Agent-based modeling of oxygen-responsive transcription factors in Escherichia coli.
Agent-based modeling of oxygen-responsive transcription factors in Escherichia coli.
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DOI：
10.1371/journal.pcbi.1003595
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发表时间：
2014-04
影响因子：
4.3
通讯作者：
Holcombe M
中科院分区：
文献类型：
--
作者：
Bai H;Rolfe MD;Jia W;Coakley S;Poole RK;Green J;Holcombe M
在氧气（O2）存在的情况下，模式细菌大肠杆菌能够通过有氧呼吸保存能量。两种主要的末端氧化酶参与了这一过程：Cyo对O2的亲和力相对较低，但能够泵送质子，因此能量效率很高；Cyd对O2有很高的亲和力，但不抽吸质子。当大肠杆菌遇到具有不同氧可利用性的环境时，编码替代末端氧化酶cydAB和cyoABCDE操作子的基因的表达受到两个O2响应转录因子ArcA（间接O2传感器）和FNR（直接O2传感器）的调控。有研究表明，位于细胞质膜的末端氧化酶对o2的消耗显著影响了细菌类核中ArcA和FNR的活性。在本研究中，采用基于agent的建模方法，基于从高度控制的趋化培养中获得的实验数据，在空间上模拟大肠杆菌对O2的摄取和消耗，以及随后对ArcA和FNR活性的调节。O2分子、转录因子和末端氧化酶被视为单独的因子，它们的行为和相互作用在模拟的三维大肠杆菌细胞中被模仿。该模型表明有两个障碍抑制FNR对O2的反应，即终端氧化酶在膜上消耗O2和O2与细胞质FNR的反应。对FNR变异的分析表明，单体-二聚体转化是FNR介导的基因表达抑制的关键步骤。模型细菌大肠杆菌具有模块化的电子传递链，使其能够在具有不同氧（O2）可用性的环境中成功竞争。它有两个表征良好的末端氧化酶，Cyd和Cyo。Cyd对O2有很高的亲和力，而Cyo的亲和力较低，但能量效率更高。编码Cyd和Cyo的基因的表达受两个o2响应调节因子ArcBA和FNR的控制。然而，O2分子如何进入大肠杆菌细胞以及末端氧化酶和调节因子的位置如何影响系统尚不清楚。提出了一种基于主体的模型，模拟了大肠杆菌细胞中O2与调节因子和氧化酶的相互作用。该模型表明，细胞质膜上的氧化酶和细胞质中的FNR消耗氧气可以保护与类核DNA结合的FNR免于失活，并且FNR响应氧气消耗的二聚化是FNR介导的抑制的关键步骤。因此，基于代理的模型对空间事件的关注提供了信息和新的见解，允许通过简单的添加或删除代理来探索系统组件失调的影响。
In the presence of oxygen (O2) the model bacterium Escherichia coli is able to conserve energy by aerobic respiration. Two major terminal oxidases are involved in this process - Cyo has a relatively low affinity for O2 but is able to pump protons and hence is energetically efficient; Cyd has a high affinity for O2 but does not pump protons. When E. coli encounters environments with different O2 availabilities, the expression of the genes encoding the alternative terminal oxidases, the cydAB and cyoABCDE operons, are regulated by two O2-responsive transcription factors, ArcA (an indirect O2 sensor) and FNR (a direct O2 sensor). It has been suggested that O2-consumption by the terminal oxidases located at the cytoplasmic membrane significantly affects the activities of ArcA and FNR in the bacterial nucleoid. In this study, an agent-based modeling approach has been taken to spatially simulate the uptake and consumption of O2 by E. coli and the consequent modulation of ArcA and FNR activities based on experimental data obtained from highly controlled chemostat cultures. The molecules of O2, transcription factors and terminal oxidases are treated as individual agents and their behaviors and interactions are imitated in a simulated 3-D E. coli cell. The model implies that there are two barriers that dampen the response of FNR to O2, i.e. consumption of O2 at the membrane by the terminal oxidases and reaction of O2 with cytoplasmic FNR. Analysis of FNR variants suggested that the monomer-dimer transition is the key step in FNR-mediated repression of gene expression. The model bacterium Escherichia coli has a modular electron transport chain that allows it to successfully compete in environments with differing oxygen (O2) availabilities. It has two well-characterized terminal oxidases, Cyd and Cyo. Cyd has a very high affinity for O2, whereas Cyo has a lower affinity, but is energetically more efficient. Expression of the genes encoding Cyd and Cyo is controlled by two O2-responsive regulators, ArcBA and FNR. However, it is not clear how O2 molecules enter the E. coli cell and how the locations of the terminal oxidases and the regulators influence the system. An agent-based model is presented that simulates the interactions of O2 with the regulators and the oxidases in an E. coli cell. The model suggests that O2 consumption by the oxidases at the cytoplasmic membrane and by FNR in the cytoplasm protects FNR bound to DNA in the nucleoid from inactivation and that dimerization of FNR in response to O2 depletion is the key step in FNR-mediated repression. Thus, the focus of the agent-based model on spatial events provides information and new insight, allowing the effects of dysregulation of system components to be explored by facile addition or removal of agents.
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影响因子：
3.2
作者：
Becker, S;Holighaus, G;Unden, G
通讯作者：
Unden, G
DOI：
10.1073/pnas.0609514104
发表时间：
2007-02-13
影响因子：
11.1
作者：
Crack, Jason C.;Green, Jeffrey;Thomson, Andrew J.
通讯作者：
Thomson, Andrew J.
影响因子：
4.5
作者：
Myers KS;Yan H;Ong IM;Chung D;Liang K;Tran F;Keleş S;Landick R;Kiley PJ
通讯作者：
Kiley PJ
影响因子：
14.9
作者：
Grainger DC;Aiba H;Hurd D;Browning DF;Busby SJ
通讯作者：
Busby SJ
影响因子：
4.8
作者：
Liu, XQ;De Wulf, P
通讯作者：
De Wulf, P