Abstract
Cells constantly adapt to unpredictably changing extracellular solute concentrations. A cornerstone of the cellular osmotic stress response is the metabolic supply of energy and building blocks to mount appropriate defenses. Yet, the extent to which osmotic stress impinges on the metabolic network remains largely unknown. Moreover, it is mostly unclear which, if any, of the metabolic responses to osmotic stress are conserved among diverse organisms or confined to particular groups of species. Here we investigate the global metabolic responses of twelve bacteria, two yeasts and two human cell lines exposed to sustained hyperosmotic salt stress by measuring semiquantitative levels of hundreds of cellular metabolites using nontargeted metabolomics. Beyond the accumulation of osmoprotectants, we observed significant changes of numerous metabolites in all species. Global metabolic responses were predominantly species-specific, yet individual metabolites were characteristically affected depending on species’ taxonomy, natural habitat, envelope structure or salt tolerance. Exploiting the breadth of our dataset, the correlation of individual metabolite response magnitudes across all species implicated lower glycolysis, tricarboxylic acid cycle, branched-chain amino acid metabolism and heme biosynthesis to be generally important for salt tolerance. Thus, our findings place the global metabolic salt stress response into a phylogenetic context and provide insights into the cellular phenotype associated with salt tolerance.
Highlights
Preventing lysis and maintaining intracellular solute concentration homeostasis in the face of unpredictably changing environments are major challenges to all cells
The selected bacteria include the Gram-negative model bacterium Escherichia coli, the Gram-positive model bacterium Bacillus subtilis commonly employed as a generally regarded as safe industrial production organism, the Gram-negative bacterium Zymomonas mobilis that efficiently converts renewable feedstock into biofuels such as ethanol, as well as the Gram-positive acid-fast bacterium Mycobacterium smegmatis, a nonpathogenic and experimentally tractable proxy for the tuberculosis agent M. tuberculosis
The observed salt tolerances varied considerably, with IC50 values ranging from 150 mM in the human MCF7 cell line to 1,500 mM NaCl in Z. mobilis
Summary
Preventing lysis and maintaining intracellular solute concentration homeostasis in the face of unpredictably changing environments are major challenges to all cells. Accumulating extracellular solutes cause water molecules to exit the cell, thereby reducing its turgor pressure and intracellular water activity. This alters thermodynamic properties of the cytoplasm, causes protein misfolding and leads to macromolecular crowding, thereby affecting the rates of various cellular processes ranging from protein-DNA binding to metabolic reactions [2,3,4,5,6]. Maintaining turgor pressure and water activity in a physiologically tolerable range is crucial for cells to survive and thrive in habitats with changing osmolalities
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