Broad Spectrum Pro-Quorum-Sensing Molecules as Inhibitors of Virulence in Vibrios

Quorum sensing (QS) is a bacterial cell-cell communication process that relies on the production and detection of extracellular signal molecules called autoinducers. QS allows bacteria to perform collective activities. Vibrio cholerae, a pathogen that causes an acute disease, uses QS to repress virulence factor production and biofilm formation. Thus, molecules that activate QS in V. cholerae have the potential to control pathogenicity in this globally important bacterium. Using a whole-cell high-throughput screen, we identified eleven molecules that activate V. cholerae QS: eight molecules are receptor agonists and three molecules are antagonists of LuxO, the central NtrC-type response regulator that controls the global V. cholerae QS cascade. The LuxO inhibitors act by an uncompetitive mechanism by binding to the pre-formed LuxO-ATP complex to inhibit ATP hydrolysis. Genetic analyses suggest that the inhibitors bind in close proximity to the Walker B motif. The inhibitors display broad-spectrum capability in activation of QS in Vibrio species that employ LuxO. To the best of our knowledge, these are the first molecules identified that inhibit the ATPase activity of a NtrC-type response regulator. Our discovery supports the idea that exploiting pro-QS molecules is a promising strategy for the development of novel anti-infectives.     

植物病原黄单胞菌退出群体感应生理状态的分子机制和生物学意义

黄单胞菌是一类引起多种作物病害的病原细菌总称.它们利用自身产生的DSF(Diffusible signaling factor)-家族群体感应(quorum sensing,QS)信号分子感应群体密度,调控致病相关基因的表达.当黄单胞菌培养达到对数生长后期时,培养体系中DSF信号分子浓度迅速降低,呈现一种典型的群体感应...     

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。     

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。     

A novel plant ferredoxin-like protein and the regulator Hor are quorum-sensing targets in the plant pathogen Erwinia carotovora

Quorum sensing (QS), a population-density-sensing mechanism, controls the production of the main virulence determinants, the plant cell-wall-degrading enzymes (PCWDEs) of the soft-rot phytopathogen Erwinia carotovora subsp. carotovora. In this study, we used random transposon mutagenesis with a gusA reporter construct to identify two new QS-controlled genes encoding the regulator Hor and a plant ferredoxin-like protein, FerE. The QS control of the identified genes was executed by the QS regulators ExpR1 and ExpR2 and mediated by the global repressor RsmA. Hor was shown to contribute to bacterial virulence at least partly through its control of PCWDE production. Our results showed that FerE contributes to oxidative stress tolerance and in planta fitness of the bacteria and suggest that QS could be central to control of oxidative stress tolerance. The presence of the FerE protein appears to be rather unique in heterotrophic bacteria and suggests an acquisition of the corresponding gene from plant host by horizontal gene transfer.     

细菌群体感应信号分子的光电检测技术

群体感应（quorum sensing，QS）是一种依赖菌群密度的细菌交流系统。在探究细菌群体感应系统的调控机制中，对QS信号分子的鉴别和检测是不可或缺的环节，其对生命科学、药学等领域涉及细菌等微生物的相互作用、高效检测和作用机制解析等具有重要的参考意义。本文在总结不同类型细菌QS信号分子来源和结构的基础上，对QS信号分子的光电检测方法和技术进行了综述，重点对光电传感检测的敏感介质、传感界面、传感机制及测试效果进行探讨，同时关注了将微流控芯片分析技术应用于细菌QS信号分子原位监测的相关研究进展。     

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.     

霍乱弧菌群体感应系统影响生物膜形成的研究进展

群体感应(quorum sensing,QS)是指细胞感知周围同类细胞的多寡或密度并调控基因表达的系统,它对大多数细菌的生物膜形成至关重要。目前对霍乱弧菌的QS系统已有较深入的研究,该菌的群体感应系统通过HapR、LuxO等多种信号分子调控生物膜的形成及消散。干扰QS系统将成为治疗生物膜相关感染的新方向。     

The vitamin riboflavin and its derivative lumichrome activate the LasR bacterial quorum-sensing receptor

Many bacteria use quorum sensing (QS) as an intercellular signaling mechanism to regulate gene expression in local populations. Plant and algal hosts, in turn, secrete compounds that mimic bacterial QS signals, allowing these hosts to manipulate QS-regulated gene expression in bacteria. Lumichrome, a derivative of the vitamin riboflavin, was purified and chemically identified from culture filtrates of the alga Chlamydomonas as a QS signal-mimic compound capable of stimulating the Pseudomonas aeruginosa LasR QS receptor. LasR normally recognizes the N-acyl homoserine lactone (AHL) signal, N-3-oxo-dodecanoyl homoserine lactone. Authentic lumichrome and riboflavin stimulated the LasR receptor in bioassays and lumichrome activated LasR in gel shift experiments. Amino acid substitutions in LasR residues required for AHL binding altered responses to both AHLs and lumichrome or riboflavin. These results and docking studies indicate that the AHL binding pocket of LasR recognizes both AHLs and the structurally dissimilar lumichrome or riboflavin. Bacteria, plants, and algae commonly secrete riboflavin or lumichrome, raising the possibility that these compounds could serve as either QS signals or as interkingdom signal mimics capable of manipulating QS in bacteria with a LasR-like receptor.     

Quorum sensing and virulence regulation in Xanthomonas campestris

It is now clear that cell–cell communication, often referred to as quorum sensing (QS), is the norm in the prokaryotic kingdom and this community-wide genetic regulatory mechanism has been adopted for regulation of many important biological functions. Since the 1980s, several types of QS signals have been identified, which are associated commonly with different types of QS mechanisms. Among them, the diffusible signal factor (DSF)-dependent QS system, originally discovered from bacterial pathogen Xanthomonas campestris pv. campestris , is a relatively new regulatory mechanism. The rapid research progress over the last few years has identified the chemical structure of the QS signal DSF, established the DSF regulon, and unveiled the general signaling pathways and mechanisms. Particular noteworthy are that DSF biosynthesis is modulated by a novel posttranslational autoinduction mechanism involving protein–protein interaction between the DSF synthase RpfF and the sensor RpfC, and that QS signal sensing is coupled to intracellular regulatory networks through a second messenger cyclic-di-GMP and a global regulator Clp. Genomic and genetic analyses show that the DSF QS-signaling pathway regulates diverse biological functions including virulence, biofilm dispersal, and ecological competence. Moreover, evidence is emerging that the DSF QS system is conserved in a range of plant and human bacterial pathogens.     

The virtue of temperance: built-in negative regulators of quorum sensing in Pseudomonas

Many bacteria are now believed to produce small signal molecules in order to communicate in a process called quorum sensing (QS), which mediates cooperative traits and a co-ordinated behaviour. Pseudomonads have been extensively studied for their QS response highlighting that it plays a major role in determining their lifestyle. The main QS signal molecules produced by Pseudomonas belong to the family of N-acyl-homoserine lactones (AHLs); these are synthesized by a LuxI-family synthase and sensed by a LuxR-family regulator. Most often in Pseudomonas, repressor genes intergenically located between luxI and luxR form an integral part of QS system. Recent studies have highlighted an important role of these repressors (called RsaL and RsaM) in containing the QS response within cost-effective levels; this is central for pseudomonads as they have very versatile genomes allowing them to live in constantly changing and highly dynamic environments. This review focuses on the role played by RsaL and RsaM repressors and discusses the important implications of this control of the QS response.