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基于启动子逻辑的细菌群体感应预测。

Prediction by promoter logic in bacterial quorum sensing.

机构信息

National Centre for Biological Sciences, Tata Institute of Fundamental Research, UAS/GKVK Campus, Bangalore, India.

出版信息

PLoS Comput Biol. 2012 Jan;8(1):e1002361. doi: 10.1371/journal.pcbi.1002361. Epub 2012 Jan 19.

Abstract

Quorum-sensing systems mediate chemical communication between bacterial cells, coordinating cell-density-dependent processes like biofilm formation and virulence-factor expression. In the proteobacterial LuxI/LuxR quorum sensing paradigm, a signaling molecule generated by an enzyme (LuxI) diffuses between cells and allosterically stimulates a transcriptional regulator (LuxR) to activate its cognate promoter (pR). By expressing either LuxI or LuxR in positive feedback from pR, these versatile systems can generate smooth (monostable) or abrupt (bistable) density-dependent responses to suit the ecological context. Here we combine theory and experiment to demonstrate that the promoter logic of pR - its measured activity as a function of LuxI and LuxR levels - contains all the biochemical information required to quantitatively predict the responses of such feedback loops. The interplay of promoter logic with feedback topology underlies the versatility of the LuxI/LuxR paradigm: LuxR and LuxI positive-feedback systems show dramatically different responses, while a dual positive/negative-feedback system displays synchronized oscillations. These results highlight the dual utility of promoter logic: to probe microscopic parameters and predict macroscopic phenotype.

摘要

群体感应系统介导细菌细胞之间的化学通讯,协调细胞密度依赖性过程,如生物膜形成和毒力因子表达。在原核生物 LuxI/LuxR 群体感应范例中,一种由酶(LuxI)产生的信号分子在细胞间扩散,并变构刺激转录调节剂(LuxR)激活其同源启动子(pR)。通过从 pR 正向表达 LuxI 或 LuxR,这些多功能系统可以生成平滑(单稳态)或突然(双稳态)的密度依赖性响应,以适应生态环境。在这里,我们结合理论和实验证明,pR 的启动子逻辑——其作为 LuxI 和 LuxR 水平函数的测量活性——包含定量预测此类反馈环响应所需的所有生化信息。启动子逻辑与反馈拓扑的相互作用是 LuxI/LuxR 范例多功能性的基础:LuxR 和 LuxI 正反馈系统显示出截然不同的响应,而双正/负反馈系统则显示出同步振荡。这些结果突出了启动子逻辑的双重用途:探测微观参数和预测宏观表型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f36d/3261908/d1323346567f/pcbi.1002361.g001.jpg

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