Emergent subpopulation behavior uncovered with a community dynamic metabolic model of Escherichia coli diauxic growth
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Citation (published version)Antonella Succurro, Daniel Segre, Oliver Ebenhoeh. 2019. "Emergent Subpopulation Behavior Uncovered with a Community Dynamic Metabolic Model of Escherichia coli Diauxic Growth." MSYSTEMS, Volume 4, Issue 1, pp. ? - ? (16). https://doi.org/10.1128/mSystems.00230-18
Microbes have adapted to greatly variable environments in order to survive both short-term perturbations and permanent changes. A classical and yet still actively studied example of adaptation to dynamic environments is the diauxic shift of Escherichia coli, in which cells grow on glucose until its exhaustion and then transition to using previously secreted acetate. Here we tested different hypotheses concerning the nature of this transition by using dynamic metabolic modeling. To reach this goal, we developed an open source modeling framework integrating dynamic models (ordinary differential equation systems) with structural models (metabolic networks) which can take into account the behavior of multiple subpopulations and smooth flux transitions between time points. We used this framework to model the diauxic shift, first with a single E. coli model whose metabolic state represents the overall population average and then with a community of two subpopulations, each growing exclusively on one carbon source (glucose or acetate). After introduction of an environment-dependent transition function that determined the balance between subpopulations, our model generated predictions that are in strong agreement with published data. Our results thus support recent experimental evidence that diauxie, rather than a coordinated metabolic shift, would be the emergent pattern of individual cells differentiating for optimal growth on different substrates. This work offers a new perspective on the use of dynamic metabolic modeling to investigate population heterogeneity dynamics. The proposed approach can easily be applied to other biological systems composed of metabolically distinct, interconverting subpopulations and could be extended to include single-cell-level stochasticity.
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