Regulatory Design Governing Progression of Population Growth Phases in Bacteria

A core circuit, formed by a subset of regulatory interactions involving five global transcription factors (FIS, HNS, IHF, RpoS and GadX), has been identified by correlating information from the well- established transcriptional regulatory network of Escherichia coli and genome-wide expression data from cultures in these different growth phases. We propose a functional role for this circuit in controlling progression through these phases. Two alternative hypotheses for controlling the transition between the growth phases are first, a continuous graded adjustment to changing environmental conditions, and second, a discontinuous hysteretic switch at critical thresholds between growth phases. We formulate a simple mathematical model of the core circuit, consisting of differential equations based on the power-law formalism, and show by mathematical and computerassisted analysis that there are critical conditions among the parameters of the model that can lead to hysteretic switch behavior, which – if validated experimentally – would suggest that the transitions between different growth phases might be analogous to cellular differentiation. Based on these provocative results, we propose experiments to test the alternative hypotheses.