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Cell size regulation has been extensively studied in symmetrically dividing cells, but the mechanisms underlying the control of size asymmetry in asymmetrically dividing bacteria remain elusive. Here, we examine the control of asymmetric division in Caulobacter crescentus , a bacterium that produces daughter cells with distinct fates and morphologies upon division. Through comprehensive analysis of multi-generational growth and shape data, we uncover a tightly regulated cell size partitioning mechanism. We find that errors in division site positioning are promptly corrected early in the division cycle through differential growth. Our analysis reveals a negative feedback between the size of daughter cell compartments and their growth rates, wherein the larger compartment grows slower to achieve a homeostatic size partitioning ratio at division. To explain these observations, we propose a mechanistic model of differential growth, in which equal amounts of growth regulators are partitioned into daughter cell compartments of unequal sizes and maintained over time via size-independent synthesis., (© 2024 Ng et al.)

Bacteria are highly adaptive microorganisms that thrive in a wide range of growth conditions via changes in cell morphologies and macromolecular composition. How bacterial morphologies are regulated in diverse environmental conditions is a long-standing question. Regulation of cell size and shape implies control mechanisms that couple the growth and division of bacteria to their cellular environment and macromolecular composition. In the past decade, simple quantitative laws have emerged that connect cell growth to proteomic composition and the nutrient availability. However, the relationships between cell size, shape, and growth physiology remain challenging to disentangle and unifying models are lacking. In this review, we focus on regulatory models of cell size control that reveal the connections between bacterial cell morphology and growth physiology. In particular, we discuss how changes in nutrient conditions and translational perturbations regulate the cell size, growth rate, and proteome composition. Integrating quantitative models with experimental data, we identify the physiological principles of bacterial size regulation, and discuss the optimization strategies of cellular resource allocation for size control., (© 2021 Federation of European Biochemical Societies.)

In April 2022, The Company of Biologists hosted their first post-pandemic in-person Workshop at Buxted Park Country House in the Sussex countryside. The Workshop, entitled 'Cell size and growth: from single cells to the tree of life', gathered a small group of early-career and senior researchers with expertise in cell size spanning a broad range of organisms, including bacteria, yeast, animal cells, embryos and plants, and working in fields from cell biology to ecology and evolutionary biology. The programme made ample room for fruitful discussions and provided a much-needed opportunity to discuss the most recent findings relating to the regulation of cell size and growth, identify the emerging challenges for the field, and build a community after the pandemic., (© 2022. Published by The Company of Biologists Ltd.)

Bacteria have evolved to develop multiple strategies for antibiotic resistance by effectively reducing intracellular antibiotic concentrations or antibiotic binding affinities, but the role of cell morphology in antibiotic resistance remains poorly understood. By analyzing cell morphological data for different bacterial species under antibiotic stress, we find that bacteria increase or decrease the cell surface-to-volume ratio depending on the antibiotic target. Using quantitative modeling, we show that by reducing the surface-to-volume ratio, bacteria can effectively reduce the intracellular antibiotic concentration by decreasing antibiotic influx. The model further predicts that bacteria can increase the surface-to-volume ratio to induce the dilution of membrane-targeting antibiotics, in agreement with experimental data. Using a whole-cell model for the regulation of cell shape and growth by antibiotics, we predict shape transformations that bacteria can utilize to increase their fitness in the presence of antibiotics. We conclude by discussing additional pathways for antibiotic resistance that may act in synergy with shape-induced resistance.

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., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Rod-shaped bacterial cells can readily adapt their lengths and widths in response to environmental changes. While many recent studies have focused on the mechanisms underlying bacterial cell size control, it remains largely unknown how the coupling between cell length and width results in robust control of rod-like bacterial shapes. In this study we uncover a conserved surface-to-volume scaling relation in Escherichia coli and other rod-shaped bacteria, resulting from the preservation of cell aspect ratio. To explain the mechanistic origin of aspect-ratio control, we propose a quantitative model for the coupling between bacterial cell elongation and the accumulation of an essential division protein, FtsZ. This model reveals a mechanism for why bacterial aspect ratio is independent of cell size and growth conditions, and predicts cell morphological changes in response to nutrient perturbations, antibiotics, MreB or FtsZ depletion, in quantitative agreement with experimental data., Competing Interests: NO, DS, SB No competing interests declared, (© 2019, Ojkic et al.)