation statements)

References 46 publications

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“…Qualitative connections have been drawn between expression data and ion homeostasis in the literature. For example, an inhibited respiration is regarded as an early response to an alkalinized cytoplasm due to a sudden efflux of hydrogen ions that accompanies potassium intake upon osmotic upshift 29 . This initial response is followed by a rapid accumulation of glutamate-a potassium counterion-through glutamate importers or its biosynthetic pathways 26,30 .…”

Section: Resultsmentioning

confidence: 99%

“…Glutamate metabolism contains some of the highest hydrogen-consuming reactions in the reduced networka possible explanation for their observed upregulation. They also carry high flux (especially GLUDy) whether or not the cell is under stress 29 , so they can effectively attenuate acidification of the cytoplasm. The upper TCA cycle is downregulated, further promoting this mechanism by directing the flux of precursors from glycolysis and lower TCA towards glutamate biosynthesis.…”

Section: Resultsmentioning

confidence: 99%

“…Many genes in the E. coli genome are involved in osmoregulation. Primary transcriptional regulatory targets include potassium transporters (e.g., trkA and kdpA) 27,61 , osmoprotectant transporters (e.g., proV) 27 , carbon-source transporters (e.g., crr and ptsG) 31 , sodium transporters (e.g., nhaA and nhaB) 26 , glutamate transporter (e.g., gadC and gltI) 28 , and the ETC (e.g., atpE and cyoD) 29 . Secondary responses affect several intracellular pathways, such as amino-acid biosynthesis, osmoprotectant biosynthesis, central-carbon metabolism, and nucleotide biosynthesis 31 .…”

Section: Methodsmentioning

confidence: 99%

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The quantitative metabolome is shaped by abiotic constraints

et al. 2021

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Living systems formed and evolved under constraints that govern their interactions with the inorganic world. These interactions are definable using basic physico-chemical principles. Here, we formulate a comprehensive set of ten governing abiotic constraints that define possible quantitative metabolomes. We apply these constraints to a metabolic network of Escherichia coli that represents 90% of its metabolome. We show that the quantitative metabolomes allowed by the abiotic constraints are consistent with metabolomic and isotope-labeling data. We find that: (i) abiotic constraints drive the evolution of high-affinity phosphate transporters; (ii) Charge-, hydrogen- and magnesium-related constraints underlie transcriptional regulatory responses to osmotic stress; and (iii) hydrogen-ion and charge imbalance underlie transcriptional regulatory responses to acid stress. Thus, quantifying the constraints that the inorganic world imposes on living systems provides insights into their key characteristics, helps understand the outcomes of evolutionary adaptation, and should be considered as a fundamental part of theoretical biology and for understanding the constraints on evolution.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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The quantitative metabolome is shaped by abiotic constraints

et al. 2021

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“…Its regulatory reach can now be extended to the control of Glu (and Asp) levels through indirect regulation of GlnPQ. Glu is the major anion in most bacteria, and its accumulation allows the cell to balance the charge of significant levels of K 1 (41,42). In the L. lactis WT, Glu is present at a high level, but the other anionic amino acid Asp is also present at a similar concentration.…”

mentioning

confidence: 99%

Cyclic di-AMP Oversight of Counter-Ion Osmolyte Pools Impacts Intrinsic Cefuroxime Resistance in Lactococcus lactis

Pham

Shi

Xiang

et al. 2021

mBio

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The broadly conserved cyclic di-AMP (c-di-AMP) is a conditionally essential bacterial second messenger. The pool of c-di-AMP is fine-tuned through diadenylate cyclase and phosphodiesterase activities, and direct binding of c-di-AMP to proteins and riboswitches allows the regulation of a broad spectrum of cellular processes. c-di-AMP has a significant impact on intrinsic β-lactam antibiotic resistance in Gram-positive bacteria; however, the reason for this is currently unclear. In this work, genetic studies revealed that suppressor mutations that decrease the activity of the potassium (K+) importer KupB or the glutamine importer GlnPQ restore cefuroxime (CEF) resistance in diadenylate cyclase (cdaA) mutants of Lactococcus lactis. Metabolite analyses showed that glutamine is imported by GlnPQ and then rapidly converted to glutamate, and GlnPQ mutations or c-di-AMP negatively affects the pools of the most abundant free amino acids (glutamate and aspartate) during growth. In a high-c-di-AMP mutant, GlnPQ activity could be increased by raising the internal K+ level through the overexpression of a c-di-AMP-insensitive KupB variant. These results demonstrate that c-di-AMP reduces GlnPQ activity and, therefore, the level of the major free anions in L. lactis through its inhibition of K+ import. Excessive ion accumulation in cdaA mutants results in greater spontaneous cell lysis under hypotonic conditions, while CEF-resistant suppressors exhibit reduced cell lysis and lower osmoresistance. This work demonstrates that the overaccumulation of major counter-ion osmolyte pools in c-di-AMP-defective mutants of L. lactis causes cefuroxime sensitivity. IMPORTANCE The bacterial second messenger cyclic di-AMP (c-di-AMP) is a global regulator of potassium homeostasis and compatible solute uptake in many Gram-positive bacteria, making it essential for osmoregulation. The role that c-di-AMP plays in β-lactam resistance, however, is unclear despite being first identified a decade ago. Here, we demonstrate that the overaccumulation of potassium or free amino acids leads to cefuroxime sensitivity in Lactococcus lactis mutants partially defective in c-di-AMP synthesis. It was shown that c-di-AMP negatively affects the levels of the most abundant free amino acids (glutamate and aspartate) in L. lactis. Regulation of these major free anions was found to occur via the glutamine transporter GlnPQ, whose activity increased in response to intracellular potassium levels, which are under c-di-AMP control. Evidence is also presented showing that they are major osmolytes that enhance osmoresistance and cell lysis. The regulatory reach of c-di-AMP can be extended to include the main free anions in bacteria.

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“…This picture is likely an over-simplification of the overall compositional changes. For example, rapid accumulation of potassium glutamate is triggered by osmotic shock [27,28], a phenomenon, which concomitantly increases DNA supercoiling levels [18]. Although the levels of potassium glutamate during the growth cycle have not been experimentally determined, gltP, the gene for the proton (and hence energy)-dependent glutamate transporter is maximally expressed immediately after nutritional shift-up [29], a situation in which the preferential expression of genes dependent of high levels of DNA superhelicity is strongly favoured [30].…”

Section: The Intracellular Contextmentioning

confidence: 99%

Composition of Transcription Machinery and Its Crosstalk with Nucleoid-Associated Proteins and Global Transcription Factors

et al. 2021

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The coordination of bacterial genomic transcription involves an intricate network of interdependent genes encoding nucleoid-associated proteins (NAPs), DNA topoisomerases, RNA polymerase subunits and modulators of transcription machinery. The central element of this homeostatic regulatory system, integrating the information on cellular physiological state and producing a corresponding transcriptional response, is the multi-subunit RNA polymerase (RNAP) holoenzyme. In this review article, we argue that recent observations revealing DNA topoisomerases and metabolic enzymes associated with RNAP supramolecular complex support the notion of structural coupling between transcription machinery, DNA topology and cellular metabolism as a fundamental device coordinating the spatiotemporal genomic transcription. We analyse the impacts of various combinations of RNAP holoenzymes and global transcriptional regulators such as abundant NAPs, on genomic transcription from this viewpoint, monitoring the spatiotemporal patterns of couplons—overlapping subsets of the regulons of NAPs and RNAP sigma factors. We show that the temporal expression of regulons is by and large, correlated with that of cognate regulatory genes, whereas both the spatial organization and temporal expression of couplons is distinctly impacted by the regulons of NAPs and sigma factors. We propose that the coordination of the growth phase-dependent concentration gradients of global regulators with chromosome configurational dynamics determines the spatiotemporal patterns of genomic expression.

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Interdependence of K+ and glutamate accumulation during osmotic adaptation of Escherichia coli.

Cited by 208 publications

References 46 publications

The quantitative metabolome is shaped by abiotic constraints

The quantitative metabolome is shaped by abiotic constraints

Cyclic di-AMP Oversight of Counter-Ion Osmolyte Pools Impacts Intrinsic Cefuroxime Resistance in Lactococcus lactis

Composition of Transcription Machinery and Its Crosstalk with Nucleoid-Associated Proteins and Global Transcription Factors

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