A stochastic model of Escherichia coli AI-2 quorum signal circuit reveals alternative synthesis pathways.
A stochastic model of Escherichia coli AI-2 quorum signal circuit reveals alternative synthesis pathways.
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DOI：
10.1038/msb4100107
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发表时间：
2006
影响因子：
9.9
通讯作者：
Bentley, William E
中科院分区：
文献类型：
--
作者：
Li, Jun;Wang, Liang;Hashimoto, Yoshifumi;Tsao, Chen-Yu;Wood, Thomas K;Valdes, James J;Zafiriou, Evanghelos;Bentley, William E
群体感应（QS）是细菌表型的重要决定因素。许多细胞功能是由复杂和多模式的QS信号转导过程调节的。LuxS/AI-2 QS系统在真细菌中高度保守，AI-2被报道为“通用”信号分子。为了理解AI-2电路的层次组织，开发了一种结合随机模拟的综合方法。我们研究了AI-2的合成、摄取和调节，提出了可检验的假设，并取得了几项发现：（1）AI-2合酶（Pfs和LuxS）的mRNA转录和蛋白水平并不导致AI-2水平的显着增加细胞在葡萄糖存在下生长时发现的AI-2;（2）在葡萄糖存在下，通过该合成途径的代谢通量的伴随增加仅部分地解释了这种差异。我们预测，“高通量”的替代途径或额外的生物步骤参与AI-2的合成;（3）实验结果验证了这一假设。这项工作表明了细胞生理学与基于系统的随机模型，可以重新组装与生化途径的部分知识的实用程序。
Quorum sensing (QS) is an important determinant of bacterial phenotype. Many cell functions are regulated by intricate and multimodal QS signal transduction processes. The LuxS/AI-2 QS system is highly conserved among Eubacteria and AI-2 is reported as a ‘universal' signal molecule. To understand the hierarchical organization of AI-2 circuitry, a comprehensive approach incorporating stochastic simulations was developed. We investigated the synthesis, uptake, and regulation of AI-2, developed testable hypotheses, and made several discoveries: (1) the mRNA transcript and protein levels of AI-2 synthases, Pfs and LuxS, do not contribute to the dramatically increased level of AI-2 found when cells are grown in the presence of glucose; (2) a concomitant increase in metabolic flux through this synthesis pathway in the presence of glucose only partially accounts for this difference. We predict that ‘high-flux' alternative pathways or additional biological steps are involved in AI-2 synthesis; and (3) experimental results validate this hypothesis. This work demonstrates the utility of linking cell physiology with systems-based stochastic models that can be assembled de novo with partial knowledge of biochemical pathways.