Quorum-sensing regulation in rhizobia and its role in symbiotic interactions with legumes

Legume-nodulating bacteria (rhizobia) usually produce N-acyl homoserine lactones, which regulate the induction of gene expression in a quorum-sensing (or population-density)-dependent manner. There is significant diversity in the types of quorum-sensing regulatory systems that are present in different rhizobia and no two independent isolates worked on in detail have the same complement of quorum-sensing genes. The genes regulated by quorum sensing appear to be rather diverse and many are associated with adaptive aspects of physiology that are probably important in the rhizosphere. It is evident that some aspects of rhizobial physiology related to the interaction between rhizobia and legumes are influenced by quorum sensing. However, it also appears that the legumes play an active role, both in terms of interfering with the rhizobial quorum-sensing systems and responding to the signalling molecules made by the bacteria. In this article, we review the diversity of quorum-sensing regulation in rhizobia and the potential role of legumes in influencing and responding to this signalling system.     

Cell to cell communication by autoinducing peptides in gram-positive bacteria

While intercellular communication systems in Gram-negative bacteria are often based on homoserine lactones as signalling molecules, it has been shown that autoinducing peptides are involved in intercellular communication in Gram-positive bacteria. Many of these peptides are exported by dedicated systems, posttranslationally modified in various ways, and finally sensed by other cells via membrane-located receptors that are part of two-component regulatory systems. In this way the expression of a variety of functions including virulence, genetic competence and the production of antimicrobial compounds can be modulated in a co-ordinated and cell density- and growth phase-dependent manner. Occasionally the autoinducing peptide has a dual function, such as in the case of nisin that is both a signalling pheromone involved in quorum sensing and an antimicrobial peptide. Moreover, biochemical, genetic and genomic studies have shown that bacteria may contain multiple quorum sensing systems, underlining the importance of intercellular communication. Finally, in some cases different peptides may be recognised by the same receptor, while also hybrid receptors have been constructed that respond to new peptides or show novel responses. This paper provides an overview of the characteristics of autoinducing peptide-based quorum sensing systems, their application in various gram-positive bacteria, and the discovery of new systems in natural and engineered ecosystems. This revised version was published online in August 2006 with corrections to the Cover Date.     

Single cell time-resolved quorum responses reveal dependence on cell density and configuration

Bacterial communication via quorum sensing has been extensively investigated in recent years. Bacteria communicate in a complex manner through the production, release, and reception of diffusible low molecular weight chemical signaling molecules. Much work has focused on understanding the basic mechanisms of quorum sensing. As more and more bacteria grow resistant to conventional antibiotics, the development of drugs that do not kill bacteria but instead interrupt their communication is of increasing interest. This study presents a method for analyzing bacterial communication by investigating single cell responses. Most conventional analysis methods for bacterial communication are based on the averaged response from many bacteria, masking how individual cells respond to their immediate environment. We applied a fiber-optic microarray to record cellular communication from single cells. Single cell quorum sensing systems have previously been employed, but the highly ordered array reported here is an improvement because it allows us to simultaneously investigate cellular communication in many different environments with known cellular densities and configurations. We employed this method to detect how genes under quorum regulation are induced or repressed over time on the single cell level and to determine whether cellular density and configuration are indicative of the single cell temporal patterns of gene expression.     

Quorum sensing in Serratia

Many bacteria use cell-cell communication to monitor their population density, synchronize their behaviour and socially interact. This communication results in a coordinated gene regulation and is generally called quorum sensing. In gram-negative bacteria, the most common quorum signal molecules are acylated homoserine lactones (AHLs), although other low-molecular-mass signalling molecules have been described such as Autoinducer-2 (AI-2). The phenotypes that are regulated in Serratia species by means of AHLs are remarkably diverse and of profound biological and ecological significance, and often interconnected with other global regulators. Furthermore, AHL- and AI-2-mediated systems (less profoundly studied) are continuously being discovered and explored in Serratia spp., many having interesting twists on the basic theme. Therefore, this review will highlight the current known quorum sensing systems in Serratia spp., including the important nosocomial pathogen Serratia marcescens.     

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。     

细菌群体感应系统与噬菌体的相互作用机制研究进展

细菌在与噬菌体的长期共进化过程中形成多种抵抗噬菌体侵染的机制,其中群体感应参与的细菌抵御噬菌体侵染机制成为近年来的研究热点。群体感应与噬菌体之间的相互作用是复杂和多样的,本文将重点综述群体感应在噬菌体侵染中的作用、调控在噬菌体裂解-溶源转变的作用,以及群体感应与噬菌体的其他相互影响等内容,为噬菌体在细菌性疾病的治疗提供理论依据。     

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。     

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.     

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.     

革兰氏阴性细菌LuxR/I型群体感应抑制剂研究进展

摘要：细菌群体感应（Quorum sensing, QS）被视为对抗细菌感染与解决细菌耐药性问题的新靶点。以AHLs为信号分子的LuxR/I型群体感应系统广泛存在于革兰氏阴性菌包括多种临床致病菌中,因此寻找LuxR/I型群体感应抑制剂（Quorum sensing inhibitors, QSIs）是研发抗革兰氏阴性致病菌药物的重要途径。迄今为止,已知的LuxR/I型小分子QSIs来源包括化学合成、天然产物与已知药物库的化合物,大分子则包括群体感应淬灭酶与群体感应淬灭抗体。本文总结了近年来LuxR/I型QSIs研究进展,为新型抗菌药物研发提供理论依据。     

Bacterial signals and antagonists: the interaction between bacteria and higher organisms

It is now well established that bacteria communicate through the secretion and uptake of small diffusable molecules. These chemical cues, or signals, are often used by bacteria to coordinate phenotypic expression and this mechanism of regulation presumably provides them with a competitive advantage in their natural environment. Examples of coordinated behaviors of marine bacteria which are regulated by signals include swarming and exoprotease production, which are important for niche colonisation or nutrient acquisition (e.g. protease breakdown of substrate). While the current focus on bacterial signalling centers on N-Acylated homoserine lactones, the quorum sensing signals of gram-negative bacteria, these are not the only types of signals used by bacteria. Indeed, there appears to be many other types of signals produced by bacteria and it also appears that a bacterium may use multiple classes of signals for phenotypic regulation. Recent work in the area of marine microbial ecology has led to the observation that some marine eukaryotes secrete their own signals which compete with the bacterial signals and thus inhibit the expression of bacterial signalling phenotypes. This type of molecular mimicry has been well characterised for the interaction of marine prokaryotes with the red alga, Delisea pulchra.     

真菌中的群体感应系统

以胞间通讯信号分子介导的细菌群体感应参与细菌多种生理功能的调控是非常普遍的。近年的研究表明,真菌中也存在类似于细菌群体感应信号分子的调节分子,并且介导着真菌某些生理行为的调节。这一过程也称为真菌的群体感应系统。文中简要介绍真菌群体感应系统的研究进展,并讨论了真菌群体感应系统作为抗真菌感染靶点的可能性。     

Monitoring of Vibrio harveyi quorum sensing activity in real time during infection of brine shrimp larvae

Quorum sensing, bacterial cell-to-cell communication, has been linked to the virulence of pathogenic bacteria. Indeed, in vitro experiments have shown that many bacterial pathogens regulate the expression of virulence genes by this cell-to-cell communication process. Moreover, signal molecules have been detected in samples retrieved from infected hosts and quorum sensing disruption has been reported to result in reduced virulence in different host–pathogen systems. However, data on in vivo quorum sensing activity of pathogens during infection of a host are currently lacking. We previously reported that quorum sensing regulates the virulence of Vibrio harveyi in a standardised model system with gnotobiotic brine shrimp (Artemia franciscana) larvae. Here, we monitored quorum sensing activity in Vibrio harveyi during infection of the shrimp, using bioluminescence as a read-out. We found that wild-type Vibrio harveyi shows a strong increase in quorum sensing activity early during infection. In this respect, the bacteria behave remarkably similar in different larvae, despite the fact that only half of them survive the infection. Interestingly, when expressed per bacterial cell, Vibrio harveyi showed around 200-fold higher maximal quorum sensing-regulated bioluminescence when associated with larvae than in the culture water. Finally, the in vivo quorum sensing activity of mutants defective in the production of one of the three signal molecules is consistent with their virulence, with no detectable in vivo quorum sensing activity in AI-2- and CAI-1-deficient mutants. These results indicate that AI-2 and CAI-1 are the dominant signals during infection of brine shrimp.     

The Influence of Fluid Flow on Modeling Quorum Sensing in Bacterial Biofilms

In this paper, we study quorum sensing in Pseudomonas aeruginosa biofilms. Quorum sensing is a process where bacteria monitor their population density through the release of extra-cellular signalling molecules. The presence of these molecules affects gene modulation leading to changes in behaviour such as the release of virulence factors. Here, we use numerical methods to approximate a 2-D model of quorum sensing. It is observed that the shape of the biofilm can have a profound effect on the onset of quorum sensing. This has serious repercussions for experimental observations since biofilms of the same biomass but different shapes can produce quite different results.     

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).     

Impact of the structure-activity relationship of AHL analogues on quorum sensing in Gram-negative bacteria

With the emergence of microbial resistance pathogens, recent research aims at studying new mechanisms of action of antibiotics. This review discusses the mechanisms and types of quorum sensing (QS) inhibitors in Gram negative bacteria. It illustrates all published data available in literature pertaining to novel compounds that showed activity against different targets in the quorum sensing pathways in Gram negative bacteria. A systemic overview has been conducted by searching PubMed, Medline, and the Cochrane Library and data extraction of all quorum sensing inhibitors with their mechanisms of action have been collected. This review will focus on signaling autoinducer AI-1 in Gram negative bacteria. The biological activity of the antagonists is mainly reported as IC₅₀ (the concentration of an inhibitor where the response is reduced by half).     

Synthesis of d-desthiobiotin-AI-2 as a novel chemical probe for autoinducer-2 quorum sensing receptors

In processes regulated by quorum sensing (QS) bacteria respond to the concentration of autoinducers in the environment to engage in group behaviours. Autoinducer-2 (AI-2) is unique as it can foster interspecies communication. Currently, two AI-2 receptors are known, LuxP and LsrB, but bacteria lacking these receptors can also respond to AI-2. In this work, we present an efficient and reproducible synthesis of a novel chemical probe, d-desthiobiotin-AI-2. This probe binds both LuxP and LsrB receptors from different species of bacteria. Thus, this probe is able to bind receptors that recognise the two known biologically active forms of AI-2, presenting the plasticity essential for the identification of novel unknown AI-2 receptors. Moreover, a protocol to pull down receptors bound to d-desthiobiotin-AI-2 with anti-biotin antibodies has also been established. Altogether, this work highlights the potential of conjugating chemical signals to biotinylated derivatives to identify and tag signal receptors involved in quorum sensing or other chemical signalling processes.     

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.     

Sociomicrobiology: the connections between quorum sensing and biofilms

In the past decade, significant debate has surrounded the relative contributions of genetic determinants versus environmental conditions to certain types of human behavior. While this debate goes on, it is with a certain degree of irony that microbiologists studying aspects of bacterial community behavior face the same questions. Information regarding two social phenomena exhibited by bacteria, quorum sensing and biofilm development, is reviewed here. These two topics have been inextricably linked, possibly because biofilms and quorum sensing represent two areas in which microbiologists focus on social aspects of bacteria. We will examine what is known about this linkage and discuss areas that might be developed. In addition, we believe that these two aspects of bacterial behavior represent a small part of the social repertoire of bacteria. Bacteria exhibit many social activities and they represent a model for dissecting social behavior at the genetic level. Therefore, we introduce the term 'sociomicrobiology'.