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Bacterial persistence is an active σS stress response to metabolic flux limitation.
Journal article

Bacterial persistence is an active σS stress response to metabolic flux limitation.

  • Radzikowski JL Molecular Systems Biology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, The Netherlands.
  • Vedelaar S Molecular Systems Biology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, The Netherlands.
  • Siegel D Analytical Biochemistry, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, The Netherlands.
  • Ortega ÁD Molecular Systems Biology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, The Netherlands.
  • Schmidt A Biozentrum, University of Basel, Basel, Switzerland.
  • Heinemann M Molecular Systems Biology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, The Netherlands m.heinemann@rug.nl.
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  • 2016-09-23
Published in:
  • Molecular systems biology. - 2016
Escherichia coli
metabolism
persistence
proteomics
stress response
Culture Media
Drug Tolerance
Escherichia coli
Escherichia coli Proteins
Gene Expression Regulation, Bacterial
Metabolism
Proteomics
Stress, Physiological
English While persisters are a health threat due to their transient antibiotic tolerance, little is known about their phenotype and what actually causes persistence. Using a new method for persister generation and high-throughput methods, we comprehensively mapped the molecular phenotype of Escherichia coli during the entry and in the state of persistence in nutrient-rich conditions. The persister proteome is characterized by σ(S)-mediated stress response and a shift to catabolism, a proteome that starved cells tried to but could not reach due to absence of a carbon and energy source. Metabolism of persisters is geared toward energy production, with depleted metabolite pools. We developed and experimentally verified a model, in which persistence is established through a system-level feedback: Strong perturbations of metabolic homeostasis cause metabolic fluxes to collapse, prohibiting adjustments toward restoring homeostasis. This vicious cycle is stabilized and modulated by high ppGpp levels, toxin/anti-toxin systems, and the σ(S)-mediated stress response. Our system-level model consistently integrates past findings with our new data, thereby providing an important basis for future research on persisters.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://sonar.ch/global/documents/231720
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