Abstract
Microbial physiology exhibits growth laws that relate the macromolecular composition of the cell to the growth rate. Recent work has shown that these empirical regularities can be derived from coarse-grained models of resource allocation. While these studies focus on steady-state growth, such conditions are rarely found in natural habitats, where microorganisms are continually challenged by environmental fluctuations. The aim of this paper is to extend the study of microbial growth strategies to dynamical environments, using a self-replicator model. We formulate dynamical growth maximization as an optimal control problem that can be solved using Pontryagin’s Maximum Principle. We compare this theoretical gold standard with different possible implementations of growth control in bacterial cells. We find that simple control strategies enabling growth-rate maximization at steady state are suboptimal for transitions from one growth regime to another, for example when shifting bacterial cells to a medium supporting a higher growth rate. A near-optimal control strategy in dynamical conditions is shown to require information on several, rather than a single physiological variable. Interestingly, this strategy has structural analogies with the regulation of ribosomal protein synthesis by ppGpp in the enterobacterium Escherichia coli. It involves sensing a mismatch between precursor and ribosome concentrations, as well as the adjustment of ribosome synthesis in a switch-like manner. Our results show how the capability of regulatory systems to integrate information about several physiological variables is critical for optimizing growth in a changing environment.
Highlights
Microorganisms adapt their physiology to changes in nutrient availability in the environment
Extending the results reviewed above to dynamical conditions raises the following questions: Are control strategies that maximize steady-state growth optimal in dynamical environments? If this is not the case, which alternative strategies would be optimal for such conditions? And how do these strategies compare with the regulatory mechanisms that have evolved in microorganisms?
Resource allocation in bacteria involves the distribution of cellular resources over processes supporting maintenance and growth [1]
Summary
Microorganisms adapt their physiology to changes in nutrient availability in the environment. The reorganization of gene expression in response to changes in environmental conditions is a resource allocation problem. It poses the question how microorganisms redistribute their protein synthesis capacity over different cellular functions when constrained by the changing environment. The mechanisms responsible for resource allocation in microbial cells are usually assumed to have been optimized through evolution, so as to maximize the offspring of cells in their natural environment. How this general principle manifests itself on the level of cellular physiology is not straightforward though. What counts as optimal is context-dependent, growth and evolution experiments in Escherichia coli have shown that in certain conditions bacterial metabolism is geared towards growth-rate maximization [8,9,10]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
