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Optimality and robustness in quorum sensing (QS)- mediated regulation of a costly public good enzyme

机译:在群体感应(QS)介导的昂贵公共物品酶调节中的最优性和鲁棒性

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Bacteria secrete a variety of public good exoproducts into their environment. These exoproducts are typically produced under the control of quorum sensing (QS), a signaling mechanism by which bacteria sense and respond to changes in their density. QS seems to provide an advantageous strategy to regulate these costly but beneficial exoproducts: it delays production until sufficiently high cell density, when the overall benefit of exoproducts outweighs cost of their production. This notion raises several fundamental questions about QS as a general control strategy adopted by bacteria. How much delay is advantageous? Under what conditions does QS-mediated regulation become advantageous? How does this advantage depend on the kinetic properties of QS? How robust is a given QS system to the stochastic events that occur over bacterial lifecycles? To quantitatively address these questions, we engineered a gene circuit in Escherichia coli to control the synthesis and secretion of a costly but beneficial exoenzyme. We show that exoenzyme production is overall advantageous only if initiated at a sufficiently high density. This property sets the potential advantage for QS-mediated regulation when the initial density is low and the growth cycle is sufficiently long compared with the exoenzyme response time. This advantage of QS-mediated regulation is robust to varying initial cell densities and growth durations, and it is particularly striking when bacteria face uncertainty, such as from stochastic dispersal during their lifecycle. We show, however, that, for QS to be optimal, its kinetic properties must be appropriately tuned; this property has implications for antibacterial treatments that target QS.
机译:细菌将各种公共物品的外产品分泌到其环境中。这些外产物通常在群体感应(QS)的控制下产生,群体感应是一种信号传导机制,细菌可通过该机制感应并响应其密度的变化。 QS似乎提供了一种有利的策略来调节这些昂贵但有益的外生产物:当外生产物的总体收益超过其生产成本时,它会延迟生产直至足够高的细胞密度。这个概念提出了关于QS作为细菌采用的一般控制策略的几个基本问​​题。延迟多少才有好处? QS介导的监管在什么条件下变得有利?这种优势如何取决于QS的动力学特性?给定的QS系统对细菌生命周期内发生的随机事件的鲁棒性如何?为了定量解决这些问题,我们在大肠杆菌中设计了一个基因电路,以控制昂贵但有益的外切酶的合成和分泌。我们表明,只有在足够高的密度下启动,外切酶的生产才具有总体优势。与外切酶反应时间相比,当初始密度低且生长周期足够长时,此属性为QS介导的调节设置了潜在的优势。 QS介导的调控的这一优势对于改变初始细胞密度和生长持续时间具有鲁棒性,当细菌面临不确定性(例如,生命周期中的随机扩散)时,这一点尤其明显。但是,我们表明,要使QS达到最佳状态,必须适当调整其动力学性能。此特性对靶向QS的抗菌治疗有影响。

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