Cell-cycle dependent growth regulation in bacterial cells

Proliferating bacterial cells exhibit stochastic growth and shape dynamics, but the regulation of bacterial growth and morphogenesis remains poorly understood. A quantitative understanding of the mathematical equations driving single cell growth, and how they change under different growth conditions, would provide better insights into cell-to-cell variability and intergenerational fluctuations in cell physiology. Using multigenerational growth and shape data of single Escherichia coli and Bacillus subtilis cells find that both deviate from exponential growth within the cell cycle. In particular, while the exponential growth rate of E. coli increases during the cell cycle irrespective of nutrient or temperature conditions, the behavior of B. subtilis is non-monotonic. We propose a mechanistic model that explains the emergence of these growth patterns from autocatalytic production of ribosomes, coupled to the rate of cell elongation and surface area synthesis. Using this model in the context of established proteomic modeling and statistical inference on large datasets, the behavior of B. subtilis can be explained by dynamic cellular resource allocation. Connecting the mechanistic modeling to the underlying transcription allows for inferences about gene expression directly from morphological data.