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Emergence of diauxie as an optimal growth strategy under resource allocation constraints in cellular metabolism.

ABSTRACT: Diauxie, or the sequential consumption of carbohydrates in bacteria such as Escherichia coli, has been hypothesized to be an evolutionary strategy which allows the organism to maximize its instantaneous specific growth-giving the bacterium a competitive advantage. Currently, the computational techniques used in industrial biotechnology fall short of explaining the intracellular dynamics underlying diauxic behavior. In particular, the understanding of the proteome dynamics in diauxie can be improved. We developed a robust iterative dynamic method based on expression- and thermodynamically enabled flux models to simulate the kinetic evolution of carbohydrate consumption and cellular growth. With minimal modeling assumptions, we couple kinetic uptakes, gene expression, and metabolic networks, at the genome scale, to produce dynamic simulations of cell cultures. The method successfully predicts the preferential uptake of glucose over lactose in E. coli cultures grown on a mixture of carbohydrates, a manifestation of diauxie. The simulated cellular states also show the reprogramming in the content of the proteome in response to fluctuations in the availability of carbon sources, and it captures the associated time lag during the diauxie phenotype. Our models suggest that the diauxic behavior of cells is the result of the evolutionary objective of maximization of the specific growth of the cell. We propose that genetic regulatory networks, such as the lac operon in E. coli, are the biological implementation of a robust control system to ensure optimal growth.

SUBMITTER: Salvy P

PROVIDER: S-EPMC7923608 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Emergence of diauxie as an optimal growth strategy under resource allocation constraints in cellular metabolism.

Salvy Pierre P Hatzimanikatis Vassily V

Proceedings of the National Academy of Sciences of the United States of America 20210201 8

Diauxie, or the sequential consumption of carbohydrates in bacteria such as <i>Escherichia coli</i>, has been hypothesized to be an evolutionary strategy which allows the organism to maximize its instantaneous specific growth-giving the bacterium a competitive advantage. Currently, the computational techniques used in industrial biotechnology fall short of explaining the intracellular dynamics underlying diauxic behavior. In particular, the understanding of the proteome dynamics in diauxie can b ...[more]

PMID: 33602812

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Project description:BackgroundThe new waves of COVID-19 outbreaks caused by the SARS-CoV-2 Omicron variant are developing rapidly and getting out of control around the world, especially in highly populated regions. The healthcare capacity (especially the testing resources, vaccination coverage, and hospital capacity) is becoming extremely insufficient as the demand will far exceed the supply. To address this time-critical issue, we need to answer a key question: How can we effectively infer the daily transmission risks in different districts using machine learning methods and thus lay out the corresponding resource prioritization strategies, so as to alleviate the impact of the Omicron outbreaks?MethodsWe propose a computational method for future risk mapping and optimal resource allocation based on the quantitative characterization of spatiotemporal transmission patterns of the Omicron variant. We collect the publicly available data from the official website of the Hong Kong Special Administrative Region (HKSAR) Government and the study period in this paper is from December 27, 2021 to July 17, 2022 (including a period for future prediction). First, we construct the spatiotemporal transmission intensity matrices across different districts based on infection case records. With the constructed cross-district transmission matrices, we forecast the future risks of various locations daily by means of the Gaussian process. Finally, we develop a transmission-guided resource prioritization strategy that enables effective control of Omicron outbreaks under limited capacity.ResultsWe conduct a comprehensive investigation of risk mapping and resource allocation in Hong Kong, China. The maps of the district-level transmission risks clearly demonstrate the irregular and spatiotemporal varying patterns of the risks, making it difficult for the public health authority to foresee the outbreaks and plan the responses accordingly. With the guidance of the inferred transmission risks, the developed prioritization strategy enables the optimal testing resource allocation for integrative case management (including case detection, quarantine, and further treatment), i.e., with the 300,000 testing capacity per day; it could reduce the infection peak by 87.1% compared with the population-based allocation strategy (case number reduces from 20,860 to 2689) and by 24.2% compared with the case-based strategy (case number reduces from 3547 to 2689), significantly alleviating the burden of the healthcare system.ConclusionsComputationally characterizing spatiotemporal transmission patterns allows for the effective risk mapping and resource prioritization; such adaptive strategies are of critical importance in achieving timely outbreak control under insufficient capacity. The proposed method can help guide public-health responses not only to the Omicron outbreaks but also to the potential future outbreaks caused by other new variants. Moreover, the investigation conducted in Hong Kong, China provides useful suggestions on how to achieve effective disease control with insufficient capacity in other highly populated countries and regions.

Dataset Information

Emergence of diauxie as an optimal growth strategy under resource allocation constraints in cellular metabolism.

Publications

Emergence of diauxie as an optimal growth strategy under resource allocation constraints in cellular metabolism.

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