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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >High Stimulus Unmasks Positive Feedback In An Autoregulated Bacterial Signaling Circuit
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High Stimulus Unmasks Positive Feedback In An Autoregulated Bacterial Signaling Circuit

机译：高刺激力掩盖了自动调节细菌信号电路中的正反馈

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摘要

We examined the effect of positive autoregulation on the steady-state behavior of the PhoQ/PhoP two-component signaling system in Escherichia coli. We found that autoregulation has no effect on the steady-state output for a large range of input stimulus, which was modulated by varying the concentration of magnesium in the growth medium. We provide an explanation for this finding with a simple model of the PhoQ/PhoP circuit. The model predicts that even when autoregulation is manifest across a range of stimulus levels, the effects of positive feedback on the steady-state output emerge only in the limit that the system is strongly stimulated. Consistent with this prediction, amplification associated with autoregulation was observed in growth-limiting levels of magnesium, a condition that strongly activates PhoQ/PhoP. In a further test of the model, we found that strains harboring a phosphatase-defective PhoQ showed strong positive feedback and considerable cell-to-cell variability under growth conditions where the wild-type circuit did not show this behavior. Our results demonstrate a simple and general mechanism for regulating the positive feedback associated with autoregulation within a bacterial signaling circuit to boost response range and maintain a relatively uniform and graded output.
机译：我们检查了阳性自动调节对大肠杆菌中PhoQ / PhoP两组分信号系统的稳态行为的影响。我们发现，对于大范围的输入刺激，自动调节对稳态输出没有影响，这通过改变生长培养基中镁的浓度来调节。我们用一个简单的PhoQ / PhoP电路模型为这一发现提供了解释。该模型预测，即使在一系列刺激水平上都表现出自动调节，正反馈对稳态输出的影响也只会在强烈刺激系统的极限内出现。与该预测一致，在镁的生长限制水平中观察到了与自动调节相关的扩增，该条件强烈激活了PhoQ / PhoP。在对该模型的进一步测试中，我们发现，带有磷酸酶缺陷的PhoQ的菌株在野生型电路未表现出此行为的生长条件下显示出强的正反馈和相当大的细胞间变异性。我们的结果证明了一种简单而通用的机制，可用于调节与细菌信号传导回路中的自动调节相关的正反馈，从而提高响应范围并保持相对均匀且分级的输出。

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