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A universal trade-off between growth and lag in fluctuating environments

机译：波动环境中增长和滞后之间的通用权衡

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摘要

The rate of cell growth is crucial for bacterial fitness and drives the allocation of bacterial resources, affecting, for example, the expression levels of proteins dedicated to metabolism and biosynthesis(1,2). It is unclear, however, what ultimately determines growth rates in different environmental conditions. Moreover, increasing evidence suggests that other objectives are also important(3-7), such as the rate of physiological adaptation to changing environments(8,9). A common challenge for cells is that these objectives cannot be independently optimized, and maximizing one often reduces another. Many such trade-offs have indeed been hypothesized on the basis of qualitative correlative studies(8-11). Here we report a trade-off between steady-state growth rate and physiological adaptability in Escherichia coli, observed when a growing culture is abruptly shifted from a preferred carbon source such as glucose to fermentation products such as acetate. These metabolic transitions, common for enteric bacteria, are often accompanied by multi-hour lags before growth resumes. Metabolomic analysis reveals that long lags result from the depletion of key metabolites that follows the sudden reversal in the central carbon flux owing to the imposed nutrient shifts. A model of sequential flux limitation not only explains the observed trade-off between growth and adaptability, but also allows quantitative predictions regarding the universal occurrence of such tradeoffs, based on the opposing enzyme requirements of glycolysis versus gluconeogenesis. We validate these predictions experimentally for many different nutrient shifts in E. coli, as well as for other respiro-fermentative microorganisms, including Bacillus subtilis and Saccharomyces cerevisiae.
机译：细胞生长的速率对于细菌性能至关重要，并且驱动细菌资源的分配，影响例如代谢和生物合成的蛋白质的表达水平（1,2）。然而，尚不清楚，最终决定了不同环境条件下的增长率。此外，越来越多的证据表明，其他目的也很重要（3-7），例如对改变环境的生理适应速率（8,9）。对细胞的共同挑战是这些目标不能独立优化，并且最大化一次通常会减少另一个。许多这样的权衡确实在定性相关研究（8-11）的基础上被假设了。在这里，我们在大肠杆菌中报告稳态生长速率和生理适应性之间的权衡，观察到越来越多的培养物从优选的碳源（例如葡萄糖）以发酵产品如乙酸盐而突然移位。这些代谢转变常见于肠道细菌，通常伴随着增长恢复前的多小时滞后。代谢组分析表明，由于施加的营养偏移，在中央碳通量突然逆转的关键代谢物的耗尽中产生了长滞后。顺序通量限制的模型不仅解释了生长和适应性之间观察到的折衷，而且还允许基于糖醇类与葡糖生成的相反酶要求，允许有关这种权衡的普遍发生的定量预测。我们在实验上实验验证这些预测，在大肠杆菌中的许多不同的营养变换以及其他呼吸症微生物，包括枯草芽孢杆菌和酿酒酵母酿酒酵母。

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  • 来源
    《Nature》 |2020年第7821期|470-474|共5页
  • 作者

    Basan Markus; Honda Tomoya; Christodoulou Dimitris; Horl Manuel; Chang Yu-Fang; Leoncini Emanuele; Mukherjee Avik; Okano Hiroyuki; Taylor Brian R.; Silverman Josh M.; Sanchez Carlos; Williamson James R.; Paulsson Johan; Hwa Terence; Sauer Uwe;

  • 作者单位

    Harvard Med Sch Dept Syst Biol Boston MA 02115 USA|Swiss Fed Inst Technol Inst Mol Syst Biol Zurich Switzerland;

    Univ Calif San Diego Div Biol Sci Sect Mol Biol La Jolla CA 92093 USA;

    Swiss Fed Inst Technol Inst Mol Syst Biol Zurich Switzerland;

    Swiss Fed Inst Technol Inst Mol Syst Biol Zurich Switzerland;

    Harvard Med Sch Dept Syst Biol Boston MA 02115 USA;

    Harvard Med Sch Dept Syst Biol Boston MA 02115 USA;

    Harvard Med Sch Dept Syst Biol Boston MA 02115 USA;

    Univ Calif San Diego Dept Phys La Jolla CA 92093 USA;

    Univ Calif San Diego Dept Phys La Jolla CA 92093 USA;

    Scripps Res Inst Dept Integrat Struct & Computat Biol La Jolla CA 92037 USA|Scripps Res Inst Skaggs Inst Chem Biol La Jolla CA 92037 USA;

    Harvard Med Sch Dept Syst Biol Boston MA 02115 USA;

    Scripps Res Inst Dept Integrat Struct & Computat Biol La Jolla CA 92037 USA|Scripps Res Inst Skaggs Inst Chem Biol La Jolla CA 92037 USA;

    Harvard Med Sch Dept Syst Biol Boston MA 02115 USA;

    Univ Calif San Diego Div Biol Sci Sect Mol Biol La Jolla CA 92093 USA|Univ Calif San Diego Dept Phys La Jolla CA 92093 USA;

    Swiss Fed Inst Technol Inst Mol Syst Biol Zurich Switzerland;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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