Emergence of growth and dormancy from a kinetic model of the Escherichia coli central carbon metabolism
Physiological states of bacterial cells exhibit a wide spectrum of timescale. Under the nutrient-rich conditions, most of the cells in an isogenic bacterial population grow at certain rates, while a small subpopulation sometimes stays in a dormant state where the growth rates slow down by orders of magnitude. What is the origin of such heterogeneity of timescales? Here we addressed this question by studying the kinetic model of Escherichia coli central carbon metabolism including the dynamics of the energy currency molecules, which have often been ignored. We found that the model robustly exhibits both the growing- and the dormant state. In order to unveil the mechanism of distinct behaviours, we developed a recursive method to simplify the model without changing the qualitative feature of the dynamics. Analytical and numerical studies of the 2-variable minimal model revealed the necessary conditions for the distinct behaviour, namely, the depletion of energy due to the futile cycle and its non-uniform impact to the kinetics because of the coexistence of the energy currency-coupled and uncoupled reactions as well as branching of the network. The result is consistent with the experimental evidences of the appearance of the futile cycle in mutants and provides a possible explanation for the appearance of dormant cells that causes antibiotic persistence.