Suboptimal resource allocation in changing environments constrains response and growth in bacteria.
Suboptimal resource allocation in changing environments constrains response and growth in bacteria.
复制标题
DOI：
10.15252/msb.202110597
复制
发表时间：
2021-12
影响因子：
9.9
通讯作者：
Cremer J
中科院分区：
文献类型：
--
作者：
Balakrishnan R;de Silva RT;Hwa T;Cremer J
为了应对波动的条件，微生物通常需要合成新的蛋白质。由于这种合成依赖于足够的生物合成前体，微生物必须设计有效的响应策略来管理消耗前体。为了更好地理解这些策略，我们研究了大肠杆菌对营养条件变化的主动反应，将瞬时基因表达与生长表型联系起来。通过在变化的条件下综合修改基因表达，我们展示了基因对有限的蛋白质合成能力的竞争如何限制细胞反应。尽管存在这种限制，细胞仍大量表达不需要的基因，从而将它们困在前体水平较低的状态，并且补充前体所需的基因在竞争中被击败。与常见的建模假设相反，我们的研究结果强调，细胞不会在不断变化的环境下优化生长，而是表现出固有的反应策略，这些策略可能已经进化以促进其在原生环境中的适应性。所发现的细胞反应的限制和次优性提供了与许多研究应用相关的概念框架，从进化的预测到生物技术中基因回路的改进。对细胞资源向不同基因的分配如何影响大肠杆菌对营养条件变化的反应的分析表明，生长转变是由所遇到的条件直接需要的基因与不需要的基因之间的竞争决定的。
To respond to fluctuating conditions, microbes typically need to synthesize novel proteins. As this synthesis relies on sufficient biosynthetic precursors, microbes must devise effective response strategies to manage depleting precursors. To better understand these strategies, we investigate the active response of Escherichia coli to changes in nutrient conditions, connecting transient gene expression to growth phenotypes. By synthetically modifying gene expression during changing conditions, we show how the competition by genes for the limited protein synthesis capacity constrains cellular response. Despite this constraint cells substantially express genes that are not required, trapping them in states where precursor levels are low and the genes needed to replenish the precursors are outcompeted. Contrary to common modeling assumptions, our findings highlight that cells do not optimize growth under changing environments but rather exhibit hardwired response strategies that may have evolved to promote fitness in their native environment. The constraint and the suboptimality of the cellular response uncovered provide a conceptual framework relevant for many research applications, from the prediction of evolution to the improvement of gene circuits in biotechnology. Analyses of how allocation of cellular resources to different genes shapes Escherichia coli's response to changing nutrient conditions show that growth transitions are determined by the competition between genes that are directly required in the encountered conditions and those that are not.
登录
查看更多内容
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
9.9
作者：
Hermsen, Rutger;Okano, Hiroyuki;Hwa, Terence
通讯作者：
Hwa, Terence
影响因子：
3.2
作者：
CAYLEY, S;RECORD, MT;LEWIS, BA
通讯作者：
LEWIS, BA
影响因子：
64.8
作者：
Erickson DW;Schink SJ;Patsalo V;Williamson JR;Gerland U;Hwa T
通讯作者：
Hwa T
大肠杆菌K-12的构造框架，单基因敲除突变体：Keio Collection。
影响因子：
9.9
作者：
通讯作者：
--