细菌群体感应信号网络及其应用

群体感应（Quorum sensing,QS）是一种细菌细胞与细胞间的通讯系统,即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。大量研究已表明,群体感应系统控制细菌多种生理行为和过程,以及与真核宿主（寄主）的互作。参与群体感应调控的信号分子多种多样,QS系统所调控的功能也具有多样性,甚至菌株专化性。通过聚焦同一细菌中由多个QS系统组成的信号网络,综合评述了不同QS系统之间如何相互作用全局调控基因表达,以及QS系统如何通过与其它全局调控系统整合精细调节细菌的社会行为以及环境适应性及其应用前景。     

细菌群体感应及其信号分子介导的植物-细菌跨界信息交流

细菌利用群体感应(Quorum sensing,QS)系统进行细胞间的通讯联系,进而参与调控细菌多种生物学功能。近年的研究表明,细菌QS信号分子也可以被细菌的真核植物宿主感应,从而介导植物-细菌的跨界信息交流。本文综述细菌QS及其介导的植物-细菌信息交流的最新研究进展,以期为通过操纵细菌QS达到提高植物病害防治效果提供理论基础和指导。     

群体感应信号分子AI-2研究进展

群体感应(QS)是细菌根据种群密度的变化调控基因表达,协调群体行为的机制。除具有种特异性的信号分子AI-1外,近年来发现一类新的信号分子AI-2在调控细菌基因表达中起重要作用。AI-2的结构和生物合成途径已被确定,其产生依赖于一种称为LuxS的蛋白。目前认为AI-2在细菌种间交流中起通用信号分子(universalsignal)的作用。了解细菌的QS调控过程以及种间细胞交流的新机制,有助于对细菌病害进行防治。     

真菌群体感应现象的研究进展

群体感应是细菌中普遍存在的细胞与细胞间的通讯系统,即细菌可通过向环境释放可扩散的信号分子来感知细胞群体密度并调控自身的某些生理行为。近年来研究发现,真菌中也存在类似于细菌群体感应信号分子的信息素,并参与调节真菌诸如菌相转化、致病性及次级代谢产物产生等生理行为。主要综述了目前真菌中群体感应系统的研究进展。     

细菌中的群体感应

群体感应(quorum sensing)是细菌根据细胞密度变化进行基因表达调控的一种生理行为。具有群体感应的细菌能产生并释放一种被称为自体诱导物(autoinducer)的信号分子,它随着细胞密度增加而同步增加。当自体诱导物积累到一定浓度时会改变细菌特定基因的表达。革兰氏阳性及阴性细菌通过群体感应与周围环境进行信息交流,从而改变细菌的一系列生理活性,这些细菌的生理特性包括共生、细菌毒性、竞争、接合、抗生素的产生、运动性、孢子及生物膜的形成。这种信号传递方式可能对低等的细胞进一步进化,并形成高等的生物体有重要作用。细菌中群体感应系统的进化可能是多细胞体形成的早期阶段。     

细菌群体感应及其干扰策略的研究进展

群体感应（QS）广泛存在于细菌中,是细菌根据细胞密度变化调控基因表达的一种机制。许多植物病原菌依赖QS调控致病基因和毒性因子的表达,导致植物发病,因此通过抑制QS效应就为控制细菌病害提供了一种有效的方法。目前发现许多途径可以干扰细菌的QS,如：产生可使信号分子降解的酶,产生病原菌信号分子的类似物与信号分子受体蛋白竞争结合来阻断病原菌的群体感应,利用QS中信号分子来诱发寄主抗性。系统阐述了细菌QS及其干扰策略。     

细菌的群体感应及与病原菌致病性的关系

微生物的群体感应(quorum sensing,QS)也称为自诱导,是微生物间通过小分子分泌物(自诱导物)在细胞与细胞之间扩散以感知群体密度,并通过自诱导物的浓度及其与转录因子的相互作用调控整个群体细胞中一系列目标基因表达的一种自我感知系统.不同的细菌类型,其QS系统也有一定的差异.根据信号分子的不同,一般可以将细菌的QS系统分为3类,即以AHL为信号分子的革兰氏阴性细菌、以寡肽类物质为信号分子的革兰氏阳性细菌和以哈氏弧菌为代表的兼具上述两种类型QS系统特征的第三类QS系统.综述革兰氏阴性细菌、革兰氏阳性细菌和哈氏弧菌的3种不同QS系统及其在病原菌致病性方面的研究进展.     

AI-2/LuxS群体感应系统介导乳酸杆菌益生特性研究进展

群体感应(quorum sensing,QS)是细菌间通过化学信号分子进行信息传递的一种形式。信号分子可以分为4大类:寡肽(oligopeptides)、酰基高丝氨酸内酯(acyl-homoserine lactone,AHL)、自体诱导物2(autoinduction-2,AI-2)和扩散信号因子(diffusible signal factor,DSF),其中AI-2和其生物合成关键酶LuxS组成的QS系统(AI-2/LuxS系统)介导革兰氏阳性(G+)和阴性(G-)细菌的种内和种间信息交流。乳酸杆菌(Lactobacillus)是一种存在于人体内的益生菌,具有抑制病原微生物、维持肠道微生态平衡和增强机体免疫力等生理功能。综述了AI-2/LuxS QS系统介导Lactobacillus耐酸、抑制病原微生物、对肠表皮细胞的黏附和形成生物膜以及在动物消化道中的存活性等益生特性方面的分子机制。     

真菌群体感应信号分子及群体感应猝灭的研究进展

群体感应(quorum sensing,QS)是微生物中普遍存在的细胞间通讯系统,细菌中的研究较为深入,近年来在真菌中也有发现。微生物通过向环境释放可扩散的群体感应信号分子(quorum sensing molecules,QSM)来感知群体密度并调控自身的生理行为,以适应环境的变化。目前验证的真菌QSM包括醇类、脂氧合物、小分子肽以及某些挥发性物质。除影响种内的生长发育及次级代谢物产生外,真菌QSM还与其侵染能力、致病性和毒素产生有关,为了抵御QS的不利影响,生物共同进化过程中相应地出现了群体感应淬灭(quorum quenching,QQ)机制,QQ能够修饰或抑制QSM的合成从而破坏QS。本文中,笔者对国内外近10年来对真菌QSM种类、生理作用及QQ的研究进展进行综述,以期为深化真菌群体感应机制的研究提供参考。     

细菌数量阈值感应系统与牙菌斑生物膜

细菌生物膜对医学的影响近年来受到越来越多的关注。研究表明,细菌生物膜的形成不是细菌细胞随意堆积的结果,而是细菌相互协调构成的具有高度分化结构的群体。细菌从浮游的生长状态到形成成长生物膜模式,涉及到多种相互交错的信号传导通路。通过各种信号传导系统,细菌来协调其生理活动,以趋利避害。细菌数量阈值感应系统(quorum sensing,QS)是目前受到广泛关注的细菌信号传导系统,     

喹诺酮信号系统研究进展

喹诺酮信号系统是铜绿假单胞菌群体感应调控网络中一个重要组成部分,对于绿脓菌素和弹性蛋白酶等毒力因子的表达及细菌生物被膜形成和细菌运动具有重要的调控作用,因此与临床细菌感染密切相关。3,4-二羟基-2-庚基-喹诺酮(Pseudomonas quinolone signal,PQS)及2-庚基-4喹诺酮(4-hydroxy-2-heptylquinoline,HHQ)是pqs调控系统中重要的信号分子。PQS对于细菌在压力下群体密度及细菌物质运输具有调控作用,从而增强细菌对于环境的适应能力。同时PQS等分子在一定程度上抑制了人体的免疫系统,帮助细菌在宿主体内生存。HHQ在其他革兰氏阴性细菌及革兰氏阳性细菌中也有合成并发挥调控作用,所以喹诺酮信号分子不仅是种内也是种间交流媒介。将喹诺酮系统作为靶点降低细菌的信号交流是抑制细菌感染的一个新思路。本文对喹诺酮信号系统进行概述。     

铜绿假单胞菌群体感应系统研究进展

群体感应系统是一种细胞密度依赖的基因表达系统,其广泛存在于细菌性病原体中,是细菌细胞通讯方式的一种。群体感应系统可利用细菌释放的信号分子不断监控周围细菌的密度。当细菌密度达到阈值时,群体感应系统网络将启动,参与调控生物被膜、细菌毒力等特定基因的表达,从而使临床抗感染治疗失败。而通过抑制群体感应系统,可一定程度上治疗铜绿假单胞菌引起的感染。本文通过查阅近年国内外相关文献,对铜绿假单胞菌群体感应系统研究进展进行总结,为临床铜绿假单胞菌治疗提供新的方向,即群体感应系统抑制剂有可能成为治疗铜绿假单胞菌感染的新策略。     

噬菌体群体感应系统及其分子机理研究进展

群体感应（Quorum Sensing,QS）是微生物群体在生长过程中,随着群体密度的增加,其分泌的“信号分子”的浓度达到一定阈值后与微生物体内特定受体结合,从而影响微生物特定基因表达,导致其生理和生化特性的变化,表现出少量菌体或单个菌体所不具备的特征。1994年Fuqua提出群体感应概念后就成为微生物领域的研究热点。然而,群体感应的研究主要集中在细菌中,但近年来群体感应在噬菌体、真菌中也不断被发现,尤其自2017年Erez在多种枯草芽孢杆菌噬菌体中发现群体感应现象,并且揭示噬菌体群体感应主要调控其溶原-裂解途径的转换。近年来的研究又陆续在其他噬菌体中发现了群体感应。本文综述了噬菌体群体感应系统最新研究进展及其相关的基因功能和分子机理。     

群体感应与微生物耐药性

微生物耐药性已成为全球关注的严重问题,其演化机制和调控机理也已成为研究热点。近年来的研究发现,一些微生物耐药性机制受到群体感应系统的调控。群体感应是一种在微生物界广泛存在并与菌体密度关联的细胞-细胞间的通讯系统。高密度的菌落群体能够产生足够数量的小分子信号,激活下游包括致病毒力和耐药性机制在内的多种细胞进程,耐受抗生素并且危害寄主。本文结合国内外最新的研究进展,对微生物群体感应系统的研究现状进行了概括性介绍,重点阐述了群体感应系统对微生物耐药性机制的调控作用,如微生物生物被膜形成和药物外排泵调控等方面的作用,并探讨了利用群体淬灭控制微生物耐药性的新策略。     

Single Cell Analysis of a Bacterial Sender-Receiver System

Monitoring gene expression dynamics on the single cell level provides important information on cellular heterogeneity and stochasticity, and potentially allows for more accurate quantitation of gene expression processes. We here study bacterial senders and receivers genetically engineered with components of the quorum sensing system derived from Aliivibrio fischeri on the single cell level using microfluidics-based bacterial chemostats and fluorescence video microscopy. We track large numbers of bacteria over extended periods of time, which allows us to determine bacterial lineages and filter out subpopulations within a heterogeneous population. We quantitatively determine the dynamic gene expression response of receiver bacteria to varying amounts of the quorum sensing inducer N-3-oxo-C6-homoserine lactone (AHL). From this we construct AHL response curves and characterize gene expression dynamics of whole bacterial populations by investigating the statistical distribution of gene expression activity over time. The bacteria are found to display heterogeneous induction behavior within the population. We therefore also characterize gene expression in a homogeneous bacterial subpopulation by focusing on single cell trajectories derived only from bacteria with similar induction behavior. The response at the single cell level is found to be more cooperative than that obtained for the heterogeneous total population. For the analysis of systems containing both AHL senders and receiver cells, we utilize the receiver cells as ‘bacterial sensors’ for AHL. Based on a simple gene expression model and the response curves obtained in receiver-only experiments, the effective AHL concentration established by the senders and their ‘sending power’ is determined.     

Early development and quorum sensing in bacterial biofilms

 We develop mathematical models to examine the formation, growth and quorum sensing activity of bacterial biofilms. The growth aspects of the model are based on the assumption of a continuum of bacterial cells whose growth generates movement, within the developing biofilm, described by a velocity field. A model proposed in Ward et al. (2001) to describe quorum sensing, a process by which bacteria monitor their own population density by the use of quorum sensing molecules (QSMs), is coupled with the growth model. The resulting system of nonlinear partial differential equations is solved numerically, revealing results which are qualitatively consistent with experimental ones. Analytical solutions derived by assuming uniform initial conditions demonstrate that, for large time, a biofilm grows algebraically with time; criteria for linear growth of the biofilm biomass, consistent with experimental data, are established. The analysis reveals, for a biologically realistic limit, the existence of a bifurcation between non-active and active quorum sensing in the biofilm. The model also predicts that travelling waves of quorum sensing behaviour can occur within a certain time frame; while the travelling wave analysis reveals a range of possible travelling wave speeds, numerical solutions suggest that the minimum wave speed, determined by linearisation, is realised for a wide class of initial conditions. Received: 10 February 2002 / Revised version: 29 October 2002 / Published online: 19 March 2003 Key words or phrases: Bacterial biofilm – Quorum sensing – Mathematical modelling – Numerical solution – Asymptotic analysis – Travelling wave analysis     

群体感应系统在合成生物学中的应用*

群体感应(quorum sensing, QS)是一种广泛存在于多种微生物中的胞间通信系统,细菌产生的自诱导物随着种群密度的增加而积累,诱导细菌对种群密度的响应,调节生物膜的形成或特定基因的表达。近年来,随着群体感应系统原理与关键元件的逐渐清晰,应用合成生物学手段进行多技术联合以及多系统间正交性设计具有极大的发展潜力,群体感应系统已成为合成生物学家动态调控胞间通信常用的重要手段之一。在群体感应是细胞-细胞间通信系统的基础上,对多种群体感应系统的联合设计在生物基化学品生产中自动化调控的研究进展进行综述;并针对群体感应系统在生物电化学转化领域实现双向生物信息交流的应用进行总结;同时归纳了医学领域中群体感应系统的动态调控功能与多种疾病诊断及治疗结合的研究进展,讨论了群体感应系统在多细胞通信和实际应用等方面的发展前景。     

Extracellular noise-induced stochastic synchronization in heterogeneous quorum sensing network

Quorum sensing is a bacterial mechanism used to synchronize the coordinated response of a microbial population. Because quorum sensing in Gram-negative bacteria depends on release and detection of a diffusible signaling molecule (autoinducer) among a multicellular group, it is considered a simple form of cell-cell communication for the purposes of mathematical analysis. Stochastic equation systems have provided a common approach to model biochemical or biophysical processes. Recently, the effect of noise to synchronize a specific homogeneous quorum sensing network was successfully modeled using a stochastic equation system with fixed parameters. The question remains of how to model quorum sensing networks in a general setting. To address this question, we first set a stochastic equation system as a general model for a heterogeneous quorum sensing network. Then, using two relevant biophysical characteristics of Gram-negative bacteria (the permeability of the cell membrane to the autoinducer and the symmetry of autoinducer diffusion) we construct the solution of the stochastic equation system at an abstract level. The solution indicates that stable synchronization of a quorum sensing network is robustly induced by an environment with a heterogenous distribution of extracellular and intracellular noise. The synchronization is independent of the initial state of the system and is solely the result of the connectivity of the cell network established through the effects of extracellular noise.     

Applications of small molecule activators and inhibitors of quorum sensing in Gram-negative bacteria

Quorum sensing is a form of intercellular communication used by many species of bacteria that facilitates concerted interactions between the cells comprising a population. The phenotypes regulated by quorum sensing are extremely diverse, with many having a significant impact upon healthcare, agriculture, and the environment. Consequently there has been significant interest in developing methods to manipulate this signalling process and recent years have witnessed significant theoretical and practical developments. A wide range of small molecule modulators of quorum sensing systems has been discovered, providing an expansive chemical toolbox for the study and modulation of this signalling mechanism. In this review, a selection of recent case studies which illustrate the value of both activators and inhibitors of quorum sensing in Gram-negative bacteria are discussed.