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。     

Quorum-sensing regulation of gene expression: Fundamental and applied aspects and the role in bacterial communication

Quorum sensing (QS) is a specific type of regulation of gene expression in bacteria; it is dependent on the population density. QS systems include two obligate components: a low-molecular-weight regulator (autoinducer), readily diffusible through the cytoplasmic membrane, and a regulatory receptor protein, which interacts with the regulator. As the bacterial population reaches a critical level of density, autoinducers accumulate to a necessary threshold value and abrupt activation (induction) of certain genes and operons occurs. By means of low-molecular-weight regulators, bacteria accomplish communication between cells belonging to the same or different species, genera, and even families. QS systems have been shown to play a key role in the regulation of various metabolic processes in bacteria and to function as global regulators of the expression of bacterial genes. Data are presented on different types of QS systems present in bacteria of various taxonomic groups, on the species specificity of these systems, and on communication of bacteria by means of QS systems. The possibility is considered of using QS regulation systems as targets while combating bacterial infections; other applied aspects of QS investigation are discussed.     

Quorum-sensing regulation of gene expression: fundamental and applied aspects and the role in bacterial communication

Quorum sensing (QS) is a specific type of regulation of gene expression in bacteria; it is dependent on the population density. QS systems include two obligate components: a low-molecular-weight regulator (autoinducer), readily diffusible through the cytoplasmic membrane, and a regulatory receptor protein, which interacts with the regulator. As the bacterial population reaches a critical level of density, autoinducers accumulate to a necessary threshold value and abrupt activation (induction) of certain genes and operons occurs. By means of low-molecular-weight regulators, bacteria accomplish communication between cells belonging to the same or different species, genera, and even families. QS systems have been shown to play a key role in the regulation of various metabolic processes in bacteria and to function as global regulators of the expression of bacterial genes. Data are presented on different types of QS systems present in bacteria of various taxonomic groups, on the species specificity of these systems, and on communication of bacteria by means of QS systems. The possibility is considered of using QS regulation systems as targets while combating bacterial infections; other applied aspects of QS investigation are discussed.     

Silencing the mob: disrupting quorum sensing as a means to fight plant disease

Bacteria are able to sense their population's density through a cell–cell communication system, termed ‘quorum sensing’ (QS). This system regulates gene expression in response to cell density through the constant production and detection of signalling molecules. These molecules commonly act as auto‐inducers through the up‐regulation of their own synthesis. Many pathogenic bacteria, including those of plants, rely on this communication system for infection of their hosts. The finding that the countering of QS‐disrupting mechanisms exists in many prokaryotic and eukaryotic organisms offers a promising novel method to fight disease. During the last decade, several approaches have been proposed to disrupt QS pathways of phytopathogens, and hence to reduce their virulence. Such studies have had varied success in vivo, but most lend promising support to the idea that QS manipulation could be a potentially effective method to reduce bacterial‐mediated plant disease. This review discusses the various QS‐disrupting mechanisms found in both bacteria and plants, as well as the different approaches applied artificially to interfere with QS pathways and thus protect plant health.     

Quorum sensing and communication in bacteria

Bacteria are able “to sense” an increase in the cell population density and to respond to it by the induction of special sets of genes. This type of regulation, called Quorum Sensing (QS), includes the production and excretion of low-molecular-weight signaling molecules (autoinducers, AI), which diffuse readily through the cell wall, from cells into the medium. As the bacterial population reaches the critical level of density, the concentration of these signaling molecules in the medium increases as a function of population density. On reaching the critical threshold concentration, AIs bind to specific receptor regulatory proteins, which induce the expression of target genes. By means of AIs, bacteria accomplish the communication that is the transmission of information between bacteria belonging to the same or different species, genera, and even families: the signaling molecules of some bacteria affect the receptors of others causing a coordinated reply of cells of the bacterial population. Bacteria of different taxonomic groups use the QS systems in regulation of a broad range of physiological activities. These processes include virulence, symbiosis, conjugation, biofilm formation, bioluminescence, synthesis of enzymes, antibiotic substances, etc. Here we review different QS systems of bacteria, the role of QS in bacterial communication, and some applied aspects of QS regulation application.     

Population Model of Quorum Sensing with Multiple Parallel Pathways

Quorum sensing (QS) is a bacterial communication mechanism that uses signal-receptor binding to regulate gene expression based on cell density, resulting in group behaviors such as biofilm formation, bioluminescence and stress response. In certain bacterial species such as Vibrio harveyi, several parallel QS signaling pathways drive a single phosphorylation–dephosphorylation cycle, which in turn regulates QS target genes. In this paper, we investigate the possible role of parallel signaling pathways by developing a mathematical model of QS in V. harveyi at both the single-cell and population levels. First we explore how signal integration may be achieved at the single-cell level, and how different model parameters influence the process. We then consider two examples of signal integration at the population level: a one-population model responding to two environmental cues (cell density and mass transfer), and a two-population model with distinct cell densities. In each case, we use contraction analysis to reduce the population model to an effective single-cell model.     

群体感应与病原菌致病性研究进展

群体感应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。当细菌密度达到临界阈值时能释放一些特定的自诱导信号分子,从而调节本种群或同环境中其他种群的群体行为。细菌群体感应参与包括人类、动植物、病原菌在内的多种生物的生物学功能调节,如生物膜的形成、毒力因子的产生、病原菌的耐药性等。深入研究病原菌群体感应系统的调控机制,将提高对病原菌发病机制的认识,有利于以群体感应作为防治疾病策略的研究。系统阐述了群体感应系统的组成类型、群体感应与病原菌致病性的关系,及其在抑制病原菌致病方面的应用。     

Quorum sensing regulation of gene expression: A promising target for drugs against bacterial pathogenicity

Bacteria are sensitive to an increase in population density and respond quickly and coordinately by induction of certain sets of genes. This mode of regulation, known as quorum sensing (QS), is based on the effect of low-molecular-weight signal molecules, autoinducers (AIs). When the population density is high, AIs accumulate in the medium and interact with regulatory receptor proteins. QS systems are global regulators of bacterial gene expression and play a key role in controlling many metabolic processes in the cell, including bacterial virulence. The review considers the molecular mechanisms of QS in different taxonomic groups of bacteria and discusses QS regulation as a possible target in treating bacterial infections. This is a new, alternative strategy of antibacterial therapy, which includes the construction of drugs acting directly against bacterial pathogenicity by suppressing QS (antipathogenicity drugs). This strategy makes it possible to avoid a wide distribution of antibiotic-resistant pathogenic bacteria and the formation of biofilms, which dramatically increase drug resistance.     

From unicellular properties to multicellular behavior: bacteria quorum sensing circuitry and applications

Cell-cell communication and coordinated population-based behavior among single cell organisms have gained considerable attention in the recent years. The ability to send, receive, and process information allows unicellular organisms to act as multicellular entities and increases their chances of survival in complex environments. Quorum sensing (QS), a density-dependent cell-signaling mechanism, is one way by which bacteria 'talk' to one another. QS is commonly associated with adverse health effects such as biofilm formation, bacteria pathogenicity, and virulence. But there exists great potential to harness QS circuitry and its properties for other applications, enabling even wider societal impact. Interesting avenues are envisioned for the detection of chemicals and pathogens, the navigation of interspecies communication, the synchronization and control of cell phenotype, and the creation of novel materials based on synthetic biology. In this review, we first highlight the recent discoveries of the molecular underpinnings of QS function, with emphasis on the formation of biofilms. We then discuss how researchers have used QS circuitry to their advantage to build synthetic networks, rewire native metabolic pathways, and engineer cells for a variety of applications.     

Quorum sensing of genes expression--perspective drug target against bacterial pathogenicity

Bacteria are capable to sense an increase of cell density population and to reply quickly and coordinately by the induction of special sets of genes. This type of the regulation was named Quorum Sensing (QS); it is based on the effect of low-molecular-weight signaling molecules of different nature (autoinducers) which accumulate in the culture at high density of bacterial population and interact with receptor regulatory proteins. QS systems are the global regulators of bacterial genes expression and play a key role in the control of many metabolic processes in cell including the regulation of virulence of bacteria. Here we review the molecular mechanisms of QS systems functioning in bacteria belonging to different taxonomic groups and discuss the potential of QS regulation as a new drug target for the treatment of bacterial infections. At present this approach is accounted as a new alternative strategy of antimicrobial therapy directed on the development of drugs inhibiting QS regulation and active just against pathogenicity of bacteria (antipathogenic drugs). Such a strategy allows to avoid a wide dissemination of resistant forms of pathogenic bacteria and the formation of biofilms increasing in many times the resistance of bacteria to drug preparations.     

Development and comparison of whole-cell assay systems for quorum-sensing inhibitors based on TraR, LasR, and QscR

Quorum sensing (QS) is a cell density-dependent signaling system that is used by bacteria to coordinate gene expression within their population. In this study, the authors describe the development and characterization of various cell-based bioassay systems for detecting QS inhibitors based on three LuxR family proteins, TraR, LasR, and the recently identified QscR. Three different gram-negative bacteria, Escherichia coli, Agrobacterium tumefaciens, and Pseudomonas aeruginosa, were employed as reporter strains to overproduce one of the aforementioned QS activator proteins and respond to inhibitors. The nine different whole-cell assay systems (three reporter strains × three QS proteins) were evaluated for their applicability and reliability by studying quantitative responses to various furanones, which are potent inhibitors of the LuxR family proteins. These results demonstrate that the cell-based bioassay systems are sensitive and reliable tools for screening of QS activators and inhibitors. This study also suggests that furanones are potentially important QS inhibitors for many LuxR-type activator proteins.     

Quorum sensing regulation in bacteria of the family enterobacteriaceae

Bacteria are able to sense an increase in population density and can respond to it by coordinated regulation of the expression of certain sets of genes in the total population of bacteria. This specific mode of regulation is known as Quorum Sensing (QS). The QS systems include low-molecular-weight signaling molecules of different chemical nature and the regulatory proteins that interact with the signaling molecules. The QS systems are global regulators of bacterial gene expression. They play an important role in controlling metabolic processes in bacteria. This review describes QS systems in members of the bacterial family Enterobacteriaceae functioning with the involvement of various signaling molecules, including N-acyl-homoserine lactones, AI-2, AI-3, peptides, and indole. The differences of the QS system in these bacteria from those in other taxonomic groups of bacteria are discussed. Data on the role of different types of QS systems in the regulation of different cellular processes in bacteria, i.e., their virulence, the synthesis of enzymes and antibiotics, biofilm formation, apoptosis, etc. are presented.     

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.     

产Ⅱ类细菌素乳酸菌群体感应及其应用

群体感应(quorum sensing,QS)是微生物通过感知与细胞密度相关的信号分子的浓度来调控基因表达的一种行为。许多产Ⅱ类细菌素乳酸菌通过自诱导肽介导的QS系统调控其细菌素的合成。本文综述了乳酸菌Ⅱ类细菌素合成的QS调控现象、调控机制、QS系统组分以及QS的应用。产Ⅱ类细菌素乳酸菌QS的研究,必将为揭示发酵调控机理、调控发酵过程提供新的研究平台,为食品级基因表达系统的开发提供新的选择。     

Linking Molecular and Population Processes in Mathematical Models of Quorum Sensing

Many bacteria alter their behaviors as a function of population density, via a process known as quorum sensing (QS). QS is achieved by the synthesis and detection of diffusible signal molecules, often involving complex signal transduction pathways and regulatory networks. Mathematical models have been developed to investigate a number of aspects of QS, resulting in a wide range of model structures; many have focused on either the molecular or the population scale. In this paper, I show that many published models fail to satisfy physical constraints (such as conservation of matter) or rely on a priori assumptions that may not be valid. I present new, simple models of canonical Gram-negative and Gram-positive QS systems, in both well-mixed and biofilm populations, focusing on the interaction between molecular and population processes. I show that this interaction may be crucial for several important features of QS, including bistability and the localization of QS in space. The results highlight the need to link molecular and population processes carefully in QS models, provide a general framework for understanding the behavior of complex system-specific models, and suggest new directions for both theoretical and experimental work.