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

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

Surface-to-volume scaling and aspect ratio preservation in rod-shaped bacteria

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 dat

Molecular and Antigenic Characterization of Reassortant H3N2 Viruses from Turkeys with a Unique Constellation of Pandemic H1N1 Internal Genes

Triple reassortant (TR) H3N2 influenza viruses cause varying degrees of loss in egg production in breeder turkeys. In this study we characterized TR H3N2 viruses isolated from three breeder turkey farms diagnosed with a drop in egg production. The eight gene segments of the virus isolated from the first case submission (FAV-003) were all of TR H3N2 lineage. However, viruses from the two subsequent case submissions (FAV-009 and FAV-010) were unique reassortants with PB2, PA, nucleoprotein (NP) and matrix (M) gene segments from 2009 pandemic H1N1 and the remaining gene segments from TR H3N2. Phylogenetic analysis of the HA and NA genes placed the 3 virus isolates in 2 separate clades within cluster IV of TR H3N2 viruses. Birds from the latter two affected farms had been vaccinated with a H3N4 oil emulsion vaccine prior to the outbreak. The HAl subunit of the H3N4 vaccine strain had only a predicted amino acid identity of 79% with the isolate from FAV-003 and 80% for the isolates from FAV-009 and FAV-0010. By comparison, the predicted amino acid sequence identity between a prototype TR H3N2 cluster IV virus A/Sw/ON/33853/2005 and the three turkey isolates from this study was 95% while the identity between FAV-003 and FAV-009/10 isolates was 91%. When the previously identified antigenic sites A, B, C, D and E of HA1 were examined, isolates from FAV-003 and FAV-009/10 had a total of 19 and 16 amino acid substitutions respectively when compared with the H3N4 vaccine strain. These changes corresponded with the failure of the sera collected from turkeys that received this vaccine to neutralize any of the above three isolates in vitro

Reduced adhesion between cells and substrate confers selective advantage in bacterial colonies

Microbial colonies cultured on agar Petri dishes have become a model system to study biological evolution in populations expanding in space. Processes such as clonal segregation and gene surfing have been shown to be affected by interactions between microbial cells and their environment. In this work we investigate the role of mechanical interactions such as cell-surface adhesion. We compare two strains of the bacterium E. coli: a wild-type strain and a "shaved" strain that adheres less to agar. We show that the shaved strain has a selective advantage over the wild type: although both strains grow with the same rate in liquid media, the shaved strain produces colonies that expand faster on agar. This allows the shaved strain outgrow the wild type when both strains compete for space. We hypothesise that, in contrast to a more common scenario in which selective advantage results from increased growth rate, the higher fitness of the shaved strain is caused by reduced adhesion and friction with the agar surface.Comment: 7 pages, 7 figures, submitted to the EPL Special Issue "Evolutionary modeling and experimental evolution

Cellular resource allocation strategies for cell size and shape control in bacteria.

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

Antibiotic Resistance via Bacterial Cell Shape-Shifting

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