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A universal trade-off between growth and lag in fluctuating environments.
Journal article

A universal trade-off between growth and lag in fluctuating environments.

  • Basan M Department of Systems Biology, Harvard Medical School, Boston, MA, USA. markus@hms.harvard.edu.
  • Honda T Section of Molecular Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, CA, USA.
  • Christodoulou D Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland.
  • Hörl M Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland.
  • Chang YF Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
  • Leoncini E Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
  • Mukherjee A Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
  • Okano H Department of Physics, University of California at San Diego, La Jolla, CA, USA.
  • Taylor BR Department of Physics, University of California at San Diego, La Jolla, CA, USA.
  • Silverman JM Department of Integrative Structural and Computational Biology, and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA.
  • Sanchez C Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
  • Williamson JR Department of Integrative Structural and Computational Biology, and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA.
  • Paulsson J Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
  • Hwa T Section of Molecular Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, CA, USA. thwa@ucsd.edu.
  • Sauer U Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland. sauer@imsb.biol.ethz.ch.
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  • 2020-07-17
Published in:
  • Nature. - 2020
Acetates
Adaptation, Physiological
Bacillus subtilis
Cell Division
Environment
Escherichia coli
Fermentation
Gluconeogenesis
Glucose
Glycolysis
Metabolomics
Models, Biological
Mutation
Saccharomyces cerevisiae
English The rate of cell growth is crucial for bacterial fitness and drives the allocation of bacterial resources, affecting, for example, the expression levels of proteins dedicated to metabolism and biosynthesis1,2. It is unclear, however, what ultimately determines growth rates in different environmental conditions. Moreover, increasing evidence suggests that other objectives are also important3-7, such as the rate of physiological adaptation to changing environments8,9. A common challenge for cells is that these objectives cannot be independently optimized, and maximizing one often reduces another. Many such trade-offs have indeed been hypothesized on the basis of qualitative correlative studies8-11. Here we report a trade-off between steady-state growth rate and physiological adaptability in Escherichia coli, observed when a growing culture is abruptly shifted from a preferred carbon source such as glucose to fermentation products such as acetate. These metabolic transitions, common for enteric bacteria, are often accompanied by multi-hour lags before growth resumes. Metabolomic analysis reveals that long lags result from the depletion of key metabolites that follows the sudden reversal in the central carbon flux owing to the imposed nutrient shifts. A model of sequential flux limitation not only explains the observed trade-off between growth and adaptability, but also allows quantitative predictions regarding the universal occurrence of such tradeoffs, based on the opposing enzyme requirements of glycolysis versus gluconeogenesis. We validate these predictions experimentally for many different nutrient shifts in E. coli, as well as for other respiro-fermentative microorganisms, including Bacillus subtilis and Saccharomyces cerevisiae.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/185206
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