Synthetic gene circuits interrogate Escherichia coli cell cycle

Bacteria tightly regulate and coordinate the various events in their cell cycles to duplicate themselves accurately and control their cell sizes. Currently, there exists several models attempting to describe cell cycle regulation in E. coli, but none can elucidate all empirical findings. Important among these findings is the Schaechter-Maaløe-Kjeldgaard growth law (S-M-K law), which says that the average cell size scales exponentially with the growth rate, with a scaling constant equal to the duration from initiation of chromosome replication to cell division. The S-M-K law is believed to be a consequence of the tight coupling between replication initiation and division. Here, we sought to constrain the models by testing the robustness of the law to systematic perturbations in cell dimensions via synthetic genetic circuits. We found that decreasing the mreB level resulted in increased cell width, with little change in cell length, whereas decreasing the ftsZ level resulted in increased cell length. Furthermore, the time from replication termination to cell division increased with the perturbed dimension in both cases. The S-M-K law still remains valid across growth rates and across cell dimensions. The robustness of the growth law further support models that regulate the cell cycle not at divisions, but at initiations.