Phenotypic bistability in Escherichia coli's central carbon metabolism.
Phenotypic bistability in Escherichia coli's central carbon metabolism.
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DOI：
10.15252/msb.20135022
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发表时间：
2014-07-01
影响因子：
9.9
通讯作者：
Heinemann M
中科院分区：
文献类型：
--
作者：
Kotte O;Volkmer B;Radzikowski JL;Heinemann M
细胞内分子丰度的波动可能导致同基因群体中不同的、共存的表型。尽管新陈代谢不断适应不可预测的环境变化，并且尽管在某些底物吸收途径中发现了双稳定性，但中心碳代谢被认为是确定性地运行的。在这里，我们结合实验和理论来证明克隆大肠杆菌群体在葡萄糖-糖异生底物转移后分裂成两个随机产生的表型亚群。大多数细胞抑制生长，进入休眠持续状态，表现为群体生长曲线的滞后期。亚群生成机制位于代谢核心，主导代谢和转录网络，并且只允许细胞生长最初达到足够高的糖异生通量。因此，中央代谢并不能确保单个细胞的糖异生生长，而是利用群体水平的适应，导致对营养变化的响应性多样化。
Fluctuations in intracellular molecule abundance can lead to distinct, coexisting phenotypes in isogenic populations. Although metabolism continuously adapts to unpredictable environmental changes, and although bistability was found in certain substrate-uptake pathways, central carbon metabolism is thought to operate deterministically. Here, we combine experiment and theory to demonstrate that a clonal Escherichia coli population splits into two stochastically generated phenotypic subpopulations after glucose-gluconeogenic substrate shifts. Most cells refrain from growth, entering a dormant persister state that manifests as a lag phase in the population growth curve. The subpopulation-generating mechanism resides at the metabolic core, overarches the metabolic and transcriptional networks, and only allows the growth of cells initially achieving sufficiently high gluconeogenic flux. Thus, central metabolism does not ensure the gluconeogenic growth of individual cells, but uses a population-level adaptation resulting in responsive diversification upon nutrient changes.