The interplay of multiple feedback loops with post-translational kinetics results in bistability of mycobacterial stress response.
The interplay of multiple feedback loops with post-translational kinetics results in bistability of mycobacterial stress response.
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DOI：
10.1088/1478-3975/7/3/036005
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发表时间：
2010-08-23
期刊：
影响因子：
2
通讯作者：
Igoshin OA
中科院分区：
文献类型：
--
作者：
Tiwari A;Balázsi G;Gennaro ML;Igoshin OA
细菌持久性是指细菌群体中基因相同的部分可以通过减少或停止生长而在压力下存活下来的现象。最近，分枝杆菌中的持久性与应激反应网络有关，该网络由 MprA/MprB 双组分系统和替代西格玛因子 σE 组成。该网络包含多个正转录反馈环，可能会产生双稳定性，使其成为控制分枝杆菌持久性开关的良好候选者。为了分析双稳态的可能性，我们开发了一种方法，该方法涉及将网络解耦为转录和翻译后交互模块。因此，我们降低了动力系统的维数，并独立分析了两个模块中的输入输出关系，以根据其对数增益制定双稳态的必要条件。我们表明，MprA/MprB 网络中的正向自动调节和 σE 介导的转录反馈都不足以在生化实际参数范围内诱导双稳态。尽管如此，RseA 对 σE 的翻译后调节增加了系统的有效协同性，从而产生对参数变化具有鲁棒性的双稳态。我们预测，控制超灵敏反应的关键元件 RseA 的过度表达或删除可以消除双稳态。
Bacterial persistence is the phenomenon in which a genetically identical fraction of a bacterial population can survive exposure to stress by reduction or cessation of growth. Persistence in mycobacteria has been recently linked to a stress-response network, consisting of the MprA/MprB two-component system and alternative sigma factor σE. This network contains multiple positive transcriptional feedback loops which may give rise to bistability, making it a good candidate for controlling the mycobacterial persistence switch. To analyze the possibility of bistability, we develop a method that involves decoupling of the network into transcriptional and post-translational interaction modules. As a result we reduce the dimensionality of the dynamical system and independently analyze input–output relations in the two modules to formulate a necessary condition for bistability in terms of their logarithmic gains. We show that neither the positive autoregulation in the MprA/MprB network nor the σE-mediated transcriptional feedback is sufficient to induce bistability in a biochemically realistic parameter range. Nonetheless, inclusion of the post-translational regulation of σE by RseA increases the effective cooperativity of the system, resulting in bistability that is robust to parameter variation. We predict that overexpression or deletion of RseA, the key element controlling the ultrasensitive response, can eliminate bistability.
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DOI：
10.1073/pnas.1631248100
发表时间：
2003-08-19
影响因子：
11.1
作者：
Dahl, JL;Kraus, CN;Barry, CE
通讯作者：
Barry, CE
DOI：
10.1126/science.1161427
发表时间：
2008-10-17
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Choi PJ;Cai L;Frieda K;Xie XS
通讯作者：
Xie XS
影响因子：
13.8
作者：
Ferrell, JE
通讯作者：
Ferrell, JE
影响因子：
3.7
作者：
Berney M;Cook GM
通讯作者：
Cook GM
影响因子：
3.2
作者：
He, HJ;Zahrt, TC
通讯作者：
Zahrt, TC