Nutrient-dependent trade-offs between ribosomes and division protein synthesis control bacterial cell size and growth

Abstract

Cell size control emerges from a regulated balance between the rates of cell growth and division. In bacteria, simple quantitative laws connect cellular growth rate to ribosome abundance. However, it remains poorly understood how translation regulates bacterial cell size and shapes under growth perturbations. Here we develop a whole-cell model for growth dynamics in rod-shaped bacteria that links ribosomal abundance with cell geometry, division control, and the extracellular environment.Our study reveals that cell shape maintenance under nutrient perturbations requires a balanced trade-off between ribosomes and division protein synthesis. Deviations from this trade-off relationship is predicted under translational perturbations, leading to distinct modes of cell morphological changes, in agreement with single-cell experimental data on Escherichia coli. Furthermore, by calibrating our model with experimental data, we predict how combinations of nutrient-, translational-and shape perturbations can be chosen to optimize bacterial growth fitness and drug resistance.

Threshold accumulation of a constitutive protein explains E. coli cell division behavior in nutrient upshifts

“…In agreement with our findings, FtsZ expression is not ppGpp-dependent [56]. Additionally, its expression rate is inversely proportional to the replication/segregation period duration [9,10,49].…”

“…We supposed that the fast and complex changes in division rate and added size observed during our shifts could be due to a coupling between the changes in biosynthetic “sectors” [48] occurring during the shift and cell-division dynamics. The literature offers models that describe proteome sector dynamics and biosynthesis in non-steady regimes [33] and recent attempts were put forward to link these sectors with cell division [49–52]. However, the descriptions differ, and current data do not allow to select a specific one.…”

“…We believe that, giving our current limited knowledge on the crosstalks between growth-and cell-cycle physiology, this "empirical" approach to forward models is preferrable to more theoretical routes postulating the behavior of different proteome sectors across shifts [49][50][51][52]. Comparing the predictions of the four possible models that can be generated by our data, we show that the data are in agreement with a model where a putative adder protein is under the control of a constitutive promoter located close to the replication terminus of the E. coli chromosome.…”

“…A recent study combining experiments and theory concludes that in order to reproduce the observed trends across conditions, this molecule should be under growth-rate control and able to sense the mean duration of the replication or segregation period of the chromosome in a given condition [10]. Several theoretical studes have speculated on the possible interactions between biosynthetic "sectors" and cell-division control [49][50][51][52]. In particular, based on the analysis of steady-state growth-division data, two studies [49,50] have suggested that the molecule effecting the adder behavior may be a protein of the "P sector" of the proteome, i.e., a constitutive promoter, in full agreement with the conclusions reached here.…”

“…Finally, using the data from four GFP reporter strains with either a ribosomal or a constitutive promoter inserted at two different locations along the genome, we could test the hypothesis that the adder molecule is a protein under the control of these kinds of promoters (whose expression is differently dependent on growth rate). We believe that, giving our current limited knowledge on the crosstalks between growth- and cell-cycle physiology, this “empirical” approach to forward models is preferrable to more theoretical routes postulating the behavior of different proteome sectors across shifts [49–52]. Comparing the predictions of the four possible models that can be generated from our data, we show that the data are in agreement with a model where a putative adder protein is under the control of a constitutive promoter located close to the replication terminus of the E. coli chromosome.…”