It is more important than ever to better understand the bases for the remarkable ability of bacteria to proliferate efficiently in a wide range of niches. The plasticity of the cell cycle is a key parameter underpinning this exceptional capacity of bacterial cells. For instance, uncoupling growth and cell division (leading to filamentation) provides a selective advantage to Escherichia coli cells under specific conditions (antibiotic exposure (Lambert & Kussell, 2015; Lin & Kussel, 2016), infection cycle of uropathogenic E. coli (Khandige et al., 2016; Mickiewicz et al., 2019)). However, the temporal coordination of cell growth with the cell cycle (replication, segregation, division) remains largely elusive. Despite significant molecular insights gathered on the replication and division machineries, no equivalent to the cyclins/CDK paradigm has been identified in bacteria, where cell cycles can overlap. This coordination underpins the efficiency of proliferation in all cell types. Knowing the fundamental bases of the coordination between cell cycle events and cell growth constitutes a critical asset to address the worldwide issue of health threatening E.coli infections.
The coupling demonstrated between cell morphology, cell cycle and growth rates for laboratory strains is so tight (Cooper & Helmstetter, 1968; Donachie, 1968; Schaechter et al., 1958) that the correlation between cell size and growth rate has been dubbed the “nutrient growth law”. The high degree of correlation makes it difficult to disentangle the respective roles of metabolic activity (approximated by the population growth rate), the cell cycle progression and cell morphology. This “law” has proven to be difficult to break and has only been altered using pleiotropic mutations or perturbations on essential genes (e.g., mreB, ftsZ, dnaA (Si et al., 2017; Zheng et al., 2016)). Instead of profoundly altering the biology of E. coli cells with engineered mutations, we propose to characterize and harness the natural diversity existing at the species level to (i) characterize new correlations and causality relationship between growth, morphology and cell cycle parameters, and (ii) identify the etiology and mechanisms underpinning this coordination.