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 . A model of sequential flux bottlenecks explains a universal trade-off between steady-state growth and physiological adaptation time in bacteria exposed to fluctuating growth conditions.

中文翻译：

---

波动环境中增长与滞后之间的普遍权衡

细胞生长速度对于细菌适应性至关重要，并推动细菌资源的分配，例如影响专用于代谢和生物合成 1, 2 的蛋白质的表达水平。然而，目前尚不清楚是什么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，其他目标也很重要 3-7，例如生理对不断变化的环境的适应率 8、9。细胞面临的一个共同挑战是这些目标无法独立优化，最大化一个目标通常会减少另一个目标。许多这样的权衡确实是在定性相关研究的基础上假设的 8 – 11 。在这里，我们报告了大肠杆菌稳态增长率和生理适应性之间的权衡，当生长的培养物突然从优选的碳源（如葡萄糖）转变为发酵产物（如乙酸盐）时观察到。这些代谢转变对于肠道细菌来说很常见，在恢复生长之前通常会出现数小时的滞后。代谢组学分析表明，由于强加的养分转移，在中心碳通量突然逆转之后，关键代谢物的消耗导致了长时间的滞后。连续通量限制模型不仅解释了观察到的生长和适应性之间的权衡，而且还允许基于糖酵解与糖异生的相反酶需求对这种权衡的普遍发生进行定量预测。我们通过实验验证了这些预测对于大肠杆菌中许多不同的营养变化，以及其他呼吸发酵微生物，包括枯草芽孢杆菌和酿酒酵母。连续通量瓶颈模型解释了暴露于波动生长条件的细菌稳态生长和生理适应时间之间的普遍权衡。