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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 1 , Jaakko J. Uusitalo 2 , Herwig Bachmann, Vera Benavente 3 , Anisha Goel, Jan Berkhout 3 , Frank J. Bruggeman 3 , Siewert-Jan Marrink 2 , Manolo Montalban-Lopez 1 , Anne De Jong 1 , Jan Kok 1 , Douwe Molenaar, Bert Poolman 4 , Bas Teusink, Oscar P. Kuipers
1  Molecular Genetics Group, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands
2  Molecular Dynamics Group, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands
3  Systems Bioinformatics, Faculty of Earth and Life Sciences, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands
4  Department of Biochemistry, University of Groningen, Nijenborgh 4, 9747 AG Groningen, the Netherlands

Published: 10 January 2019 by Springer Nature in BMC Evolutionary Biology
Springer Nature, Volume 19; 10.1186/s12862-018-1331-x
Abstract: 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. 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. 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. The online version of this article (10.1186/s12862-018-1331-x) contains supplementary material, which is available to authorized users.
Keywords: evolution, lactic acid bacteria, systems biology
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