title: Ubiquinone accumulation improves osmotic-stress tolerance in Escherichia coli.
abstract: Bacteria are thought to cope with fluctuating environmental solute concentrations primarily by adjusting the osmolality of their cytoplasm. To obtain insights into the underlying metabolic adaptations, we analyzed the global metabolic response of Escherichia coli to sustained hyperosmotic stress using nontargeted mass spectrometry. We observed that 52% of 1,071 detected metabolites, including known osmoprotectants, changed abundance with increasing salt challenge. Unexpectedly, unsupervised data analysis showed a substantial increase of most intermediates in the ubiquinone-8 (Q8) biosynthesis pathway and a 110-fold accumulation of Q8 itself, as confirmed by quantitative lipidomics. We then demonstrated that Q8 is necessary for acute and sustained osmotic-stress tolerance using Q8 mutants and tolerance rescue through feeding nonrespiratory Q8 analogs. Finally, in vitro experiments with artificial liposomes showed that mechanical membrane stabilization is a principal mechanism of Q8-mediated osmoprotection. Thus, we find that besides regulating intracellular osmolality, E. coli enhances its cytoplasmic membrane stability to withstand osmotic stress.
authors: 1] Institute of Molecular Systems Biology, Swiss Federal Institute of Technology (ETH) Zürich, Zürich, Switzerland. [2] PhD Program on Systems Biology, Life Science Zürich, Zürich, Switzerland.
authors: Daniel C
authors: DC
authors: Sévin
authors: Institute of Molecular Systems Biology, Swiss Federal Institute of Technology (ETH) Zürich, Zürich, Switzerland.
authors: Uwe
authors: U
authors: Sauer
mesh_terms: D002462:Cell Membrane / Q000187:drug effects; D003627:Data Interpretation, Statistical; D004579:Electron Transport / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D008081:Liposomes; D013058:Mass Spectrometry; D055432:Metabolomics; D008856:Microscopy, Fluorescence; D009997:Osmotic Pressure / Q000187:drug effects*; D017382:Reactive Oxygen Species; D013312:Stress, Physiological / Q000187:drug effects*; D014451:Ubiquinone / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D008081:Liposomes; D017382:Reactive Oxygen Species; D014451:Ubiquinone; C030778:ubiquinone 8