Mechanistic basis for non-exponential bacterial growth

Abstract

Bacterial populations typically exhibit exponential growth under resource-rich conditions, yet individual cells often deviate from this pattern. Recent work has shown that the elongation rates of Escherichia coli and Caulobacter crescentus increase throughout the cell cycle (super-exponential growth), while Bacillus subtilis displays a mid-cycle minimum (convex growth), and Mycobacterium tuberculosis grows linearly. Here, we develop a single-cell model linking gene expression, proteome allocation, and mass growth to explain these diverse growth trajectories. By calibrating model parameters with experimental data, we show that DNA-proportional mRNA transcription produces near-exponential growth, whereas deviations from this proportionality yield the observed non-exponential growth patterns. Analysis of gene expression perturbations reveals that ribosome expression primarily controls dry mass growth rate, whereas envelope expression more strongly affects cell elongation rate. Fitting our model to single-cell experimental data reproduces convex, super-exponential, and linear modes of growth, demonstrating how envelope and ribosome expression schedules drive cell-cycle-specific behaviors. These findings provide a mechanistic basis for non-exponential single-cell growth and offer insights into how bacterial cells dynamically regulate elongation rates within each generation.