Metabolic shifts in Lactococcus lactis: Regulation, evolution and phenotypic heterogeneity

Ana Solopova

Research output: ThesisThesis fully internal (DIV)

1858 Downloads (Pure)


The research presented in this thesis aims to shed more light on carbohydrate metabolism, its regulation and evolution in the lactic acid bacterium Lactococcus lactis with a special focus on the single cell. The major goal was to assess the role of population heterogeneity during various substrate shifts. We discovered that a complex system of specific and global regulation factors underlies the behavior of a single cell in the population; and that the population consists of many metabolic phenotypes. Our evolutionary model suggests that the observed phenotypic heterogeneity might be an example of evolutionary beneficial bet-hedging strategy.
This thesis was also dedicated to studying the unresolved intriguing phenomena in L. lactis, such as growth of lactose-/cellobiose- or galactose-negative strains on lactose, cellobiose or galactose, respectively. All these occurrences have been noticed before, yet they have never been attributed to specific metabolic systems. Different activation mechanisms were shown to be required to revive the silent plant sugar utilization gene clusters that then gain new functions and help the cells to escape stressful situations. To further explore the adaptive capacity of the strain with re-activated lactose utilization ability, we continuously propagated it in a chemically-defined medium supplemented with lactose. Although a priori one might have expected alterations in sugar uptake- and utilization systems, we found that the evolved strains adjusted their nitrogen metabolism.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Groningen
  • Kuipers, Oscar, Supervisor
  • Kok, Jan, Supervisor
Award date13-Oct-2017
Place of Publication[Groningen]
Print ISBNs978-94-028-0778-3
Publication statusPublished - 2017

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