Evolution and dynamics of regulatory architectures controlling polymyxin B resistance in enteric bacteria.
Evolution and dynamics of regulatory architectures controlling polymyxin B resistance in enteric bacteria.
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控制肠细菌中多粘质B抗性的调节结构的进化和动力学。
DOI：
10.1371/journal.pgen.1000233
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发表时间：
2008-10
期刊：
影响因子：
4.5
通讯作者：
Groisman, Eduardo A.
中科院分区：
文献类型：
--
作者：
Mitrophanov, Alexander Y.;Jewett, Mollie W.;Hadley, Tricia J.;Groisman, Eduardo A.
复杂的遗传网络由决定细胞反应水平和时间的结构模块组成。虽然组成这些模块的监管架构的功能特性已被广泛研究，但监管架构的进化历史在很大程度上仍未被探索。在这里，我们调查之间的过渡直接和间接的监管途径管理诱导耐药性的抗生素多粘菌素B在肠道细菌。我们确定了一种新的监管架构-指定的前馈连接器环-依赖于一个调节蛋白，连接信号转导系统post-acquisitionally，允许一个系统响应激活另一个系统的信号。与直接调节回路相比，前馈连接器回路的特征在于快速激活、缓慢失活和mRNA表达水平升高。我们的研究结果表明，在功能和进化上，前馈连接环是直接转录控制和间接调控之间的过渡阶段。调节蛋白可以直接激活靶基因的表达，即，通过与基因的启动子结合，或间接地，即，通过改变调节因子的表达，进而结合靶基因的启动子并诱导或抑制其转录。间接调节回路可以包含多个组件和功能元件，例如前馈和反馈回路。间接调节的复杂结构提出了其进化起源的问题。在这里，我们研究的动态和进化特性的监管架构，涉及最近出现的一类细菌蛋白质称为连接器的成员。这些蛋白质在炎症后调节双组分系统和磷酸中继的活性，这构成了细菌信号转导的普遍形式。我们描述了一种新的连接器介导的调节电路，结合了直接和间接调节的结构和功能特性。我们的研究结果表明，这种架构是直接和连接器依赖的监管设计之间的进化联系。
Complex genetic networks consist of structural modules that determine the levels and timing of a cellular response. While the functional properties of the regulatory architectures that make up these modules have been extensively studied, the evolutionary history of regulatory architectures has remained largely unexplored. Here, we investigate the transition between direct and indirect regulatory pathways governing inducible resistance to the antibiotic polymyxin B in enteric bacteria. We identify a novel regulatory architecture—designated feedforward connector loop—that relies on a regulatory protein that connects signal transduction systems post-translationally, allowing one system to respond to a signal activating another system. The feedforward connector loop is characterized by rapid activation, slow deactivation, and elevated mRNA expression levels in comparison with the direct regulation circuit. Our results suggest that, both functionally and evolutionarily, the feedforward connector loop is the transitional stage between direct transcriptional control and indirect regulation. A regulatory protein can activate the expression of a target gene either directly, i.e., by binding to the gene's promoter, or indirectly, i.e., by altering the expression of regulators, which, in turn, bind to the target gene's promoter and induce or inhibit its transcription. Indirect regulatory circuits can contain multiple components and functional elements, such as feedforward and feedback loops. The complex structure of indirect regulation raises the question of its evolutionary origins. Here, we study the dynamic and evolutionary properties of regulatory architectures that involve members of the recently emerged class of bacterial proteins termed connectors. Such proteins post-translationally modulate the activity of two-component systems and phosphorelays, which constitute the prevalent form of bacterial signal transduction. We describe a novel connector-mediated regulatory circuit that combines the structural and functional properties of direct and indirect regulation. Our results indicate that this architecture is the evolutionary link between direct and connector-dependent regulatory designs.
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影响因子：
5.6
作者：
Chamnongpol, S;Groisman, EA
通讯作者：
Groisman, EA
影响因子：
3.6
作者：
Gunn, JS;Lim, KB;Miller, SI
通讯作者：
Miller, SI
影响因子：
11.4
作者：
Kox, LFF;Wösten, MMSM;Groisman, EA
通讯作者：
Groisman, EA
影响因子：
2
作者：
Dekel, E;Mangan, S;Alon, U
通讯作者：
Alon, U
DOI：
10.1073/pnas.0408507102
发表时间：
2005-03-08
影响因子：
11.1
作者：
Hooshangi, S;Thiberge, S;Weiss, R
通讯作者：
Weiss, R