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研究揭示细菌在波动环境中存在生长与停滞的权衡
2020-07-16 17:07

瑞士苏黎世联邦理工学院Uwe Sauer、Markus Basan和美国加州大学圣地亚哥分校Terence Hwa课题组合作发现,在波动环境中细菌存在生长与生长滞后间的普遍权衡 。2020年7月15日出版的《自然》杂志在线发表了这项成果。

研究人员观察到当生长培养基从一种首选碳源(例如葡萄糖)突然转移到发酵产物(例如乙酸盐)时,大肠杆菌在稳态生长速率和生理适应性之间需要进行权衡。肠道细菌这些常见的新陈代谢转变通常会伴随数小时的滞后才能恢复生长。代谢组学分析表明,长期滞后是由于关键营养物耗竭导致的,而关键代谢物的耗竭是由于外加养分的变化使中心碳通量突然反转所致。

有序能量限制模型不仅可以解释研究人员观察到的增长与适应性之间的协调,而且可以基于糖酵解与糖异生对酶的需求,对这种普遍发生的协调进行定量预测。研究人员通过实验验证了大肠杆菌中许多不同养分变化的影响以及预测了其他的呼吸发酵微生物(包括枯草芽孢杆菌和酿酒酵母)。

据了解,细菌的生长速度对于细菌适应性至关重要,并调控细菌资源分配,例如影响专门用于代谢和生物合成蛋白质的表达水平。但是,目前尚不清楚什么最终决定了不同环境条件下细菌的增长率。此外,越来越多的证据表明,其他条件也很重要,例如对不断变化环境的生理适应速度。细胞面临的共同挑战是这些影响因素无法独立优化,往往最大化一个条件会降低另一个。人们在相关定性研究的基础上假设了许多折衷的方案。

附:英文原文

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

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

Issue&Volume: 2020-07-15

Abstract: 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 biosynthesis1,2. It is unclear, however, what ultimately determines growth rates in different environmental conditions. Moreover, increasing evidence suggests that other objectives are also important3,4,5,6,7, such as the rate of physiological adaptation to changing environments8,9. 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 studies8,9,10,11. 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.

DOI: 10.1038/s41586-020-2505-4

Source: https://www.nature.com/articles/s41586-020-2505-4

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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