How bacteria talk to each other: regulation of gene expression by quorum sensing

Quorum sensing, or the control of gene expression in response to cell density, is used by both gram-negative and gram-positive bacteria to regulate a variety of physiological functions. In all cases, quorum sensing involves the production and detection of extracellular signalling molecules called autoinducers. While universal signalling themes exist, variations in the design of the extracellular signals, the signal detection apparatuses, and the biochemical mechanisms of signal relay have allowed quorum sensing systems to be exquisitely adapted for their varied uses. Recent studies show that quorum sensing modulates both intra- and inter-species cell-cell communication, and it plays a major role in enabling bacteria to architect complex community structures.     

Look who's talking: communication and quorum sensing in the bacterial world

For many years bacteria were considered primarily as autonomous unicellular organisms with little capacity for collective behaviour. However, we now appreciate that bacterial cells are in fact, highly communicative. The generic term 'quorum sensing' has been adopted to describe the bacterial cell-to-cell communication mechanisms which co-ordinate gene expression usually, but not always, when the population has reached a high cell density. Quorum sensing depends on the synthesis of small molecules (often referred to as pheromones or autoinducers) that diffuse in and out of bacterial cells. As the bacterial population density increases, so does the synthesis of quorum sensing signal molecules, and consequently, their concentration in the external environment rises. Once a critical threshold concentration has been reached, a target sensor kinase or response regulator is activated (or repressed) so facilitating the expression of quorum sensing-dependent genes. Quorum sensing enables a bacterial population to mount a co-operative response that improves access to nutrients or specific environmental niches, promotes collective defence against other competitor prokaryotes or eukaryotic defence mechanisms and facilitates survival through differentiation into morphological forms better able to combat environmental threats. Quorum sensing also crosses the prokaryotic-eukaryotic boundary since quorum sensing-dependent signalling can be exploited or inactivated by both plants and mammals.     

Optimal Census by Quorum Sensing

Quorum sensing is the regulation of gene expression in response to changes in cell density. To measure their cell density, bacterial populations produce and detect diffusible molecules called autoinducers. Individual bacteria internally represent the external concentration of autoinducers via the level of monitor proteins. In turn, these monitor proteins typically regulate both their own production and the production of autoinducers, thereby establishing internal and external feedbacks. Here, we ask whether feedbacks can increase the information available to cells about their local density. We quantify available information as the mutual information between the abundance of a monitor protein and the local cell density for biologically relevant models of quorum sensing. Using variational methods, we demonstrate that feedbacks can increase information transmission, allowing bacteria to resolve up to two additional ranges of cell density when compared with bistable quorum-sensing systems. Our analysis is relevant to multi-agent systems that track an external driver implicitly via an endogenously generated signal.     

Bacterial quorum sensing: circuits and applications

Bacterial quorum sensing (QS) systems are cell density—dependent regulatory networks that coordinate bacterial behavioural changes from single cellular organisms at low cell densities to multicellular types when their population density reaches a threshold level. At this stage, bacteria produce and perceive small diffusible signal molecules, termed autoinducers in order to mediate gene expression. This often results in phenotypic shifts, like planktonic to biofilm or non-virulent to virulent. In this way, they regulate varied physiological processes by adjusting gene expression in concert with their population size. In this review we give a synopsis of QS mediated cell–cell communication in bacteria. The first part focuses on QS circuits of some Gram-negative and Gram-positive bacteria. Thereafter, attention is drawn on the recent applications of QS in development of synthetic biology modules, for studying the principles of pattern formation, engineering bi-directional communication system and building artificial communication networks. Further, the role of QS in solving the problem of biofouling is also discussed.     

厌氧氨氧化菌群体感应系统研究

厌氧氨氧化(Anammox)是以铵为电子供体将亚硝酸盐转化为氮气的生物过程。厌氧氨氧化菌(AAOB)生理代谢和细胞结构均十分特殊,且在氮素循环中起着十分重要的作用。厌氧氨氧化已成为环境学、微生物学、海洋学等领域的研究热点。但是,至今人们未能对厌氧氨氧化菌进行纯培养,这严重限制了对厌氧氨氧化菌的深入研究。群体感应是一种普遍存在于微生物细胞之间的通讯机制,它具有根据菌群密度和周围环境变化调节基因表达,以控制细菌群体行为的功能。厌氧氨氧化菌活性的细胞密度效应和生物团聚行为与细菌中普遍存在的群体感应现象相符。探讨了厌氧氨氧化菌群体感应系统存在的可能性、工作机制及其生态学意义,以期为厌氧氨氧化菌的分离培养、团聚体培育等提供理论指导。     

Quorum sensing intervened bacterial signaling: Pursuit of its cognizance and repression

Bacteria communicate within a system by means of a density dependent mechanism known as quorum sensing which regulate the metabolic and behavioral activities of a bacterial community. This sort of interaction occurs through a dialect of chemical signals called as autoinducers synthesized by bacteria. Bacterial quorum sensing occurs through various complex pathways depending upon specious diversity. Therefore the cognizance of quorum sensing mechanism will enable the regulation and thereby constrain bacterial communication. Inhibition strategies of quorum sensing are collectively called as quorum quenching; through which bacteria are incapacitated of its interaction with each other. Many virulence mechanism such as sporulation, biofilm formation, toxin production can be blocked by quorum quenching. Usually quorum quenching mechanisms can be broadly classified into enzymatic methods and non-enzymatic methods. Substantial understanding of bacterial communication and its inhibition enhances the development of novel antibacterial therapeutic drugs. In this review we have discussed the types and mechanisms of quorum sensing and various methods to inhibit and regulate density dependent bacterial communication.     

Information processing and signal integration in bacterial quorum sensing

Bacteria communicate using secreted chemical signaling molecules called autoinducers in a process known as quorum sensing. The quorum‐sensing network of the marine bacterium Vibrio harveyi uses three autoinducers, each known to encode distinct ecological information. Yet how cells integrate and interpret the information contained within these three autoinducer signals remains a mystery. Here, we develop a new framework for analyzing signal integration on the basis of information theory and use it to analyze quorum sensing in V. harveyi. We quantify how much the cells can learn about individual autoinducers and explain the experimentally observed input–output relation of the V. harveyi quorum‐sensing circuit. Our results suggest that the need to limit interference between input signals places strong constraints on the architecture of bacterial signal‐integration networks, and that bacteria probably have evolved active strategies for minimizing this interference. Here, we analyze two such strategies: manipulation of autoinducer production and feedback on receptor number ratios.     

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。     

群感效应与链霉菌次生代谢调控

群感效应是细菌协调群体行为的一种外界信号传递机制,在细菌中普遍存在,参与细胞的多种生理过程。链霉菌中也存在群感效应,在抗生素等次生代谢产物的生物合成中起重要的调控作用;从自诱导信号分子的结构到信号传递机制都存在一定多样性,其中以A-因子为代表的γ-丁酸内酯类信号分子的作用机制研究最为深入。近几年在链霉菌中发现的PI-因子、M-因子以及一些特定的代谢产物则代表几类结构较新颖的信号分子,通过群感效应机制调控次生代谢过程;链霉菌中还发现胆固醇氧化酶、甘油等分子具有信号分子特征,不排除是通过群感效应来参与抗生素生物合成调控。本文主要就参与链霉菌次生代谢调控的几类群感效应系统的研究状况进行综述,重点阐述各类群感信号分子的结构和信号传递机制的不同,并对链霉菌群感效应的研究趋势以及在抗生素高产菌遗传育种中的应用前景进行了展望。     

Conversation game: talking bacteria

The story of autonomous unicellular organisms, bacteria with unimaginable computational and evolutionary capabilities along with collective behavior has been running since the first six decades of the twentieth Century. However, do not consider them to be small and simple, because they possess the generic term quorum sensing adopted to describe the cell communication process which co-ordinate gene expression, when the population has reached a high cell density. Bacteria release diffusible signal molecules known as autoinducers or quorum sensing molecules. In recent research, the direction for activating or deactivating nature of a wave of gene expression is predicted experimentally which control bacterial populations subject to a diffusing autoinducer signal. On the other hand, it has been observed that the accumulation of the quorum sensing molecules leads to a negative diffusion coefficient in the solution of governing differential equation.     

细菌的信息交流

细菌与细菌之间的信息交流是通过相互交换一种自动诱导物(autoinducer)的信号分子来实现的。这种信息交换的过程被称为群体感应(quorumsystem)。细菌根据这种特定信号分子浓度的变化来监测环境中其它细菌数量的变化。细菌的群体感应系统分为种内和种间信息交流两大类。细菌间的信息交流涉及到细菌的多种生理功能,如细菌的致病能力等。因此研究细菌间的信息交流有可能找到一条新的防治细菌感染途径。     

从进化谈细菌细胞间的群体感应信号传递

传统观念认为细菌是一种个体的、非社会性的生物体。近年来的研究表明细菌可以产生化学信号并通过它们实现细菌间信息传递。细菌的群体感应调节系统(Quorum sensing,QS)调节着个体细胞之间的相互合作,使其表现出类似多细胞的群体行为。文章以近年来的一些最新研究进展为基础,在了解细菌间的信息传递系统的基础上,从进化角度讨论了QS系统的遗传产生过程,探讨了细菌细胞间的相互作用。细菌间的信息交流是一种动态的过程,受到了环境中的营养物质的水平、温度、pH等多种因素的影响。作者推测细菌信号传递系统的进化是受到环境条件以及基因交换、所在微生物群体变化等因素影响下的一种不断变化的动态过程,这也许有别于动植物这类的高等生物的进化过程。这种动态的变化过程也就暗示:从长远来看,信息传递系统中的偷机者只是在一定条件下的暂时存在。     

The LuxS family of bacterial autoinducers: biosynthesis of a novel quorum-sensing signal molecule

Many bacteria control gene expression in response to cell population density, and this phenomenon is called quorum sensing. In Gram-negative bacteria, quorum sensing typically involves the production, release and detection of acylated homoserine lactone signalling molecules called autoinducers. Vibrio harveyi, a Gram-negative bioluminescent marine bacterium, regulates light production in response to two distinct autoinducers (AI-1 and AI-2). AI-1 is a homoserine lactone. The structure of AI-2 is not known. We have suggested previously that V. harveyi uses AI-1 for intraspecies communication and AI-2 for interspecies communication. Consistent with this idea, we have shown that many species of Gram-negative and Gram-positive bacteria produce AI-2 and, in every case, production of AI-2 is dependent on the function encoded by the luxS gene. We show here that LuxS is the AI-2 synthase and that AI-2 is produced from S-adenosylmethionine in three enzymatic steps. The substrate for LuxS is S-ribosylhomocysteine, which is cleaved to form two products, one of which is homocysteine, and the other is AI-2. In this report, we also provide evidence that the biosynthetic pathway and biochemical intermediates in AI-2 biosynthesis are identical in Escherichia coli, Salmonella typhimurium, V. harveyi, Vibrio cholerae and Enterococcus faecalis. This result suggests that, unlike quorum sensing via the family of related homoserine lactone autoinducers, AI-2 is a unique, 'universal' signal that could be used by a variety of bacteria for communication among and between species.     

细菌的信息交流

细菌与细菌之间的信息交流是通过相互交换一种自动诱导物(autoinducer)的信号分子来实现的.这种信息交换的过程被称为群体感应(quorum system).细菌根据这种特定信号分子浓度的变化来监测环境中其它细菌数量的变化.细菌的群体感应系统分为种内和种间信息交流两大类.细菌间的信息交流涉及到细菌的多种生理功能,如细菌的致病能力等.因此研究细菌间的信息交流有可能找到一条新的防治细菌感染途径.     

MexEF-OprN efflux pump exports the Pseudomonas quinolone signal (PQS) precursor HHQ (4-hydroxy-2-heptylquinoline)

Bacterial cells have evolved the capacity to communicate between each other via small diffusible chemical signals termed autoinducers. Pseudomonas aeruginosa is an opportunistic pathogen involved, among others, in cystic fibrosis complications. Virulence of P. aeruginosa relies on its ability to produce a number of autoinducers, including 4-hydroxy-2-alkylquinolines (HAQ). In a cell density-dependent manner, accumulated signals induce the expression of multiple targets, especially virulence factors. This phenomenon, called quorum sensing, promotes bacterial capacity to cause disease. Furthermore, P. aeruginosa possesses many multidrug efflux pumps conferring adaptive resistance to antibiotics. Activity of some of these efflux pumps also influences quorum sensing. The present study demonstrates that the MexEF-OprN efflux pump modulates quorum sensing through secretion of a signalling molecule belonging to the HAQ family. Moreover, activation of MexEF-OprN reduces virulence factor expression and swarming motility. Since MexEF-OprN can be activated in infected hosts even in the absence of antibiotic selective pressure, it could promote establishment of chronic infections in the lungs of people suffering from cystic fibrosis, thus diminishing the immune response to virulence factors. Therapeutic drugs that affect multidrug efflux pumps and HAQ-mediated quorum sensing would be valuable tools to shut down bacterial virulence.     

Quorum sensing and swarming migration in bacteria

Bacterial cells can produce and sense signal molecules, allowing the whole population to initiate a concerted action once a critical concentration (corresponding to a particular population density) of the signal has been reached, a phenomenon known as quorum sensing. One of the possible quorum sensing-regulated phenotypes is swarming, a flagella-driven movement of differentiated swarmer cells (hyperflagellated, elongated, multinucleated) by which bacteria can spread as a biofilm over a surface. The glycolipid or lipopeptide biosurfactants thereby produced function as wetting agent by reducing the surface tension. Quorum sensing systems are almost always integrated into other regulatory circuits. This effectively expands the range of environmental signals that influence target gene expression beyond population density. In this review, we first discuss the regulation of AHL-mediated surface migration and the involvement of other low-molecular-mass signal molecules (such as the furanosyl borate diester AI-2) in biosurfactant production of different bacteria. In addition, population density-dependent regulation of swarmer cell differentiation is reviewed. Also, several examples of interspecies signalling are reported. Different signal molecules either produced by bacteria (such as other AHLs and diketopiperazines) or excreted by plants (such as furanones, plant signal mimics) might influence the quorum sensing-regulated swarming behaviour in bacteria different from the producer. On the other hand, specific bacteria can reduce the local available concentration of signal molecules produced by others. In the last part, the role and regulation of a surface-associated movement in biofilm formation is discussed. Here we also describe how quorum sensing may disperse existing biofilms and control the interaction between bacteria and higher organisms (such as the Rhizobium-bean symbiosis).