Quantitative modelling of bacterial growth physiology, cell size and shape control

Bacteria are highly adaptive microorganisms that proliferate in a wide range of environmental conditions via changes in cell size, shape and molecular composition. How bacterial cell size, shapes and physiological properties are regulated in diverse environmental conditions are questions of longstanding interest. Regulation of cell size and shape imply cellular control mechanisms that couple bacterial growth and division processes to their cellular environment and molecular composition. Studies in the past decades have revealed many fundamental principles of bacterial growth physiology, in particular the relationship between cellular growth rate, proteome composition and the nutrient environment. However, the quantitative relations defining the interdependence of cell growth and morphology, together with the molecular mechanisms underlying the control of bacterial cell morphology remain poorly understood. In this thesis I develop quantitative theory and models for bacterial growth dynamics that link cellular proteome with cell size and division control (Chapter 2), cell shape control (Chapter 3), regulation of bacterial growth and morphology in the presence of antibiotic stress (Chapter 4), and energy allocation strategies for cellular growth and shape control (Chapter 5). My work reveals that cell size maintenance under nutrient perturbations requires a balanced trade-off between ribosomes and division protein synthesis. Deviations from this tradeoff relationship are predicted under translation inhibition, leading to distinct modes of cell morphological changes, in agreement with single-cell data on Escherichia coli growth and cell morphology. Using the particular example of ribosome-targeting antibiotics, I present a systems-level model for the regulation of cell shape and growth physiology under antibiotic stress, and uncover various feedback mechanisms that bacteria can harness to increase their fitness in the presence of antibiotics