Parameters, architecture and emergent properties of the Pseudomonas aeruginosa LasI/LasR quorum-sensing circuit
Parameters, architecture and emergent properties of the Pseudomonas aeruginosa LasI/LasR quorum-sensing circuit
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DOI：
10.1098/rsif.2022.0825
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发表时间：
2023-03-15
影响因子：
3.9
通讯作者：
Kuttler，Christina
中科院分区：
文献类型：
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作者：
Schuster，Martin;Li，Christina;Kuttler，Christina
群体感应是细菌中广泛存在的过程，它控制集体行为以响应细胞密度。细胞群体通过感知自身产生的化学信号来协调基因表达。虽然这一过程是很好的特点，遗传和生物化学，定量信息的网络特性，包括感应动力学和稳态行为，是稀缺的。在这里，我们将实验与数学建模定量分析的LasI/LasR群体感应途径中的机会致病菌铜绿假单胞菌。我们确定的途径的关键动力学参数，并使用参数化模型，表明群体感应的行为作为一个非线性滞后开关，具有稳定的开和关状态。我们研究了反馈结构的意义，发现信号产生的正反馈对诱导动力学和双稳态至关重要，而受体表达的正反馈和信号产生的负反馈则起次要作用。综上所述，我们基于数据的建模方法揭示了细菌群体感应电路的基本和紧急特性，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发挥作用。
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 pathogenPseudomonas aeruginosa. 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.