The dynamic balance of import and export of zinc in Escherichia coli suggests a heterogeneous population response to stress.
The dynamic balance of import and export of zinc in Escherichia coli suggests a heterogeneous population response to stress.
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DOI：
10.1098/rsif.2015.0069
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发表时间：
2015-05-06
期刊：
影响因子：
--
通讯作者：
Stekel DJ
中科院分区：
文献类型：
--
作者：
Takahashi H;Oshima T;Hobman JL;Doherty N;Clayton SR;Iqbal M;Hill PJ;Tobe T;Ogasawara N;Kanaya S;Stekel DJ
锌是生命所必需的，但过量有毒。因此，所有细胞都必须控制其内部锌浓度。我们使用了一个系统的方法，交替轮的实验和模型，以进一步阐明大肠杆菌中的锌控制系统。我们测量了野生型和一系列缺失突变株中主要特异性锌输入和输出系统对锌的反应。我们用详细的数学模型和贝叶斯模型拟合程序解释了这些数据。有三个关键的发现：第一，替代的、不可诱导的进口商和出口商是重要的。第二，内部锌库对于维持内部锌浓度是必不可少的。第三，我们的数据拟合使我们提出细胞对锌产生异质反应：一些细胞有效反应，而另一些细胞死亡或停止生长。在进一步的实验中，我们证明了暴露于过量锌的突变株中活细胞计数较低，与这一假设一致。一个随机模型模拟表明相当大的波动，在ZntA出口蛋白的细胞水平，加强了这一建议。我们假设，保持种群异质性可能是一种赌注对冲反应，允许细胞种群在变化和波动的环境中生存。
Zinc is essential for life, but toxic in excess. Thus all cells must control their internal zinc concentration. We used a systems approach, alternating rounds of experiments and models, to further elucidate the zinc control systems in Escherichia coli. We measured the response to zinc of the main specific zinc import and export systems in the wild-type, and a series of deletion mutant strains. We interpreted these data with a detailed mathematical model and Bayesian model fitting routines. There are three key findings: first, that alternate, non-inducible importers and exporters are important. Second, that an internal zinc reservoir is essential for maintaining the internal zinc concentration. Third, our data fitting led us to propose that the cells mount a heterogeneous response to zinc: some respond effectively, while others die or stop growing. In a further round of experiments, we demonstrated lower viable cell counts in the mutant strain tested exposed to excess zinc, consistent with this hypothesis. A stochastic model simulation demonstrated considerable fluctuations in the cellular levels of the ZntA exporter protein, reinforcing this proposal. We hypothesize that maintaining population heterogeneity could be a bet-hedging response allowing a population of cells to survive in varied and fluctuating environments.
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