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首页> 外文期刊>Journal of Bioinformatics and Computational Biology >Mathematical model of LsrR- binding and derepression in Escherichia coli K12
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Mathematical model of LsrR- binding and derepression in Escherichia coli K12

机译：大肠杆菌K12中LsrR结合和去抑制的数学模型

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Quorum sensing (QS) enables bacterial communication and collective behavior in response to self-secreted signaling molecules. Unlocking its genetic regulation will provide insight towards understanding its influence on pathogenesis, formation of biofilms, and many other phenotypes. There are few datasets available that link QS-mediated gene expression to its regulatory components and even fewer mathematical models that incorporate known mechanistic detail. By integrating these data with annotated sequence information, mathematical inferences can be pieced together that shed light on regulatory structure. A first principles model, developed here for the E. coli QS system, builds on known mechanistic detail and is used to develop a working model of LuxS-regulated (Lsr) activity. That is, our model is meant to discriminate among hypothetical mechanisms governing lsr transcriptional regulation. Our simulations are in qualitative agreement with experimentally observed data. Importantly, our results point to the importance of transcriptional regulator, LsrR, cycling on genetic control. We also found several experimental observations in E. coli and homologous systems that were not explained by current mechanistic understanding. For example, by comparing simulations with reports of the integrating host factor in Aggrigatibacter actinomycetemcomitans, we conclude that additional transcriptional components are likely involved. An iterative process of simulation and experiment, therefore, is needed to inform new experiments and incorporate new model detail, the benefit of which will more rapidly validate mechanistic understanding.
机译：群体感应 （QS） 使细菌能够响应自我分泌的信号分子进行交流和集体行为。解开其遗传调控将为了解其对发病机制、生物膜形成和许多其他表型的影响提供见解。很少有可用的数据集将QS介导的基因表达与其调控成分联系起来，而包含已知机制细节的数学模型就更少了。通过将这些数据与带注释的序列信息相结合，可以拼凑出数学推论，从而阐明监管结构。这里为大肠杆菌QS系统开发的第一性原理模型建立在已知的机理细节之上，用于开发LuxS调节（Lsr）活性的工作模型。也就是说，我们的模型旨在区分控制lsr转录调控的假设机制。我们的模拟结果与实验观测数据在质量上是一致的。重要的是，我们的研究结果指出了转录调节因子LsrR循环对遗传控制的重要性。我们还在大肠杆菌和同源系统中发现了一些实验观察结果，这些观察结果无法用目前的机制理解来解释。例如，通过将模拟与放线菌中整合宿主因子的报告进行比较，我们得出结论，可能涉及其他转录成分。因此，需要一个模拟和实验的迭代过程来为新的实验提供信息，并纳入新的模型细节，其好处将更快地验证机理理解。

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