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建模反馈在细菌群体感应自适应反应中的作用。

Modeling the Role of Feedback in the Adaptive Response of Bacterial Quorum Sensing.

机构信息

Department of Mathematics, University of Utah, Salt Lake City, UT, 84112, USA.

出版信息

Bull Math Biol. 2019 May;81(5):1479-1505. doi: 10.1007/s11538-019-00570-8. Epub 2019 Jan 28.

DOI:10.1007/s11538-019-00570-8
PMID:30693430
Abstract

Bacterial quorum sensing (QS) is a form of intercellular communication that relies on the production and detection of diffusive signaling molecules called autoinducers. Such a mechanism allows the bacteria to track their cell density in order to regulate group behavior, such as biofilm formation and bioluminescence. In a number of bacterial QS systems, including V. harveyi, multiple signaling pathways are integrated into a single phosphorylation-dephosphorylation cycle. In this paper, we propose a weight control mechanism, in which QS uses feedback loops to 'decode' the integrated signals by actively changing the sensitivity in different pathways. We first use a slow/fast analysis to reduce a single-cell model to a planar dynamical system involving the concentrations of phosphorylated signaling protein LuxU and a small non-coding RNA. In addition to identifying the weight control mechanism, we show that adding a feedback loop can lead to a bistable QS response in certain parameter regimes. We then combine the slow/fast analysis with a contraction mapping theorem in order to reduce a population model to an effective single-cell model, and show how the weight control mechanism allows bacteria to have a finer discrimination of their social and physical environment.

摘要

细菌群体感应 (QS) 是一种细胞间通讯形式,依赖于扩散信号分子(称为自诱导物)的产生和检测。这种机制使细菌能够跟踪其细胞密度,以调节群体行为,如生物膜形成和生物发光。在包括 V. harveyi 在内的许多细菌 QS 系统中,多个信号通路被整合到一个单一的磷酸化-去磷酸化循环中。在本文中,我们提出了一种权重控制机制,其中 QS 通过主动改变不同通路中的敏感性来利用反馈回路“解码”整合信号。我们首先使用慢/快分析将单细胞模型简化为一个涉及磷酸化信号蛋白 LuxU 和一个小非编码 RNA 浓度的平面动力系统。除了识别权重控制机制外,我们还表明,在某些参数范围内,添加反馈回路可以导致 QS 响应的双稳态。然后,我们将慢/快分析与收缩映射定理结合起来,将群体模型简化为有效的单细胞模型,并展示权重控制机制如何使细菌能够更精细地识别其社会和物理环境。

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