Nutrient-Dependent Trade-Offs between Ribosomes and Division Protein Synthesis Control Bacterial Cell Size and Growth

• Published in: Cell reports (Cambridge) Vol. 32; no. 12; p. 108183
• Main Authors: Serbanescu, Diana, Ojkic, Nikola, Banerjee, Shiladitya
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22-09-2020; Elsevier
• Subjects: Anti-Bacterial Agents - pharmacology; antibiotics; bacterial growth control; Cell Division - drug effects; Cell Membrane - drug effects; Cell Membrane - metabolism; cell shape; cell size regulation; Escherichia coli; Escherichia coli - cytology; Escherichia coli - drug effects; Escherichia coli - growth & development; Models, Biological; Protein Biosynthesis - drug effects; Ribosomes - drug effects; Ribosomes - metabolism; translation; whole-cell model; whole-cell model; bacterial growth control; cell shape; Escherichia coli; translation; antibiotics; cell size regulation
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.108183

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 shape under growth perturbations. Here, we develop a whole-cell model for growth dynamics of rod-shaped bacteria that links ribosomal abundance with cell geometry, division control, and the extracellular environment. Our study reveals that cell size maintenance under nutrient perturbations requires a balanced trade-off between ribosomes and division protein synthesis. Deviations from this trade-off relationship are predicted under translation inhibition, 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 antibiotic resistance.
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•A trade-off between ribosomal and division protein synthesis sets bacterial size•In nutrient-poor media, cells grow larger under translation inhibition•Fast-growing cells spend more resources on division under translation inhibition•Bacteria actively regulate cell size and shape to promote fitness under stress
How protein synthesis regulates cell size remains poorly understood. Serbanescu et al. show that cell size is controlled by a trade-off between the allocation of cellular resources toward ribosomal and division protein synthesis. This principle quantitatively determines bacterial cell morphology and growth rates under nutrient shifts or translational perturbations.