Department of Microbiology, Oregon State University, Corvallis, OR 97331, USA.
Department of Mathematics, Technische Universität München, 85748 Garching, Germany.
J R Soc Interface. 2023 Mar;20(200):20220825. doi: 10.1098/rsif.2022.0825. Epub 2023 Mar 15.
Quorum sensing is a widespread process in bacteria that controls collective behaviours in response to cell density. Populations of cells coordinate gene expression through the perception of self-produced chemical signals. Although this process is well-characterized genetically and biochemically, quantitative information about network properties, including induction dynamics and steady-state behaviour, is scarce. Here we integrate experiments with mathematical modelling to quantitatively analyse the LasI/LasR quorum sensing pathway in the opportunistic pathogen . We determine key kinetic parameters of the pathway and, using the parametrized model, show that quorum sensing behaves as a bistable hysteretic switch, with stable on and off states. We investigate the significance of feedback architecture and find that positive feedback on signal production is critical for induction dynamics and bistability, whereas positive feedback on receptor expression and negative feedback on signal production play a minor role. Taken together, our data-based modelling approach reveals fundamental and emergent properties of a bacterial quorum sensing circuit, and provides evidence that native quorum sensing can indeed function as the gene expression switch it is commonly perceived to be.
群体感应是一种广泛存在于细菌中的过程，它可以根据细胞密度来控制集体行为。细菌通过感知自身产生的化学信号来协调基因表达。尽管这一过程在遗传和生化方面已经得到了很好的描述，但关于网络特性的定量信息，包括诱导动力学和稳态行为，仍然很少。在这里，我们将实验与数学建模相结合，对机会性病原体 中的 LasI/LasR 群体感应途径进行定量分析。我们确定了该途径的关键动力学参数，并使用参数化模型表明，群体感应行为表现为双稳态滞后开关，具有稳定的开启和关闭状态。我们研究了反馈架构的重要性，并发现信号产生的正反馈对于诱导动力学和双稳态性至关重要，而受体表达的正反馈和信号产生的负反馈则起着次要作用。总之，我们基于数据的建模方法揭示了细菌群体感应回路的基本和新兴特性，并提供了证据表明，天然群体感应确实可以作为基因表达开关，这是人们普遍认为的。
