细菌群体感应系统在细胞间通讯中的应用及其合成生物学研究进展

doi:10.12211/2096-8280.2020-043

摘要/Abstract

摘要：

群体感应（quorum sensing，QS）是一种细菌细胞与细胞间的通讯系统，细菌通过分泌扩散性小分子信号感知细菌群体的密度，从而引起一组特定基因在转录水平协调表达。随着研究的不断深入，群体感应相关基因元件及调控原理逐渐清晰。近年来通过合成生物学手段构建包含细菌QS系统组成部分的基因线路，实现了种内和种间的人工通讯，而且这些基于QS的基因线路在生物技术和生物医药等领域有着巨大的应用潜力。本文综述了几种目前研究相对清楚且有代表性的微生物群体感应系统及其主要功能作用，介绍了基于群体感应系统构建的合成生物学基因线路在种内细胞间通讯和种间细胞间通讯的应用，并讨论了微生物群体感应系统研究在构建生物计算工具、调控种群密度和调节代谢流等方面的未来发展前景。

关键词: 群体感应, 种内细胞间通讯, 种间细胞间通讯, 基因线路, 合成生物学

Abstract:

Quorum sensing (QS) is a bacterial cell-to-cell communication system. Bacteria sense the density of bacterial population by secreting diffuse small molecular signals, thus causing the coordinated expression of a group of specific genes at the transcriptional level. With continuous research, the quorum-sensing related genetic elements and the regulatory principles have gradually become clear. In recent years, genetic circuits containing components of the bacterial QS system have been constructed through synthetic biology to achieve intra-species and inter-species artificial communication, and these genetic circuits based on QS have great application potential in biotechnology and biomedicine. This paper reviews several relatively clear and representative microbial quorum sensing systems and their functional roles, and introduces the application of genetic circuits based on quorum sensing systems to intra-species and inter-species cell communication, and discusses the microbial quorum sensing system in constructing biological computing tools, regulating the population density and the flow of metabolism of the future development prospect. For intra-cell communication, we mainly introduced the applications of quorum sensing system in the construction of biological computing tools, which are mainly reflected in the research of toggle switches, biosensors and logic gates in synthetic biology. Toggle switches, biosensors, and logic gates designed based on quorum sensing mechanism can better coordinate cell behavior at the population level by combining with some biological control circuits to achieve precise regulation at the spatial, temporal, and population level. For inter-species cell communication, we mainly discuss the influence of introducing quorum sensing system on controlling population density and regulating metabolic flow. Quorum sensing system is used to redistribute the metabolic fluxes of the desired pathways through the recombination of metabolic network, to realize the regulation of population density and co-culture of mixed strains. Meanwhile, it is also found that the combination of QS system and oscillator model has great potential in regulating the synchronicity of microbial complexes. In summary, the in-depth research on the quorum sensing mechanism and application not only lays a certain foundation for elucidating the mechanism of microbial ecological competition and dynamic balance, but also provides an idea for clarifying the regulation mechanism of pathogenic bacteria and developing new disease control strategies.

Key words: quorum sensing, intra-species cell communication, inter-species cell communication, genetic circuits, synthetic biology

中图分类号:

Q 939.97

李晓萌, 姜威, 梁泉峰, 祁庆生. 细菌群体感应系统在细胞间通讯中的应用及其合成生物学研究进展[J]. 合成生物学, 2020, 1(5): 540-555.

LI Xiaomeng, JIANG Wei, LIANG Quanfeng, QI Qingsheng. Application of bacterial quorum sensing system in intercellular communication and its progress in synthetic biology[J]. Synthetic Biology Journal, 2020, 1(5): 540-555.

图/表 2

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Bacterial species	Regulatory gene	Signal molecule(s)	Functions
Vibrio fischeri	luxI/luxR, luxS-luxP/Q	3-oxo-C6-HSL AI-2	bioluminescence, motility
Pseudomonas aeruginosa	lasI/lasR, rhlI/rhlR, pqsABCDE	3-oxo-C12-HSL C4-HSL HHQ/PQS	virulence, motility and biofilms
Agrobacterium tumefaciens	traI/traR	3-oxo-C8-HSL	plasmid conjugation
Yersinia pseudotuberculosis	ypsI/ypsR, ytbI/ytbR	C6-HSL, 3-oxo-C6-HSL, C8-HSL	motility, clumping and biofilms
Burkholderia cepacia	cepI/cepR	C8-HSL	protease synthesis
Erwinia carotovora	expI/expR, carI/carR	3-oxo-C6-HSL	antibiotic synthesis
Serratia plymuthica	splI/splR, spsI/spsR, sptR	3-oxo-C6-HSL, C6-HSL, C4-HSL	biofilms
Erwinia stewartii	esaI/esaR	3-oxo-C6-HSL	virulence
Rhizobium leguminosarum	rhiI/ rhiR	C6-HSL, C8-HSL 3-hydroxy-7- cis-C14-HSL	expression of rhizosphere genes
Rhodobacter sphaeroides	cerI/cerR	7-cis-C14-HSL	evacuated bacterial accumulation
Aeromonas hydrophila	ahyI/ahyR	C4-HSL	biofilms, exoproteases

Bacterial species	Regulatory gene	Signal molecule(s)	Functions
Vibrio fischeri	luxI/luxR, luxS-luxP/Q	3-oxo-C6-HSL AI-2	bioluminescence, motility
Pseudomonas aeruginosa	lasI/lasR, rhlI/rhlR, pqsABCDE	3-oxo-C12-HSL C4-HSL HHQ/PQS	virulence, motility and biofilms
Agrobacterium tumefaciens	traI/traR	3-oxo-C8-HSL	plasmid conjugation
Yersinia pseudotuberculosis	ypsI/ypsR, ytbI/ytbR	C6-HSL, 3-oxo-C6-HSL, C8-HSL	motility, clumping and biofilms
Burkholderia cepacia	cepI/cepR	C8-HSL	protease synthesis
Erwinia carotovora	expI/expR, carI/carR	3-oxo-C6-HSL	antibiotic synthesis
Serratia plymuthica	splI/splR, spsI/spsR, sptR	3-oxo-C6-HSL, C6-HSL, C4-HSL	biofilms
Erwinia stewartii	esaI/esaR	3-oxo-C6-HSL	virulence
Rhizobium leguminosarum	rhiI/ rhiR	C6-HSL, C8-HSL 3-hydroxy-7- cis-C14-HSL	expression of rhizosphere genes
Rhodobacter sphaeroides	cerI/cerR	7-cis-C14-HSL	evacuated bacterial accumulation
Aeromonas hydrophila	ahyI/ahyR	C4-HSL	biofilms, exoproteases

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