title: Bet-hedging during bacterial diauxic shift.
abstract: When bacteria grow in a medium with two sugars, they first use the preferred sugar and only then start metabolizing the second one. After the first exponential growth phase, a short lag phase of nongrowth is observed, a period called the diauxie lag phase. It is commonly seen as a phase in which the bacteria prepare themselves to use the second sugar. Here we reveal that, in contrast to the established concept of metabolic adaptation in the lag phase, two stable cell types with alternative metabolic strategies emerge and coexist in a culture of the bacterium Lactococcus lactis. Only one of them continues to grow. The fraction of each metabolic phenotype depends on the level of catabolite repression and the metabolic state-dependent induction of stringent response, as well as on epigenetic cues. Furthermore, we show that the production of alternative metabolic phenotypes potentially entails a bet-hedging strategy. This study sheds new light on phenotypic heterogeneity during various lag phases occurring in microbiology and biotechnology and adjusts the generally accepted explanation of enzymatic adaptation proposed by Monod and shared by scientists for more than half a century.
authors.affiliation: Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, and.
authors.forename: Ana
authors.initials: A
authors.lastname: Solopova
authors.affiliation: Theoretical Biology Group, Centre for Ecological and Evolutionary Studies, University of Groningen, 9747 AG, Groningen, The Netherlands;
authors.forename: Jordi
authors.initials: J
authors.lastname: van Gestel
authors.affiliation: Theoretical Biology Group, Centre for Ecological and Evolutionary Studies, University of Groningen, 9747 AG, Groningen, The Netherlands;Systems Biology Centre Groningen, University of Groningen, 9713 AV, Groningen, The Netherlands;
authors.forename: Franz J
authors.initials: FJ
authors.lastname: Weissing
authors.affiliation: Faculty of Earth and Life Sciences, Systems Bioinformatics, Centre for Integrative Bioinformatics Vrije Universiteit/Netherlands Institute for Systems Biology, Vrije Universiteit Amsterdam, 1081 HV, Amsterdam, The Netherlands;Top Institute Food and Nutrition, 6700 AN, Wageningen, The Netherlands; and.
authors.forename: Herwig
authors.initials: H
authors.lastname: Bachmann
authors.affiliation: Faculty of Earth and Life Sciences, Systems Bioinformatics, Centre for Integrative Bioinformatics Vrije Universiteit/Netherlands Institute for Systems Biology, Vrije Universiteit Amsterdam, 1081 HV, Amsterdam, The Netherlands;Kluyver Centre for Genomics of Industrial Fermentation, 2628 BC, Delft, The Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: Teusink
authors.affiliation: Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, andTop Institute Food and Nutrition, 6700 AN, Wageningen, The Netherlands; and.
authors.forename: Jan
authors.initials: J
authors.lastname: Kok
authors.affiliation: Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, andTop Institute Food and Nutrition, 6700 AN, Wageningen, The Netherlands; andKluyver Centre for Genomics of Industrial Fermentation, 2628 BC, Delft, The Netherlands o.p.kuipers@rug.nl.
authors.forename: Oscar P
authors.initials: OP
authors.lastname: Kuipers
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D018407:Bacterial Physiological Phenomena; D002241:Carbohydrates / Q000737:chemistry; D018929:Cell Culture Techniques; D002475:Cellobiose / Q000737:chemistry; D044127:Epigenesis, Genetic; D005947:Glucose / Q000737:chemistry; D013294:Lactococcus lactis / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D013997:Time Factors
chemical_list: D002241:Carbohydrates; D002475:Cellobiose; D005947:Glucose
keywords: Gram-positive bacteria; metabolic fitness; phenotypic heterogeneity