The dynamic response of quorum sensing to density is robust to signal supplementation and individual signal synthase knockouts.
The dynamic response of quorum sensing to density is robust to signal supplementation and individual signal synthase knockouts.
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DOI：
10.1099/mic.0.001321
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发表时间：
2023-05
期刊：
影响因子：
2.8
通讯作者：
Brown, Sam P.
中科院分区：
文献类型：
--
作者：
Rattray, Jennifer B.;Kramer, Patrick J.;Gurney, James;Thomas, Stephen;Brown, Sam P.
群体感应（Quorum sensing，QS）是细菌广泛存在的环境感知和行为协调机制。在其核心，QS是基于生产，传感和响应小信号分子。以前的工作与 铜绿假单胞菌 表明QS可用于实现定量分辨率并对细菌的密度环境提供剂量响应，这意味着控制的复杂机制。为了阐明机械信号成分如何有助于对密度的分级响应，我们评估了遗传（阿勒信号合酶缺失）和/或信号补充（外源性阿勒添加）扰动对lasB反应规范密度变化的影响。我们的方法将来自2000个时间序列（超过74000个单独观察）的数据浓缩为QS控制的基因表达的全面视图，涵盖lasB表达的遗传、环境和信号决定因素的变化。我们首先证实，删除（️ lasI、️ rhlI）或两者（️ lasIrhlI）阿勒信号合酶基因会减弱QS对密度的响应。在rhLII背景下，我们显示了由于天然3-oxo-C12-HSL信号传导而导致的持续但衰减的密度依赖性lasB表达。然后，我们测试添加到WT中的阿勒信号（3-氧代-C12-HSL、C4-HSL）的密度无关量是否使对密度的响应性变平或增加，并发现WT响应对所有测试浓度的信号（单独或组合）都是稳健的。然后，我们逐步补充基因敲除，发现单一阿勒信号的同源信号补充（AlasI +3-oxo-C12-HSL，AlrhII + C4 HSL）足以恢复以密度依赖性方式响应密度增加的能力。我们还发现，双重阿勒合酶敲除的双重信号补充恢复了对密度增加产生分级反应的能力，尽管增加了与密度无关的信号量。只有加入高浓度的AHLs和PQS才能迫使最大的lasB表达和消融对密度的反应性。我们的研究结果表明，lasB表达的密度依赖性控制是强大的QS基因缺失和密度无关的信号补充的多种组合。我们的工作开发了一个模块化的方法来查询的鲁棒性和机械基础的中央环境感应表型的群体感应。
Quorum sensing (QS) is a widespread mechanism of environment sensing and behavioural coordination in bacteria. At its core, QS is based on the production, sensing and response to small signalling molecules. Previous work with Pseudomonas aeruginosa shows that QS can be used to achieve quantitative resolution and deliver a dosed response to the bacteria’s density environment, implying a sophisticated mechanism of control. To shed light on how the mechanistic signal components contribute to graded responses to density, we assess the impact of genetic (AHL signal synthase deletion) and/or signal supplementation (exogenous AHL addition) perturbations on lasB reaction-norms to changes in density. Our approach condenses data from 2000 timeseries (over 74 000 individual observations) into a comprehensive view of QS-controlled gene expression across variation in genetic, environmental and signal determinants of lasB expression. We first confirm that deleting either (∆lasI, ∆rhlI) or both (∆lasIrhlI) AHL signal synthase gene attenuates QS response to density. In the ∆rhlI background we show persistent yet attenuated density-dependent lasB expression due to native 3-oxo-C12-HSL signalling. We then test if density-independent quantities of AHL signal (3-oxo-C12-HSL, C4-HSL) added to the WT either flatten or increase responsiveness to density and find that the WT response is robust to all tested concentrations of signal, alone or in combination. We then move to progressively supplementing the genetic knockouts and find that cognate signal supplementation of a single AHL signal (∆lasI +3-oxo-C12-HSL, ∆rhlI +C4HSL) is sufficient to restore the ability to respond in a density-dependent manner to increasing density. We also find that dual signal supplementation of the double AHL synthase knockout restores the ability to produce a graded response to increasing density, despite adding a density-independent amount of signal. Only the addition of high concentrations of both AHLs and PQS can force maximal lasB expression and ablate responsiveness to density. Our results show that density-dependent control of lasB expression is robust to multiple combinations of QS gene deletion and density-independent signal supplementation. Our work develops a modular approach to query the robustness and mechanistic bases of the central environmental sensing phenotype of quorum sensing.
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