General quantitative relations linking cell growth and the cell cycle in Escherichia coli

Nat Microbiol. 2020 Aug;5(8):995-1001. doi: 10.1038/s41564-020-0717-x. Epub 2020 May 18.

Abstract

Growth laws emerging from studies of cell populations provide essential constraints on the global mechanisms that coordinate cell growth1-3. The foundation of bacterial cell cycle studies relies on two interconnected dogmas that were proposed more than 50 years ago-the Schaechter-Maaloe-Kjeldgaard growth law that relates cell mass to growth rate1 and Donachie's hypothesis of a growth-rate-independent initiation mass4. These dogmas spurred many efforts to understand their molecular bases and physiological consequences5-14. Although they are generally accepted in the fast-growth regime, that is, for doubling times below 1 h, extension of these dogmas to the slow-growth regime has not been consistently achieved. Here, through a quantitative physiological study of Escherichia coli cell cycles over an extensive range of growth rates, we report that neither dogma holds in either the slow- or fast-growth regime. In their stead, linear relations between the cell mass and the rate of chromosome replication-segregation were found across the range of growth rates. These relations led us to propose an integral-threshold model in which the cell cycle is controlled by a licensing process, the rate of which is related in a simple way to chromosomal dynamics. These results provide a quantitative basis for predictive understanding of cell growth-cell cycle relationships.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle*
  • Cell Division*
  • Chromosome Segregation
  • Chromosomes, Bacterial / genetics
  • Culture Media / chemistry
  • DNA Replication
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins
  • Proteomics

Substances

  • Culture Media
  • Escherichia coli Proteins