Synthesis and degradation of FtsZ determines the first cell division in starved bacteria

Abstract

In natural environments, microbes are typically non-dividing. Such quiescent cells manage fleeting nutrients and gauge when intra- and extracellular resources permit division. Quantitative prediction of the division event as a function of nutritional status is currently achieved through phenomenological models for nutrient-rich, exponentially growing cultures. Such models, however, cannot predict the first division of cells under limiting nutrient availability. To address this, we analyzed the metabolic capability of starved Escherichia coli that were fed pulsed glucose at defined frequencies. Real-time metabolomics and microfluidic single-cell microscopy revealed unexpected, rapid protein and nucleic acid synthesis already in non-dividing cells. Additionally, the lag time to first division shortened as pulsing frequency increased. Here, we demonstrate that the first division from a non-dividing state occurs when the facilitating protein FtsZ reaches division-supporting concentration. A dynamic model quantitatively relates lag time to FtsZ synthesis from nutrient pulses and its protease-dependent degradation. Consistent with model predictions, lag time shortened when FtsZ synthesis was supplemented or protease inhibitors were added. Lag time prolonged when ftsZ was repressed or FtsZ degradation rate was increased. Thus, we provide a basis to quantitatively predict bacterial division using information about molecular determinants and the nutrient input.