合成生物学应用于微生物群体感应的研究进展

Research advance in the application of synthetic biology methods in microbial quorum sensing

细菌是一种单细胞生物,在自然环境中具有群体特征与组织化特性.群体感应信号(quorum sensing,QS)是细菌适应环境变化、调控基因表达和协调群体行为的通讯语言.QS系统广泛存在于各类微生物(细菌、真菌、古菌)并调控多种生理行为,包括生物发光、生物被膜(biofilm)的形成、毒力因子的产生和共生关系的建立等.然而,鉴于自然界中微生物群落结构的多样性和功能的复杂性,QS介导下的调控网络和生态机制依然存在未知领域.近年来,合成生物学的蓬勃发展为认识QS效应提供了新的契机.合成生物学在设计遗传元件库、组装生物装置、设计遗传电路和创建预见性群落行为等方面取得了卓越的研究成果;该方法也为研究QS在调节微生物群落的组成和功能上提供了重要工具.鉴于此,本文尝试对最新的进展作一综述.首先介绍了QS系统及其主要功能作用和信号传导途径;其次,讨论了如何利用合成生物学来设计QS过程信号通路和遗传电路,并减少感应通路的串扰;最后,评估了合成感应系统的方法以及该方法在微生物种内和种间通讯中的表现.本文旨在梳理合成生物学的先进理念,加深对基于微生物QS系统构建计算工具、调控种群密度和代谢流等方面的理解,拓展合成生物学手段操纵QS领域的应用范围.

Bacteria exist as a unicellular organism with their community and systematization characteristics in the environment. Quorum sensing(QS), a language for cell-cell communication, helps bacteria regulate gene expression and community behavior, leading to adaptation to environmental changes. QS system is widespread in many kingdoms of microbiomes(bacteria, fungi, and archaea), which could manipulate various physiological behaviors, including bioluminescence, biofilm formation, producing virulence factors, and establishing symbiosis. However, due to the diversity of the microbial community structure and functional complexity in nature, there are still unknown areas for QS-mediated regulatory networks and ecological mechanisms. The recent vigorous development of synthetic biology may provide new opportunities to probe and explore QS effects. This method has made great achievements in designing genetic element libraries, assembling biological devices, designing genetic circuits, and creating predefined and predictable microbiome consortia. In parallel, synthetic biology can be used as a tool in quorum sensing to regulate the composition and function of communities. Hence, an attempt was made in this review to summarize the latest research. First, we presented several typical QS systems, their functions and signaling pathways. Second, we discussed how to design QS signaling pathways and genetic circuits and how to reduce crosstalk using synthetic biology strategies. Finally, we evaluated the assay on the synthetic QS system and its performance in microbial inter-and intraspecies communication. Thus, this review aims to sort out advanced concepts of synthetic biology, deepen the understanding of constructing a bio-calculation toolkit based on the QS system, control population density and metabolic flow, and expand the application scope of synthetic biology strategy in manipulating QS.