Apparent simplicity and emergent robustness in bacterial cell cycle control

To examine how bacteria achieve robust cell proliferation across diverse conditions, we developed a method that quantifies 77 cell morphological, cell cycle and growth phenotypes of a fluorescently-labeled Escherichia coli strain and >800 gene deletion derivatives under multiple nutrient conditions. This approach revealed extensive phenotypic plasticity and deviating mutant phenotypes were often found to be nutrient-dependent. From this broad phenotypic landscape emerged simple and robust unifying rules (laws) that connect DNA replication initiation, nucleoid segregation, FtsZ-ring formation, and cell constriction to specific aspects of cell size (volume, length, or added length). Furthermore, completion of cell division followed the initiation of cell constriction after a constant time delay across strains and nutrient conditions, identifying cell constriction as a key control point for cell size determination. Our work provides a systems-level understanding of the design principles by which E. coli integrates cell cycle processes and growth rate with cell size to achieve its robust proliferative capability.