Publication

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

Radzikowski, J. L., Vedelaar, S., Siegel, D., Ortega, Á. D., Schmidt, A. & Heinemann, M., Sep-2016, In : Molecular Systems Biology. 12, 9, p. 1-18 18 p., 882.

Research output: Contribution to journalArticleAcademicpeer-review

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 sigma(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 sigma(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.

Original languageEnglish
Article number882
Pages (from-to)1-18
Number of pages18
JournalMolecular Systems Biology
Volume12
Issue number9
Publication statusPublished - Sep-2016

    Keywords

  • Escherichia coli, metabolism, persistence, proteomics, stress response, MEDIATE ANTIBIOTIC TOLERANCE, ESCHERICHIA-COLI, GENE-EXPRESSION, RIBONUCLEIC-ACID, MESSENGER-RNA, STARVATION, CELLS, GROWTH, PROTEIN, PPGPP
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