Adaption to glucose limitation is modulated by the pleotropic regulator CcpA, independent of selection pressure strength

Claire E. Price, Filipe Branco Dos Santos, Anne Hesseling, Jaakko J. Uusitalo, Herwig Bachmann, Vera Benavente, Anisha Goel, Jan Berkhout, Frank J. Bruggeman, Siewert Jan Marrink, Manolo Montalban-Lopez, Anne De Jong, Jan Kok, Douwe Molenaar, Bert Poolman, Bas Teusink, Oscar P. Kuipers

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Background: A central theme in (micro)biology is understanding the molecular basis of fitness i.e. which strategies are successful under which conditions; how do organisms implement such strategies at the molecular level; and which constraints shape the trade-offs between alternative strategies. Highly standardized microbial laboratory evolution experiments are ideally suited to approach these questions. For example, prolonged chemostats provide a constant environment in which the growth rate can be set, and the adaptive process of the organism to such environment can be subsequently characterized. Results: We performed parallel laboratory evolution of Lactococcus lactis in chemostats varying the quantitative value of the selective pressure by imposing two different growth rates. A mutation in one specific amino acid residue of the global transcriptional regulator of carbon metabolism, CcpA, was selected in all of the evolution experiments performed. We subsequently showed that this mutation confers predictable fitness improvements at other glucose-limited growth rates as well. In silico protein structural analysis of wild type and evolved CcpA, as well as biochemical and phenotypic assays, provided the underpinning molecular mechanisms that resulted in the specific reprogramming favored in constant environments. Conclusion: This study provides a comprehensive understanding of a case of microbial evolution and hints at the wide dynamic range that a single fitness-enhancing mutation may display. It demonstrates how the modulation of a pleiotropic regulator can be used by cells to improve one trait while simultaneously work around other limiting constraints, by fine-tuning the expression of a wide range of cellular processes.

LanguageEnglish
Article number15
Pages1-15
Number of pages15
JournalBMC Evolutionary Biology
Volume19
Issue number1
DOIs
Publication statusPublished - 10 Jan 2019

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strength (mechanics)
glucose
mutation
chemostat
fitness
Lactococcus lactis
structural proteins
organisms
structural analysis
transcription factors
amino acid
experiment
metabolism
assay
Biological Sciences
amino acids
protein
selection pressure
carbon
assays

Keywords

  • Evolution
  • Lactic acid bacteria
  • Systems biology

Cite this

Price, Claire E. ; Branco Dos Santos, Filipe ; Hesseling, Anne ; Uusitalo, Jaakko J. ; Bachmann, Herwig ; Benavente, Vera ; Goel, Anisha ; Berkhout, Jan ; Bruggeman, Frank J. ; Marrink, Siewert Jan ; Montalban-Lopez, Manolo ; De Jong, Anne ; Kok, Jan ; Molenaar, Douwe ; Poolman, Bert ; Teusink, Bas ; Kuipers, Oscar P. / Adaption to glucose limitation is modulated by the pleotropic regulator CcpA, independent of selection pressure strength. In: BMC Evolutionary Biology. 2019 ; Vol. 19, No. 1. pp. 1-15.
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Price, CE, Branco Dos Santos, F, Hesseling, A, Uusitalo, JJ, Bachmann, H, Benavente, V, Goel, A, Berkhout, J, Bruggeman, FJ, Marrink, SJ, Montalban-Lopez, M, De Jong, A, Kok, J, Molenaar, D, Poolman, B, Teusink, B & Kuipers, OP 2019, 'Adaption to glucose limitation is modulated by the pleotropic regulator CcpA, independent of selection pressure strength', BMC Evolutionary Biology, vol. 19, no. 1, 15, pp. 1-15. https://doi.org/10.1186/s12862-018-1331-x

Adaption to glucose limitation is modulated by the pleotropic regulator CcpA, independent of selection pressure strength. / Price, Claire E.; Branco Dos Santos, Filipe; Hesseling, Anne; Uusitalo, Jaakko J.; Bachmann, Herwig; Benavente, Vera; Goel, Anisha; Berkhout, Jan; Bruggeman, Frank J.; Marrink, Siewert Jan; Montalban-Lopez, Manolo; De Jong, Anne; Kok, Jan; Molenaar, Douwe; Poolman, Bert; Teusink, Bas; Kuipers, Oscar P.

In: BMC Evolutionary Biology, Vol. 19, No. 1, 15, 10.01.2019, p. 1-15.

Research output: Contribution to JournalArticleAcademicpeer-review

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AU - Price, Claire E.

AU - Branco Dos Santos, Filipe

AU - Hesseling, Anne

AU - Uusitalo, Jaakko J.

AU - Bachmann, Herwig

AU - Benavente, Vera

AU - Goel, Anisha

AU - Berkhout, Jan

AU - Bruggeman, Frank J.

AU - Marrink, Siewert Jan

AU - Montalban-Lopez, Manolo

AU - De Jong, Anne

AU - Kok, Jan

AU - Molenaar, Douwe

AU - Poolman, Bert

AU - Teusink, Bas

AU - Kuipers, Oscar P.

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