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, Anne De Jong, More Authors

    Research output: Contribution to journalArticleScientificpeer-review

    13 Citations (Scopus)
    105 Downloads (Pure)

    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.

    Original languageEnglish
    Number of pages15
    JournalBMC Evolutionary Biology
    Volume19
    Issue number1
    DOIs
    Publication statusPublished - 2019

    Keywords

    • Evolution
    • Lactic acid bacteria
    • Systems biology

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