Threshold accumulation of a constitutive protein explains E. coli cell-division behavior in nutrient upshifts

The mechanism leading to cell division in the bacterium Escherichia coli is unknown, but we know that it results in adding a roughly constant size every cell cycle, regardless of size at birth. While most available studies try to infer information on cell division from steadily dividing cells in constant nutrient conditions, this study leverages a high-resolution device to monitor single-cell growth division upon nutrient changes. Comparing these data with different mathematical models, we are able to discriminate among fundamentally different mechanisms of cell-division control, and we show that the data support a model where an unregulated protein accumulates to a threshold and triggers division.Despite a boost of recent progress in dynamic single-cell measurements and analyses in Escherichia coli, we still lack a mechanistic understanding of the determinants of the decision to divide. Specifically, the debate is open regarding the processes linking growth and chromosome replication to division and on the molecular origin of the observed “adder correlations,” whereby cells divide, adding roughly a constant volume independent of their initial volume. In order to gain insight into these questions, we interrogate dynamic size-growth behavior of single cells across nutrient upshifts with a high-precision microfluidic device. We find that the division rate changes quickly after nutrients change, much before growth rate goes to a steady state, and in a way that adder correlations are robustly conserved. Comparison of these data to simple mathematical models falsifies proposed mechanisms, where replication–segregation or septum completions are the limiting step for cell division. Instead, we show that the accumulation of a putative constitutively expressed “P-sector divisor” protein explains the behavior during the shift.Experimental datasets and code used in this study have been deposited at Mendeley Data (DOI: 10.17632/5d4yhyjn8j.1). The bugpipe package and its complete documentation is available at GitHub (https://github.com/panlilio/bugpipe).