A general quantitative relation linking bacterial cell growth and the cell cycle

The foundation of bacterial cell cycle studies has long resided in two interconnected dogmas between biomass growth, DNA replication, and cell division during exponential growth: the SMK growth law that relates cell mass (a measure of cell size) to growth rate1, and Donachies hypothesis of a growth-rate-independent initiation mass2. These dogmas have spurred many efforts to understand their molecular bases and physiological consequences3-12. Most of these studies focused on fast-growing cells, with doubling times shorter than 60 min. Here, we systematically studied the cell cycle of E. coli for a broad range of doubling times (24 min to over 10 hr), with particular attention on steady-state growth. Surprisingly, we observed that neither dogma held across the range of growth rates examined. In their stead, a new linear relation unifying the slow- and fast-growth regimes was revealed between the cell mass and the number of cell divisions it takes to replicate and segregate a newly initiated pair of replication origins. This and other findings in this study suggest a single-cell division model, which not only reproduces the bulk relations observed but also recapitulates the adder phenomenon established recently for stochastically dividing cells13-15. These results allowed us to develop quantitative insight into the bacterial cell cycle, providing a firm new foundation for the study of bacterial growth physiology.