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Sample records for quorum sensing systems

  1. Inhibition of Lux quorum-sensing system by synthetic N-acyl-L-homoserine lactone analogous

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    In the present study, we investigated the inhibition of the Lux quorum-sensing system by N-acyi cyclopentylamine (Cn-CPA). The Lux quorum-sensing system regulates luminescence gene expression in Vibriofischeri. We have already reported on the synthesis of Cn-CPA and their abilities as inhibitors of the quorum-sensing systems in Pseudomonas aeruginosa and Serratia marcescens. In the case of Pseudomonas aeruginosa (Las and Rhl quorum-sensing system) and Serratia marcescens (Spn quorum-sensing system), specific Cn-CPA with a particular acyi chain length showed the strongest inhibitory effect. In the case of the Lux quorum-sensing system, it was found that several kinds of Cn-CPA with a range from C5 to C10 showed similar strong inhibitory effects. Moreover, the inhibitory effect of Cn-CPA on the Lux quorum-sensing system was stronger than that of halogenated furanone, a natural quorum-sensing inhibitor.

  2. Inhibition of Lux quorum-sensing system by synthetic N-acyl-L-homoserine lactone analogous.

    Science.gov (United States)

    Wang, Wenzhao; Morohoshi, Tomohiro; Ikeda, Tsukasa; Chen, Liang

    2008-12-01

    In the present study, we investigated the inhibition of the Lux quorum-sensing system by N-acyl cyclopentylamine (Cn-CPA). The Lux quorum-sensing system regulates luminescence gene expression in Vibrio fischeri. We have already reported on the synthesis of Cn-CPA and their abilities as inhibitors of the quorum-sensing systems in Pseudomonas aeruginosa and Serratia marcescens. In the case of Pseudomonas aeruginosa (Las and Rhl quorum-sensing system) and Serratia marcescens (Spn quorum-sensing system), specific Cn-CPA with a particular acyl chain length showed the strongest inhibitory effect. In the case of the Lux quorum-sensing system, it was found that several kinds of Cn-CPA with a range from C5 to C10 showed similar strong inhibitory effects. Moreover, the inhibitory effect of Cn-CPA on the Lux quorum-sensing system was stronger than that of halogenated furanone, a natural quorum-sensing inhibitor.

  3. Quorum sensing inhibition

    DEFF Research Database (Denmark)

    Persson, T.; Givskov, Michael Christian; Nielsen, J.

    2005-01-01

    Quorum sensing (QS) systems comprise a new therapeutic target potentially substitutive or complementary to traditional antibiotic treatment of chronic diseases. One route to disrupt the previously established interrelationship between pathogenesis and QS is by blocking the dual functioning signal...

  4. Quorum Sensing of Periodontal Pathogens.

    Science.gov (United States)

    Plančak, Darije; Musić, Larisa; Puhar, Ivan

    2015-09-01

    The term 'quorum sensing' describes intercellular bacterial communication which regulates bacterial gene expression according to population cell density. Bacteria produce and secrete small molecules, named autoinducers, into the intercellular space. The concentration of these molecules increases as a function of population cell density. Once the concentration of the stimulatory threshold is reached, alteration in gene expression occurs. Gram-positive and Gram-negative bacteria possess different types of quorum sensing systems. Canonical LuxI/R-type/acyl homoserine lactone mediated quorum sensing system is the best studied quorum sensing circuit and is described in Gram-negative bacteria which employ it for inter-species communication mostly. Gram-positive bacteria possess a peptide-mediated quorum sensing system. Bacteria can communicate within their own species (intra-species) but also between species (inter-species), for which they employ an autoinducer-2 quorum sensing system which is called the universal language of the bacteria. Periodontal pathogenic bacteria possess AI-2 quorum sensing systems. It is known that they use it for regulation of biofilm formation, iron uptake, stress response and virulence factor expression. A better understanding of bacterial communication mechanisms will allow the targeting of quorum sensing with quorum sensing inhibitors to prevent and control disease.

  5. Quasisynchronization in Quorum Sensing Systems with Parameter Mismatches

    Directory of Open Access Journals (Sweden)

    Jianbao Zhang

    2014-01-01

    Full Text Available The paper investigates quasisynchronization in a communication system, which consists of cells communicating through quorum sensing. With the help of Lyapunov function method and Lur’e system approach, some sufficient conditions for quasisynchronization are presented, and a bound on the synchronization errors is derived. The obtained theoretical results show that the synchronization quality is influenced by two parameters detrimentally: the error bound depends almost linearly on the mismatches between cells and depends sensitively on the diffusion rates of the signals inward the cell membrane. Numerical experiments are carried out to verify the theoretical results.

  6. Bacterial quorum sensing and biofilm formation

    Science.gov (United States)

    Quorum sensing is a cell density-dependent signaling system by which bacteria can regulate gene expression through the production, secretion, and subsequent detection of extracellular signaling molecules called autoinducers. Bacteria use quorum sensing to regulate various physiological activities, ...

  7. Evidence for existence of quorum sensing in a bioaugmented system by acylated homoserine lactone-dependent quorum quenching.

    Science.gov (United States)

    Zhang, Kun; Zheng, Xin; Shen, Dong-sheng; Wang, Mei-zhen; Feng, Hua-jun; He, Hong-zhen; Wang, Shuo; Wang, Jue-hua

    2015-04-01

    The introduction of a gene, strain, or microbial consortium into an indigenous bacterial population is known as bioaugmentation. This technique has been proposed as an effective strategy for accelerating and enhancing the removal of recalcitrant and toxic compounds during wastewater treatment. In this study, three types of reactors were used to test whether quorum sensing plays an important role in bioaugmented systems. Reverse transcriptase polymerase chain reaction showed that the inoculated strain, HF-1, successfully colonized in the bioaugmented reactor. Meanwhile, no HF-1 colonization was observed in the quorum-quenching and non-bioaugmented reactors. Removal of nicotine in the bioaugmented reactor was almost 100%, and removal of total organic carbon (TOC) was higher than 50%. However, less than 20% of nicotine and 30% of TOC was removed in quorum-quenching and non-bioaugmented reactors. Moreover, the release of acylated homoserine lactones reached the threshold for HF-1 biofilm formation in bioaugmented reactors but not in quorum-quenching or non-bioaugmented reactors. The addition of porcine kidney acylase I, a quenching reagent, to the quorum-quenching reactor hampered the colonization of HF-1. Together, these results demonstrate that quorum sensing plays an important role in HF-1 colonization of bioaugmented systems.

  8. Quorum sensing signal-response systems in Gram-negative bacteria.

    Science.gov (United States)

    Papenfort, Kai; Bassler, Bonnie L

    2016-08-11

    Bacteria use quorum sensing to orchestrate gene expression programmes that underlie collective behaviours. Quorum sensing relies on the production, release, detection and group-level response to extracellular signalling molecules, which are called autoinducers. Recent work has discovered new autoinducers in Gram-negative bacteria, shown how these molecules are recognized by cognate receptors, revealed new regulatory components that are embedded in canonical signalling circuits and identified novel regulatory network designs. In this Review we examine how, together, these features of quorum sensing signal-response systems combine to control collective behaviours in Gram-negative bacteria and we discuss the implications for host-microbial associations and antibacterial therapy.

  9. Optimal census by quorum sensing

    Science.gov (United States)

    Taillefumier, Thibaud

    Bacteria regulate their gene expression in response to changes in local cell density in a process called quorum sensing. To synchronize their gene-expression programs, these bacteria need to glean as much information as possible about local density. Our study is the first to physically model the flow of information in a quorum-sensing microbial community, wherein the internal regulator of the individual's response tracks the external cell density via an endogenously generated shared signal. Combining information theory and Lagrangian optimization, we find that quorum-sensing systems can improve their information capabilities by tuning circuit feedbacks. At the population level, external feedback adjusts the dynamic range of the shared input to individuals' detection channels. At the individual level, internal feedback adjusts the regulator's response time to dynamically balance output noise reduction and signal tracking ability. Our analysis suggests that achieving information benefit via feedback requires dedicated systems to control gene expression noise, such as sRNA-based regulation.

  10. Variability of the Quorum Sensing System in Natural Isolates of Bacillus sp.

    Directory of Open Access Journals (Sweden)

    Ines Mandic-Mulec

    2003-01-01

    Full Text Available Bacteria communicate with one another by (emitting and/or reacting to chemical signals. These communications, also known as quorum sensing, enable cells to control gene expression in response to cell density at the intra- and inter-species level. While bacteria use common signaling themes, variations in the design of the extracellular signals, the signal detection apparatus, and the biochemical mechanisms of signal relay have allowed quorum sensing systems to be adapted to diverse uses. The quorum sensing systems that govern natural genetic competence in Bacillus subtilis involve the ComX pheromones and the ComP-ComA, two-component regulator. ComX is synthesized as an inactive precursor and is then cleaved and modified by ComQ before export to the extra-cellular environment. The comQXP' loci of a set of natural Bacillus isolates have been sequenced and a striking polymorphism that correlates with specific patterns of activation of the quorum sensing response was shown. The ComX molecules representing different pherotypes were purified and characterized by mass spectroscopy. The analyses revealed that ComX variants also differ at the level of posttranslational modification of a conserved tryptophane residue, which was found to be an isoprenoid. The striking variability found in competence quorum sensing systems might be important for the survival of these bacteria in nature to escape the inappropriate induction of competence by closely related strains, playing the role of a sexual isolation mechanism.

  11. Quorum sensing inhibitors

    DEFF Research Database (Denmark)

    Rasmussen, Thomas Bovbjerg; Givskov, Michael Christian

    2006-01-01

    Many opportunistic pathogenic bacteria rely on quorum sensing (QS) circuits as central regulators of virulence expression. In Pseudomonas aeruginosa, QS-regulated gene expression contributes to the formation and maintenance of biofilms and their tolerance to conventional antimicrobials and the host...

  12. Quorum sensing inhibitors

    DEFF Research Database (Denmark)

    Rasmussen, Thomas Bovbjerg; Givskov, Michael Christian

    2006-01-01

    Many opportunistic pathogenic bacteria rely on quorum sensing (QS) circuits as central regulators of virulence expression. In Pseudomonas aeruginosa, QS-regulated gene expression contributes to the formation and maintenance of biofilms and their tolerance to conventional antimicrobials and the host...

  13. Size of quorum sensing communities

    DEFF Research Database (Denmark)

    Ferkinghoff-Borg, Jesper; Sams, Thomas

    2014-01-01

    Ensembles of bacteria are able to coordinate their phenotypic behavior in accordance with the size, density, and growth state of the ensemble. This is achieved through production and exchange of diffusible signal molecules in a cell–cell regulatory system termed quorum sensing. In the generic...

  14. Pseudomonas aeruginosa mutations in lasI and rhlI quorum sensing systems result in milder chronic lung infection

    DEFF Research Database (Denmark)

    Wu, H; Song, Z; Givskov, Michael

    2001-01-01

    To understand the importance of quorum sensing in chronic Pseudomonas aeruginosa lung infection, the in vivo pathogenic effects of the wild-type P. aeruginosa PAO1 and its double mutant, PAO1 lasI rhlI, in which the signal-generating parts of the quorum sensing systems are defective were compared...

  15. Size of quorum sensing communities

    DEFF Research Database (Denmark)

    Ferkinghoff-Borg, Jesper; Sams, Thomas

    2014-01-01

    Ensembles of bacteria are able to coordinate their phenotypic behavior in accordance with the size, density, and growth state of the ensemble. This is achieved through production and exchange of diffusible signal molecules in a cell–cell regulatory system termed quorum sensing. In the generic...... quorum sensor a positive feedback in the production of signal molecules defines the conditions at which the collective behavior switches on. In spite of its conceptual simplicity, a proper measure of biofilm colony ‘‘size’’ appears to be lacking. We establish that the cell density multiplied...

  16. Quorum Systems

    DEFF Research Database (Denmark)

    Förster, Klaus-Tycho

    2017-01-01

    What happens if a single server is no longer powerful enough to service all your customers? The obvious choice is to add more servers and to use the majority approach (e.g. Paxos, Chapter 2) to guarantee consistency. However, even if you buy one million servers, a client still has to access more ...... study the theory behind overlapping sets, known as quorum systems....

  17. Small RNA target genes and regulatory connections in the Vibrio cholerae quorum sensing system

    DEFF Research Database (Denmark)

    Hammer, Brian K; Svenningsen, Sine Lo

    2011-01-01

    The two-component quorum sensing (QS) system, first described in the marine bacterium Vibrio harveyi and evolutionarily conserved among members of the genus Vibrio, has been best studied in the human pathogen Vibrio cholerae (1, 2). In the V. cholerae QS system, the response to the accumulation...

  18. Cross-Talk between Staphylococcus aureus and Other Staphylococcal Species via the agr Quorum Sensing System

    DEFF Research Database (Denmark)

    Canovas de la Nuez, Jaime; Baldry, Mara; Bojer, Martin S;

    2016-01-01

    Staphylococci are associated with both humans and animals. While most are non-pathogenic colonizers, Staphylococcus aureus is an opportunistic pathogen capable of causing severe infections. S. aureus virulence is controlled by the agr quorum sensing system responding to secreted auto-inducing pep...

  19. Engineering of quorum-sensing systems for improved production of alkaline protease by Bacillus subtilis

    NARCIS (Netherlands)

    Tjalsma, H; Koetje, EJ; Kiewiet, R; Kuipers, OP; Kolkman, M; van der Laan, J; Daskin, R; Ferrari, E; Bron, S

    2004-01-01

    Aim: Engineering of Rap-Phr quorum-sensing systems of Bacillus subtilis and subsequent evaluation of the transcription of the aprE gene, encoding a major extracellular alkaline protease. Methods and Results: Addition of synthetic Phr pentapeptides to the growth medium, or overproduction of pre-Phr p

  20. Farnesol and Candida albicans: quorum sensing or not quorum sensing?

    NARCIS (Netherlands)

    Krom, B.P.; Levy, N.; Meijler, M.M.; Jabra-Rizk, M.A.

    2016-01-01

    Quorum sensing (QS) molecules function within communities of single-cell organisms to allow concerted behavior in response to changing conditions, and certain criteria have been established to determine whether a particular molecule is quorum sensing or not. Farnesol has been identified as a secrete

  1. Quorum Sensing Inhibition, Relevance to Periodontics

    OpenAIRE

    Yada, Sudheer; Kamalesh, B; Sonwane, Siddharth; Guptha, Indra; Swetha, R K

    2015-01-01

    Quorum sensing helps bacteria to communicate with each other and in coordinating their behavior. Many diseases of human beings, plants, and animals are mediated by quorum sensing. Various approaches are being tried to inhibit this communication to control the diseases caused by bacteria. Periodontal pathogens also communicate through quorum sensing and new approaches to treat periodontal disease using quorum sensing inhibition need to explored.

  2. Quorum sensing inhibition, relevance to periodontics.

    Science.gov (United States)

    Yada, Sudheer; Kamalesh, B; Sonwane, Siddharth; Guptha, Indra; Swetha, R K

    2015-01-01

    Quorum sensing helps bacteria to communicate with each other and in coordinating their behavior. Many diseases of human beings, plants, and animals are mediated by quorum sensing. Various approaches are being tried to inhibit this communication to control the diseases caused by bacteria. Periodontal pathogens also communicate through quorum sensing and new approaches to treat periodontal disease using quorum sensing inhibition need to explored.

  3. The Social Life of Aeromonas through Biofilm and Quorum Sensing Systems

    Science.gov (United States)

    Talagrand-Reboul, Emilie; Jumas-Bilak, Estelle; Lamy, Brigitte

    2017-01-01

    Bacteria of the genus Aeromonas display multicellular behaviors herein referred to as “social life”. Since the 1990s, interest has grown in cell-to-cell communication through quorum sensing signals and biofilm formation. As they are interconnected, these two self-organizing systems deserve to be considered together for a fresh perspective on the natural history and lifestyles of aeromonads. In this review, we focus on the multicellular behaviors of Aeromonas, i.e., its social life. First, we review and discuss the available knowledge at the molecular and cellular levels for biofilm and quorum sensing. We then discuss the complex, subtle, and nested interconnections between the two systems. Finally, we focus on the aeromonad multicellular coordinated behaviors involved in heterotrophy and virulence that represent technological opportunities and applied research challenges. PMID:28163702

  4. Quorum sensing control of Type VI secretion factors restricts the proliferation of quorum-sensing mutants.

    Science.gov (United States)

    Majerczyk, Charlotte; Schneider, Emily; Greenberg, E Peter

    2016-05-16

    Burkholderia thailandensis uses acyl-homoserine lactone-mediated quorum sensing systems to regulate hundreds of genes. Here we show that cell-cell contact-dependent type VI secretion (T6S) toxin-immunity systems are among those activated by quorum sensing in B. thailandensis. We also demonstrate that T6S is required to constrain proliferation of quorum sensing mutants in colony cocultures of a BtaR1 quorum-sensing signal receptor mutant and its parent. However, the BtaR1 mutant is not constrained by and outcompetes its parent in broth coculture, presumably because no cell contact occurs and there is a metabolic cost associated with quorum sensing gene activation. The increased fitness of the wild type over the BtaR1 mutant during agar surface growth is dependent on an intact T6SS-1 apparatus. Thus, quorum sensing activates B. thailandensis T6SS-1 growth inhibition and this control serves to police and constrain quorum-sensing mutants. This work defines a novel role for T6SSs in intraspecies mutant control.

  5. Quorum sensing in gram-negative bacteria

    DEFF Research Database (Denmark)

    Wu, H.; Song, Z.J.; Høiby, N.

    2004-01-01

    Bacteria can communicate with each other by means of signal molecules to coordinate the behavior of the entire community, and the mechanism is referred to as quorum sensing (QS). Signal systems enable bacteria to sense the size of their densities by monitoring the concentration of the signal...... molecules. Among Gram-negative bacteria N-acyl-L-homoserine lactone (acyl-HSL)-dependent quorum sensing systems are particularly widespread. These systems are used to coordinate expression of phenotypes that are fundamental to the interaction of bacteria with each other and with their environment...

  6. Expression and Quorum Sensing Regulation of Type III Secretion System Genes of Vibrio harveyi during Infection of Gnotobiotic Brine Shrimp.

    Science.gov (United States)

    Ruwandeepika, H A Darshanee; Karunasagar, Indrani; Bossier, Peter; Defoirdt, Tom

    2015-01-01

    Type III secretion systems enable pathogens to inject their virulence factors directly into the cytoplasm of the host cells. The type III secretion system of Vibrio harveyi, a major pathogen of aquatic organisms and a model species in quorum sensing studies, is repressed by the quorum sensing master regulator LuxR. In this study, we found that during infection of gnotobiotic brine shrimp larvae, the expression levels of three type III secretion operons in V. harveyi increased within the first 12h after challenge and decreased again thereafter. The in vivo expression levels were highest in a mutant with a quorum sensing system that is locked in low cell density configuration (minimal LuxR levels) and lowest in a mutant with a quorum sensing system that is locked in the high cell density configuration (maximal LuxR levels), which is consistent with repression of type III secretion by LuxR. Remarkably, in vivo expression levels of the type III secretion system genes were much (> 1000 fold) higher than the in vitro expression levels, indicating that (currently unknown) host factors significantly induce the type III secretion system. Given the fact that type III secretion is energy-consuming, repression by the quorum sensing master regulators might be a mechanism to save energy under conditions where it does not provide an advantage to the cells.

  7. Reciprocal regulation by the CepIR and CciIR quorum sensing systems in Burkholderia cenocepacia

    Directory of Open Access Journals (Sweden)

    Malott Rebecca J

    2009-09-01

    Full Text Available Abstract Background Burkholderia cenocepacia belongs to a group of closely related organisms called the B. cepacia complex (Bcc which are important opportunistic human pathogens. B. cenocepacia utilizes a mechanism of cell-cell communication called quorum sensing to control gene expression including genes involved in virulence. The B. cenocepacia quorum sensing network includes the CepIR and CciIR regulatory systems. Results Global gene expression profiles during growth in stationary phase were generated using microarrays of B. cenocepacia cepR, cciR and cepRcciIR mutants. This is the first time CciR was shown to be a global regulator of quorum sensing gene expression. CepR was primarily responsible for positive regulation of gene expression while CciR generally exerted negative gene regulation. Many of the genes that were regulated by both quorum sensing systems were reciprocally regulated by CepR and CciR. Microarray analysis of the cepRcciIR mutant suggested that CepR is positioned upstream of CciR in the quorum sensing hierarchy in B. cenocepacia. A comparison of CepIR-regulated genes identified in previous studies and in the current study showed a substantial amount of overlap validating the microarray approach. Several novel quorum sensing-controlled genes were confirmed using qRT-PCR or promoter::lux fusions. CepR and CciR inversely regulated flagellar-associated genes, the nematocidal protein AidA and a large gene cluster on Chromosome 3. CepR and CciR also regulated genes required for iron transport, synthesis of extracellular enzymes and surface appendages, resistance to oxidative stress, and phage-related genes. Conclusion For the first time, the influence of CciIR on global gene regulation in B. cenocepacia has been elucidated. Novel genes under the control of the CepIR and CciIR quorum sensing systems in B. cenocepacia have been identified. The two quorum sensing systems exert reciprocal regulation of many genes likely enabling fine

  8. Quorum Sensing Regulation in Aeromonas hydrophila

    DEFF Research Database (Denmark)

    Garde, Christian; Bjarnsholt, Thomas; Givskov, Michael;

    2010-01-01

    We present detailed results on the C4-HSL-mediated quorum sensing (QS) regulatory system of the opportunistic Gram-negative bacterium Aeromonas hydrophila. This bacterium contains a particularly simple QS system that allows for a detailed modeling of kinetics. In a model system (i...

  9. Quorum quenching enzymes and their application in degrading signal molecules to block quorum sensing-dependent infection.

    Science.gov (United States)

    Chen, Fang; Gao, Yuxin; Chen, Xiaoyi; Yu, Zhimin; Li, Xianzhen

    2013-08-26

    With the emergence of antibiotic-resistant strains of bacteria, the available options for treating bacterial infections have become very limited, and the search for a novel general antibacterial therapy has received much greater attention. Quorum quenching can be used to control disease in a quorum sensing system by triggering the pathogenic phenotype. The interference with the quorum sensing system by the quorum quenching enzyme is a potential strategy for replacing traditional antibiotics because the quorum quenching strategy does not aim to kill the pathogen or limit cell growth but to shut down the expression of the pathogenic gene. Quorum quenching enzymes have been identified in quorum sensing and non-quorum sensing microbes, including lactonase, acylase, oxidoreductase and paraoxonase. Lactonase is widely conserved in a range of bacterial species and has variable substrate spectra. The existence of quorum quenching enzymes in the quorum sensing microbes can attenuate their quorum sensing, leading to blocking unnecessary gene expression and pathogenic phenotypes. In this review, we discuss the physiological function of quorum quenching enzymes in bacterial infection and elucidate the enzymatic protection in quorum sensing systems for host diseases and their application in resistance against microbial diseases.

  10. Quorum Quenching Enzymes and Their Application in Degrading Signal Molecules to Block Quorum Sensing-Dependent Infection

    Directory of Open Access Journals (Sweden)

    Xianzhen Li

    2013-08-01

    Full Text Available With the emergence of antibiotic-resistant strains of bacteria, the available options for treating bacterial infections have become very limited, and the search for a novel general antibacterial therapy has received much greater attention. Quorum quenching can be used to control disease in a quorum sensing system by triggering the pathogenic phenotype. The interference with the quorum sensing system by the quorum quenching enzyme is a potential strategy for replacing traditional antibiotics because the quorum quenching strategy does not aim to kill the pathogen or limit cell growth but to shut down the expression of the pathogenic gene. Quorum quenching enzymes have been identified in quorum sensing and non-quorum sensing microbes, including lactonase, acylase, oxidoreductase and paraoxonase. Lactonase is widely conserved in a range of bacterial species and has variable substrate spectra. The existence of quorum quenching enzymes in the quorum sensing microbes can attenuate their quorum sensing, leading to blocking unnecessary gene expression and pathogenic phenotypes. In this review, we discuss the physiological function of quorum quenching enzymes in bacterial infection and elucidate the enzymatic protection in quorum sensing systems for host diseases and their application in resistance against microbial diseases.

  11. Modeling quorum sensing trade-offs between bacterial cell density and system extension from open boundaries

    Science.gov (United States)

    Marenda, Mattia; Zanardo, Marina; Trovato, Antonio; Seno, Flavio; Squartini, Andrea

    2016-12-01

    Bacterial communities undergo collective behavioural switches upon producing and sensing diffusible signal molecules; a mechanism referred to as Quorum Sensing (QS). Exemplarily, biofilm organic matrices are built concertedly by bacteria in several environments. QS scope in bacterial ecology has been debated for over 20 years. Different perspectives counterpose the role of density reporter for populations to that of local environment diffusivity probe for individual cells. Here we devise a model system where tubes of different heights contain matrix-embedded producers and sensors. These tubes allow non-limiting signal diffusion from one open end, thereby showing that population spatial extension away from an open boundary can be a main critical factor in QS. Experimental data, successfully recapitulated by a comprehensive mathematical model, demonstrate how tube height can overtake the role of producer density in triggering sensor activation. The biotic degradation of the signal is found to play a major role and to be species-specific and entirely feedback-independent.

  12. Can the natural diversity of quorum sensing advance synthetic biology?

    Directory of Open Access Journals (Sweden)

    Rene Michele Davis

    2015-03-01

    Full Text Available Quorum-sensing networks enable bacteria to sense and respond to chemical signals produced by neighboring bacteria. They are widespread: over one hundred morphologically and genetically distinct species of eubacteria are known to use quorum sensing to control gene expression. This diversity suggests the potential to use natural protein variants to engineer parallel, input-specific, cell-cell communication pathways. However, only three distinct signaling pathways, Lux, Las, and Rhl, have been adapted for and broadly used in engineered systems. The paucity of unique quorum-sensing systems and their propensity for crosstalk limits the usefulness of our current quorum-sensing toolkit. This review discusses the need for more signaling pathways, roadblocks to using multiple pathways in parallel, and strategies for expanding the quorum-sensing toolbox for synthetic biology.

  13. Gluconacetobacter diazotrophicus PAL5 possesses an active quorum sensing regulatory system.

    Science.gov (United States)

    Bertini, Elisa V; Nieto Peñalver, Carlos G; Leguina, Ana C; Irazusta, Verónica P; de Figueroa, Lucía I C

    2014-09-01

    The endophytic bacterium Gluconacetobacter diazotrophicus colonizes a broad range of host plants. Its plant growth-promoting capability is related to the capacity to perform biological nitrogen fixation, the biosynthesis of siderophores, antimicrobial substances and the solubilization of mineral nutrients. Colonization of and survival in these endophytic niche requires a complex regulatory network. Among these, quorum sensing systems (QS) are signaling mechanisms involved in the control of several genes related to microbial interactions, host colonization and stress survival. G. diazotrophicus PAL5 possesses a QS composed of a luxR and a luxI homolog, and produces eight molecules from the AHL family as QS signals. In this report data are provided showing that glucose concentration modifies the relative levels of these signal molecules. The activity of G. diazotrophicus PAL5 QS is also altered in presence of other carbon sources and under saline stress conditions. Inactivation of the QS system of G. diazotrophicus PAL5 by means of a quorum quenching strategy allowed the identification of extracellular and intracellular proteins under the control of this regulatory mechanism.

  14. Metagenomic approaches to understanding phylogenetic diversity in quorum sensing.

    Science.gov (United States)

    Kimura, Nobutada

    2014-04-01

    Quorum sensing, a form of cell-cell communication among bacteria, allows bacteria to synchronize their behaviors at the population level in order to control behaviors such as luminescence, biofilm formation, signal turnover, pigment production, antibiotics production, swarming, and virulence. A better understanding of quorum-sensing systems will provide us with greater insight into the complex interaction mechanisms used widely in the Bacteria and even the Archaea domain in the environment. Metagenomics, the use of culture-independent sequencing to study the genomic material of microorganisms, has the potential to provide direct information about the quorum-sensing systems in uncultured bacteria. This article provides an overview of the current knowledge of quorum sensing focused on phylogenetic diversity, and presents examples of studies that have used metagenomic techniques. Future technologies potentially related to quorum-sensing systems are also discussed.

  15. Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors

    DEFF Research Database (Denmark)

    Hentzer, Morten; Wu, H.; Andersen, Jens Bo

    2003-01-01

    Traditional treatment of infectious diseases is based on compounds that kill or inhibit growth of bacteria. A major concern with this approach is the frequent development of resistance to antibiotics. The discovery of communication systems (quorum sensing systems) regulating bacterial virulence has...... of natural furanone compounds can act as a potent antagonist of bacterial quorum sensing. We employed GeneChip((R)) microarray technology to identify furanone target genes and to map the quorum sensing regulon. The transcriptome analysis showed that the furanone drug specifically targeted quorum sensing...... systems and inhibited virulence factor expression. Application of the drug to P.aeruginosa biofilms increased bacterial susceptibility to tobramycin and SDS. In a mouse pulmonary infection model, the drug inhibited quorum sensing of the infecting bacteria and promoted their clearance by the mouse immune...

  16. Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors

    DEFF Research Database (Denmark)

    Hentzer, Morten; Wu, Hong; Andersen, Jens Bo

    2003-01-01

    Traditional treatment of infectious diseases is based on compounds that kill or inhibit growth of bacteria. A major concern with this approach is the frequent development of resistance to antibiotics. The discovery of communication systems (quorum sensing systems) regulating bacterial virulence has...... of natural furanone compounds can act as a potent antagonist of bacterial quorum sensing. We employed GeneChip microarray technology to identify furanone target genes and to map the quorum sensing regulon. The transcriptome analysis showed that the furanone drug specifically targeted quorum sensing systems...... and inhibited virulence factor expression. Application of the drug to P.aeruginosa biofilms increased bacterial susceptibility to tobramycin and SDS. In a mouse pulmonary infection model, the drug inhibited quorum sensing of the infecting bacteria and promoted their clearance by the mouse immune response....

  17. An agr quorum sensing system that regulates granulose formation and sporulation in Clostridium acetobutylicum.

    Science.gov (United States)

    Steiner, Elisabeth; Scott, Jamie; Minton, Nigel P; Winzer, Klaus

    2012-02-01

    The Gram-positive, anaerobic, endospore-forming bacterium Clostridium acetobutylicum has considerable biotechnological potential due to its ability to produce solvents as fermentation products, in particular the biofuel butanol. Its genome contains a putative agr locus, agrBDCA, known in staphylococci to constitute a cyclic peptide-based quorum sensing system. In staphylococci, agrBD is required for the generation of a peptide signal that, upon extracellular accumulation, is sensed by an agrCA-encoded two-component system. Using ClosTron technology, agrB, agrC, and agrA mutants of C. acetobutylicum ATCC 824 were generated and phenotypically characterized. Mutants and wild type displayed similar growth kinetics and no apparent differences in solvent formation under the conditions tested. However, the number of heat-resistant endospores formed by the mutants in liquid culture was reduced by about one order of magnitude. On agar-solidified medium, spore formation was more strongly affected, particularly in agrA and agrC mutants. Similarly, accumulation of the starch-like storage compound granulose was almost undetectable in colonies of agrB, agrA, and agrC mutants. Importantly, these defects could be genetically complemented, demonstrating that they were directly linked to agr inactivation. A diffusible factor produced by agrBD-expressing strains was found to restore granulose and spore formation in the agrB mutant. Furthermore, a synthetic cyclic peptide, designed on the basis of the C. acetobutylicum AgrD sequence, was also capable of complementing the defects of the agrB mutant when added exogenously to the culture. Together, these findings support the hypothesis that agr-dependent quorum sensing is involved in the regulation of sporulation and granulose formation in C. acetobutylicum.

  18. An agr Quorum Sensing System That Regulates Granulose Formation and Sporulation in Clostridium acetobutylicum

    Science.gov (United States)

    Steiner, Elisabeth; Scott, Jamie

    2012-01-01

    The Gram-positive, anaerobic, endospore-forming bacterium Clostridium acetobutylicum has considerable biotechnological potential due to its ability to produce solvents as fermentation products, in particular the biofuel butanol. Its genome contains a putative agr locus, agrBDCA, known in staphylococci to constitute a cyclic peptide-based quorum sensing system. In staphylococci, agrBD is required for the generation of a peptide signal that, upon extracellular accumulation, is sensed by an agrCA-encoded two-component system. Using ClosTron technology, agrB, agrC, and agrA mutants of C. acetobutylicum ATCC 824 were generated and phenotypically characterized. Mutants and wild type displayed similar growth kinetics and no apparent differences in solvent formation under the conditions tested. However, the number of heat-resistant endospores formed by the mutants in liquid culture was reduced by about one order of magnitude. On agar-solidified medium, spore formation was more strongly affected, particularly in agrA and agrC mutants. Similarly, accumulation of the starch-like storage compound granulose was almost undetectable in colonies of agrB, agrA, and agrC mutants. Importantly, these defects could be genetically complemented, demonstrating that they were directly linked to agr inactivation. A diffusible factor produced by agrBD-expressing strains was found to restore granulose and spore formation in the agrB mutant. Furthermore, a synthetic cyclic peptide, designed on the basis of the C. acetobutylicum AgrD sequence, was also capable of complementing the defects of the agrB mutant when added exogenously to the culture. Together, these findings support the hypothesis that agr-dependent quorum sensing is involved in the regulation of sporulation and granulose formation in C. acetobutylicum. PMID:22179241

  19. [THE ROLE OF SYSTEM QUORUM SENSING UNDER CHRONIC UROGENITAL CHLAMYDIA INFECTION].

    Science.gov (United States)

    2015-10-01

    It is established that system quorum sensing (QS) assure social behavior of bacteria in regulation of genes of virulence and generalization of inflectional inflammatory process under chronic urogenital chlamydia infection. The techniques of gas chromatography and mass-spectrometry were applied to detect molecular markers of generalization of infectious process under urogenital chlamydiasis--activators of QS microbes (lactones, quinolones, furan ethers). The developed diagnostic gas chromatography and mass-spectrometry criteria of indexation of molecular markers under chronic urogenital chlamydia infection have high level of diagnostic sensitivity, specificity and prognostic value of positive and negative result. The application of techniques of gas chromatography and mass-spectrometry permits enhancing effectiveness of diagnostic of chronic inflectional inflammatory diseases of urogenital system of chlamydia etiology with identification of prognostic criteria of generalization of infectious process and subsequent prescription of timely and appropriate therapy

  20. Quorum sensing in gram-negative bacteria

    DEFF Research Database (Denmark)

    Wu, H.; Song, Z.J.; Høiby, N.

    2004-01-01

    Bacteria can communicate with each other by means of signal molecules to coordinate the behavior of the entire community, and the mechanism is referred to as quorum sensing (QS). Signal systems enable bacteria to sense the size of their densities by monitoring the concentration of the signal...... molecules. Among Gram-negative bacteria N-acyl-L-homoserine lactone (acyl-HSL)-dependent quorum sensing systems are particularly widespread. These systems are used to coordinate expression of phenotypes that are fundamental to the interaction of bacteria with each other and with their environment...... and particularly higher organisms, covering a variety of functions ranging from pathogenic to symbiotic interactions. The detailed knowledge of these bacterial communication systems has opened completely new perspectives for controlling undesired microbial activities....

  1. Quorum sensing in Gram-negative bacteria

    Institute of Scientific and Technical Information of China (English)

    WU Hong; SONG Zhijun; Niels HФIBY; Michael GIVSKOV

    2004-01-01

    Bacteria can communicate with each other by means of signal molecules to coordinate the behavior of the entire community,and the mechanism is referred to as quorum sensing (QS).Signal systems enable bacteria to sense the size of their densities by monitoring the concentration of the signal molecules.Among Gram-negative bacteria N-acyl-L-homoserine lactone (acyl-HSL)-dependent quorum sensing systems are particularly widespread.These systems are used to coordinate expression of phenotypes that are fundamental to the interaction of bacteria with each other and with their environment and particularly higher organisms,covering a variety of functions ranging from pathogenic to symbiotic interactions.The detailed knowledge of these bacterial communication systems has opened completely new perspectives for controlling undesired microbial activities.

  2. Novel linear polymers able to inhibit bacterial quorum sensing.

    Science.gov (United States)

    Cavaleiro, Eliana; Duarte, Ana Sofia; Esteves, Ana Cristina; Correia, António; Whitcombe, Michael J; Piletska, Elena V; Piletsky, Sergey A; Chianella, Iva

    2015-05-01

    Bacterial phenotypes, such as biofilm formation, antibiotic resistance and virulence expression, are associated with quorum sensing. Quorum sensing is a density-dependent regulatory system of gene expression controlled by specific signal molecules, such as N-acyl homoserine lactones (AHLs), produced and released by bacteria. This study reports the development of linear polymers capable to attenuate quorum sensing by adsorption of AHLs. Linear polymers were synthesized using MMA as backbone monomer and methacrylic acid and itaconic acid as functional monomers. Two different quorum sensing-controlled phenotypes, Vibrio fischeri bioluminescence and Aeromonas hydrophila biofilm formation, were evaluated to test the polymers' efficiency. Results showed that both phenotypes were significantly affected by the polymers, with the itaconic acid-containing material being more effective than the methacrylic acid one. The polymer inhibitory effects were reverted by the addition of lactones, confirming attenuation of quorum sensing through sequestration of signal molecules. The polymers also showed no cytotoxicity when tested using a mammalian cell line.

  3. The response of Serratia marcescens JG to environmental changes by quorum sensing system.

    Science.gov (United States)

    Sun, Shu-Jing; Liu, Hui-Jun; Weng, Cai-Hong; Lai, Chun-Fen; Ai, Liu-Ying; Liu, Yu-Chen; Zhu, Hu

    2016-08-01

    Many bacterial cells are known to regulate their cooperative behaviors and physiological processes through a molecular mechanism called quorum sensing. Quorum sensing in Serratia marcescens JG is mediated by the synthesis of autoinducer 2 (AI-2) which is a furanosyl borate diester. In this study, the response of quorum sensing in S. marcescens JG to environment changes such as the initial pH, carbon sources and boracic acid was investigated by a bioreporter and real-time PCR analysis. The results show that glucose can affect AI-2 synthesis to the greatest extent, and 2.0 % glucose can stimulate S. marcescens JG to produce more AI-2, with a 3.5-fold increase in activity compared with control culture. Furthermore, the response of quorum sensing to changes in glucose concentration was performed by changing the amount of luxS RNA transcripts. A maximum of luxS transcription appeared during the exponential growth phase when the glucose concentration was 20.0 g/L. AI-2 production was also slightly impacted by the low initial pH. It is significant for us that the addition of boracic acid at microdosage (0.1-0.2 g/L) can also induce AI-2 synthesis, which probably demonstrated the feasible fact that the 4,5-dihydroxy-2, 3-pentanedione cyclizes by the addition of borate and the loss of water, is hydrated and is converted to the final AI-2 in S. marcescens JG.

  4. Lichen secondary metabolite evernic acid as potential quorum sensing inhibitor against Pseudomonas aeruginosa.

    Science.gov (United States)

    Gökalsın, Barış; Sesal, Nüzhet Cenk

    2016-09-01

    Cystic Fibrosis is a genetic disease and it affects the respiratory and digestive systems. Pseudomonas aeruginosa infections in Cystic Fibrosis are presented as the main cause for high mortality and morbidity rates. Pseudomonas aeruginosa populations can regulate their virulence gene expressions via the bacterial communication system: quorum sensing. Inhibition of quorum sensing by employing quorum sensing inhibitors can leave the bacteria vulnerable. Therefore, determining natural sources to obtain potential quorum sensing inhibitors is essential. Lichens have ethnobotanical value for their medicinal properties and it is possible that their secondary metabolites have quorum sensing inhibitor properties. This study aims to investigate an alternative treatment approach by utilizing lichen secondary metabolite evernic acid to reduce the expressions of Pseudomonas aeruginosa virulence factors by inhibiting quorum sensing. For this purpose, fluorescent monitor strains were utilized for quorum sensing inhibitor screens and quantitative reverse-transcriptase PCR analyses were conducted for comparison. Results indicate that evernic acid is capable of inhibiting Pseudomonas aeruginosa quorum sensing systems.

  5. Social Evolution Selects for Redundancy in Bacterial Quorum Sensing.

    Science.gov (United States)

    Even-Tov, Eran; Bendori, Shira Omer; Valastyan, Julie; Ke, Xiaobo; Pollak, Shaul; Bareia, Tasneem; Ben-Zion, Ishay; Bassler, Bonnie L; Eldar, Avigdor

    2016-02-01

    Quorum sensing is a process of chemical communication that bacteria use to monitor cell density and coordinate cooperative behaviors. Quorum sensing relies on extracellular signal molecules and cognate receptor pairs. While a single quorum-sensing system is sufficient to probe cell density, bacteria frequently use multiple quorum-sensing systems to regulate the same cooperative behaviors. The potential benefits of these redundant network structures are not clear. Here, we combine modeling and experimental analyses of the Bacillus subtilis and Vibrio harveyi quorum-sensing networks to show that accumulation of multiple quorum-sensing systems may be driven by a facultative cheating mechanism. We demonstrate that a strain that has acquired an additional quorum-sensing system can exploit its ancestor that possesses one fewer system, but nonetheless, resume full cooperation with its kin when it is fixed in the population. We identify the molecular network design criteria required for this advantage. Our results suggest that increased complexity in bacterial social signaling circuits can evolve without providing an adaptive advantage in a clonal population.

  6. Social Evolution Selects for Redundancy in Bacterial Quorum Sensing.

    Directory of Open Access Journals (Sweden)

    Eran Even-Tov

    2016-02-01

    Full Text Available Quorum sensing is a process of chemical communication that bacteria use to monitor cell density and coordinate cooperative behaviors. Quorum sensing relies on extracellular signal molecules and cognate receptor pairs. While a single quorum-sensing system is sufficient to probe cell density, bacteria frequently use multiple quorum-sensing systems to regulate the same cooperative behaviors. The potential benefits of these redundant network structures are not clear. Here, we combine modeling and experimental analyses of the Bacillus subtilis and Vibrio harveyi quorum-sensing networks to show that accumulation of multiple quorum-sensing systems may be driven by a facultative cheating mechanism. We demonstrate that a strain that has acquired an additional quorum-sensing system can exploit its ancestor that possesses one fewer system, but nonetheless, resume full cooperation with its kin when it is fixed in the population. We identify the molecular network design criteria required for this advantage. Our results suggest that increased complexity in bacterial social signaling circuits can evolve without providing an adaptive advantage in a clonal population.

  7. Quorum sensing and policing of Pseudomonas aeruginosa social cheaters.

    Science.gov (United States)

    Wang, Meizhen; Schaefer, Amy L; Dandekar, Ajai A; Greenberg, E Peter

    2015-02-17

    The bacterium Pseudomonas aeruginosa is an opportunistic human pathogen that uses a quorum sensing signal cascade to activate expression of dozens of genes when sufficient population densities have been reached. Quorum sensing controls production of several key virulence factors, including secreted proteases such as elastase. Cooperating groups of bacteria growing on protein are susceptible to social cheating by quorum-sensing defective mutants. A possible way to restrict cheater emergence is by policing where cooperators produce costly goods to sanction or punish cheats. The P. aeruginosa LasR-LasI quorum sensing system controls genes including those encoding proteases and also those encoding a second quorum-sensing system, the RhlR-RhlI system, which controls numerous genes including those for cyanide production. By using RhlR quorum sensing mutants and cyanide synthesis mutants, we show that cyanide production is costly and cyanide-producing cooperators use cyanide to punish LasR-null social cheaters. Cooperators are less susceptible to cyanide than are LasR mutants. These experiments demonstrate policing in P. aeruginosa, provide a mechanistic understanding of policing, and show policing involves the cascade organization of the two quorum sensing systems in this bacterium.

  8. The Evolution of Quorum Sensing as a Mechanism to Infer Kinship.

    Science.gov (United States)

    Schluter, Jonas; Schoech, Armin P; Foster, Kevin R; Mitri, Sara

    2016-04-01

    Bacteria regulate many phenotypes via quorum sensing systems. Quorum sensing is typically thought to evolve because the regulated cooperative phenotypes are only beneficial at certain cell densities. However, quorum sensing systems are also threatened by non-cooperative "cheaters" that may exploit quorum-sensing regulated cooperation, which begs the question of how quorum sensing systems are maintained in nature. Here we study the evolution of quorum sensing using an individual-based model that captures the natural ecology and population structuring of microbial communities. We first recapitulate the two existing observations on quorum sensing evolution: density-dependent benefits favor quorum sensing but competition and cheating will destabilize it. We then model quorum sensing in a dense community like a biofilm, which reveals a novel benefit to quorum sensing that is intrinsically evolutionarily stable. In these communities, competing microbial genotypes gradually segregate over time leading to positive correlation between density and genetic similarity between neighboring cells (relatedness). This enables quorum sensing to track genetic relatedness and ensures that costly cooperative traits are only activated once a cell is safely surrounded by clonemates. We hypothesize that under similar natural conditions, the benefits of quorum sensing will not result from an assessment of density but from the ability to infer kinship.

  9. Quorum sensing and bacterial pathogenicity: From molecules to disease

    Directory of Open Access Journals (Sweden)

    Antariksh Deep

    2011-01-01

    Full Text Available Quorum sensing in prokaryotic biology refers to the ability of a bacterium to sense information from other cells in the population when they reach a critical concentration (i.e. a Quorum and communicate with them. The "language" used for this intercellular communication is based on small, self-generated signal molecules called as autoinducers. Quorum sensing is thought to afford pathogenic bacteria a mechanism to minimize host immune responses by delaying the production of tissue-damaging virulence factors until sufficient bacteria have amassed and are prepared to overwhelm host defense mechanisms and establish infection. Quorum sensing systems are studied in a large number of gram-negative bacterial species belonging to α, β, and γ subclasses of proteobacteria. Among the pathogenic bacteria, Pseudomonas aeruginosa is perhaps the best understood in terms of the virulence factors regulated and the role the Quorum sensing plays in pathogenicity. Presently, Quorum sensing is considered as a potential novel target for antimicrobial therapy to control multi/all drug-resistant infections. This paper reviews Quorum sensing in gram positive and gram negative bacteria and its role in biofilm formation.

  10. QUORUM SENSING AND ITS ROLE IN ORAL BIOFILMS DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Boy M. Bachtiar

    2006-04-01

    Full Text Available Quorum sensing systems has been identified as one of mechanism carried out by numerous Gram-positive and Gram-negative bacteria to coordinate virulence and biofilm development. Using quorum sensing bacterial colonies synchronize gene expression and phenotype change allowing them to protect their niche. The purpose of this review is to present a synopsis of the literature on bacterial quorum sensing and we highlight the role of specific signaling molecules that might be used as a target of inhibitor agent in dental preventive perspective.

  11. Pseudomonas aeruginosa Quorum-Sensing Systems May Control Virulence Factor Expression in the Lungs of Patients with Cystic Fibrosis

    OpenAIRE

    Erickson, David L.; Endersby, Ryan; Kirkham, Amanda; Stuber, Kent; Vollman, Dolina D.; Rabin, Harvey R; Mitchell, Ian; Storey, Douglas G.

    2002-01-01

    Individuals with cystic fibrosis (CF) are commonly colonized with Pseudomonas aeruginosa. The chronic infections caused by P. aeruginosa are punctuated by acute exacerbations of the lung disease, which lead to significant morbidity and mortality. As regulators of virulence determinants, P. aeruginosa quorum-sensing systems may be active in the chronic lung infections associated with CF. We have examined the levels of autoinducer molecules and transcript accumulation from the bacterial populat...

  12. The metabolic flux regulation of Klebsiella pneumoniae based on quorum sensing system

    Science.gov (United States)

    Sun, Shujing; Zhang, Haiyang; Lu, Shuyi; Lai, Chunfen; Liu, Huijun; Zhu, Hu

    2016-01-01

    Quorum-sensing (QS) systems exist universally in bacteria to regulate multiple biological functions. Klebsiella pneumoniae, an industrially important bacterium that produces bio-based chemicals such as 2,3-butanediol and acetoin, can secrete a furanosyl borate diester (AI-2) as the signalling molecule mediating a QS system, which plays a key regulatory role in the biosynthesis of secondary metabolites. In this study, the molecular regulation and metabolic functions of a QS system in K. pneumoniae were investigated. The results showed that after the disruption of AI-2-mediated QS by the knockout of luxS, the production of acetoin, ethanol and acetic acid were relatively lower in the K. pneumoniae mutant than in the wild type bacteria. However, 2,3-butanediol production was increased by 23.8% and reached 54.93 g/L. The observed enhancement may be attributed to the improvement of the catalytic activity of 2,3-butanediol dehydrogenase (BDH) in transforming acetoin to 2,3-butanediol. This possibility is consistent with the RT-PCR-verified increase in the transcriptional level of budC, which encodes BDH. These results also demonstrated that the physiological metabolism of K. pneumoniae was adversely affected by a QS system. This effect was reversed through the addition of synthetic AI-2. This study provides the basis for a QS-modulated metabolic engineering study of K. pneumoniae. PMID:27924940

  13. Pseudomonas aeruginosa quorum-sensing systems may control virulence factor expression in the lungs of patients with cystic fibrosis.

    Science.gov (United States)

    Erickson, David L; Endersby, Ryan; Kirkham, Amanda; Stuber, Kent; Vollman, Dolina D; Rabin, Harvey R; Mitchell, Ian; Storey, Douglas G

    2002-04-01

    Individuals with cystic fibrosis (CF) are commonly colonized with Pseudomonas aeruginosa. The chronic infections caused by P. aeruginosa are punctuated by acute exacerbations of the lung disease, which lead to significant morbidity and mortality. As regulators of virulence determinants, P. aeruginosa quorum-sensing systems may be active in the chronic lung infections associated with CF. We have examined the levels of autoinducer molecules and transcript accumulation from the bacterial populations found in the lungs of patients with CF. We detected biologically active levels of N-(3-oxododecanoyl)-L-homoserine (3-oxo-C12-HSL) and N-butyryl-L-homoserine lactone (C4-HSL) in sputum from CF patients. Interestingly, it appears that C4-HSL is less frequently detected than 3-oxo-C12-HSL in the lungs of patients with CF. We also examined the transcription of the autoinducer synthase gene lasI and showed that it is frequently expressed in the lungs of patients with CF. We observed a significant correlation between the expression of lasI and four target genes of the Las quorum-sensing system. Taken together, our results indicate that quorum-sensing systems are active and may control virulence factor expression in the lungs of patients with CF.

  14. Global convergence of quorum-sensing networks

    Science.gov (United States)

    Russo, Giovanni; Slotine, Jean Jacques E.

    2010-10-01

    In many natural synchronization phenomena, communication between individual elements occurs not directly but rather through the environment. One of these instances is bacterial quorum sensing, where bacteria release signaling molecules in the environment which in turn are sensed and used for population coordination. Extending this motivation to a general nonlinear dynamical system context, this paper analyzes synchronization phenomena in networks where communication and coupling between nodes are mediated by shared dynamical quantities, typically provided by the nodes’ environment. Our model includes the case when the dynamics of the shared variables themselves cannot be neglected or indeed play a central part. Applications to examples from system biology illustrate the approach.

  15. Global convergence of quorum-sensing networks

    CERN Document Server

    Russo, Giovanni

    2010-01-01

    In many natural synchronization phenomena, communication between individual elements occurs not directly, but rather through the environment. One of these instances is bacterial quorum sensing, where bacteria release signaling molecules in the environment which in turn are sensed and used for population coordination. Extending this motivation to a general non- linear dynamical system context, this paper analyzes synchronization phenomena in networks where communication and coupling between nodes are mediated by shared dynamical quan- tities, typically provided by the nodes' environment. Our model includes the case when the dynamics of the shared variables themselves cannot be neglected or indeed play a central part. Applications to examples from systems biology illustrate the approach.

  16. Synthetic quorum sensing in model microcapsule colonies.

    Science.gov (United States)

    Shum, Henry; Balazs, Anna C

    2017-08-08

    Biological quorum sensing refers to the ability of cells to gauge their population density and collectively initiate a new behavior once a critical density is reached. Designing synthetic materials systems that exhibit quorum sensing-like behavior could enable the fabrication of devices with both self-recognition and self-regulating functionality. Herein, we develop models for a colony of synthetic microcapsules that communicate by producing and releasing signaling molecules. Production of the chemicals is regulated by a biomimetic negative feedback loop, the "repressilator" network. Through theory and simulation, we show that the chemical behavior of such capsules is sensitive to both the density and number of capsules in the colony. For example, decreasing the spacing between a fixed number of capsules can trigger a transition in chemical activity from the steady, repressed state to large-amplitude oscillations in chemical production. Alternatively, for a fixed density, an increase in the number of capsules in the colony can also promote a transition into the oscillatory state. This configuration-dependent behavior of the capsule colony exemplifies quorum-sensing behavior. Using our theoretical model, we predict the transitions from the steady state to oscillatory behavior as a function of the colony size and capsule density.

  17. Vfm a new quorum sensing system controls the virulence of Dickeya dadantii.

    Science.gov (United States)

    Nasser, William; Dorel, Corinne; Wawrzyniak, Julien; Van Gijsegem, Frédérique; Groleau, Marie-Christine; Déziel, Eric; Reverchon, Sylvie

    2013-03-01

    Dickeya dadantii is a plant pathogen that secretes cell wall-degrading enzymes (CWDE) that are responsible for soft-rot symptoms. Virulence genes are expressed in a concerted manner and culminate when bacterial multiplication slows. We identify a 25 kb vfm cluster required for D. dadantii CWDE production and pathogenesis. The vfm cluster encodes proteins displaying similarities both with enzymes involved in amino acid activation and with enzymes involved in fatty acid biosynthesis. These similarities suggest that the vfm genes direct the production of a metabolite. Cell-free supernatant from the D. dadantii wild-type strain restores CWDE production in vfm mutants. Collectively, our results indicate that vfm genes direct the synthesis of an extracellular signal and constitute a new quorum sensing system. Perception of the signal is achieved by the two-component system VfmH-VfmI, which activates the expression of the vfmE gene encoding an AraC regulator. VfmE then activates both the transcription of the CWDE genes and the expression of the vfm operons. The vfm gene cluster does not seem to be widespread among bacterial species but is conserved in other Dickeya species and could have been laterally transferred to Rahnella. This work highlights that entirely new families of bacterial languages remain to be discovered.

  18. Quorum sensing regulates the osmotic stress response in Vibrio harveyi.

    Science.gov (United States)

    van Kessel, Julia C; Rutherford, Steven T; Cong, Jian-Ping; Quinodoz, Sofia; Healy, James; Bassler, Bonnie L

    2015-01-01

    Bacteria use a chemical communication process called quorum sensing to monitor cell density and to alter behavior in response to fluctuations in population numbers. Previous studies with Vibrio harveyi have shown that LuxR, the master quorum-sensing regulator, activates and represses >600 genes. These include six genes that encode homologs of the Escherichia coli Bet and ProU systems for synthesis and transport, respectively, of glycine betaine, an osmoprotectant used during osmotic stress. Here we show that LuxR activates expression of the glycine betaine operon betIBA-proXWV, which enhances growth recovery under osmotic stress conditions. BetI, an autorepressor of the V. harveyi betIBA-proXWV operon, activates the expression of genes encoding regulatory small RNAs that control quorum-sensing transitions. Connecting quorum-sensing and glycine betaine pathways presumably enables V. harveyi to tune its execution of collective behaviors to its tolerance to stress.

  19. A Mathematical Model of Quorum Sensing Induced Biofilm Detachment.

    Science.gov (United States)

    Emerenini, Blessing O; Hense, Burkhard A; Kuttler, Christina; Eberl, Hermann J

    2015-01-01

    Cell dispersal (or detachment) is part of the developmental cycle of microbial biofilms. It can be externally or internally induced, and manifests itself in discrete sloughing events, whereby many cells disperse in an instance, or in continuous slower dispersal of single cells. One suggested trigger of cell dispersal is quorum sensing, a cell-cell communication mechanism used to coordinate gene expression and behavior in groups based on population densities. To better understand the interplay of colony growth and cell dispersal, we develop a dynamic, spatially extended mathematical model that includes biofilm growth, production of quorum sensing molecules, cell dispersal triggered by quorum sensing molecules, and re-attachment of cells. This is a highly nonlinear system of diffusion-reaction equations that we study in computer simulations. Our results show that quorum sensing induced cell dispersal can be an efficient mechanism for bacteria to control the size of a biofilm colony, and at the same time enhance its downstream colonization potential. In fact we find that over the lifetime of a biofilm colony the majority of cells produced are lost into the aqueous phase, supporting the notion of biofilms as cell nurseries. We find that a single quorum sensing based mechanism can explain both, discrete dispersal events and continuous shedding of cells from a colony. Moreover, quorum sensing induced cell dispersal affects the structure and architecture of the biofilm, for example it might lead to the formation of hollow inner regions in a biofilm colony.

  20. Quorum sensing inhibitors disable bacterial biofilms

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Tolker-Nielsen, Tim; Givskov, Michael

    2011-01-01

    It is now evident that bacteria assume the biofilm mode of growth during chronic infections. The important hallmarks of biofilm infections are development of local inflammations, extreme tolerance to the action of conventional antimicrobial agents and an almost infinite capacity to evade the host...... defence systems in particular innate immunity. In the biofilm mode, bacteria use cell to cell communication termed quorum-sensing (QS) to coordinate expression of virulence, tolerance towards a number of antimicrobial agents and shielding against the host defence system. Chemical biology approaches may...

  1. Quorum-sensing system affects gall development incited by Pantoea agglomerans pv. gypsophilae.

    Science.gov (United States)

    Chalupowicz, Laura; Manulis-Sasson, Shulamit; Itkin, Maxim; Sacher, Ayelet; Sessa, Guido; Barash, Isaac

    2008-08-01

    The quorum-sensing (QS) regulatory system of the gall-forming Pantoea agglomerans pv. gypsophilae was identified. Mass spectral analysis, together with signal-specific biosensors, demonstrated that P. agglomerans pv. gypsophilae produced N-butanoyl-l-homoserine lactone (C4-HSL) as a major and N-hexanoyl-l-homoserine lactone (C6-HSL) as a minor QS signal. Homologs of luxI and luxR regulatory genes, pagI and pagR, were characterized in strain P. agglomerans pv. gypsophilae Pag824-1 and shown to be convergently transcribed and separated by 14 bp. The deduced PagI (23.8 kDa) and PagR (26.9 kDa) show high similarity with SmaI (41% identity) and SmaR (43% identity), respectively, of Serratia sp. American Type Culture Collection 39006. PagR possesses characteristic autoinducer binding and a helix-turn-helix DNA-binding domain. Gall formation by P. agglomerans pv. gypsophilae depends on a plasmid-borne hrp/hrc gene cluster, type III effectors, and phytohormones. Disruption of pagI, pagR, or both genes simultaneously in Pag824-1 reduced gall size in gypsophila cuttings by 50 to 55% when plants were inoculated with 10(6) CFU/ml. Higher reductions in gall size (70 to 90%) were achieved by overexpression of pagI or addition of exogenous C4-HSL. Expression of the hrp/hrc regulatory gene hrpL and the type III effector pthG in the pagI mutant, as measured with quantitative reverse-transcriptase polymerase chain reaction, was reduced by 5.8 and 6.6, respectively, compared with the wild type, suggesting an effect of the QS system on the Hrp regulon.

  2. IMPACT OF BACTERIAL QUORUM SENSING SYSTEM ON CHANGES OF ORGANOLEPTIC MARKERS OF STORAGE CABBAGE

    Directory of Open Access Journals (Sweden)

    Kamila Myszka

    2015-04-01

    Full Text Available The regulation of phenotypes of vegetable-associated bacteria can be mediated through the production of acylated homoserine lactones (AHLs. This knowledge is essential for successful control of bacterial diseases of vegetable. The purpose of these investigations was to define the AHL patterns of gram-negative bacteria presented in storage cabbage by LC/MS technique. The phenomenon of regulating the pectinolytic activity and the exopolysaccharide (EPS production by AHLs that are associated with microbial spoilage of cabbage was also examined. Among 100 strains isolated from storage cabbage, 47 isolates produced AHLs. The results of the 16S rDNA sequence analysis indicated that selected microflora was highly closely related to Pantoea agglomerans, Rahnella aquatilis, Pseudomonas fluorescens, Pseudomonas syringae, and Pseudomonas cedrina (approximately 98%-99% confidence. The chemical nature of AHLs produced by selected microflora differ from species to species. The pattern of AHLs of Ps. cedrina consisting of C8-HSL, 3-oxo-C10-HSL, and 3-hydroxy-C14-HSL, has not been previously reported. The present study demonstrates that bacterial spoilage of storage cabbage is influenced by quorum sensing. Application of furanone C-30 that acts as quorum sensing inhibitor, caused the significant reduction in the production of EPS and pectinolytic enzymes by examined bacteria.

  3. Cross-talk between Staphylococcus aureus and other staphylococcal species via the agr quorum sensing system

    Directory of Open Access Journals (Sweden)

    Jaime Canovas de la Nuez

    2016-11-01

    Full Text Available Staphylococci are associated with both humans and animals. While most are non-pathogenic colonizers, Staphylococcus aureus is an opportunistic pathogen capable of causing severe infections. S. aureus virulence is controlled by the agr quorum sensing system responding to secreted auto-inducing peptides (AIPs sensed by AgrC, a two component histidine kinase. agr loci are found also in other staphylococcal species and for S. epidermidis, the encoded AIP represses expression of agr regulated virulence genes in S. aureus. In this study we aimed to determine how other staphylococci affect S. aureus agr, and if such interaction may point to new anti-virulence candidates to target S. aureus infections. Here we show that culture supernatants of 37 out of 52 staphylococcal isolates representing 17 different species inhibit S. aureus agr. The dog pathogen, S. schleiferi, expressed the most potent inhibitory activity and was active against all four agr classes found in S. aureus. By employing a S. aureus strain encoding a constitutively active AIP receptor we show that the activity is mediated via agr. Subsequent cloning and heterologous expression of the S. schleiferi AIP in S. aureus demonstrated that this molecule was likely responsible for the inhibitory activity, and further proof was provided when pure synthetic S. schleiferi AIP was able to completely abolish agr induction of an S. aureus reporter strain. To assess impact on S. aureus virulence, we co-inoculated S. aureus and S. schleiferi in vivo in the Galleria Mellonella wax moth larva, and found that expression of key S. aureus virulence factors was abrogated. Our data show that the S. aureus agr locus is highly responsive to other staphylococcal species suggesting that agr is an inter-species communication system. Based on these results we speculate that interactions between S. aureus and other colonizing staphylococci will significantly influence the ability of S. aureus to cause infection, and

  4. Quorum Sensing and Quorum Quenching in the Phycosphere of Phytoplankton: a Case of Chemical Interactions in Ecology.

    Science.gov (United States)

    Rolland, Jean Luc; Stien, Didier; Sanchez-Ferandin, Sophie; Lami, Raphaël

    2016-12-01

    The interactions between bacteria and phytoplankton regulate many important biogeochemical reactions in the marine environment, including those in the global carbon, nitrogen, and sulfur cycles. At the microscopic level, it is now well established that important consortia of bacteria colonize the phycosphere, the immediate environment of phytoplankton cells. In this microscale environment, abundant bacterial cells are organized in a structured biofilm, and exchange information through the diffusion of small molecules called semiochemicals. Among these processes, quorum sensing plays a particular role as, when a sufficient abundance of cells is reached, it allows bacteria to coordinate their gene expression and physiology at the population level. In contrast, quorum quenching mechanisms are employed by many different types of microorganisms that limit the coordination of antagonistic bacteria. This review synthesizes quorum sensing and quorum quenching mechanisms evidenced to date in the phycosphere, emphasizing the implications that these signaling systems have for the regulation of bacterial communities and their activities. The diversity of chemical compounds involved in these processes is examined. We further review the bacterial functions regulated in the phycosphere by quorum sensing, which include biofilm formation, nutrient acquisition, and emission of algaecides. We also discuss quorum quenching compounds as antagonists of quorum sensing, their function in the phycosphere, and their potential biotechnological applications. Overall, the current state of the art demonstrates that quorum sensing and quorum quenching regulate a balance between a symbiotic and a parasitic way of life between bacteria and their phytoplankton host.

  5. Toward development of an autonomous network of bacteria-based delivery systems (BacteriaBots): spatiotemporally high-throughput characterization of bacterial quorum-sensing response.

    Science.gov (United States)

    Sahari, Ali; Traore, Mahama A; Stevens, Ann M; Scharf, Birgit E; Behkam, Bahareh

    2014-12-02

    Characterization of bacterial innate and engineered cooperative behavior, regulated through chemical signaling in a process known as quorum sensing, is critical to development of a myriad of bacteria-enabled systems including biohybrid drug delivery systems and biohybrid mobile sensor networks. Here, we demonstrate, for the first time, that microfluidic diffusive mixers can be used for spatiotemporally high-throughput characterization of bacterial quorum-sensing response. Using this batch characterization method, the quorum-sensing response in Escherichia coli MG1655, transformed with a truncated lux operon from Vibrio fischeri, in the presence of 1-100 nM exogenous acyl-homoserine lactone molecules has been quantified. This method provides a rapid and facile tool for high-throughput characterization of the quorum-sensing response of genetically modified bacteria in the presence of a wide concentration range of signaling molecules with a precision of ±0.5 nM. Furthermore, the quorum-sensing response of BacteriaBots has been characterized to determine if the results obtained from a large bacterial population can serve as a robust predictive tool for the small bacterial population attached to each BacteriaBot.

  6. Quorum-Sensing Synchronization of Synthetic Toggle Switches: A Design Based on Monotone Dynamical Systems Theory.

    Directory of Open Access Journals (Sweden)

    Evgeni V Nikolaev

    2016-04-01

    Full Text Available Synthetic constructs in biotechnology, biocomputing, and modern gene therapy interventions are often based on plasmids or transfected circuits which implement some form of "on-off" switch. For example, the expression of a protein used for therapeutic purposes might be triggered by the recognition of a specific combination of inducers (e.g., antigens, and memory of this event should be maintained across a cell population until a specific stimulus commands a coordinated shut-off. The robustness of such a design is hampered by molecular ("intrinsic" or environmental ("extrinsic" noise, which may lead to spontaneous changes of state in a subset of the population and is reflected in the bimodality of protein expression, as measured for example using flow cytometry. In this context, a "majority-vote" correction circuit, which brings deviant cells back into the required state, is highly desirable, and quorum-sensing has been suggested as a way for cells to broadcast their states to the population as a whole so as to facilitate consensus. In this paper, we propose what we believe is the first such a design that has mathematically guaranteed properties of stability and auto-correction under certain conditions. Our approach is guided by concepts and theory from the field of "monotone" dynamical systems developed by M. Hirsch, H. Smith, and others. We benchmark our design by comparing it to an existing design which has been the subject of experimental and theoretical studies, illustrating its superiority in stability and self-correction of synchronization errors. Our stability analysis, based on dynamical systems theory, guarantees global convergence to steady states, ruling out unpredictable ("chaotic" behaviors and even sustained oscillations in the limit of convergence. These results are valid no matter what are the values of parameters, and are based only on the wiring diagram. The theory is complemented by extensive computational bifurcation analysis

  7. Quorum-Sensing Synchronization of Synthetic Toggle Switches: A Design Based on Monotone Dynamical Systems Theory.

    Science.gov (United States)

    Nikolaev, Evgeni V; Sontag, Eduardo D

    2016-04-01

    Synthetic constructs in biotechnology, biocomputing, and modern gene therapy interventions are often based on plasmids or transfected circuits which implement some form of "on-off" switch. For example, the expression of a protein used for therapeutic purposes might be triggered by the recognition of a specific combination of inducers (e.g., antigens), and memory of this event should be maintained across a cell population until a specific stimulus commands a coordinated shut-off. The robustness of such a design is hampered by molecular ("intrinsic") or environmental ("extrinsic") noise, which may lead to spontaneous changes of state in a subset of the population and is reflected in the bimodality of protein expression, as measured for example using flow cytometry. In this context, a "majority-vote" correction circuit, which brings deviant cells back into the required state, is highly desirable, and quorum-sensing has been suggested as a way for cells to broadcast their states to the population as a whole so as to facilitate consensus. In this paper, we propose what we believe is the first such a design that has mathematically guaranteed properties of stability and auto-correction under certain conditions. Our approach is guided by concepts and theory from the field of "monotone" dynamical systems developed by M. Hirsch, H. Smith, and others. We benchmark our design by comparing it to an existing design which has been the subject of experimental and theoretical studies, illustrating its superiority in stability and self-correction of synchronization errors. Our stability analysis, based on dynamical systems theory, guarantees global convergence to steady states, ruling out unpredictable ("chaotic") behaviors and even sustained oscillations in the limit of convergence. These results are valid no matter what are the values of parameters, and are based only on the wiring diagram. The theory is complemented by extensive computational bifurcation analysis, performed for a

  8. Quorum sensing system regulation on bacterial resistance%群体感应系统对细菌耐药的调控作用

    Institute of Scientific and Technical Information of China (English)

    朱艮苗; 杨维青

    2011-01-01

    Quorum sensing was a common mechanism that bacteria regulated the adapting ability of communities depending on cell density. Bacterial quorum sensing system regulated a number of specific functions,such as bacterial resistance-related traits. This paper reviewed the regulation of quorum sensing system on bacterial resistance-related traits.%群体感应是细菌依赖于细胞密度、调节群体适应能力的一种普遍机制.细菌群体感应系统调节许多特定的功能,如对细菌耐药相关性状的调节.本文就群体感应系统对细菌耐药相关性状的调控作用进行综述.

  9. Effect of low Reynolds number flow on the quorum sensing behavior of sessile bacteria

    Science.gov (United States)

    Ingremeau, Francois; Minyoung, Kevin Kim; Bassler, Bonnie; Stone, Howard; Mechanical; Aerospace Engineering, Complex fluids Group Team; Molecular Biology Lab Team

    2014-11-01

    Sessile and planktonic bacteria can be sensitive to the bacteria cell density around them through a chemical mediated communication called quorum sensing. When the quorum sensing molecules reach a certain value, the metabolism of the bacteria changes. Quorum sensing is usually studied in static conditions or in well mixed environments. However, bacteria biofilms can form in porous media or in the circulatory system of an infected body: quorum sensing in such flowing environment at low Reynolds number is not well studied. Using microfluidic devices, we observe how the flow of a pure media affects quorum sensing of bacteria attached to the wall. The biofilm formation is quantified by measuring the optical density in brightfield microscopy and the quorum sensing gene expression is observed through the fluorescence of a green fluorescent protein, which is a reporter for one of the quorum sensing genes. We measured without flow the amount of Staphylococcus aureus biofilm when the quorum sensing gene expression starts. In contrast, when the media is flowing in the microchannel, the quorum sensing expression is delayed. This effect can be understood and modelled by considering the diffusion of the quorum sensing molecules in the biofilm and their convection by the flowing media.

  10. Quorum-sensing in yeast and its potential in wine making.

    Science.gov (United States)

    Avbelj, Martina; Zupan, Jure; Raspor, Peter

    2016-09-01

    This mini-review synthesises the present knowledge of microbial quorum-sensing, with a specific focus on quorum-sensing in yeast, and especially in wine yeast. In vine and wine ecosystems, yeast co-interact with a large variety of microorganisms, thereby affecting the fermentation process and, consequently, the flavour of the wine. The precise connections between microbial interactions and quorum-sensing remain unclear, but we describe here how and when some species start to produce quorum-sensing molecules to synchronously adapt their collective behaviour to new conditions. In Saccharomyces cerevisiae, the quorum-sensing molecules were identified as 2-phenylethanol and tryptophol. However, it was recently shown that also a quorum-sensing molecule formerly identified only in Candida albicans, tyrosol, appears to be regulated in S. cerevisiae according to cell density. This review describes the methods for detection and quantification of those quorum-sensing molecules, their underlying mechanisms of action, and their genetic background. It also examines the external stimuli that evoke the quorum-sensing mechanism in the wine-processing environment. The review closes with insight into the biotechnological applications that are already making use of the advantages of quorum-sensing systems and indicates the important questions that still need to be addressed in future research into quorum-sensing.

  11. Quorum Sensing Peptides Selectively Penetrate the Blood-Brain Barrier.

    Science.gov (United States)

    Wynendaele, Evelien; Verbeke, Frederick; Stalmans, Sofie; Gevaert, Bert; Janssens, Yorick; Van De Wiele, Christophe; Peremans, Kathelijne; Burvenich, Christian; De Spiegeleer, Bart

    2015-01-01

    Bacteria communicate with each other by the use of signaling molecules, a process called 'quorum sensing'. One group of quorum sensing molecules includes the oligopeptides, which are mainly produced by Gram-positive bacteria. Recently, these quorum sensing peptides were found to biologically influence mammalian cells, promoting i.a. metastasis of cancer cells. Moreover, it was found that bacteria can influence different central nervous system related disorders as well, e.g. anxiety, depression and autism. Research currently focuses on the role of bacterial metabolites in this bacteria-brain interaction, with the role of the quorum sensing peptides not yet known. Here, three chemically diverse quorum sensing peptides were investigated for their brain influx (multiple time regression technique) and efflux properties in an in vivo mouse model (ICR-CD-1) to determine blood-brain transfer properties: PhrCACET1 demonstrated comparatively a very high initial influx into the mouse brain (Kin = 20.87 μl/(g×min)), while brain penetrabilities of BIP-2 and PhrANTH2 were found to be low (Kin = 2.68 μl/(g×min)) and very low (Kin = 0.18 μl/(g×min)), respectively. All three quorum sensing peptides were metabolically stable in plasma (in vitro) during the experimental time frame and no significant brain efflux was observed. Initial tissue distribution data showed remarkably high liver accumulation of BIP-2 as well. Our results thus support the potential role of some quorum sensing peptides in different neurological disorders, thereby enlarging our knowledge about the microbiome-brain axis.

  12. Transcriptome analysis of acyl-homoserine lactone-based quorum sensing regulation in Yersinia pestis [corrected].

    Science.gov (United States)

    LaRock, Christopher N; Yu, Jing; Horswill, Alexander R; Parsek, Matthew R; Minion, F Chris

    2013-01-01

    The etiologic agent of bubonic plague, Yersinia pestis, senses self-produced, secreted chemical signals in a process named quorum sensing. Though the closely related enteric pathogen Y. pseudotuberculosis uses quorum sensing system to regulate motility, the role of quorum sensing in Y. pestis has been unclear. In this study we performed transcriptional profiling experiments to identify Y. pestis quorum sensing regulated functions. Our analysis revealed that acyl-homoserine lactone-based quorum sensing controls the expression of several metabolic functions. Maltose fermentation and the glyoxylate bypass are induced by acyl-homoserine lactone signaling. This effect was observed at 30°C, indicating a potential role for quorum sensing regulation of metabolism at temperatures below the normal mammalian temperature. It is proposed that utilization of alternative carbon sources may enhance growth and/or survival during prolonged periods in natural habitats with limited nutrient sources, contributing to maintenance of plague in nature.

  13. Transcriptome analysis of acyl-homoserine lactone-based quorum sensing regulation in Yersinia pestis [corrected].

    Directory of Open Access Journals (Sweden)

    Christopher N LaRock

    Full Text Available The etiologic agent of bubonic plague, Yersinia pestis, senses self-produced, secreted chemical signals in a process named quorum sensing. Though the closely related enteric pathogen Y. pseudotuberculosis uses quorum sensing system to regulate motility, the role of quorum sensing in Y. pestis has been unclear. In this study we performed transcriptional profiling experiments to identify Y. pestis quorum sensing regulated functions. Our analysis revealed that acyl-homoserine lactone-based quorum sensing controls the expression of several metabolic functions. Maltose fermentation and the glyoxylate bypass are induced by acyl-homoserine lactone signaling. This effect was observed at 30°C, indicating a potential role for quorum sensing regulation of metabolism at temperatures below the normal mammalian temperature. It is proposed that utilization of alternative carbon sources may enhance growth and/or survival during prolonged periods in natural habitats with limited nutrient sources, contributing to maintenance of plague in nature.

  14. Strain-dependent diversity in the Pseudomonas aeruginosa quorum-sensing regulon.

    Science.gov (United States)

    Chugani, Sudha; Kim, Byoung Sik; Phattarasukol, Somsak; Brittnacher, Mitchell J; Choi, Sang Ho; Harwood, Caroline S; Greenberg, E Peter

    2012-10-09

    Quorum sensing allows bacteria to sense and respond to changes in population density. Acyl-homoserine lactones serve as quorum-sensing signals for many Proteobacteria, and acyl-homoserine lactone signaling is known to control cooperative activities. Quorum-controlled activities vary from one species to another. Quorum-sensing controls a constellation of genes in the opportunistic pathogen Pseudomonas aeruginosa, which thrives in a number of habitats ranging from soil and water to animal hosts. We hypothesized that there would be significant variation in quorum-sensing regulons among strains of P. aeruginosa isolated from different habitats and that differences in the quorum-sensing regulons might reveal insights about the ecology of P. aeruginosa. As a test of our hypothesis we used RNA-seq to identify quorum-controlled genes in seven P. aeruginosa isolates of diverse origins. Although our approach certainly overlooks some quorum-sensing-regulated genes we found a shared set of genes, i.e., a core quorum-controlled gene set, and we identified distinct, strain-variable sets of quorum-controlled genes, i.e., accessory genes. Some quorum-controlled genes in some strains were not present in the genomes of other strains. We detected a correlation between traits encoded by some genes in the strain-variable subsets of the quorum regulons and the ecology of the isolates. These findings indicate a role for quorum sensing in extension of the range of habitats in which a species can thrive. This study also provides a framework for understanding the molecular mechanisms by which quorum-sensing systems operate, the evolutionary pressures by which they are maintained, and their importance in disparate ecological contexts.

  15. Pseudomonas aeruginosa las and rhl quorum-sensing systems are important for infection and inflammation in a rat prostatitis model.

    Science.gov (United States)

    Nelson, Lisa K; D'Amours, Genevieve H; Sproule-Willoughby, Kimberley M; Morck, Douglas W; Ceri, Howard

    2009-08-01

    Pseudomonas aeruginosa frequently acts as an opportunistic pathogen of mucosal surfaces; yet, despite causing aggressive prostatitis in some men, its role as a pathogen in the prostate has not been investigated. Consequently, we developed a Ps. aeruginosa infection model in the rat prostate by instilling wild-type (WT) Ps. aeruginosa strain PAO1 into the rat prostate. It was found that Ps. aeruginosa produced acute and chronic infections in this mucosal tissue as determined by bacterial colonization, gross morphology, tissue damage and inflammatory markers. WT strain PAO1 and its isogenic mutant PAO-JP2, in which both the lasI and rhlI quorum-sensing signal systems have been silenced, were compared during both acute and chronic prostate infections. In acute infections, bacterial numbers and inflammatory markers were comparable between WT PA01 and PAO-JP2; however, considerably less tissue damage occurred in infections with PAO-JP2. Chronic infections with PAO-JP2 resulted in reduced bacterial colonization, tissue damage and inflammation as compared to WT PAO1 infections. Therefore, the quorum-sensing lasI and rhlI genes in Ps. aeruginosa affect acute prostate infections, but play a considerably more important role in maintaining chronic infections. We have thus developed a highly reproducible model for the study of Ps. aeruginosa virulence in the prostate.

  16. Pseudomonas aeruginosa quorum sensing modulates immune responses: An updated review article.

    Science.gov (United States)

    Kariminik, Ashraf; Baseri-Salehi, Majid; Kheirkhah, Babak

    2017-07-08

    Pseudomonas aeruginosa is an opportunistic bacterium which induces some complications in immunocompromised patients. Pseudomonas aeruginosa is a quorum-sensing using bacterium which regulates its genes expression. The bacterium uses two famous pathways for quorum sensing entitled LasI/LasR and RhlI/RhlR systems. It has been documented that the bacteria which use quorum sensing are able to overcome immune responses. This review article aims to present recent information regarding the effects of Pseudomonas aeruginosa quorum sensing systems on the host immune responses. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  17. Triazole-containing N-acyl homoserine lactones targeting the quorum sensing system in Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Hansen, Mette Reimert; Jakobsen, Tim H.; Bang, Claus Gunnar;

    2015-01-01

    In an attempt to devise new antimicrobial treatments for biofilm infections, the bacterial cell-cell communication system termed quorum sensing has emerged as an attractive target. It has proven possible to intercept the communication system by synthetic non-native ligands and thereby lower the p...

  18. Regulation of aromatics biodegradation by rhl quorum sensing system through induction of catechol meta-cleavage pathway.

    Science.gov (United States)

    Yong, Yang-Chun; Zhong, Jian-Jiang

    2013-05-01

    The mechanism for quorum sensing (QS) regulation on aromatics degradation was investigated. Deletion of rhl QS system resulted in a significant decrease in aromatics biodegradation as well as the activity of catechol 2,3-dioxygenase (C23O, key enzyme for catechol meta-cleavage pathway) in Pseudomonas aeruginosa CGMCC1.860. Interestingly, this repression could be relieved by N-butyryl homoserine lactone (the signaling molecule of rhl QS system) addition. In accordance, the transcription level of nahH (the gene encoding C23O) and nahR (transcriptional activator) also responded to rhl perturbation in a similar way. The results indicated that rhl QS system positively controlled the catechol meta-cleavage pathway, and hence improved aromatics biodegradation. It suggested manipulation of QS system could be a promising strategy to tune the catechol cleavage pathway and to control aromatics biodegradation.

  19. Escherichia coli O157:H7 lacking qseBC encoded quorum sensing system outcompetes the parent strain in colonization of cattle intestine

    Science.gov (United States)

    The qseBC encoded quorum-sensing system (QS) regulates motility of enterohemorrhagic Escherichia coli (EHEC) O157:H7 in response to bacterial autoinducer-3 (AI-3) and mammalian stress hormones epinephrine (E) and norepinephrine (NE). The qseC gene encodes a sensory kinase that post-autophosphorylati...

  20. Identification and characterization of a GDSL esterase gene located proximal to the swr quorum-sensing system of Serratia liquefaciens MG1

    DEFF Research Database (Denmark)

    Riedel, K.; Talker-Huiber, D.; Givskov, Michael Christian

    2003-01-01

    and by the analysis of a transcriptional fusion of the estA promoter to the promoterless lux4B genes, we showed that expression of the esterase is not regulated by the swr quorum-sensing system. An estA mutant was generated and was found to exhibit growth defects on minimal medium containing Tween 20 or Tween 80...

  1. Specific quorum sensing-disrupting activity (A QSI) of thiophenones and their therapeutic potential.

    Science.gov (United States)

    Yang, Qian; Scheie, Anne Aamdal; Benneche, Tore; Defoirdt, Tom

    2015-12-09

    Disease caused by antibiotic resistant pathogens is becoming a serious problem, both in human and veterinary medicine. The inhibition of quorum sensing, bacterial cell-to-cell communication, is a promising alternative strategy to control disease. In this study, we determined the quorum sensing-disrupting activity of 20 thiophenones towards the quorum sensing model bacterium V. harveyi. In order to exclude false positives, we propose a new parameter (AQSI) to describe specific quorum sensing activity. AQSI is defined as the ratio between inhibition of quorum sensing-regulated activity in a reporter strain and inhibition of the same activity when it is independent of quorum sensing. Calculation of AQSI allowed to exclude five false positives, whereas the six most active thiophenones (TF203, TF307, TF319, TF339, TF342 and TF403) inhibited quorum sensing at 0.25 μM, with AQSI higher than 10. Further, we determined the protective effect and toxicity of the thiophenones in a highly controlled gnotobiotic model system with brine shrimp larvae. There was a strong positive correlation between the specific quorum sensing-disrupting activity of the thiophenones and the protection of brine shrimp larvae against pathogenic V. harveyi. Four of the most active quorum sensing-disrupting thiophenones (TF 203, TF319, TF339 and TF342) were considered to be promising since they have a therapeutic potential of at least 10.

  2. Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors

    DEFF Research Database (Denmark)

    Hentzer, Morten; Wu, H.; Andersen, Jens Bo

    2003-01-01

    Traditional treatment of infectious diseases is based on compounds that kill or inhibit growth of bacteria. A major concern with this approach is the frequent development of resistance to antibiotics. The discovery of communication systems (quorum sensing systems) regulating bacterial virulence has...

  3. Quorum sensing and density-dependent dispersal in an aquatic model system.

    Directory of Open Access Journals (Sweden)

    Simon Fellous

    Full Text Available Many organisms use cues to decide whether to disperse or not, especially those related to the composition of their environment. Dispersal hence sometimes depends on population density, which can be important for the dynamics and evolution of sub-divided populations. But very little is known about the factors that organisms use to inform their dispersal decision. We investigated the cues underlying density-dependent dispersal in inter-connected microcosms of the freshwater protozoan Paramecium caudatum. In two experiments, we manipulated (i the number of cells per microcosm and (ii the origin of their culture medium (supernatant from high- or low-density populations. We found a negative relationship between population density and rates of dispersal, suggesting the use of physical cues. There was no significant effect of culture medium origin on dispersal and thus no support for chemical cues usage. These results suggest that the perception of density - and as a result, the decision to disperse - in this organism can be based on physical factors. This type of quorum sensing may be an adaptation optimizing small scale monitoring of the environment and swarm formation in open water.

  4. The evolution of quorum sensing in bacterial biofilms.

    Science.gov (United States)

    Nadell, Carey D; Xavier, Joao B; Levin, Simon A; Foster, Kevin R

    2008-01-01

    Bacteria have fascinating and diverse social lives. They display coordinated group behaviors regulated by quorum-sensing systems that detect the density of other bacteria around them. A key example of such group behavior is biofilm formation, in which communities of cells attach to a surface and envelope themselves in secreted polymers. Curiously, after reaching high cell density, some bacterial species activate polymer secretion, whereas others terminate polymer secretion. Here, we investigate this striking variation in the first evolutionary model of quorum sensing in biofilms. We use detailed individual-based simulations to investigate evolutionary competitions between strains that differ in their polymer production and quorum-sensing phenotypes. The benefit of activating polymer secretion at high cell density is relatively straightforward: secretion starts upon biofilm formation, allowing strains to push their lineages into nutrient-rich areas and suffocate neighboring cells. But why use quorum sensing to terminate polymer secretion at high cell density? We find that deactivating polymer production in biofilms can yield an advantage by redirecting resources into growth, but that this advantage occurs only in a limited time window. We predict, therefore, that down-regulation of polymer secretion at high cell density will evolve when it can coincide with dispersal events, but it will be disfavored in long-lived (chronic) biofilms with sustained competition among strains. Our model suggests that the observed variation in quorum-sensing behavior can be linked to the differing requirements of bacteria in chronic versus acute biofilm infections. This is well illustrated by the case of Vibrio cholerae, which competes within biofilms by polymer secretion, terminates polymer secretion at high cell density, and induces an acute disease course that ends with mass dispersal from the host. More generally, this work shows that the balance of competition within and among

  5. Quorum Sensing in Marine Microbial Environments

    Science.gov (United States)

    Hmelo, Laura R.

    2017-01-01

    Quorum sensing (QS) is a form of chemical communication used by certain bacteria that regulates a wide range of biogeochemically important bacterial behaviors. Although QS was first observed in a marine bacterium nearly four decades ago, only in the past decade has there been a rise in interest in the role that QS plays in the ocean. It has become clear that QS, regulated by signals such as acylated homoserine lactones (AHLs) or furanosyl-borate diesters [autoinducer-2 (AI-2) molecules], is involved in important processes within the marine carbon cycle, in the health of coral reef ecosystems, and in trophic interactions between a range of eukaryotes and their bacterial associates. The most well-studied QS systems in the ocean occur in surface-attached (biofilm) communities and rely on AHL signaling. AHL-QS is highly sensitive to the chemical and biological makeup of the environment and may respond to anthropogenic change, including ocean acidification and rising sea surface temperatures.

  6. A Strategy for Antagonizing Quorum Sensing

    Energy Technology Data Exchange (ETDEWEB)

    G Chen; L Swem; D Swem; D Stauff; C OLoughlin; P Jeffrey; B Bassler; F Hughson

    2011-12-31

    Quorum-sensing bacteria communicate via small molecules called autoinducers to coordinate collective behaviors. Because quorum sensing controls virulence factor expression in many clinically relevant pathogens, membrane-permeable quorum sensing antagonists that prevent population-wide expression of virulence genes offer a potential route to novel antibacterial therapeutics. Here, we report a strategy for inhibiting quorum-sensing receptors of the widespread LuxR family. Structure-function studies with natural and synthetic ligands demonstrate that the dimeric LuxR-type transcription factor CviR from Chromobacterium violaceum is potently antagonized by molecules that bind in place of the native acylated homoserine lactone autoinducer, provided that they stabilize a closed conformation. In such conformations, each of the two DNA-binding domains interacts with the ligand-binding domain of the opposing monomer. Consequently, the DNA-binding helices are held apart by {approx}60 {angstrom}, twice the {approx}30 {angstrom} separation required for operator binding. This approach may represent a general strategy for the inhibition of multidomain proteins.

  7. Targeting quorum sensing in Pseudomonas aeruginosa biofilms

    DEFF Research Database (Denmark)

    Jakobsen, Tim Holm; Bjarnsholt, Thomas; Jensen, Peter Østrup

    2013-01-01

    alternative antibacterial strategies. Here, we review state of the art research of quorum sensing inhibitors against the opportunistic human pathogen Pseudomonas aeruginosa, which is found in a number of biofilm-associated infections and identified as the predominant organism infecting the lungs of cystic...

  8. Bacillus globigii cell size is influenced by variants of the quorum sensing peptide extracellular death factor

    NARCIS (Netherlands)

    Sijbrandij, T.; Kaman, W.E.; Ligtenberg, A.J.M.; Nazmi, K.; Veerman, E.C.I.; Bikker, F.J.

    2014-01-01

    Toxin-antitoxin modules are necessary for the mode of action of several antibiotics. One of the most studied toxin-antitoxin modules is the quorum sensing - dependent MazEF system in Escherichia coli. The quorum sensing factor in this system is called the extracellular death factor (EDF), a linear p

  9. Bacillus globigii cell size is influenced by variants of the quorum sensing peptide extracellular death factor

    NARCIS (Netherlands)

    T. Sijbrandij (T.); W.E. Kaman (Wendy); A.J.M. Ligtenberg (A. J M); K. Nazmi (Kamran); E.C.I. Veerman (Enno); F.J. Bikker (Floris)

    2014-01-01

    textabstractToxin-antitoxin modules are necessary for the mode of action of several antibiotics. One of the most studied toxin-antitoxin modules is the quorum sensing - dependent MazEF system in Escherichia coli. The quorum sensing factor in this system is called the extracellular death factor (EDF)

  10. Quorum sensing by peptide pheromones and two-component signal-transduction systems in Gram-positive bacteria

    NARCIS (Netherlands)

    Kleerebezem, Michiel; Quadri, Luis E.N.; Kuipers, Oscar P.; Vos, Willem M. de

    1997-01-01

    Cell-density-dependent gene expression appears to be widely spread in bacteria. This quorum-sensing phenomenon has been well established in Gram-negative bacteria, where N-acyl homoserine lactones are the diffusible communication molecules that modulate cell-density-dependent phenotypes. Similarly,

  11. Quorum sensing by peptide pheromones and two-component signal-transduction systems in Gram-positive bacteria

    NARCIS (Netherlands)

    Kleerebezem, Michiel; Quadri, Luis E.N.; Kuipers, Oscar P.; Vos, Willem M. de

    1997-01-01

    Cell-density-dependent gene expression appears to be widely spread in bacteria. This quorum-sensing phenomenon has been well established in Gram-negative bacteria, where N-acyl homoserine lactones are the diffusible communication molecules that modulate cell-density-dependent phenotypes. Similarly,

  12. Imaging N-acyl homoserine lactone quorum sensing in vivo

    DEFF Research Database (Denmark)

    Christensen, Louise Dahl; van Gennip, Maria; Jakobsen, Tim Holm

    2011-01-01

    In order to study N-acyl homoserine lactone (AHL)-based quorum sensing in vivo, we present a protocol using an Escherichia coli strain equipped with a luxR-based monitor system, which in the presence of exogenous AHL molecules expresses a green fluorescent protein (GFP). Lungs from mice challenged...

  13. Can the natural diversity of quorum-sensing advance synthetic biology?

    Science.gov (United States)

    Davis, René Michele; Muller, Ryan Yue; Haynes, Karmella Ann

    2015-01-01

    Quorum-sensing networks enable bacteria to sense and respond to chemical signals produced by neighboring bacteria. They are widespread: over 100 morphologically and genetically distinct species of eubacteria are known to use quorum sensing to control gene expression. This diversity suggests the potential to use natural protein variants to engineer parallel, input-specific, cell-cell communication pathways. However, only three distinct signaling pathways, Lux, Las, and Rhl, have been adapted for and broadly used in engineered systems. The paucity of unique quorum-sensing systems and their propensity for crosstalk limits the usefulness of our current quorum-sensing toolkit. This review discusses the need for more signaling pathways, roadblocks to using multiple pathways in parallel, and strategies for expanding the quorum-sensing toolbox for synthetic biology.

  14. A mathematical model and quantitative comparison of the small RNA circuit in the Vibrio harveyi and Vibrio cholerae quorum sensing systems

    Science.gov (United States)

    Hunter, G. A. M.; Guevara Vasquez, F.; Keener, J. P.

    2013-08-01

    Quorum sensing is the process by which bacteria regulate their gene expression based on the local cell-population density. The quorum sensing systems of Vibrio harveyi and Vibrio cholerae are comprised of a phosphorelay cascade coupled to a small RNA (sRNA) circuit. The sRNA circuit contains multiple quorum regulated small RNA (Qrr) that regulate expression of the homologous master transcriptional regulators LuxR (in V. harveyi) and HapR (in V. cholerae). Their quorum sensing systems are topologically similar and homologous thereby making it difficult to understand why repression of HapR is more robust than LuxR to changes in Qrr. In this work we formulate and parameterize a novel mathematical model of the V. harveyi and V. cholerae sRNA circuit. We parameterize the model by fitting it to a variety of empirical data from both species. We show that we can distinguish all of the parameters and that the parameterizations (one for each species) are robust to errors in the data. We then use our model to propose some experiments to identify and explain kinetic differences between the species. We find that V. cholerae Qrr are more abundant and more sensitive to changes in LuxO than V. harveyi Qrr and argue that this is why expression of HapR is more robust than LuxR to changes in Qrr.

  15. A mathematical model and quantitative comparison of the small RNA circuit in the Vibrio harveyi and Vibrio cholerae quorum sensing systems.

    Science.gov (United States)

    Hunter, G A M; Vasquez, F Guevara; Keener, J P

    2013-08-01

    Quorum sensing is the process by which bacteria regulate their gene expression based on the local cell-population density. The quorum sensing systems of Vibrio harveyi and Vibrio cholerae are comprised of a phosphorelay cascade coupled to a small RNA (sRNA) circuit. The sRNA circuit contains multiple quorum regulated small RNA (Qrr) that regulate expression of the homologous master transcriptional regulators LuxR (in V. harveyi) and HapR (in V. cholerae). Their quorum sensing systems are topologically similar and homologous thereby making it difficult to understand why repression of HapR is more robust than LuxR to changes in Qrr. In this work we formulate and parameterize a novel mathematical model of the V. harveyi and V. cholerae sRNA circuit. We parameterize the model by fitting it to a variety of empirical data from both species. We show that we can distinguish all of the parameters and that the parameterizations (one for each species) are robust to errors in the data. We then use our model to propose some experiments to identify and explain kinetic differences between the species. We find that V. cholerae Qrr are more abundant and more sensitive to changes in LuxO than V. harveyi Qrr and argue that this is why expression of HapR is more robust than LuxR to changes in Qrr.

  16. Quadruple Quorum-Sensing Inputs Control Vibrio cholerae Virulence and Maintain System Robustness

    Science.gov (United States)

    Jung, Sarah A.; Chapman, Christine A.; Ng, Wai-Leung

    2015-01-01

    Bacteria use quorum sensing (QS) for cell-cell communication to carry out group behaviors. This intercellular signaling process relies on cell density-dependent production and detection of chemical signals called autoinducers (AIs). Vibrio cholerae, the causative agent of cholera, detects two AIs, CAI-1 and AI-2, with two histidine kinases, CqsS and LuxQ, respectively, to control biofilm formation and virulence factor production. At low cell density, these two signal receptors function in parallel to activate the key regulator LuxO, which is essential for virulence of this pathogen. At high cell density, binding of AIs to their respective receptors leads to deactivation of LuxO and repression of virulence factor production. However, mutants lacking CqsS and LuxQ maintain a normal LuxO activation level and remain virulent, suggesting that LuxO is activated by additional, unidentified signaling pathways. Here we show that two other histidine kinases, CqsR (formerly known as VC1831) and VpsS, act upstream in the central QS circuit of V. cholerae to activate LuxO. V. cholerae strains expressing any one of these four receptors are QS proficient and capable of colonizing animal hosts. In contrast, mutants lacking all four receptors are phenotypically identical to LuxO-defective mutants. Importantly, these four functionally redundant receptors act together to prevent premature induction of a QS response caused by signal perturbations. We suggest that the V. cholerae QS circuit is composed of quadruple sensory inputs and has evolved to be refractory to sporadic AI level perturbations. PMID:25874462

  17. The quorum sensing system of Pseudomonas aeruginosa: progress on studies%铜绿假单胞菌群体感应系统的研究进展

    Institute of Scientific and Technical Information of China (English)

    陈树林; 黄彬

    2012-01-01

    Bacterial Quorum-sensing is also called autoinduce, which means the process that bacteria coordinate their group behavior through monitoring their population density via the production and detection of small signaling compounds. The level of autoinducers becomes higher with the increase of cell density. These signal molecules will bind to and activate their cognate transcriptional regulators when the level of autoinducer reaches a threshold concentration, then induce or inhibit several genes' expression. Three quorum sensing systems, the LasR-LasI system, RhlR-RhlI system and Pseudomonas quinolone signal system have been identified in Pseudomonas aeruginosa. Quorum-sensing system utilizes the diffusion of one or several signal molecules, embedded in a complex network of global regulation, influence bacterial group behavior. In addition, Quorum-sensing system participate the pathogenesis of Pseudomonas aeruginosa infections by regulating the production of virulence factors. With the increase of multi-drug resistant bacteria, many researchers focus on interfering with the bacterial quorum-sensing system to prevent infections by drug-resistant pathogens as a new antibiotic strategy. This review is about the research progress of Pseudomonas aeruginosa quorum-sensing system and the relationship with hosts.%细菌的群体感应也称自身诱导,是指细菌通过产生和感应信号分子浓度的变化来监测其群体密度,协调群体行为的过程.自身诱导物随着细菌密度增高而增高,当自身诱导物达到某一阈值后,会与一些转录调节子结合,从而诱导或抑制多种基因的表达.群体感应系统内由多种信号分子和效应蛋白组成复杂的调节网络,调控包括细菌毒力因子产生与释放、生物膜形成、接合反应等,从而影响细菌的致病过程.本文主要对铜绿假单胞菌的群体感应系统及其与宿主关系、群体感应抑制剂等方面的研究进展进行综述.

  18. Pandoraea sp. RB-44, A Novel Quorum Sensing Soil Bacterium

    Directory of Open Access Journals (Sweden)

    Robson Ee Han-Jen

    2013-10-01

    Full Text Available Proteobacteria are known to communicate via signaling molecules and this process is known as quorum sensing. The most commonly studied quorum sensing molecules are N-acylhomoserine lactones (AHLs that consists of a homoserine lactone moiety and an N-acyl side chain with various chain lengths and degrees of saturation at the C-3 position. We have isolated a bacterium, RB-44, from a site which was formally a landfill dumping ground. Using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF mass spectrometry analysis, this isolate was identified as a Pandoraea sp.which was then screened for AHL production using biosensors which indicated its quorum sensing properties. To identify the AHL profile of Pandoraea sp. RB-44, we used high resolution tandem mass spectrometry confirming that this isolate produced N-octanoylhomoserine lactone (C8-HSL. To the best of our knowledge, this is the first report that showed quorum sensing activity exhibited by Pandoraea sp. Our data add Pandoraea sp. to the growing number of bacteria that possess QS systems.

  19. Interaction of a P. aeruginosa Quorum Sensing Signal with Lipid Membranes

    Science.gov (United States)

    Morrison, Rebecca; Hall, Amelia; Hutchison, Ellen; Nguyen, Thuc; Cooley, Benjamin; Gordon, Vernita

    2011-03-01

    Bacteria use a signaling and regulatory system called ``quorum sensing'' to alter their gene expressions in response to the concentration of neighboring bacteria and to environmental conditions that make collective activity favorable for bacteria. P. aeruginosa is an opportunistic human pathogen that uses quorum sensing to govern processes such as virulence and biofilm formation. This organism's two main quorum sensing circuits use two different signaling molecules that are amphiphilic and differ primarily in the length of their hydrocarbon side chain and thus in their hydrophobic physical chemistry. How these physical chemistries govern the propagation and spatial localization of signals and thus of quorum sensing is not known. We present preliminary results showing that signals preferentially sequester to amphiphilic lipid membranes, which can act as reservoirs for signal. This is promising for future characterization of how the quorum sensing signals of many bacteria and yeast partition to spatially-differentiated amphiphilic environments, in a host or biofilm.

  20. An EAL domain protein and cyclic AMP contribute to the interaction between the two quorum sensing systems in Escherichia coli

    Institute of Scientific and Technical Information of China (English)

    Xianxuan Zhou; Xiaoming Meng; Baolin Sun

    2008-01-01

    Quorum sensing (QS) is a bacterial cell-cell communication process by which bacteria communicate using extracellular signals called autoinducers. Two QS systems have been identified in Escherichia coli K-12,including an intact QS system 2 that is stimulated by the cyclic AMP (cAMP)-cAMP receptor protein (CRP) complex and a partial QS system 1 that consists of SdiA (suppressor of cell division inhibitor) responding to signals generated by other microbialspecies. The relationship between QS system 1 and system 2 in E. coli,however,remains obscure. Here,we show that an EAL domain protein,encoded by ydiV,,and cAMP are involved in the interaction between the two QS systems in E.coli. Expression of sdiA and ydiV is inhibited by glucose. SdiA binds to the ydiV promoter region in a dose-dependent,hut nonspecific,manner; extracellular autoinducer 1 from other species stimulates ydiV expression in an sdiA-depen-dent manner. Furthermore,we discovered that the double sdiA-ydiV mutation,but not the single mutation,causes a 2-fold decrease in intracellular cAMP concentration that leads to the inhibition of QS system 2. These results indicate that signaling pathways that respond to important environmental cues,such as autoinducers and glucose,are linkedtogether for their control in E. coll.

  1. Rhodococcus erythropolis and Its γ-Lactone Catabolic Pathway: An Unusual Biocontrol System That Disrupts Pathogen Quorum Sensing Communication

    Directory of Open Access Journals (Sweden)

    Xavier Latour

    2013-12-01

    Full Text Available Rhodococcus erythropolis is an environmental Gram-positive Actinobacterium with a versatile metabolism involved in various bioconversions and degradations. Rhodococci are best known for their great potential in numerous decontamination and industrial processes. However, they can also prevent plant disease by disrupting quorum sensing-based communication of Gram-negative soft-rot bacteria, by degrading N-acyl-homoserine lactone signaling molecules. Such biocontrol activity results partly from the action of the γ-lactone catabolic pathway. This pathway is responsible for cleaving the lactone bond of a wide range of compounds comprising a γ-butyrolactone ring coupled to an alkyl or acyl chain. The aliphatic products of this hydrolysis are then activated and enter fatty acid metabolism. This short pathway is controlled by the presence of the γ-lactone, presumably sensed by a TetR-like transcriptional regulator, rather than the presence of the pathogen or the plant-host in the environment of the Rhodococci. Both the density and biocontrol activity of R. erythropolis may be boosted in crop systems. Treatment with a cheap γ-lactone stimulator, for example, the food flavoring γ-caprolactone, induces the activity in the biocontrol agent, R. erythropolis, of the pathway degrading signaling molecules; such treatments thus promote plant protection.

  2. Noisy neighbourhoods: quorum sensing in fungal-polymicrobial infections.

    Science.gov (United States)

    Dixon, Emily F; Hall, Rebecca A

    2015-10-01

    Quorum sensing was once considered a way in which a species was able to sense its cell density and regulate gene expression accordingly. However, it is now becoming apparent that multiple microbes can sense particular quorum-sensing molecules, enabling them to sense and respond to other microbes in their neighbourhood. Such interactions are significant within the context of polymicrobial disease, in which the competition or cooperation of microbes can alter disease progression. Fungi comprise a small but important component of the human microbiome and are in constant contact with bacteria and viruses. The discovery of quorum-sensing pathways in fungi has led to the characterization of a number of interkingdom quorum-sensing interactions. Here, we review the recent developments in quorum sensing in medically important fungi, and the implications these interactions have on the host's innate immune response.

  3. Role of quorum sensing in bacterial infections

    Science.gov (United States)

    Castillo-Juárez, Israel; Maeda, Toshinari; Mandujano-Tinoco, Edna Ayerim; Tomás, María; Pérez-Eretza, Berenice; García-Contreras, Silvia Julieta; Wood, Thomas K; García-Contreras, Rodolfo

    2015-01-01

    Quorum sensing (QS) is cell communication that is widely used by bacterial pathogens to coordinate the expression of several collective traits, including the production of multiple virulence factors, biofilm formation, and swarming motility once a population threshold is reached. Several lines of evidence indicate that QS enhances virulence of bacterial pathogens in animal models as well as in human infections; however, its relative importance for bacterial pathogenesis is still incomplete. In this review, we discuss the present evidence from in vitro and in vivo experiments in animal models, as well as from clinical studies, that link QS systems with human infections. We focus on two major QS bacterial models, the opportunistic Gram negative bacteria Pseudomonas aeruginosa and the Gram positive Staphylococcus aureus, which are also two of the main agents responsible of nosocomial and wound infections. In addition, QS communication systems in other bacterial, eukaryotic pathogens, and even immune and cancer cells are also reviewed, and finally, the new approaches proposed to combat bacterial infections by the attenuation of their QS communication systems and virulence are also discussed. PMID:26244150

  4. 群体感应系统的合成生物学研究进展%Research Progress of Synthetic Biology in Quorum-Sensing System

    Institute of Scientific and Technical Information of China (English)

    胡译丹; 王兆守; 吴忻; 方柏山

    2013-01-01

    群体感应系统通过释放到环境中的信号分子来进行交流,进而协调群体行为,因其结构简单、机理清晰而广泛应用于合成生物学的研究.简要介绍合成生物学的概念,着重阐述基于群体感应系统的合成生物学研究及其在细胞浓度控制、生物被膜信号通路和生物化工领域的应用.最后,探讨群体感应系统研究的不足,并做进一步展望.%Quorum-sensing system coordinates bacterium behaviour via the secretion of specific signaling molecules in a population density-dependent manner. This system is widely used in synthetic biology because of its simple structure and clear mechanism. In this article, the concept of synthetic biology is introduced briefly. This article mainly focuses on synthetic biology basing on quorum-sensing system and its applications in fields of cell density control, biofilm signal pathways and biochemical industry. Finally, limition of study on quorum-sensing system is discussed. And the prospect of future development is presented.

  5. Quorum sensing Inhibitors as anti-pathogenic drugs

    DEFF Research Database (Denmark)

    Rasmussen, Thomas Bovbjerg; Givskov, Michael Christian

    2006-01-01

    Quorum-sensing (QS) signalling systems of pathogens are central regulators for the expression of virulence factors and represent highly attractive targets for the development of novel therapeutics. In Pseudomonas aeruginosa, QS systems are also involved in elevated antibiotic tolerance of biofilms...... identified. Promising QSI compounds have been shown to make biofilms more susceptible to antimicrobial treatments, and are capable of reducing mortality and virulence as well as promoting clearance of bacteria in experimental animal models of infection....

  6. Quorum signaling and sensing by nontypeable Haemophilus influenzae

    OpenAIRE

    2012-01-01

    Quorum signals are diffusible factors produced by bacteria that coordinate communal responses. For nontypeable Haemophilus influenzae (NTHi), a series of recent papers indicate that production and sensing of quorum signals are determinants of biofilm formation/maturation and persistence in vivo. In this mini-review I will summarize the current knowledge about quorum signaling/sensing by this organism, and identify specific topics for additional study.

  7. Quorum-Sensing of Bacteria and Its Application

    Institute of Scientific and Technical Information of China (English)

    JIANG Guoliang; SU Mingxia

    2009-01-01

    Quorum sensing, or auto induction, as a cell density dependent signaling mechanism in many microorganisms, is triggered via auto inducers which passively diffuse across the bacterial envelope and therefore intracellulaly accumulate only at higher bacterial densities to regulate specialized processes such as genetic competence, bioluminescence, virulence and sporulation. N-acyl homoserine lactones are the most common type of signal molecules. Aquaculture is one of the fastest-growing food-producing industries, but disease outbreaks caused by pathogenic bacteria are a significant constraint on the development of the sector worldwide. Many of these pathogens have been found to be controlled by their quorum sensing systems. As there is relevance between the pathogenic bacteria's virulence factor expression and their auto inducers, quorum quenching is a new effective anti-infective strategy to control infections caused by bacterial pathogens in aquaculture. The techniques used to do this mainly include the following: (1) the inhibition of signal molecule biosynthesis, (2) blocking signal transduction, and (3) chemical inactivation and biodegradation of signal molecules. To provide a basis for finding alternative means of controlling aquatic diseases by quorum quenching instead of treatment by antibiotics and disinfectants, we will discuss the examination, purification and identification of auto inducers in this paper.

  8. Two-Component Regulatory Systems – implication in the quorum sensing mechanisms and bacteriocin production in lactic acid bacteria

    Directory of Open Access Journals (Sweden)

    Lia–Mara Ditu

    2014-08-01

    Full Text Available For lactic acid bacteria, the mechanisms of quorum sensing and response are mediated by peptides or pheromones that interfere with the synthesis of antimicrobial peptides (AMP called bacteriocins, when these molecules reach a certain critical level of concentration. Generally, the synthesis and activity of pheromones is adjusted by means of a two-component regulatory system. The observation that some microorganisms, in particular lactic acid bacteria, produce bacteriocins according to the cell density, has led to the discovery of the involvement of QS mechanisms in the synthesis of these peptides. Bacteriocins synthesis is inducible, the process requiring the extracellular accumulation of peptides that functions as chemical messengers activators of bacteriocins synthesis. This minireview presents the molecular architecture and functions of two-component regulatory systems and ABC transporters implicated in the synthesis and secretion of nisin, one of the most studied bacteriocin. The elucidation of the intimate mechanisms of bacteriocins synthesis is equally of biotechnological and medical importance, opening interesting perspectives for the development of improved technologies for the production of bacteriocins with good yields, and also, for increasing the beneficial anti-infective roles of probiotic bacteria when administered in vivo.

  9. Analysis of Autoinducer-2 Quorum Sensing in Yersinia pestis

    Science.gov (United States)

    Yu, Jing; Madsen, Melissa L.; Carruthers, Michael D.; Phillips, Gregory J.; Kavanaugh, Jeffrey S.; Boyd, Jeff M.; Horswill, Alexander R.

    2013-01-01

    The autoinducer-2 (AI-2) quorum-sensing system has been linked to diverse phenotypes and regulatory changes in pathogenic bacteria. In the present study, we performed a molecular and biochemical characterization of the AI-2 system in Yersinia pestis, the causative agent of plague. In strain CO92, the AI-2 signal is produced in a luxS-dependent manner, reaching maximal levels of 2.5 μM in the late logarithmic growth phase, and both wild-type and pigmentation (pgm) mutant strains made equivalent levels of AI-2. Strain CO92 possesses a chromosomal lsr locus encoding factors involved in the binding and import of AI-2, and confirming this assignment, an lsr deletion mutant increased extracellular pools of AI-2. To assess the functional role of AI-2 sensing in Y. pestis, microarray studies were conducted by comparing Δpgm strain R88 to a Δpgm ΔluxS mutant or a quorum-sensing-null Δpgm ΔypeIR ΔyspIR ΔluxS mutant at 37°C. Our data suggest that AI-2 quorum sensing is associated with metabolic activities and oxidative stress genes that may help Y. pestis survive at the host temperature. This was confirmed by observing that the luxS mutant was more sensitive to killing by hydrogen peroxide, suggesting a potential requirement for AI-2 in evasion of oxidative damage. We also show that a large number of membrane protein genes are controlled by LuxS, suggesting a role for quorum sensing in membrane modeling. Altogether, this study provides the first global analysis of AI-2 signaling in Y. pestis and identifies potential roles for the system in controlling genes important to disease. PMID:23959719

  10. [Quorum sensing systems of regulation, synthesis of phenazine antibiotics, and antifungal (corrected) activity in rhizospheric bacterium Pseudomonas chlororaphis 449].

    Science.gov (United States)

    Veselova, M a; Klein, Sh; Bass, I A; Lipasova, V A; Metlitskaia, A Z; Ovadis, M I; Chernin, L S; Khmel', I A

    2008-12-01

    Strain Pseudomonas chlororaphis 449, an antagonist of a broad spectrum of phytopathogenic microorganisms isolated from the maize rhizosphere, was shown to produce three phenazine antibiotics: phenazine-1-carboxylic acid (PCA), 2-hydroxylphenazine-1-carboxylic acid (2-OH-PCA), and 2-hydroxylphenazine (2-OH-PHZ). Two Quorum Sensing (QS) systems of regulation were identified: PhzIR and CsaI/R. Genes phzI and csaI were cloned and sequenced. Cells of strain 449 synthesize at least three types of AHL: N-butanoyl-L-homoserine lactone (C4-AHL), N-hexanoyl-L-homoserine lactone (C6-AHL), and N-(3-oxo-hexanoyl)-L-homoserine lactone (30C6-AHL). Transposon mutagenesis was used to generate mutants of strain 449 deficient in synthesis of phenazines, which carried inactivated phzA and phzB genes of the phenazine operon and gene phzO. Mutations phzA- and phzB-caused a drastic reduction in the antagonistic activity of bacteria toward phytopathogenic fungi. Both mutants lost the ability to protect cucumber and leguminous plants against phytopathogenic fungi Rhizoctonia solani and Sclerotinia sclerotiorum. These results suggest a significant role of phenazines in the antagonistic activity of P. chlororaphis 449.

  11. Quorum Sensing Enhances the Stress Response in Vibrio cholerae▿

    OpenAIRE

    Joelsson, Adam; Kan, Biao; Zhu, Jun

    2007-01-01

    Vibrio cholerae lives in aquatic environments and causes cholera. Here, we show that quorum sensing enhances V. cholerae viability under certain stress conditions by upregulating the expression of RpoS, and this regulation acts through HapR, suggesting that a quorum-sensing-enhanced stress response plays a role in V. cholerae environmental survival.

  12. Tobramycin at subinhibitory concentration inhibits the RhlI/R quorum sensing system in a Pseudomonas aeruginosa environmental isolate

    Directory of Open Access Journals (Sweden)

    Venturi Vittorio

    2010-06-01

    Full Text Available Abstract Background Antibiotics are not only small molecules with therapeutic activity in killing or inhibiting microbial growth, but can also act as signaling molecules affecting gene expression in bacterial communities. A few studies have demonstrated the effect of tobramycin as a signal molecule on gene expression at the transcriptional level and its effect on bacterial physiology and virulence. These have shown that subinhibitory concentrations (SICs of tobramycin induce biofilm formation and enhance the capabilities of P. aeruginosa to colonize specific environments. Methods Environmental P. aeruginosa strain PUPa3 was grown in the presence of different concentrations of tobramycin and it was determined at which highest concentration SIC, growth, total protein levels and translation efficiency were not affected. At SIC it was then established if phenotypes related to cell-cell signaling known as quorum sensing were altered. Results In this study it was determined whether tobramycin sensing/response at SICs was affecting the two independent AHL QS systems in an environmental P. aeruginosa strain. It is reasonable to assume that P. aeruginosa encounters tobramycin in nature since it is produced by niche mate Streptomyces tenebrarius. It was established that SICs of tobramycin inhibited the RhlI/R system by reducing levels of C4-HSL production. This effect was not due to a decrease of rhlI transcription and required tobramycin-ribosome interaction. Conclusions Tobramycin signaling in P. aeruginosa occurs and different strains can have a different response. Understanding the tobramycin response by an environmental P. aeruginosa will highlight possible inter-species signalling taking place in nature and can possible also have important implications in the mode of utilization for human use of this very important antibiotic.

  13. Ambroxol interferes with Pseudomonas aeruginosa quorum sensing.

    Science.gov (United States)

    Lu, Qi; Yu, Jialin; Yang, Xiqiang; Wang, Jiarong; Wang, Lijia; Lin, Yayin; Lin, Lihua

    2010-09-01

    The mucolytic agent ambroxol has been reported to interfere with the formation of Pseudomonas aeruginosa-derived biofilms in addition to reducing alginate production by undefined mechanisms. Since quorum sensing is a key regulator of virulence and biofilm formation, we examined the effects of ambroxol on P. aeruginosa PAO1 wild-type bacterial clearance rates, adhesion profiles and biofilm formation compared with the quorum sensing-deficient, double-mutant strains DeltalasR DeltarhlR and DeltalasI DeltarhlI. Data presented in this report demonstrated that ambroxol treatment reduced survival rates of the double-mutant strains compared with the wild-type strain in a dose-dependent manner even though the double-mutants had increased adhesion in the presence of ambroxol compared with the wild-type strain. The PAO1 wild-type strain produced a significantly thicker biofilm (21.64+/-0.57 microm) compared with the biofilms produced by the DeltalasR DeltarhlR (7.36+/-0.2 microm) and DeltalasI DeltarhlI (6.62+/-0.31 microm) isolates. Ambroxol treatment reduced biofilm thickness, increased areal porosity, and decreased the average diffusion distance and textual entropy of wild-type and double-mutant strains. However, compared with the double-mutant strains, the changes observed for the wild-type strain were more clearly defined. Finally, ambroxol exhibited significant antagonistic quorum-sensing properties, suggesting that it could be adapted for use clinically in the treatment of cystic fibrosis and to reduce biofilm formation and in the colonisation of indwelling devices.

  14. Quorum sensing inhibitors: how strong is the evidence?

    Science.gov (United States)

    Defoirdt, Tom; Brackman, Gilles; Coenye, Tom

    2013-12-01

    Because of its promising effect as an alternative to antibiotics, quorum sensing disruption is an intensively studied field, and there are many studies that describe the quorum sensing inhibitory activity of natural and synthetic compounds. In this opinion article, we present an overview of recent literature with respect to quorum sensing inhibitors. Most of this research is based on experiments with quorum sensing signal molecule reporter strains. However, these experiments are prone to bias due to other effects compounds may have on reporter strains. We argue that researchers should perform adequate control experiments and should carefully assess toxicity of the compounds in the bacterial species they are working with in order to confirm that what they observe really is quorum sensing inhibition.

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

    Science.gov (United States)

    Defoirdt, Tom; Sorgeloos, Patrick

    2012-12-01

    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.

  16. Simple models for quorum sensing: Nonlinear dynamical analysis

    Science.gov (United States)

    Chiang, Wei-Yin; Li, Yue-Xian; Lai, Pik-Yin

    2011-10-01

    Quorum sensing refers to the change in the cooperative behavior of a collection of elements in response to the change in their population size or density. This behavior can be observed in chemical and biological systems. These elements or cells are coupled via chemicals in the surrounding environment. Here we focus on the change of dynamical behavior, in particular from quiescent to oscillatory, as the cell population changes. For instance, the silent behavior of the elements can become oscillatory as the system concentration or population increases. In this work, two simple models are constructed that can produce the essential representative properties in quorum sensing. The first is an excitable or oscillatory phase model, which is probably the simplest model one can construct to describe quorum sensing. Using the mean-field approximation, the parameter regime for quorum sensing behavior can be identified, and analytical results for the detailed dynamical properties, including the phase diagrams, are obtained and verified numerically. The second model consists of FitzHugh-Nagumo elements coupled to the signaling chemicals in the environment. Nonlinear dynamical analysis of this mean-field model exhibits rich dynamical behaviors, such as infinite period bifurcation, supercritical Hopf, fold bifurcation, and subcritical Hopf bifurcations as the population parameter changes for different coupling strengths. Analytical result is obtained for the Hopf bifurcation phase boundary. Furthermore, two elements coupled via the environment and their synchronization behavior for these two models are also investigated. For both models, it is found that the onset of oscillations is accompanied by the synchronized dynamics of the two elements. Possible applications and extension of these models are also discussed.

  17. Stereochemical insignificance discovered in Acinetobacter baumannii quorum sensing.

    Directory of Open Access Journals (Sweden)

    Amanda L Garner

    Full Text Available Stereochemistry is a key aspect of molecular recognition for biological systems. As such, receptors and enzymes are often highly stereospecific, only recognizing one stereoisomer of a ligand. Recently, the quorum sensing signaling molecules used by the nosocomial opportunistic pathogen, Acinetobacter baumannii, were identified, and the primary signaling molecule isolated from this species was N-(3-hydroxydodecanoyl-L-homoserine lactone. A plethora of bacterial species have been demonstrated to utilize 3-hydroxy-acylhomoserine lactone autoinducers, and in virtually all cases, the (R-stereoisomer was identified as the natural ligand and exhibited greater autoinducer activity than the corresponding (S-stereoisomer. Using chemical synthesis and biochemical assays, we have uncovered a case of stereochemical insignificance in A. baumannii and provide a unique example where stereochemistry appears nonessential for acylhomoserine lactone-mediated quorum sensing signaling. Based on previously reported phylogenetic studies, we suggest that A. baumannii has evolutionarily adopted this unique, yet promiscuous quorum sensing system to ensure its survival, particularly in the presence of other proteobacteria.

  18. Identity and effects of quorum sensing inhibitors produced by Penicillium species

    DEFF Research Database (Denmark)

    Rasmussen, Thomas Bovbjerg; Skindersø, Mette Elena; Bjarnsholt, Thomas;

    2005-01-01

    Quorum sensing (QS) communication systems are thought to afford bacteria with a mechanism to strategically cause disease. One example is Pseudomonas aeruginosa, which infects immunocompromised individuals such as cystic fibrosis patients. The authors have previously documented that blockage...

  19. Identification and characterization of new LuxR/LuxI-type quorum sensing systems from metagenomic libraries.

    Science.gov (United States)

    Hao, Youai; Winans, Stephen C; Glick, Bernard R; Charles, Trevor C

    2010-01-01

    Quorum sensing (QS) cell-cell communication systems are utilized by bacteria to coordinate their behaviour according to cell density. Several different types of QS signal molecules have been identified, among which acyl-homoserine lactones (AHLs) produced by Proteobacteria have been studied to the greatest extent. Although QS has been studied extensively in cultured microorganisms, little is known about the QS systems of uncultured microorganisms and the roles of these systems in microbial communities. To extend our knowledge of QS systems and to better understand the signalling that takes place in the natural environment, metagenomic libraries constructed using DNA from activated sludge and soil were screened, using an Agrobacterium biosensor strain, for novel QS synthase genes. Three cosmids (QS6-1, QS10-1 and QS10-2) that encode the production of QS signals were identified and DNA sequence analysis revealed that all three clones encode a novel luxI family AHL synthase and a luxR family transcriptional regulator. Thin layer chromatography revealed that these LuxI homologue proteins are able to synthesize multiple AHL signals. Tandem mass spectrometry analysis revealed that LuxI(QS6-1) directs the synthesis of at least three AHLs, 3-O-C14:1 HSL, 3-O-C16:1 HSL and 3-O-C14 HSL; LuxI(QS10-1) directs the synthesis of at least 3-O-C12 HSL and 3-O-C14 HSL; while LuxI(QS10-2) directs the synthesis of at least C8 HSL and C10 HSL. Two possible new AHLs, C14:3 HSL and (?)-hydroxymethyl-3-O-C14 HSL, were also found to be synthesized by LuxI(QS6-1).

  20. Is there a role for quorum sensing signals in bacterial biofilms?

    DEFF Research Database (Denmark)

    Kjelleberg, S.; Molin, Søren

    2002-01-01

    Bacteria form multicellular biofilm communities on most surfaces. Genetic analysis of biofilm formation has led to the proposal that extracellular signals and quorum-sensing regulatory systems are essential for differentiated biofilms. Although such a model fits the concept of density-driven cell...... adaptation during the different stages of biofilm formation. Hence, differentiated biofilms may also be the net result of many independent interactions, rather than being determined by a particular global quorum sensing system....

  1. Pharmacological inhibition of quorum sensing for the treatment of chronic bacterial infections

    DEFF Research Database (Denmark)

    Hentzer, Morten; Givskov, Michael Christian

    2003-01-01

    Traditional treatment of infectious diseases is based on compounds that aim to kill or inhibit bacterial growth. A major concern with this approach is the frequently observed development of resistance to antimicrobial compounds. The discovery of bacterial-communication systems (quorum-sensing...... mechanisms and potential antipathogenic drugs that specifically target quorum-sensing systems in a manner unlikely to pose a selective pressure for the development of resistant mutants....

  2. Quorum-sensing regulation of constitutive plantaricin by Lactobacillus plantarum strains under a model system for vegetables and fruits.

    Science.gov (United States)

    Rizzello, Carlo G; Filannino, Pasquale; Di Cagno, Raffaella; Calasso, Maria; Gobbetti, Marco

    2014-01-01

    This study aimed at investigating the regulatory system of bacteriocin synthesis by Lactobacillus plantarum strains in vegetables and fruits in a model system. Sterile and neutralized cell-free supernatant (CFS) from L. plantarum strains grown in MRS broth showed in vitro antimicrobial activities toward various indicator strains. The highest activity was that of L. plantarum C2. The antimicrobial activity was further assayed on vegetable and fruit agar plates (solid conditions) and in juices (liquid conditions). A regulatory mechanism of bacteriocin synthesis via quorum sensing was hypothesized. The synthesis of antimicrobial compounds seemed to be constitutive under solid conditions of growth on vegetable and fruit agar plates. In contrast, it depended on the size of the inoculum when L. plantarum C2 was grown in carrot juice. Only the inoculum of ca. 9.0 log CFU ml(-1) produced detectable activity. The genes plnA, plnEF, plnG, and plnH were found in all L. plantarum strains. The genes plnJK and plnN were detected in only three or four strains. Reverse-phase high-performance liquid chromatography purification and mass spectrometry analysis revealed the presence of a mixture of eight peptides in the most active fraction of the CFS from L. plantarum C2. Active peptides were encrypted into bacteriocin precursors, such as plantaricins PlnJ/K and PlnH and PlnG, which are involved in the ABC transport system. A real-time PCR assay showed an increase in the expression of plnJK and plnG during growth of L. plantarum C2 in carrot juice.

  3. A novel pheromone quorum-sensing system controls the development of natural competence in Streptococcus thermophilus and Streptococcus salivarius.

    Science.gov (United States)

    Fontaine, Laetitia; Boutry, Céline; de Frahan, Marie Henry; Delplace, Brigitte; Fremaux, Christophe; Horvath, Philippe; Boyaval, Patrick; Hols, Pascal

    2010-03-01

    In streptococcal species, the key step of competence development is the transcriptional induction of comX, which encodes the alternative sigma factor sigma(X), which positively regulates genes necessary for DNA transformation. In Streptococcus species belonging to the mitis and mutans groups, induction of comX relies on the activation of a three-component system consisting of a secreted pheromone, a histidine kinase, and a response regulator. In Streptococcus thermophilus, a species belonging to the salivarius group, the oligopeptide transporter Ami is essential for comX expression under competence-inducing conditions. This suggests a different regulation pathway of competence based on the production and reimportation of a signal peptide. The objective of our work was to identify the main actors involved in the early steps of comX induction in S. thermophilus LMD-9. Using a transcriptomic approach, four highly induced early competence operons were identified. Among them, we found a Rgg-like regulator (Ster_0316) associated with a nonannotated gene encoding a 24-amino-acid hydrophobic peptide (Shp0316). Through genetic deletions, we showed that these two genes are essential for comX induction. Moreover, addition to the medium of synthetic peptides derived from the C-terminal part of Shp0316 restored comX induction and transformation of a Shp0316-deficient strain. These peptides also induced competence in S. thermophilus and Streptococcus salivarius strains that are poorly transformable or not transformable. Altogether, our results show that Ster_0316 and Shp0316, renamed ComRS, are the two members of a novel quorum-sensing system responsible for comX induction in species from the salivarius group, which differs from the classical phosphorelay three-component system identified previously in streptococci.

  4. Quorum sensing via static coupling demonstrated by Chua's circuits

    Science.gov (United States)

    Singh, Harpartap; Parmananda, P.

    2013-10-01

    Dynamical quorum sensing, the population based phenomenon, is believed to occur when the elements of a system interact via dynamic coupling. In the present work, we demonstrate an alternate scenario, involving static coupling, that could also lead to quorum sensing behavior. These static and dynamic coupling terms have already been employed by Konishi [Int. J. Bifurcation Chaos Appl. Sci. Eng.IJBEE40218-127410.1142/S0218127407018750 17, 2781 (2007)]. In our context, the coupling is defined as static or dynamic, on the basis of the relative time scales at which the surrounding dynamics and the elements' dynamics evolve. According to this, if the variation in the surrounding dynamics happens on a much larger (fast) time scale than that at which the elements' dynamics are varying (such as seconds and μs), then the coupling is considered to be static, otherwise it is considered to be dynamic. A series of experiments have been performed starting from a system of three Chua's circuits to a system of 20 Chua's circuits to study two types of quorum transitions: the emergence and the extinction of global oscillations (period-1). The numerics involving up to 100 Chua's circuits validate the experimental observations.

  5. A quorum-sensing-induced bacteriophage defense mechanism

    DEFF Research Database (Denmark)

    Høyland-Kroghsbo, Nina Molin; Mærkedahl, Rasmus Baadsgaard; Svenningsen, Sine

    2013-01-01

    of uninfected survivor cells after a potent attack by virulent phages. Notably, this mechanism may apply to a broader range of phages, as AHLs also reduce the risk of ¿ phage infection through a different receptor. IMPORTANCE To enable the successful manipulation of bacterial populations, a comprehensive...... sensing plays an important role in determining the susceptibility of E. coli to infection by bacteriophages ¿ and ¿. On the basis of our findings in the classical Escherichia coli-¿ model system, we suggest that quorum sensing may serve as a general strategy to protect bacteria specifically under...

  6. Zingerone silences quorum sensing and attenuates virulence of Pseudomonas aeruginosa.

    Science.gov (United States)

    Kumar, Lokender; Chhibber, Sanjay; Kumar, Rajnish; Kumar, Manoj; Harjai, Kusum

    2015-04-01

    Quorum sensing in Pseudomonas aeruginosa plays an imperative role in virulence factor, biofilm formation and antimicrobial resistance. Blocking quorum sensing pathways are viewed as viable anti-virulent therapy in association with traditional antimicrobial therapy. Anti-quorum sensing dietary phytochemicals with may prove to be a safe and viable choice as anti-virulent drug candidates. Previously, our lab proved zingerone as potent anti-biofilm agent hence; further its anti-virulent and anti-quorum activities were evaluated. Zingerone, besides decreasing swimming, swarming and twitching phenotypes of P. aeruginosa PAO1, reduced biofilm forming capacity and production of virulence factors including rhamnolipid, elastase, protease, pyocyanin, cell free and cell bound hemolysin (pquorum sensing signal molecules by clinical isolates of P. aeruginosa but also showed significant interference with the activation of QS reporter strains. To study the mechanism of blocking quorum sensing cascade, in silico analysis was carried out. Anti-QS activity was attributed to interference with the ligand receptor interaction of zingerone with QS receptors (TraR, LasR, RhlR and PqsR). Zingerone showed a good comparative docking score to respective autoinducer molecules which was even higher than that of vanillin, a proven anti-quorum sensing phytochemical. The results of the present study revealed the anti-quorum sensing activity of zingerone targeting ligand-receptor interaction, hence proposing zingerone as a suitable anti-virulent drug candidate against P. aeruginosa infections.

  7. Cell density- and quorum sensing-dependent expression of type VI secretion system 2 in Vibrio parahaemolyticus.

    Directory of Open Access Journals (Sweden)

    Li Wang

    Full Text Available BACKGROUND: Vibrio parahaemolyticus AphA and OpaR are the two master quorum sensing (QS regulators that are abundantly expressed at low cell density (LCD and high cell density (HCD, respectively, with a feature of reciprocally gradient production of them with transition between LCD and HCD. The type VI secretion system 2 (T6SS2 gene cluster can be assigned into three putative operons, namely VPA1027-1024, VPA1043-1028, and VPA1044-1046. T6SS2 contributes to adhesion of V. parahaemolyticus to host cells. METHODOLOGY/PRINCIPAL FINDINGS: OpaR box-like sequences were found within the upstream promoter regions of all the above three operons, while none of AphA box-like elements could be identified for them. The subsequent primer extension, LacZ fusion, electrophoretic mobility shift, and DNase I footprinting assays disclosed that OpaR bound to the promoter regions of these three operons to stimulate their transcription, while AphA negatively regulated their transcription most likely through acting on OpaR. This regulation led to a gradient increase of T6SS2 transcription with transition from LCD to HCD. CONCLUSIONS/SIGNIFICANCE: V. parahaemolyticus OpaR and AphA positively and negatively regulate T6SS2 expression, respectively, leading to a gradient elevation of T6SS2 expression with transition from LCD to HCD. T6SS2 genes are thus assigned as the QS regulon members in V. parahaemolyticus.

  8. Composition, anti-quorum sensing and antimicrobial activity of essential oils from Lippia alba

    OpenAIRE

    Jesus Olivero-Verbel; Ana Barreto-Maya; Angela Bertel-Sevilla; Elena E. Stashenko

    2014-01-01

    Many Gram-negative pathogens have the ability to produce N-acylhomoserine lactones (AHLs) as signal molecules for quorum sensing (QS). This cell-cell communication system allows them to coordinate gene expression and regulate virulence. Strategies to inhibit QS are promising for the control of infectious diseases or antibiotic resistant bacterial pathogens. The aim of the present study was to evaluate the anti-quorum sensing (anti-QS) and antibacterial potential of five essential oils isolate...

  9. Functional characterization of a three-component regulatory system involved in quorum sensing-based regulation of peptide antibiotic production in Carnobacterium maltaromaticum

    Directory of Open Access Journals (Sweden)

    Quadri Luis EN

    2006-10-01

    Full Text Available Abstract Background Quorum sensing is a form of cell-to-cell communication that allows bacteria to control a wide range of physiological processes in a population density-dependent manner. Production of peptide antibiotics is one of the processes regulated by quorum sensing in several species of Gram-positive bacteria, including strains of Carnobacterium maltaromaticum. This bacterium and its peptide antibiotics are of interest due to their potential applications in food preservation. The molecular bases of the quorum sensing phenomenon controlling peptide antibiotic production in C. maltaromaticum remain poorly understood. The present study was aimed at gaining a deeper insight into the molecular mechanism involved in quorum sensing-mediated regulation of peptide antibiotic (bacteriocin production by C. maltaromaticum. We report the functional analyses of the CS (autoinducer-CbnK (histidine protein kinase-CbnR (response regulator three-component regulatory system and the three regulated promoters involved in peptide antibiotic production in C. maltaromaticum LV17B. Results CS-CbnK-CbnR system-dependent activation of carnobacterial promoters was demonstrated in both homologous and heterologous hosts using a two-plasmid system with a β-glucuronidase (GusA reporter read-out. The results of our analyses support a model in which the CbnK-CbnR two-component signal transduction system is necessary and sufficient to transduce the signal of the peptide autoinducer CS into the activation of the promoters that drive the expression of the genes required for production of the carnobacterial peptide antibiotics and the immunity proteins that protect the producer bacterium. Conclusions The CS-CbnK-CbnR triad forms a three-component regulatory system by which production of peptide antibiotics by C. maltaromaticum LV17B is controlled in a population density-dependent (or cell proximity-dependent manner. This regulatory mechanism would permit the bacterial

  10. Interspecies Quorum Sensing as a Stress-Anticipation Signal in E. coli

    DEFF Research Database (Denmark)

    Høyland-Kroghsbo, Nina Molin

    Abstract Uncovering how bacteria perceive environmental signals and how they interpret these, in order to constantly adapt to changes in their environment, is important for understanding not only microbial ecology but also bacterial pathogenesis. Furthermore, it provides cues as to how we might...... interfere with these systems, in order to prevent undesirable bacterial behavior. In a process known as quorum sensing, bacteria emit and detect small diffusible molecules, which upon reaching a certain extracellular concentration, activate cellular quorum sensing receptors and thereby turn on group...... behavior genes. Quorum sensing controls important bacterial behaviors, including bioluminescence, biofilm formation, and virulence. Inter- and intraspecies quorum sensing signals enable bacteria to estimate the abundance and species complexity of a microbial community. A long standing question...

  11. Mechanistic insights into the LsrK kinase required for autoinducer-2 quorum sensing activation

    OpenAIRE

    Zhu, Jie; Hixon, Mark S.; Globisch, Daniel; Kaufmann, Gunnar F.; Janda, Kim D.

    2013-01-01

    In enteric bacteria, the kinase LsrK catalyzes the phosphorylation of the C5-hydroxyl group in the linear form of 4,5-dihydroxy-2,3-pentanedione (DPD), the precursor of the type II bacterial quorum sensing molecule (AI-2). This phosphorylation is required for AI-2 sequestration in the cytoplasm and subsequent derepression of AI-2 related genes necessary for quorum development. While LsrK is a critical enzyme within the DPD quorum sensing relay system, kinetic details of this kinase have yet t...

  12. An OmpA Family Protein, a Target of the GinI/GinR Quorum-Sensing System in Gluconacetobacter intermedius, Controls Acetic Acid Fermentation▿ †

    Science.gov (United States)

    Iida, Aya; Ohnishi, Yasuo; Horinouchi, Sueharu

    2008-01-01

    Via N-acylhomoserine lactones, the GinI/GinR quorum-sensing system in Gluconacetobacter intermedius NCI1051, a gram-negative acetic acid bacterium, represses acetic acid and gluconic acid fermentation. Two-dimensional polyacrylamide gel electrophoretic analysis of protein profiles of strain NCI1051 and ginI and ginR mutants identified a protein that was produced in response to the GinI/GinR regulatory system. Cloning and nucleotide sequencing of the gene encoding this protein revealed that it encoded an OmpA family protein, named GmpA. gmpA was a member of the gene cluster containing three adjacent homologous genes, gmpA to gmpC, the organization of which appeared to be unique to vinegar producers, including “Gluconacetobacter polyoxogenes.” In addition, GmpA was unique among the OmpA family proteins in that its N-terminal membrane domain forming eight antiparallel transmembrane β-strands contained an extra sequence in one of the surface-exposed loops. Transcriptional analysis showed that only gmpA of the three adjacent gmp genes was activated by the GinI/GinR quorum-sensing system. However, gmpA was not controlled directly by GinR but was controlled by an 89-amino-acid protein, GinA, a target of this quorum-sensing system. A gmpA mutant grew more rapidly in the presence of 2% (vol/vol) ethanol and accumulated acetic acid and gluconic acid in greater final yields than strain NCI1051. Thus, GmpA plays a role in repressing oxidative fermentation, including acetic acid fermentation, which is unique to acetic acid bacteria and allows ATP synthesis via ethanol oxidation. Consistent with the involvement of gmpA in oxidative fermentation, its transcription was also enhanced by ethanol and acetic acid. PMID:18487322

  13. An OmpA family protein, a target of the GinI/GinR quorum-sensing system in Gluconacetobacter intermedius, controls acetic acid fermentation.

    Science.gov (United States)

    Iida, Aya; Ohnishi, Yasuo; Horinouchi, Sueharu

    2008-07-01

    Via N-acylhomoserine lactones, the GinI/GinR quorum-sensing system in Gluconacetobacter intermedius NCI1051, a gram-negative acetic acid bacterium, represses acetic acid and gluconic acid fermentation. Two-dimensional polyacrylamide gel electrophoretic analysis of protein profiles of strain NCI1051 and ginI and ginR mutants identified a protein that was produced in response to the GinI/GinR regulatory system. Cloning and nucleotide sequencing of the gene encoding this protein revealed that it encoded an OmpA family protein, named GmpA. gmpA was a member of the gene cluster containing three adjacent homologous genes, gmpA to gmpC, the organization of which appeared to be unique to vinegar producers, including "Gluconacetobacter polyoxogenes." In addition, GmpA was unique among the OmpA family proteins in that its N-terminal membrane domain forming eight antiparallel transmembrane beta-strands contained an extra sequence in one of the surface-exposed loops. Transcriptional analysis showed that only gmpA of the three adjacent gmp genes was activated by the GinI/GinR quorum-sensing system. However, gmpA was not controlled directly by GinR but was controlled by an 89-amino-acid protein, GinA, a target of this quorum-sensing system. A gmpA mutant grew more rapidly in the presence of 2% (vol/vol) ethanol and accumulated acetic acid and gluconic acid in greater final yields than strain NCI1051. Thus, GmpA plays a role in repressing oxidative fermentation, including acetic acid fermentation, which is unique to acetic acid bacteria and allows ATP synthesis via ethanol oxidation. Consistent with the involvement of gmpA in oxidative fermentation, its transcription was also enhanced by ethanol and acetic acid.

  14. 细菌生物膜群体感应系统研究进展%Research Progress on Quorum Sensing System of Bacterial Biofilm

    Institute of Scientific and Technical Information of China (English)

    张曙梅; 徐向荣; 徐浩

    2016-01-01

    The quorum sensing system of bacterial biofilm is the one that the bacteria secrete signaling molecules and sense their concentration of the surrounding environment so that to regulate the expressions of certain specific genes,and to change some physiological functions and life habits of bacteria. It is one of the main regulatory mechanisms in bacteria. Based on the research of the bacterial biofilm’s quorum sensing,we can understand its internal mechanism and features,and find the best way to inhibit harmful effects of biofilms. This review focus on bacterial biofilm’s quorum sensing,such as the types,the characteristics and the related applications.%细菌生物膜群体感应系统是指细菌通过分泌信号分子并通过感知其在周围环境中的浓度,调控某些基因的特异性表达及生理功能和生活习性的系统,是细菌生命活动的主要调控机制之一。通过对细菌生物膜群体感应的研究,可以了解其内部机理和特性,从而找到抑制生物膜有害作用的最好方法。对细菌生物膜群体感应系统的种类、特征和相关应用的研究进行综述。

  15. [Quorum sensing involved in the regulation of secondary metabolism in streptomycetes--a review].

    Science.gov (United States)

    Liu, Ming; Li, Aiying

    2011-05-01

    Quorum sensing as an extracellular signal transduction system is distributed widely among many bacteria to coordinate their behaviors or actions by mediating gene expression, and plays key roles in many physiological processes and pathogenicity. Quorum sensing was also observed among many streptomycetes, as an important regulatory mechanism of secondary metabolite biosynthesis and/or cell differentiation, and displayed certain diversity of the autoinducer structures and action mechanisms. The participation of A-factor-driven quorum sensing systems in the secondary metabolism has been extensively studied, and triggered the identification of a major signal class featured with gamma-butyrolactone core. Additionally, PI-factor, M-factor and certain small antibiotic molecules recently found in streptomycetes clearly could play important roles in the biosynthetic pathways of some antibiotics, and might represent extracellular autoinducer classes with novel structures. Meanwhile, some specific products of streptomycetes including cholesterol oxidase and glycerol have been identified to function as cell-signaling molecules which modulate the secondary metabolic activities in streptomycetes, probably by the mode of quorum sensing. Here, we reviewed research advances on quorum sensing systems involved in the accumulation of secondary metabolites in streptomycetes, mainly focusing on the clarification of their action modes and structural diversity of autoinducers. We also prospected the research trends in this field and application of autoinducers through quorum-sensing in metabolic engineering of natural products.

  16. The Role of the QseC Sensor Kinase in Salmonella enterica serovar Typhimurium Quorum Sensing and Swine Colonization

    Science.gov (United States)

    At least two quorum sensing molecules, autoinducer-3 (AI-3) and norepinephrine (NE), are present in the gastrointestinal tract and activate the E. coli QseBC quorum sensing system. AI-3 is produced by enteric bacteria, whereas NE is produced by the animal host, often during stress. Both 10% pre-co...

  17. Quorum Sensing: An Under-Explored Phenomenon in the Phylum Actinobacteria.

    Science.gov (United States)

    Polkade, Ashish V; Mantri, Shailesh S; Patwekar, Umera J; Jangid, Kamlesh

    2016-01-01

    Quorum sensing is known to play a major role in the regulation of secondary metabolite production, especially, antibiotics, and morphogenesis in the phylum Actinobacteria. Although it is one of the largest bacterial phylum, only 25 of the 342 genera have been reported to use quorum sensing. Of these, only nine have accompanying experimental evidence; the rest are only known through bioinformatic analysis of gene/genome sequences. It is evident that this important communication mechanism is not extensively explored in Actinobacteria. In this review, we summarize the different quorum sensing systems while identifying the limitations of the existing screening strategies and addressing the improvements that have taken place in this field in recent years. The γ-butyrolactone system turned out to be almost exclusively limited to this phylum. In addition, methylenomycin furans, AI-2 and other putative AHL-like signaling molecules are also reported in Actinobacteria. The lack of existing screening systems in detecting minute quantities and of a wider range of signaling molecules was a major reason behind the limited information available on quorum sensing in this phylum. However, recent improvements in screening strategies hold a promising future and are likely to increase the discovery of new signaling molecules. Further, the quorum quenching ability in many Actinobacteria has a great potential in controlling the spread of plant and animal pathogens. A systematic and coordinated effort is required to screen and exploit the enormous potential that quorum sensing in the phylum Actinobacteria has to offer for human benefit.

  18. Plant-derived natural products as sources of anti-quorum sensing compounds.

    Science.gov (United States)

    Koh, Chong-Lek; Sam, Choon-Kook; Yin, Wai-Fong; Tan, Li Ying; Krishnan, Thiba; Chong, Yee Meng; Chan, Kok-Gan

    2013-05-13

    Quorum sensing is a system of stimuli and responses in relation to bacterial cell population density that regulates gene expression, including virulence determinants. Consequently, quorum sensing has been an attractive target for the development of novel anti-infective measures that do not rely on the use of antibiotics. Anti-quorum sensing has been a promising strategy to combat bacterial infections as it is unlikely to develop multidrug resistant pathogens since it does not impose any selection pressure. A number of anti-quorum sensing approaches have been documented and plant-based natural products have been extensively studied in this context. Plant matter is one of the major sources of chemicals in use today in various industries, ranging from the pharmaceutical, cosmetic, and food biotechnology to the textile industries. Just like animals and humans, plants are constantly exposed to bacterial infections, it is therefore logical to expect that plants have developed sophisticated of chemical mechanisms to combat pathogens. In this review, we have surveyed the various types of plant-based natural products that exhibit anti-quorum sensing properties and their anti-quorum sensing mechanisms.

  19. Plant-Derived Natural Products as Sources of Anti-Quorum Sensing Compounds

    Directory of Open Access Journals (Sweden)

    Kok-Gan Chan

    2013-05-01

    Full Text Available Quorum sensing is a system of stimuli and responses in relation to bacterial cell population density that regulates gene expression, including virulence determinants. Consequently, quorum sensing has been an attractive target for the development of novel anti-infective measures that do not rely on the use of antibiotics. Anti-quorum sensing has been a promising strategy to combat bacterial infections as it is unlikely to develop multidrug resistant pathogens since it does not impose any selection pressure. A number of anti-quorum sensing approaches have been documented and plant-based natural products have been extensively studied in this context. Plant matter is one of the major sources of chemicals in use today in various industries, ranging from the pharmaceutical, cosmetic, and food biotechnology to the textile industries. Just like animals and humans, plants are constantly exposed to bacterial infections, it is therefore logical to expect that plants have developed sophisticated of chemical mechanisms to combat pathogens. In this review, we have surveyed the various types of plant-based natural products that exhibit anti-quorum sensing properties and their anti-quorum sensing mechanisms.

  20. Research progress on inhibitors toward quorum sensing system%群体感应抑制剂研究进展

    Institute of Scientific and Technical Information of China (English)

    齐莉莉; 陈炳; 王进波

    2016-01-01

    细菌群体感应(quorum sensing,QS)是一种依赖于菌体密度而普遍存在于微生物之间的沟通协调机制,控制着细菌的生长、增殖、致病性、生物膜形成及相关群体活动行为.通过阻断细菌群体感应信号,可以抑制病原菌的致病性.本文从群体感应角度总结了抑制病原菌的方法和研究进展,为临床新型抗菌药物的设计提供理论依据和新策略.

  1. Cross-Talk between Staphylococcus aureus and Other Staphylococcal Species via the agr Quorum Sensing System

    DEFF Research Database (Denmark)

    Canovas de la Nuez, Jaime; Baldry, Mara; Bojer, Martin S;

    2016-01-01

    between staphylococci and S. aureus, and show that this interaction may eventually lead to the identification of new anti-virulence candidates to target S. aureus infections. Here we show that culture supernatants of 37 out of 52 staphylococcal isolates representing 17 different species inhibit S. aureus......-inducing peptides (AIPs) sensed by AgrC, a two component histidine kinase. agr loci are found also in other staphylococcal species and for Staphylococcus epidermidis, the encoded AIP represses expression of agr regulated virulence genes in S. aureus. In this study we aimed to better understand the interaction....... To assess impact on S. aureus virulence, we co-inoculated S. aureus and S. schleiferi in vivo in the Galleria mellonella wax moth larva, and found that expression of key S. aureus virulence factors was abrogated. Our data show that the S. aureus agr locus is highly responsive to other staphylococcal species...

  2. The Fsr Quorum-Sensing System of Enterococcus faecalisModulates Surface Display of the Collagen-Binding MSCRAMM Ace through Regulation of gelE▿

    Science.gov (United States)

    Pinkston, Kenneth L.; Gao, Peng; Diaz-Garcia, Daniel; Sillanpää, Jouko; Nallapareddy, Sreedhar R.; Murray, Barbara E.; Harvey, Barrett R.

    2011-01-01

    Ace, a known virulence factor and the first identified microbial surface component recognizing adhesive matrix molecule (MSCRAMM) of Enterococcus faecalisis associated with host cell adherence and endocarditis. The Fsr quorum-sensing system of E. faecalis, a two-component signal transduction system, has also been repeatedly linked to virulence in E. faecalis, due in part to the transcriptional induction of an extracellular metalloprotease, gelatinase (GelE). In this study, we discovered that disruption of the Fsr pathway significantly increased the levels of Ace on the cell surface in the latter phases of growth. Furthermore, we observed that, in addition to fsrBmutants, other strains identified as deficient in GelE activity also demonstrated a similar phenotype. Additional experiments demonstrated the GelE-dependent cleavage of Ace from the surface of E. faecalis, confirming that GelE specifically reduces Ace cell surface display. In addition, disruption of the Fsr system or GelE expression significantly improved the ability of E. faecalisto adhere to collagen, which is consistent with higher levels of Ace on the E. faecalissurface. These results demonstrate that the display of Ace is mediated by quorum sensing through the action of GelE, providing insight into the complicated world of Gram-positive pathogen adhesion and colonization. PMID:21705589

  3. The fsr quorum sensing system in Enterococci—A review%肠球菌fsr群体感应系统的研究进展

    Institute of Scientific and Technical Information of China (English)

    刘凌; 董卫超; 杜向党

    2013-01-01

    肠球菌现已成为人和动物感染的重要机会病原菌.肠球菌fsrr群体感应系统在明胶酶和丝氨酸蛋白酶的产生,生物膜的形成以及在宿主感染部位的扩散等方面发挥重要的调控作用.深入认识肠球菌fsr群体感应系统具有重要意义,以fsr群体感应系统为靶点,可设计和发展新型“抗毒力”抗生素,为治疗肠球菌感染提供新的策略和手段.%Enterococci have emerged as important opportunistic pathogens that cause animal and human infection.The fsr quorum sensing system in Enterococci has played a vital regulatory role in the production of gelatinase and serine protease,biofilm development and its dissemination in primary infection site.Further elucidation of the fsr quorum sensing system can give aid to the rational design and development of the novel "anti-virulence" antibiotic and using it as the antimicrobial target,which can provide the new strategies and methods in the treatment of enterococcal infections.

  4. Positive Autoregulation of an Acyl-Homoserine Lactone Quorum-Sensing Circuit Synchronizes the Population Response.

    Science.gov (United States)

    Scholz, Rebecca L; Greenberg, E Peter

    2017-07-25

    Many proteobacteria utilize acyl-homoserine lactone quorum-sensing signals. At low population densities, cells produce a basal level of signal, and when sufficient signal has accumulated in the surrounding environment, it binds to its receptor, and quorum-sensing-dependent genes can be activated. A common characteristic of acyl-homoserine lactone quorum sensing is that signal production is positively autoregulated. We have examined the role of positive signal autoregulation in Pseudomonas aeruginosa We compared population responses and individual cell responses in populations of wild-type P. aeruginosa to responses in a strain with the signal synthase gene controlled by an arabinose-inducible promoter so that signal was produced at a constant rate per cell regardless of cell population density. At a population level, responses of the wild type and the engineered strain were indistinguishable, but the responses of individual cells in a population of the wild type showed greater synchrony than the responses of the engineered strain. Although sufficient signal is required to activate expression of quorum-sensing-regulated genes, it is not sufficient for activation of certain genes, the late genes, and their expression is delayed until other conditions are met. We found that late gene responses were reduced in the engineered strain. We conclude that positive signal autoregulation is not a required element in acyl-homoserine lactone quorum sensing, but it functions to enhance synchrony of the responses of individuals in a population. Synchrony might be advantageous in some situations, whereas a less coordinated quorum-sensing response might allow bet hedging and be advantageous in other situations.IMPORTANCE There are many quorum-sensing systems that involve a transcriptional activator, which responds to an acyl-homoserine lactone signal. In all of the examples studied, the gene coding for signal production is positively autoregulated by the signal, and it has even

  5. Quorum sensing in Acinetobacter: with special emphasis on antibiotic resistance, biofilm formation and quorum quenching

    Directory of Open Access Journals (Sweden)

    Bindu Subhadra

    2016-02-01

    Full Text Available Acinetobacter is an important nosocomial, opportunistic human pathogen that is gradually gaining more attention as a major health threat worldwide. Quorum sensing (QS is a cell-cell communication system in which specific signaling molecules called autoinducers accumulate in the medium as the population density grows and control various physiological processes including production of virulence factors, biofilm and development of antibiotic resistance. The complex QS machinery in Acinetobacter is mediated by a two-component system which is homologous to the typical LuxI/LuxR system found in Gram-negative bacteria. This cell signaling system comprises of a sensor protein that functions as autoinducer synthase and a receptor protein which binds to the signal molecules, acyl homoserine lactones inducing a cascade of reactions. Lately, disruption of QS has emerged as an anti-virulence strategy with great therapeutic potential. Here, we depict the current understanding of the existing QS network in Acinetobacter and describe important anti-virulent strategies developed in order to effectively tackle this pathogen. In addition, the prospects of quorum quenching to control Acinetobacter infections is also been discussed.

  6. LuxS and quorum-sensing in Campylobacter

    Directory of Open Access Journals (Sweden)

    Paul ePlummer

    2012-03-01

    Full Text Available Several intercellular bacterial communication mechanisms have been identified in a broad range of bacterial species. These systems, collectively termed quorum-sensing systems, have been demonstrated to play significant roles in a variety of bacterial processes including motility, biofilm formation, expression of virulence genes and animal colonization. Campylobacter jejuni is known to poses a LuxS/ autoinducer-2 mediated system that has been partially characterized over the last decade. AI-2 is formed as a byproduct of the activated methyl recycling pathway, specifically by the LuxS enzyme. Previous work in our laboratory and that of others has demonstrated that this gene is involved in a variety of physiologic pathways of C. jejuni including motility, autoagglutination, CDT expression, flagellar expression, oxidative stress and animal colonization. This review article will summarize the current research associated with LuxS in C. jejuni and will provide insights into the role of this system in the metabolism and intercellular communication of this organism. Additionally, the evidence for other quorum sensing pathways in Campylobacter will be discussed.

  7. Experimental and Theoretical Investigation of Signaling in Quorum Sensing of Pseudomonas Aeruginosa

    DEFF Research Database (Denmark)

    Claussen, Anetta

    Quorum sensing (QS) is an intercellular communication system by which some bacterial cells are capable of indirectly monitoring their own population density through exchange of signal molecules. The expression of virulence factors is kept low until the population density (signal molecule...... concentration) reaches a threshold value, after which the host system is surprised by a stealth attack. The focus of this study is on the Quorum Sensing regulatory system of Pseudomonas aeruginosa called the Las system. In this thesis, two distinct methods to obtain information about the system are considered...

  8. luxS Mutant Regulation: Quorum Sensing Impairment or Methylation Disorder?

    Directory of Open Access Journals (Sweden)

    Zhengwei Huang

    2012-05-01

    Full Text Available AI-2–mediated quorum sensing has been identified in various bacteria, including both Gram-negative and Gram-positive species, and numerous phenotypes have been reported to be regulated by this mechanism, using the luxS-mutant strain. But the AI-2 production process confused this regulatory function; some considered this regulation as the result of a metabolic change, which refers to an important metabolic cycle named activated methyl cycle (AMC, caused by luxS-mutant simultaneously with the defect of AI-2. Herein we hypothesized that the quorum sensing system—not the metabolic aspect—is responsible for such a regulatory function. In this study, we constructed plasmids infused with sahH and induced protein expression in the luxS-mutant strain to make the quorum-sensing system and metabolic system independent. The biofilm-related genes were investigated by real-time polymerase chain reaction (PCR, and the results demonstrated that the quorum-sensing completed strain restored the gene expression of the defective strain, but the metabolically completed one did not. This evidence supported our hypothesis that the autoinducer-2-mediated, quorum-sensing system, not the AMC, was responsible for luxS mutant regulation.

  9. Interspecies Quorum Sensing as a Stress-Anticipation Signal in E. coli

    DEFF Research Database (Denmark)

    Høyland-Kroghsbo, Nina Molin

    behavior genes. Quorum sensing controls important bacterial behaviors, including bioluminescence, biofilm formation, and virulence. Inter- and intraspecies quorum sensing signals enable bacteria to estimate the abundance and species complexity of a microbial community. A long standing question...

  10. Progress in research of quorum sensing system in Vibrio cholerae%霍乱弧菌密度感应系统研究进展

    Institute of Scientific and Technical Information of China (English)

    赵璇; 阚飙; 崔志刚; 梁未丽

    2012-01-01

    密度感应( Quorum sensing,QS)系统在细菌中普遍存在,细菌细胞通过识别和密度依赖性应答其自身或周围环境中其他菌细胞分泌的一种或多种信号分子来影响一系列基因的转录表达,从而参与细菌多种生理功能的调节.革兰阴性菌的密度感应现象最早发现于海洋弧菌中,本文主要综述了烈性肠道传染病病原体-霍乱弧菌中密度感应系统的研究进展,包括系统组成、信号传递过程、调节的生理功能及与其他全局性调控因子的相互作用.%Quorum-sensing(QS) systems commonly exist in procaryote kingdom and regulate various cellular biological functions, which involves the production and sensing of one or more signal molecules secreted by the members of same species and others, regulation of target genes, expression to coordinate cell behavior in response to cell density. The Gram-negative QS systems were first discovered and extensively characterized in the marine Vibrios. This review focuses on the composition of QS networks in human pathogen Vibrio cholerae; how chemical information is integrated, processed and transduced to control gene expression and how QS interfere with other global regulators.

  11. Quorum sensing-controlled gene expression in lactic acid bacteria

    NARCIS (Netherlands)

    Kuipers, Oscar P.; Ruyter, Pascalle G.G.A. de; Kleerebezem, Michiel; Vos, Willem M. de

    1998-01-01

    Quorum sensing in lactic acid bacteria (LAB) involves peptides that are directly sensed by membrane-located histidine kinases, after which the signal is transmitted to an intracellular response regulator. This regulator in turn activates transcription of target genes, that commonly include the struc

  12. Quorum sensing-controlled gene expression in lactic acid bacteria

    NARCIS (Netherlands)

    Kuipers, Oscar P.; Ruyter, Pascalle G.G.A. de; Kleerebezem, Michiel; Vos, Willem M. de

    1998-01-01

    Quorum sensing in lactic acid bacteria (LAB) involves peptides that are directly sensed by membrane-located histidine kinases, after which the signal is transmitted to an intracellular response regulator. This regulator in turn activates transcription of target genes, that commonly include the

  13. The impact of quorum sensing and swarming motility on Pseudomonas aeruginosa biofilm formation is nutritionally conditional

    DEFF Research Database (Denmark)

    Shrout, J.D.; Chopp, D.L.; Just, C.L.

    2006-01-01

    The role of quorum sensing in Pseudomonas aeruginosa biofilm formation is unclear. Some researchers have shown that quorum sensing is important for biofilm development, while others have indicated it has little or no role. In this study, the contribution of quorum sensing to biofilm development...

  14. Recent progresses on AI-2 bacterial quorum sensing inhibitors.

    Science.gov (United States)

    Zhu, Peng; Li, Minyong

    2012-01-01

    Quorum sensing (QS) is a communication procedure that predominates gene expression in response to cell density and fluctuations in the neighboring environment as a result of discerning molecules termed autoinducers (AIs). It has been embroiled that QS can govern bacterial behaviors such as the secretion of virulence factors, biofilm formation, bioluminescence production, conjugation, sporulation and swarming motility. Autoinducer 2 (AI-2), a QS signaling molecule brought up to be involved in interspecies communication, exists in both gram-negative and -positive bacteria. Therefore, novel approaches to interrupt AI-2 quorum sensing are being recognized as next generation antimicrobials. In the present review article, we summarized recent progresses on AI-2 bacterial quorum sensing inhibitors and discussed their potential as the antibacterial agents.

  15. Facultative cheating supports the coexistence of diverse quorum-sensing alleles.

    Science.gov (United States)

    Pollak, Shaul; Omer-Bendori, Shira; Even-Tov, Eran; Lipsman, Valeria; Bareia, Tasneem; Ben-Zion, Ishay; Eldar, Avigdor

    2016-02-23

    Bacterial quorum sensing enables bacteria to cooperate in a density-dependent manner via the group-wide secretion and detection of specific autoinducer molecules. Many bacterial species show high intraspecific diversity of autoinducer-receptor alleles, called pherotypes. The autoinducer produced by one pherotype activates its coencoded receptor, but not the receptor of another pherotype. It is unclear what selection forces drive the maintenance of pherotype diversity. Here, we use the ComQXPA system of Bacillus subtilis as a model system, to show that pherotype diversity can be maintained by facultative cheating--a minority pherotype exploits the majority, but resumes cooperation when its frequency increases. We find that the maintenance of multiple pherotypes by facultative cheating can persist under kin-selection conditions that select against "obligate cheaters" quorum-sensing response null mutants. Our results therefore support a role for facultative cheating and kin selection in the evolution of quorum-sensing diversity.

  16. Biomimicry of quorum sensing using bacterial lifecycle model.

    Science.gov (United States)

    Niu, Ben; Wang, Hong; Duan, Qiqi; Li, Li

    2013-01-01

    Recent microbiologic studies have shown that quorum sensing mechanisms, which serve as one of the fundamental requirements for bacterial survival, exist widely in bacterial intra- and inter-species cell-cell communication. Many simulation models, inspired by the social behavior of natural organisms, are presented to provide new approaches for solving realistic optimization problems. Most of these simulation models follow population-based modelling approaches, where all the individuals are updated according to the same rules. Therefore, it is difficult to maintain the diversity of the population. In this paper, we present a computational model termed LCM-QS, which simulates the bacterial quorum-sensing (QS) mechanism using an individual-based modelling approach under the framework of Agent-Environment-Rule (AER) scheme, i.e. bacterial lifecycle model (LCM). LCM-QS model can be classified into three main sub-models: chemotaxis with QS sub-model, reproduction and elimination sub-model and migration sub-model. The proposed model is used to not only imitate the bacterial evolution process at the single-cell level, but also concentrate on the study of bacterial macroscopic behaviour. Comparative experiments under four different scenarios have been conducted in an artificial 3-D environment with nutrients and noxious distribution. Detailed study on bacterial chemotatic processes with quorum sensing and without quorum sensing are compared. By using quorum sensing mechanisms, artificial bacteria working together can find the nutrient concentration (or global optimum) quickly in the artificial environment. Biomimicry of quorum sensing mechanisms using the lifecycle model allows the artificial bacteria endowed with the communication abilities, which are essential to obtain more valuable information to guide their search cooperatively towards the preferred nutrient concentrations. It can also provide an inspiration for designing new swarm intelligence optimization algorithms

  17. N-Acyl Homoserine Lactone-Mediated Quorum Sensing with Special Reference to Use of Quorum Quenching Bacteria in Membrane Biofouling Control

    Directory of Open Access Journals (Sweden)

    Harshad Lade

    2014-01-01

    Full Text Available Membrane biofouling remains a severe problem to be addressed in wastewater treatment systems affecting reactor performance and economy. The finding that many wastewater bacteria rely on N-acyl homoserine lactone-mediated quorum sensing to synchronize their activities essential for biofilm formations; the quenching bacterial quorum sensing suggests a promising approach for control of membrane biofouling. A variety of quorum quenching compounds of both synthetic and natural origin have been identified and found effective in inhibition of membrane biofouling with much less environmental impact than traditional antimicrobials. Work over the past few years has demonstrated that enzymatic quorum quenching mechanisms are widely conserved in several prokaryotic organisms and can be utilized as a potent tool for inhibition of membrane biofouling. Such naturally occurring bacterial quorum quenching mechanisms also play important roles in microbe-microbe interactions and have been used to develop sustainable nonantibiotic antifouling strategies. Advances in membrane fabrication and bacteria entrapment techniques have allowed the implication of such quorum quenching bacteria for better design of membrane bioreactor with improved antibiofouling efficacies. In view of this, the present paper is designed to review and discuss the recent developments in control of membrane biofouling with special emphasis on quorum quenching bacteria that are applied in membrane bioreactors.

  18. N-acyl homoserine lactone-mediated quorum sensing with special reference to use of quorum quenching bacteria in membrane biofouling control.

    Science.gov (United States)

    Lade, Harshad; Paul, Diby; Kweon, Ji Hyang

    2014-01-01

    Membrane biofouling remains a severe problem to be addressed in wastewater treatment systems affecting reactor performance and economy. The finding that many wastewater bacteria rely on N-acyl homoserine lactone-mediated quorum sensing to synchronize their activities essential for biofilm formations; the quenching bacterial quorum sensing suggests a promising approach for control of membrane biofouling. A variety of quorum quenching compounds of both synthetic and natural origin have been identified and found effective in inhibition of membrane biofouling with much less environmental impact than traditional antimicrobials. Work over the past few years has demonstrated that enzymatic quorum quenching mechanisms are widely conserved in several prokaryotic organisms and can be utilized as a potent tool for inhibition of membrane biofouling. Such naturally occurring bacterial quorum quenching mechanisms also play important roles in microbe-microbe interactions and have been used to develop sustainable nonantibiotic antifouling strategies. Advances in membrane fabrication and bacteria entrapment techniques have allowed the implication of such quorum quenching bacteria for better design of membrane bioreactor with improved antibiofouling efficacies. In view of this, the present paper is designed to review and discuss the recent developments in control of membrane biofouling with special emphasis on quorum quenching bacteria that are applied in membrane bioreactors.

  19. The Vibrio fischeri quorum-sensing systems ain and lux sequentially induce luminescence gene expression and are important for persistence in the squid host.

    Science.gov (United States)

    Lupp, Claudia; Urbanowski, Mark; Greenberg, E Peter; Ruby, Edward G

    2003-10-01

    Bacterial quorum sensing using acyl-homoserine lactones (acyl-HSLs) as cell-density dependent signalling molecules is important for the transcriptional regulation of many genes essential in the establishment and the maintenance of bacteria-host associations. Vibrio fischeri, the symbiotic partner of the Hawaiian bobtail squid Euprymna scolopes, possesses two distinct acyl-HSL synthase proteins, LuxI and AinS. Whereas the cell density-dependent regulation of luminescence by the LuxI-produced signal is a well-described phenomenon, and its role in light organ symbiosis has been defined, little is known about the ain system. We have investigated the impact of the V. fischeri acyl-HSL synthase AinS on both luminescence and symbiotic colonization. Through phenotypic studies of V. fischeri mutants we have found that the AinS-signal is the predominant inducer of luminescence expression in culture, whereas the impact of the LuxI-signal is apparent only at the high cell densities occurring in symbiosis. Furthermore, our studies revealed that ainS regulates activities essential for successful colonization of E. scolopes, i.e. the V. fischeri ainS mutant failed to persist in the squid light organ. Mutational inactivation of the transcriptional regulator protein LuxO in the ainS mutant partially or completely reversed all the observed phenotypes, demonstrating that the AinS-signal regulates expression of downstream genes through the inactivation of LuxO. Taken together, our results suggest that the two quorum-sensing systems in V. fischeri, ain and lux, sequentially induce the expression of luminescence genes and possibly other colonization factors.

  20. Quorum-sensing systems LuxS/autoinducer 2 and Com regulate Streptococcus pneumoniae biofilms in a bioreactor with living cultures of human respiratory cells.

    Science.gov (United States)

    Vidal, Jorge E; Howery, Kristen E; Ludewick, Herbert P; Nava, Porfirio; Klugman, Keith P

    2013-04-01

    Streptococcus pneumoniae forms organized biofilms in the human upper respiratory tract that may play an essential role in both persistence and acute respiratory infection. However, the production and regulation of biofilms on human cells is not yet fully understood. In this work, we developed a bioreactor with living cultures of human respiratory epithelial cells (HREC) and a continuous flow of nutrients, mimicking the microenvironment of the human respiratory epithelium, to study the production and regulation of S. pneumoniae biofilms (SPB). SPB were also produced under static conditions on immobilized HREC. Our experiments demonstrated that the biomass of SPB increased significantly when grown on HREC compared to the amount on abiotic surfaces. Additionally, pneumococcal strains produced more early biofilms on lung cells than on pharyngeal cells. Utilizing the bioreactor or immobilized human cells, the production of early SPB was found to be regulated by two quorum-sensing systems, Com and LuxS/AI-2, since a mutation in either comC or luxS rendered the pneumococcus unable to produce early biofilms on HREC. Interestingly, while LuxS/autoinducer 2 (AI-2) regulated biofilms on both HREC and abiotic surfaces, Com control was specific for those structures produced on HREC. The biofilm phenotypes of strain D39-derivative ΔcomC and ΔluxS QS mutants were reversed by genetic complementation. Of note, SPB formed on immobilized HREC and incubated under static conditions were completely lysed 24 h postinoculation. Biofilm lysis was also regulated by the Com and LuxS/AI-2 quorum-sensing systems.

  1. Quorum Sensing Activity in Pandoraea pnomenusa RB38

    Directory of Open Access Journals (Sweden)

    Robson Ee

    2014-06-01

    Full Text Available Strain RB38 was recovered from a former dumping area in Malaysia. MALDI-TOF mass spectrometry and genomic analysis identified strain RB-38 as Pandoraea pnomenusa. Various biosensors confirmed its quorum sensing properties. High resolution triple quadrupole liquid chromatography–mass spectrometry analysis was subsequently used to characterize the N-acyl homoserine lactone production profile of P. pnomenusa strain RB38, which validated that this isolate produced N-octanoyl homoserine lactone as a quorum sensing molecule. This is the first report of the production of N-octanoyl homoserine lactone by P. pnomenusa strain RB38.

  2. Fremmedlegemeinfektioner--nyt om biofilm og quorum sensing

    DEFF Research Database (Denmark)

    Høiby, Niels; Johansen, Helle Krogh; Ciofu, Oana

    2007-01-01

    Biofilms are structured consortia of bacteria embedded in self-produced polymer matrix. Biofilms are resistant to antibiotics, disinfectives and phagocytosis. The persistence of foreign body infections is due to biofilms. Chronic P. aeruginosa lung infection in cystic fibrosis patients is a biofilm....... Bacteria in biofilms communicate by means of quorum sensing which activates genes for virulence factors. Biofilms can be prevented by antibiotic prophylaxis or early therapy or by quorum sensing inhibitors which make them susceptible to antibiotics and phagocytosis. Udgivelsesdato: 2007-Nov-26...

  3. Crowd Synchrony and Quorum Sensing in Delay-Coupled Lasers

    Science.gov (United States)

    Zamora-Munt, Jordi; Masoller, C.; Garcia-Ojalvo, Jordi; Roy, Rajarshi

    2010-12-01

    Crowd synchrony and quorum sensing arise when a large number of dynamical elements communicate with each other via a common information pool. Previous evidence has shown that this type of coupling leads to synchronization, when coupling is instantaneous and the number of coupled elements is large enough. Here we consider a situation in which the transmission of information between the system components and the coupling pool is not instantaneous. To that end, we model a system of semiconductor lasers optically coupled to a central laser with a delay. Our results show that, even though the lasers are nonidentical due to their distinct optical frequencies, zero-lag synchronization arises. By changing a system parameter, we can switch between two different types of synchronization transition. The dependence of the transition with respect to the delay-coupling parameters is studied.

  4. Crowd synchrony and quorum sensing in delay-coupled lasers

    CERN Document Server

    Zamora-Munt, Jordi; Garcia-Ojalvo, Jordi; Roy, Rajarshi

    2010-01-01

    Crowd synchrony and quorum sensing arise when a large number of dynamical elements communicate with each other via a common information pool. Previous evidence in different fields, including chemistry, biology and civil engineering, has shown that this type of coupling leads to synchronization, when coupling is instantaneous and the number of coupled elements is large enough. Here we consider a situation in which the transmission of information between the system components and the coupling pool is not instantaneous. To that end, we model a system of semiconductor lasers optically coupled to a central laser with a delay. Our results show that, even though the lasers are non-identical due to their distinct optical frequencies, zero-lag synchronization arises. By changing a system parameter, we can switch between two different types of synchronization transition. The dependence of the transition with respect to the delay-coupling parameters is studied.

  5. Quorum sensing-controlled biofilm development in Serratia liquefaciens MG1

    DEFF Research Database (Denmark)

    Labbate, M.; Queek, S.Y.; Koh, K.S.

    2004-01-01

    Serratia liquefaciens MG1 contains an N-acylhomoserine lactone-mediated quorum-sensing system that is known to regulate swarming motility colonization. In this study, we describe for S. liquefaciens MG1 the development of a novel biofilm consisting of cell aggregates and differentiated cell types......, such as cell chains and long filamentous cells. Furthermore, quorum sensing is shown to be crucial for normal biofilm development and for elaborate differentiation. A mutant of S. liquefaciens MG1 that was incapable of synthesizing extracellular signal formed a thin and nonmature biofilm lacking cell...... aggregates and differentiated cell chains. Signal-based complementation of this mutant resulted in a biofilm with the wild-type architecture. Two quorum-sensing-regulated genes (bsmA and bsmB) involved in biofilm development were identified, and we propose that these genes are engaged in fine...

  6. Ultrasensitivity and noise amplification in a model of V. harveyi quorum sensing

    Science.gov (United States)

    Bressloff, Paul C.

    2016-06-01

    We analyze ultrasensitivity in a model of Vibrio harveyi quorum sensing. We consider a feedforward model consisting of two biochemical networks per cell. The first represents the interchange of a signaling molecule (autoinducer) between the cell cytoplasm and an extracellular domain and the binding of intracellular autoinducer to cognate receptors. The unbound and bound receptors within each cell act as kinases and phosphotases, respectively, which then drive a second biochemical network consisting of a phosphorylation-dephosphorylation cycle. We ignore subsequent signaling pathways associated with gene regulation and the possible modification in the production rate of an autoinducer (positive feedback). We show how the resulting quorum sensing system exhibits ultrasensitivity with respect to changes in cell density. We also demonstrate how quorum sensing can protect against the noise amplification of fast environmental fluctuations in comparison to a single isolated cell.

  7. Ultrasensitivity and noise amplification in a model of V. harveyi quorum sensing.

    Science.gov (United States)

    Bressloff, Paul C

    2016-06-01

    We analyze ultrasensitivity in a model of Vibrio harveyi quorum sensing. We consider a feedforward model consisting of two biochemical networks per cell. The first represents the interchange of a signaling molecule (autoinducer) between the cell cytoplasm and an extracellular domain and the binding of intracellular autoinducer to cognate receptors. The unbound and bound receptors within each cell act as kinases and phosphotases, respectively, which then drive a second biochemical network consisting of a phosphorylation-dephosphorylation cycle. We ignore subsequent signaling pathways associated with gene regulation and the possible modification in the production rate of an autoinducer (positive feedback). We show how the resulting quorum sensing system exhibits ultrasensitivity with respect to changes in cell density. We also demonstrate how quorum sensing can protect against the noise amplification of fast environmental fluctuations in comparison to a single isolated cell.

  8. Synthesis of furanone-based natural product analogues with quorum sensing antagonist activity

    DEFF Research Database (Denmark)

    Hjelmgaard, Thomas; Persson, T.; Rasmussen, Thomas Bovbjerg;

    2003-01-01

    The synthesis of 5- and 3-(1'-hydroxyalkyl)-substituted 5H-furan-2-ones 4a-d and 8a-d as well as 5-alkylidene-5H-furan-2-ones 5a-d is described. A study of the structure-activity relationship of these furanone-based natural product analogues towards two different quorum sensing systems is reported....... Although the synthesized compounds are not as potent quorum sensing inhibitors as some natural counterparts and a synthetic analogue hereof, interesting structure-activity relationships are seen....

  9. Synthesis of new 3-and 4-substituted analogues of acyl homoserine lactone quorum sensing autoinducers

    DEFF Research Database (Denmark)

    Olsen, Jacob Alsbæk; Severinsen, Rune Eg; Rasmussen, Thomas Bovbjerg

    2002-01-01

    The quorum sensing mechanism in Gram-negative bacteria uses small intercellular signal molecules, N-acyl-homoserine lactones (AHLs), to control transcription of specific genes in relation to population density. In this communication, we describe the parallel synthesis of new AHL analogues, in whi...... substituents have been introduced into the 3- and 4-positions of the lactone ring. These analogues have been screened for their ability to activate and inhibit a Vibrio fischeri LuxI/LuxR-derived quorum sensing reporter system....

  10. Synthesis of new 3- and 4-substituted analogues of acyl homoserine lactone quorum sensing autoinducers

    DEFF Research Database (Denmark)

    Olsen, J. A.; Severinsen, R.; Rasmussen, T. B.

    2002-01-01

    The quorum sensing mechanism in Gram-negative bacteria uses small intercellular signal molecules, N-acyl-homoserine lactones (AHLs), to control transcription of specific genes in relation to population density. In this communication, we describe the parallel synthesis of new AHL analogues, in whi...... substituents have been introduced into the 3- and 4-positions of the lactone ring. These analogues have been screened for their ability to activate and inhibit a Vibrio fischeri LuxI/LuxR-derived quorum sensing reporter system. © 2002 Elsevier Science Ltd. All rights reserved....

  11. A model for signal transduction during quorum sensing in Vibrio harveyi

    Science.gov (United States)

    Banik, Suman K.; Fenley, Andrew T.; Kulkarni, Rahul V.

    2009-12-01

    We present a framework for analyzing luminescence regulation during quorum sensing in the bioluminescent bacterium Vibrio harveyi. Using a simplified model for signal transduction in the quorum sensing pathway, we identify key dimensionless parameters that control the system's response. These parameters are estimated using experimental data on luminescence phenotypes for different mutant strains. The corresponding model predictions are consistent with results from other experiments which did not serve as input for determining model parameters. Furthermore, the proposed framework leads to novel testable predictions for luminescence phenotypes and for responses of the network to different perturbations.

  12. Quorum sensing inhibitory potential and molecular docking studies of sesquiterpene lactones from Vernonia blumeoides.

    Science.gov (United States)

    Aliyu, Abubakar Babando; Koorbanally, Neil Anthony; Moodley, Brenda; Singh, Parvesh; Chenia, Hafizah Yousuf

    2016-06-01

    The increasing incidence of multidrug-resistant Gram-negative bacterial pathogens has focused research on the suppression of bacterial virulence via quorum sensing inhibition strategies, rather than the conventional antimicrobial approach. The anti-virulence potential of eudesmanolide sesquiterpene lactones previously isolated from Vernonia blumeoides was assessed by inhibition of quorum sensing and in silico molecular docking. Inhibition of quorum sensing-controlled violacein production in Chromobacterium violaceum was quantified using violacein inhibition assays. Qualitative modulation of quorum sensing activity and signal synthesis was investigated using agar diffusion double ring assays and C. violaceum and Agrobacterium tumefaciens biosensor systems. Inhibition of violacein production was concentration-dependent, with ⩾90% inhibition being obtained with ⩾2.4 mg ml(-1) of crude extracts. Violacein inhibition was significant for the ethyl acetate extract with decreasing inhibition being observed with dichloromethane, hexane and methanol extracts. Violacein inhibition ⩾80% was obtained with 0.071 mg ml(-1) of blumeoidolide B in comparison with ⩾3.6 mg ml(-1) of blumeoidolide A. Agar diffusion double ring assays indicated that only the activity of the LuxI synthase homologue, CviI, was modulated by blumeoidolides A and B, and V. blumeoides crude extracts, suggesting that quorum sensing signal synthesis was down-regulated or competitively inhibited. Finally, molecular docking was conducted to explore the binding conformations of sesquiterpene lactones into the binding sites of quorum sensing regulator proteins, CviR and CviR'. The computed binding energy data suggested that the blumeoidolides have a tendency to inhibit both CviR and CviR' with varying binding affinities. Vernonia eudesmanolide sesquiterpene lactones have the potential to be novel therapeutic agents, which might be important in reducing virulence and pathogenicity of drug-resistant bacteria

  13. Computer-aided identification of recognized drugs as Pseudomonas aeruginosa quorum-sensing inhibitors

    DEFF Research Database (Denmark)

    Yang, Liang; Rybtke, Morten Theil; Jakobsen, Tim Holm

    2009-01-01

    Attenuation of Pseudomonas aeruginosa virulence by the use of small-molecule quorum-sensing inhibitors (referred to as the antipathogenic drug principle) is likely to play a role in future treatment strategies for chronic infections. In this study, structure-based virtual screening was used...... in a search for putative quorum-sensing inhibitors from a database comprising approved drugs and natural compounds. The database was built from compounds which showed structural similarities to previously reported quorum-sensing inhibitors, the ligand of the P. aeruginosa quorum-sensing receptor Las......R, and a quorum-sensing receptor agonist. Six top-ranking compounds, all recognized drugs, were identified and tested for quorum-sensing-inhibitory activity. Three compounds, salicylic acid, nifuroxazide, and chlorzoxazone, showed significant inhibition of quorum-sensing-regulated gene expression and related...

  14. Bacterial attraction and quorum sensing inhibition in Caenorhabditis elegans exudates.

    Science.gov (United States)

    Kaplan, Fatma; Badri, Dayakar V; Zachariah, Cherian; Ajredini, Ramadan; Sandoval, Francisco J; Roje, Sanja; Levine, Lanfang H; Zhang, Fengli; Robinette, Steven L; Alborn, Hans T; Zhao, Wei; Stadler, Michael; Nimalendran, Rathika; Dossey, Aaron T; Brüschweiler, Rafael; Vivanco, Jorge M; Edison, Arthur S

    2009-08-01

    Caenorhabditis elegans, a bacterivorous nematode, lives in complex rotting fruit, soil, and compost environments, and chemical interactions are required for mating, monitoring population density, recognition of food, avoidance of pathogenic microbes, and other essential ecological functions. Despite being one of the best-studied model organisms in biology, relatively little is known about the signals that C. elegans uses to interact chemically with its environment or as defense. C. elegans exudates were analyzed by using several analytical methods and found to contain 36 common metabolites that include organic acids, amino acids, and sugars, all in relatively high abundance. Furthermore, the concentrations of amino acids in the exudates were dependent on developmental stage. The C. elegans exudates were tested for bacterial chemotaxis using Pseudomonas putida (KT2440), a plant growth promoting rhizobacterium, Pseudomonas aeruginosa (PAO1), a soil bacterium pathogenic to C. elegans, and Escherichia coli (OP50), a non-motile bacterium tested as a control. The C. elegans exudates attracted the two Pseudomonas species, but had no detectable antibacterial activity against P. aeruginosa. To our surprise, the exudates of young adult and adult life stages of C. elegans exudates inhibited quorum sensing in the reporter system based on the LuxR bacterial quorum sensing (QS) system, which regulates bacterial virulence and other factors in Vibrio fischeri. We were able to fractionate the QS inhibition and bacterial chemotaxis activities, thus demonstrating that these activities are chemically distinct. Our results demonstrate that C. elegans can attract its bacterial food and has the potential of partially regulating the virulence of bacterial pathogens by inhibiting specific QS systems.

  15. Cationic Conjugated Polymers-Induced Quorum Sensing of Bacteria Cells.

    Science.gov (United States)

    Zhang, Pengbo; Lu, Huan; Chen, Hui; Zhang, Jiangyan; Liu, Libing; Lv, Fengting; Wang, Shu

    2016-03-15

    Bacteria quorum sensing (QS) has attracted significant interest for understanding cell-cell communication and regulating biological functions. In this work, we demonstrate that water-soluble cationic conjugated polymers (PFP-G2) can interact with bacteria to form aggregates through electrostatic interactions. With bacteria coated in the aggregate, PFP-G2 can induce the bacteria QS system and prolong the time duration of QS signal molecules (autoinducer-2 (AI-2)) production. The prolonged AI-2 can bind with specific protein and continuously regulate downstream gene expression. Consequently, the bacteria show a higher survival rate against antibiotics, resulting in decreased antimicrobial susceptibility. Also, AI-2 induced by PFP-G2 can stimulate 55.54 ± 12.03% more biofilm in E. coli. This method can be used to understand cell-cell communication and regulate biological functions, such as the production of signaling molecules, antibiotics, other microbial metabolites, and even virulence.

  16. Quorum-sensing regulates biofilm formation in Vibrio scophthalmi

    Directory of Open Access Journals (Sweden)

    García-Aljaro Cristina

    2012-12-01

    Full Text Available Abstract Background In a previous study, we demonstrated that Vibrio scophthalmi, the most abundant Vibrio species among the marine aerobic or facultatively anaerobic bacteria inhabiting the intestinal tract of healthy cultured turbot (Scophthalmus maximus, contains at least two quorum-sensing circuits involving two types of signal molecules (a 3-hydroxy-dodecanoyl-homoserine lactone and the universal autoinducer 2 encoded by luxS. The purpose of this study was to investigate the functions regulated by these quorum sensing circuits in this vibrio by constructing mutants for the genes involved in these circuits. Results The presence of a homologue to the Vibrio harveyi luxR gene encoding a main transcriptional regulator, whose expression is modulated by quorum–sensing signal molecules in other vibrios, was detected and sequenced. The V. scophthalmi LuxR protein displayed a maximum amino acid identity of 82% with SmcR, the LuxR homologue found in Vibrio vulnificus. luxR and luxS null mutants were constructed and their phenotype analysed. Both mutants displayed reduced biofilm formation in vitro as well as differences in membrane protein expression by mass-spectrometry analysis. Additionally, a recombinant strain of V. scophthalmi carrying the lactonase AiiA from Bacillus cereus, which causes hydrolysis of acyl homoserine lactones, was included in the study. Conclusions V. scophthalmi shares two quorum sensing circuits, including the main transcriptional regulator luxR, with some pathogenic vibrios such as V. harveyi and V. anguillarum. However, contrary to these pathogenic vibrios no virulence factors (such as protease production were found to be quorum sensing regulated in this bacterium. Noteworthy, biofilm formation was altered in luxS and luxR mutants. In these mutants a different expression profile of membrane proteins were observed with respect to the wild type strain suggesting that quorum sensing could play a role in the regulation of

  17. Evidence that the Agr-like quorum sensing system regulates the toxin production, cytotoxicity and pathogenicity of Clostridium perfringens type C isolate CN3685.

    Science.gov (United States)

    Vidal, Jorge E; Ma, Menglin; Saputo, Julian; Garcia, Jorge; Uzal, Francisco A; McClane, Bruce A

    2012-01-01

    Clostridium perfringens possesses at least two functional quorum sensing (QS) systems, i.e. an Agr-like system and a LuxS-dependent AI-2 system. Both of those QS systems can reportedly control in vitro toxin production by C. perfringens but their importance for virulence has not been evaluated. Therefore, the current study assessed whether these QS systems might regulate the pathogenicity of CN3685, a C. perfringens type C strain. Since type C isolates cause both haemorrhagic necrotic enteritis and fatal enterotoxemias (where toxins produced in the intestines are absorbed into the circulation to target other internal organs), the ability of isogenic agrB or luxS mutants to cause necrotizing enteritis in rabbit small intestinal loops or enterotoxemic lethality in mice was evaluated. Results obtained strongly suggest that the Agr-like QS system, but not the LuxS-dependent AI-2 QS system, is required for CN3685 to cause haemorrhagic necrotizing enteritis, apparently because the Agr-like system regulates the production of beta toxin, which is essential for causing this pathology. The Agr-like system, but not the LuxS-mediated AI-2 system, was also important for CN3685 to cause fatal enterotoxemia. These results provide the first direct evidence supporting a role for any QS system in clostridial infections.

  18. Exploring the chemical space of quorum sensing peptides.

    Science.gov (United States)

    Wynendaele, Evelien; Gevaert, Bert; Stalmans, Sofie; Verbeke, Frederick; De Spiegeleer, Bart

    2015-09-01

    Quorum sensing peptides are signalling molecules that are produced by mainly gram-positive bacteria. These peptides can exert different effects, ranging from intra- and interspecies bacterial virulence to bacterial-host interactions. To better comprehend these functional differences, we explored their chemical space, bacterial species distribution and receptor-binding properties using multivariate data analyses, with information obtained from the Quorumpeps database. The quorum sensing peptides can be categorized into three main clusters, which, in turn, can be divided into several subclusters: the classification is based on characteristic chemical properties, including peptide size/compactness, hydrophilicity/lipophilicity, cyclization and the presence of (unnatural) S-containing and aromatic amino acids. Most of the bacterial species synthesize peptides located into one cluster. However, some Streptococcus, Stapylococcus, Clostridium, Bacillus and Lactobacillus species produce peptides that are distributed over more than one cluster, with the quorum sensing peptides of Bacillus subtilis even occupying the total peptide space. The AgrC, FsrC and LamC receptors are only activated by cyclic (thio)lacton or lactam quorum sensing peptides, while the lipophilic isoprenyl-modified peptides solely bind the ComP receptor in Bacillus species.

  19. Quorum-Sensing in CD4(+) T Cell Homeostasis: A Hypothesis and a Model.

    Science.gov (United States)

    Almeida, Afonso R M; Amado, Inês F; Reynolds, Joseph; Berges, Julien; Lythe, Grant; Molina-París, Carmen; Freitas, Antonio A

    2012-01-01

    Homeostasis of lymphocyte numbers is believed to be due to competition between cellular populations for a common niche of restricted size, defined by the combination of interactions and trophic factors required for cell survival. Here we propose a new mechanism: homeostasis of lymphocyte numbers could also be achieved by the ability of lymphocytes to perceive the density of their own populations. Such a mechanism would be reminiscent of the primordial quorum-sensing systems used by bacteria, in which some bacteria sense the accumulation of bacterial metabolites secreted by other elements of the population, allowing them to "count" the number of cells present and adapt their growth accordingly. We propose that homeostasis of CD4(+) T cell numbers may occur via a quorum-sensing-like mechanism, where IL-2 is produced by activated CD4(+) T cells and sensed by a population of CD4(+) Treg cells that expresses the high-affinity IL-2Rα-chain and can regulate the number of activated IL-2-producing CD4(+) T cells and the total CD4(+) T cell population. In other words, CD4(+) T cell populations can restrain their growth by monitoring the number of activated cells, thus preventing uncontrolled lymphocyte proliferation during immune responses. We hypothesize that malfunction of this quorum-sensing mechanism may lead to uncontrolled T cell activation and autoimmunity. Finally, we present a mathematical model that describes the key role of IL-2 and quorum-sensing mechanisms in CD4(+) T cell homeostasis during an immune response.

  20. Impact of Environmental Cues on Staphylococcal Quorum Sensing and Biofilm Development.

    Science.gov (United States)

    Kavanaugh, Jeffrey S; Horswill, Alexander R

    2016-06-10

    Staphylococci are commensal bacteria that colonize the epithelial surfaces of humans and many other mammals. These bacteria can also attach to implanted medical devices and develop surface-associated biofilm communities that resist clearance by host defenses and available chemotherapies. These communities are often associated with persistent staphylococcal infections that place a tremendous burden on the healthcare system. Understanding the regulatory program that controls staphylococcal biofilm development, as well as the environmental conditions that modulate this program, has been a focal point of research in recent years. A central regulator controlling biofilm development is a peptide quorum-sensing system, also called the accessory gene regulator or agr system. In the opportunistic pathogen Staphylococcus aureus, the agr system controls production of exo-toxins and exo-enzymes essential for causing infections, and simultaneously, it modulates the ability of this pathogen to attach to surfaces and develop a biofilm, or to disperse from the biofilm state. In this review, we explore advances on the interconnections between the agr quorum-sensing system and biofilm mechanisms, and topics covered include recent findings on how different environmental conditions influence quorum sensing, the impact on biofilm development, and ongoing questions and challenges in the field. As our understanding of the quorum sensing and biofilm interconnection advances, there are growing opportunities to take advantage of this knowledge and develop therapeutic approaches to control staphylococcal infections.

  1. Artificially constructed quorum-sensing circuits are used for subtle control of bacterial population density.

    Science.gov (United States)

    Wang, Zhaoshou; Wu, Xin; Peng, Jianghai; Hu, Yidan; Fang, Baishan; Huang, Shiyang

    2014-01-01

    Vibrio fischeri is a typical quorum-sensing bacterium for which lux box, luxR, and luxI have been identified as the key elements involved in quorum sensing. To decode the quorum-sensing mechanism, an artificially constructed cell-cell communication system has been built. In brief, the system expresses several programmed cell-death BioBricks and quorum-sensing genes driven by the promoters lux pR and PlacO-1 in Escherichia coli cells. Their transformation and expression was confirmed by gel electrophoresis and sequencing. To evaluate its performance, viable cell numbers at various time periods were investigated. Our results showed that bacteria expressing killer proteins corresponding to ribosome binding site efficiency of 0.07, 0.3, 0.6, or 1.0 successfully sensed each other in a population-dependent manner and communicated with each other to subtly control their population density. This was also validated using a proposed simple mathematical model.

  2. Artificially constructed quorum-sensing circuits are used for subtle control of bacterial population density.

    Directory of Open Access Journals (Sweden)

    Zhaoshou Wang

    Full Text Available Vibrio fischeri is a typical quorum-sensing bacterium for which lux box, luxR, and luxI have been identified as the key elements involved in quorum sensing. To decode the quorum-sensing mechanism, an artificially constructed cell-cell communication system has been built. In brief, the system expresses several programmed cell-death BioBricks and quorum-sensing genes driven by the promoters lux pR and PlacO-1 in Escherichia coli cells. Their transformation and expression was confirmed by gel electrophoresis and sequencing. To evaluate its performance, viable cell numbers at various time periods were investigated. Our results showed that bacteria expressing killer proteins corresponding to ribosome binding site efficiency of 0.07, 0.3, 0.6, or 1.0 successfully sensed each other in a population-dependent manner and communicated with each other to subtly control their population density. This was also validated using a proposed simple mathematical model.

  3. How Quorum Sensing Connects Sporulation to Necrotrophism in Bacillus thuringiensis.

    Science.gov (United States)

    Perchat, Stéphane; Talagas, Antoine; Poncet, Sandrine; Lazar, Noureddine; Li de la Sierra-Gallay, Inès; Gohar, Michel; Lereclus, Didier; Nessler, Sylvie

    2016-08-01

    Bacteria use quorum sensing to coordinate adaptation properties, cell fate or commitment to sporulation. The infectious cycle of Bacillus thuringiensis in the insect host is a powerful model to investigate the role of quorum sensing in natural conditions. It is tuned by communication systems regulators belonging to the RNPP family and directly regulated by re-internalized signaling peptides. One such RNPP regulator, NprR, acts in the presence of its cognate signaling peptide NprX as a transcription factor, regulating a set of genes involved in the survival of these bacteria in the insect cadaver. Here, we demonstrate that, in the absence of NprX and independently of its transcriptional activator function, NprR negatively controls sporulation. NprR inhibits expression of Spo0A-regulated genes by preventing the KinA-dependent phosphorylation of the phosphotransferase Spo0F, thus delaying initiation of the sporulation process. This NprR function displays striking similarities with the Rap proteins, which also belong to the RNPP family, but are devoid of DNA-binding domain and indirectly control gene expression via protein-protein interactions in Bacilli. Conservation of the Rap residues directly interacting with Spo0F further suggests a common inhibition of the sporulation phosphorelay. The crystal structure of apo NprR confirms that NprR displays a highly flexible Rap-like structure. We propose a molecular regulatory mechanism in which key residues of the bifunctional regulator NprR are directly and alternatively involved in its two functions. NprX binding switches NprR from a dimeric inhibitor of sporulation to a tetrameric transcriptional activator involved in the necrotrophic lifestyle of B. thuringiensis. NprR thus tightly coordinates sporulation and necrotrophism, ensuring survival and dissemination of the bacteria during host infection.

  4. Quorum sensing signals are produced by Aeromonas salmonicida and quorum sensing inhibitors can reduce production of a potential virulence factor

    DEFF Research Database (Denmark)

    Rasch, Maria; Kastbjerg, Vicky Gaedt; Bruhn, Jesper Bartholin

    2007-01-01

    . Pigment production was only observed in broth under highly aerated conditions. Quorum sensing inhibitors (QSIs) are compounds that specifically block QS systems without affecting bacterial growth and 2 such compounds, sulphur-containing AHL-analogues, reduced production of protease in a typical strain...... of Aeromonas salmonicida strains. All 31 typical strains were AHL producers as were 21 of 26 atypical strains, but on a strain population basis, production of virulence factors such as protease, lipase, A-layer or pigment did not correlate with the production and accumulation of AHLs in the growth medium...... of these were completely down regulated by HepS-AHL. Hence, QSIs can curb virulence in some strains and could potentially be pursued as bacterial disease control measures in aquaculture....

  5. Pseudomonas quinolone signalling system: a component of quorum sensing cascade is a crucial player in the acute urinary tract infection caused by Pseudomonas aeruginosa.

    Science.gov (United States)

    Bala, Anju; Chhibber, Sanjay; Harjai, Kusum

    2014-11-01

    Pseudomonas aeruginosa is an opportunistic pathogen which employs quorum sensing system to regulate several genes required for its survival and pathogenicity within the host. Besides acylhomoserine lactone (AHL) mediated las and rhl systems, this organism possesses Pseudomonas quinolone signalling (PQS) system based on alkyl quinolone signal molecules. The quinolone system represents another layer of sophistication in the complex quorum sensing cascade. Therefore, in the present study, we evaluated the contribution of the PQS system in the establishment of acute urinary tract infection (UTI) in the mouse model. For this, wild-type parent strain of P. aeruginosa MPAO1 and its isogenic single transposon mutant strains pqsH and pqsA were employed to induce UTI in mice. PQS molecules in the tissue homogenates of mice were detected by high performance thin layer chromatography (HP-TLC) method. Virulence of strains was assessed in terms of bacteriological count, histopathological lesions in the renal and bladder tissue and generation of pathological index markers like reactive nitrogen intermediates and malondialdehyde. HP-TLC analysis showed presence of PQS molecules in the renal and bladder tissue of mice infected with MPAO1 while no PQS was detected in case of pqsH and pqsA mutant strains. Results indicated that MPAO1 possessing fully functional PQS biosynthetic genes was highly virulent and caused acute pyelonephritis with severe inflammation and tissue destruction. On the contrary, significant reduction in the log count, mild tissue damage and declined levels of pathological markers were observed in mice infected with mutant strains as compared to MPAO1. Further among mutants, all these parameters were maximally impaired in the pqsA mutant in which synthesis of alkyl quinolones was completely abolished due to the transposon mutation in respective gene. Virulence of the pqsH mutant strain was lesser than that of the MPAO1 but higher than pqsA mutant. In addition, the

  6. MicroBQs: a centralized database for use in studying bacterial biofilms and quorum sensing

    Science.gov (United States)

    Biofilm formation in many bacterial species may be negatively or positively regulated by cell-to-cell signaling systems referred to as quorum sensing (QS). To assist in understanding research related to biofilms, QS, and the role of QS in biofilm formation, a comprehensive, centralized database, kn...

  7. Quorum Sensing and Virulence of Pseudomonas aeruginosa during Lung Infection of Cystic Fibrosis Patients

    DEFF Research Database (Denmark)

    Bjarnsholt, T.; Jensen, P.O.; Jakobsen, T.H.;

    2010-01-01

    from the intermittent strains. Dominating changes are the switch to mucoidity ( alginate overproduction) and loss of epigenetic regulation of virulence such as the Quorum Sensing (QS). To elucidate the dynamics of P. aeruginosa QS systems during long term infection of the CF lung, we have investigated...

  8. Disulfide Bond-Containing Ajoene Analogues As Novel Quorum Sensing Inhibitors of Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Fong, July; Yuan, Mingjun; Jakobsen, Tim Holm

    2017-01-01

    Since its discovery 22 years ago, the bacterial cell-to-cell communication system, termed quorum sensing (QS), has shown potential as antipathogenic target. Previous studies reported that ajoene from garlic inhibits QS in opportunistic human pathogen Pseudomonas aeruginosa. In this study, screening...

  9. Identification of quorum-sensing regulated proteins in the opportunistic pathogen Pseudomonas aeruginosa by proteomics

    DEFF Research Database (Denmark)

    Arevalo-Ferro, C.; Hentzer, Morten; Reil, G.

    2003-01-01

    The Gram-negative bacterium Pseudomonas aeruginosa is an opportunistic human pathogen which is responsible for severe nosocomial infections in immunocompromised patients and is the major pathogen in cystic fibrosis. The bacterium utilizes two interrelated quorum-sensing (QS) systems, which rely...

  10. Quorum Sensing and the Use of Quorum Quenchers as Natural Biocides to Inhibit Sulfate-Reducing Bacteria

    Science.gov (United States)

    Scarascia, Giantommaso; Wang, Tiannyu; Hong, Pei-Ying

    2016-01-01

    Sulfate-reducing bacteria (SRB) are one of the main protagonist groups of biocorrosion in the seawater environment. Given their principal role in biocorrosion, it remains a crucial task to develop strategies to reduce the abundance of SRBs. Conventional approaches include the use of biocides and antibiotics, which can impose health, safety, and environmental concerns. This review examines an alternative approach to this problem. This is achieved by reviewing the role of quorum sensing (QS) in SRB populations and its impact on the biofilm formation process. Genome databases of SRBs are mined to look for putative QS systems and homologous protein sequences representative of autoinducer receptors or synthases. Subsequently, this review puts forward the potential use of quorum quenchers as natural biocides against SRBs and outlines the potential strategies for the implementation of this approach. PMID:27983678

  11. Quorum Sensing and the Use of Quorum Quenchers as Natural Biocides to Inhibit Sulfate-Reducing Bacteria

    KAUST Repository

    Scarascia, Giantommaso

    2016-12-15

    Sulfate-reducing bacteria (SRB) are one of the main protagonist groups of biocorrosion in the seawater environment. Given their principal role in biocorrosion, it remains a crucial task to develop strategies to reduce the abundance of SRBs. Conventional approaches include the use of biocides and antibiotics, which can impose health, safety, and environmental concerns. This review examines an alternative approach to this problem. This is achieved by reviewing the role of quorum sensing (QS) in SRB populations and its impact on the biofilm formation process. Genome databases of SRBs are mined to look for putative QS systems and homologous protein sequences representative of autoinducer receptors or synthases. Subsequently, this review puts forward the potential use of quorum quenchers as natural biocides against SRBs and outlines the potential strategies for the implementation of this approach.

  12. Quorum Sensing and the Use of Quorum Quenchers as Natural Biocides to Inhibit Sulfate-Reducing Bacteria

    Directory of Open Access Journals (Sweden)

    Giantommaso Scarascia

    2016-12-01

    Full Text Available Sulfate-reducing bacteria (SRB are one of the main protagonist groups of biocorrosion in the seawater environment. Given their principal role in biocorrosion, it remains a crucial task to develop strategies to reduce the abundance of SRBs. Conventional approaches include the use of biocides and antibiotics, which can impose health, safety, and environmental concerns. This review examines an alternative approach to this problem. This is achieved by reviewing the role of quorum sensing (QS in SRB populations and its impact on the biofilm formation process. Genome databases of SRBs are mined to look for putative QS systems and homologous protein sequences representative of autoinducer receptors or synthases. Subsequently, this review puts forward the potential use of quorum quenchers as natural biocides against SRBs and outlines the potential strategies for the implementation of this approach.

  13. Resilience of bacterial quorum sensing against fluid flow

    Science.gov (United States)

    Emge, Philippe; Moeller, Jens; Jang, Hongchul; Rusconi, Roberto; Yawata, Yutaka; Stocker, Roman; Vogel, Viola

    2016-09-01

    Quorum sensing (QS) is a population-density dependent chemical process that enables bacteria to communicate based on the production, secretion and sensing of small inducer molecules. While recombinant constructs have been widely used to decipher the molecular details of QS, how those findings translate to natural QS systems has remained an open question. Here, we compare the activation of natural and synthetic Pseudomonas aeruginosa LasI/R QS systems in bacteria exposed to quiescent conditions and controlled flows. Quantification of QS-dependent GFP expression in suspended cultures and in surface-attached microcolonies revealed that QS onset in both systems was similar under quiescent conditions but markedly differed under flow. Moderate flow (Pe > 25) was sufficient to suppress LasI/R QS recombinantly expressed in Escherichia coli, whereas only high flow (Pe > 102) suppressed QS in wild-type P. aeruginosa. We suggest that this difference stems from the differential production of extracellular matrix and that the matrix confers resilience against moderate flow to QS in wild-type organisms. These results suggest that the expression of a biofilm matrix extends the environmental conditions under which QS-based cell-cell communication is effective and that findings from synthetic QS circuits cannot be directly translated to natural systems.

  14. A direct pre-screen for marine bacteria producing compounds inhibiting quorum sensing reveals diverse planktonic bacteria that are bioactive.

    Science.gov (United States)

    Linthorne, Jamie S; Chang, Barbara J; Flematti, Gavin R; Ghisalberti, Emilio L; Sutton, David C

    2015-02-01

    A promising new strategy in antibacterial research is inhibition of the bacterial communication system termed quorum sensing. In this study, a novel and rapid pre-screening method was developed to detect the production of chemical inhibitors of this system (quorum-quenching compounds) by bacteria isolated from marine and estuarine waters. This method involves direct screening of mixed populations on an agar plate, facilitating specific isolation of bioactive colonies. The assay showed that between 4 and 46 % of culturable bacteria from various samples were bioactive, and of the 95 selectively isolated bacteria, 93.7 % inhibited Vibrio harveyi bioluminescence without inhibiting growth, indicating potential production of quorum-quenching compounds. Of the active isolates, 21 % showed further activity against quorum-sensing-regulated pigment production by Serratia marcescens. The majority of bioactive isolates were identified by 16S ribosomal DNA (rDNA) amplification and sequencing as belonging to the genera Vibrio and Pseudoalteromonas. Extracts of two strongly bioactive Pseudoalteromonas isolates (K1 and B2) were quantitatively assessed for inhibition of growth and quorum-sensing-regulated processes in V. harveyi, S. marcescens and Chromobacterium violaceum. Extracts of the isolates reduced V. harveyi bioluminescence by as much as 98 % and C. violaceum pigment production by 36 % at concentrations which had no adverse effect on growth. The activity found in the extracts indicated that the isolates may produce quorum-quenching compounds. This study further supports the suggestion that quorum quenching may be a common attribute among culturable planktonic marine and estuarine bacteria.

  15. The CckA-ChpT-CtrA phosphorelay system is regulated by quorum sensing and controls flagellar motility in the marine sponge symbiont Ruegeria sp. KLH11.

    Directory of Open Access Journals (Sweden)

    Jindong Zan

    Full Text Available Bacteria respond to their environment via signal transduction pathways, often two-component type systems that function through phosphotransfer to control expression of specific genes. Phosphorelays are derived from two-component systems but are comprised of additional components. The essential cckA-chpT-ctrA phosphorelay in Caulobacter crescentus has been well studied and is important in orchestrating the cell cycle, polar development and flagellar biogenesis. Although cckA, chpT and ctrA homologues are widespread among the Alphaproteobacteria, relatively few is known about their function in the large and ecologically significant Roseobacter clade of the Rhodobacterales. In this study the cckA-chpT-ctrA system of the marine sponge symbiont Ruegeria sp. KLH11 was investigated. Our results reveal that the cckA, chpT and ctrA genes positively control flagellar biosynthesis. In contrast to C. crescentus, the cckA, chpT and ctrA genes in Ruegeria sp. KLH11 are non-essential and do not affect bacterial growth. Gene fusion and transcript analyses provide evidence for ctrA autoregulation and the control of motility-related genes. In KLH11, flagellar motility is controlled by the SsaRI system and acylhomoserine lactone (AHL quorum sensing. SsaR and long chain AHLs are required for cckA, chpT and ctrA gene expression, providing a regulatory link between flagellar locomotion and population density in KLH11.

  16. The RpfB-Dependent Quorum Sensing Signal Turnover System Is Required for Adaptation and Virulence in Rice Bacterial Blight Pathogen Xanthomonas oryzae pv. oryzae.

    Science.gov (United States)

    Wang, Xing-Yu; Zhou, Lian; Yang, Jun; Ji, Guang-Hai; He, Ya-Wen

    2016-03-01

    Xanthomonas oryzae pv. oryzae, the bacterial blight pathogen of rice, produces diffusible signal factor (DSF) family quorum sensing signals to regulate virulence. The biosynthesis and perception of DSF family signals require components of the rpf (regulation of pathogenicity factors) cluster. In this study, we report that RpfB plays an essential role in DSF family signal turnover in X. oryzae pv. oryzae PXO99A. The production of DSF family signals was boosted by deletion of the rpfB gene and was abolished by its overexpression. The RpfC/RpfG-mediated DSF signaling system negatively regulates rpfB expression via the global transcription regulator Clp, whose activity is reversible in the presence of cyclic diguanylate monophosphate. These findings indicate that the DSF family signal turnover system in PXO99A is generally consistent with that in Xanthomonas campestris pv. campestris. Moreover, this study has revealed several specific roles of RpfB in PXO99A. First, the rpfB deletion mutant produced high levels of DSF family signals but reduced extracellular polysaccharide production, extracellular amylase activity, and attenuated pathogenicity. Second, the rpfB/rpfC double-deletion mutant was partially deficient in xanthomonadin production. Taken together, the RpfB-dependent DSF family signal turnover system is a conserved and naturally presenting signal turnover system in Xanthomonas spp., which plays unique roles in X. oryzae pv. oryzae adaptation and pathogenesis.

  17. 以病原菌群体感应系统为靶标的新型抗菌药物的研究进展%Research progress of new antibacterial drugs that target bacterial quorum sensing systems

    Institute of Scientific and Technical Information of China (English)

    尹守亮; 常亚婧; 邓苏萍; 王清池; 于文功; 宫倩红

    2011-01-01

    In recent years, antibiotic resistance of bacteria has become a global health crisis. Especially, the new class of "superbug" was found in South Asia, which is resistant to almost known antibiotics and causes worldwide alarm. Through the underlying mechanisms of bacterial pathogenecity, the expression of many pathogen virulence factors is regulated by the process of quonun sensing. Screening efficient quorum sensing inhibitors is an especially compelling approach to the future treatment of bacterial infections and antibiotic resistance. This article focuses on bacterial quorum sensing system, quorum sensing screening model for in vitro and evaluation of animal models in vivo. recent research of quorum sensing inhibitors and so on.%近年来,日益严重的细菌耐药性成为全球关注的焦点,尤其是南亚发现的新型"超级细菌"几乎对绝大多数抗生素都具有抗性,在世界范围内引起了恐慌.对病原菌致病机制的研究发现,许多病原菌的致病机制都依赖细菌群体感应系统的调节和控制.筛选高效的群体感应抑制剂有望成为解决细菌感染以及耐药性问题的一个有效途径.本文主要阐述了细菌群体感应信号调控系统、群体感应抑制因子体外筛选模型及体内动物模型评价,群体感应抑制因子的研究近况等内容.

  18. SigMol: repertoire of quorum sensing signaling molecules in prokaryotes.

    Science.gov (United States)

    Rajput, Akanksha; Kaur, Karambir; Kumar, Manoj

    2016-01-04

    Quorum sensing is a widespread phenomenon in prokaryotes that helps them to communicate among themselves and with eukaryotes. It is driven through quorum sensing signaling molecules (QSSMs) in a density dependent manner that assists in numerous biological functions like biofilm formation, virulence factors secretion, swarming motility, bioluminescence, etc. Despite immense implications, dedicated resources of QSSMs are lacking. Therefore, we have developed SigMol (http://bioinfo.imtech.res.in/manojk/sigmol), a specialized repository of these molecules in prokaryotes. SigMol harbors information on QSSMs pertaining to different quorum sensing signaling systems namely acylated homoserine lactones (AHLs), diketopiperazines (DKPs), 4-hydroxy-2-alkylquinolines (HAQs), diffusible signal factors (DSFs), autoinducer-2 (AI-2) and others. Database contains 1382: entries of 182: unique signaling molecules from 215: organisms. It encompasses biological as well as chemical aspects of signaling molecules. Biological information includes genes, preliminary bioassays, identification assays and applications, while chemical detail comprises of IUPAC name, SMILES and structure. We have provided user-friendly browsing and searching facilities for easy data retrieval and comparison. We have gleaned information of diverse QSSMs reported in literature at a single platform 'SigMol'. This comprehensive resource will assist the scientific community in understanding intraspecies, interspecies or interkingdom networking and further help to unfold different facets of quorum sensing and related therapeutics.

  19. SigMol: repertoire of quorum sensing signaling molecules in prokaryotes

    Science.gov (United States)

    Rajput, Akanksha; Kaur, Karambir; Kumar, Manoj

    2016-01-01

    Quorum sensing is a widespread phenomenon in prokaryotes that helps them to communicate among themselves and with eukaryotes. It is driven through quorum sensing signaling molecules (QSSMs) in a density dependent manner that assists in numerous biological functions like biofilm formation, virulence factors secretion, swarming motility, bioluminescence, etc. Despite immense implications, dedicated resources of QSSMs are lacking. Therefore, we have developed SigMol (http://bioinfo.imtech.res.in/manojk/sigmol), a specialized repository of these molecules in prokaryotes. SigMol harbors information on QSSMs pertaining to different quorum sensing signaling systems namely acylated homoserine lactones (AHLs), diketopiperazines (DKPs), 4-hydroxy-2-alkylquinolines (HAQs), diffusible signal factors (DSFs), autoinducer-2 (AI-2) and others. Database contains 1382 entries of 182 unique signaling molecules from 215 organisms. It encompasses biological as well as chemical aspects of signaling molecules. Biological information includes genes, preliminary bioassays, identification assays and applications, while chemical detail comprises of IUPAC name, SMILES and structure. We have provided user-friendly browsing and searching facilities for easy data retrieval and comparison. We have gleaned information of diverse QSSMs reported in literature at a single platform ‘SigMol’. This comprehensive resource will assist the scientific community in understanding intraspecies, interspecies or interkingdom networking and further help to unfold different facets of quorum sensing and related therapeutics. PMID:26490957

  20. Las-like quorum-sensing system negatively regulates both pyoluteorin and phenazine-1-carboxylic acid production in Pseudomonas sp. M18

    Institute of Scientific and Technical Information of China (English)

    CHEN Yun; WANG XiaoLei; HUANG XianQing; ZHANG XueHong; XU YuQuan

    2008-01-01

    A las-like quorum-sensing system in Pseudornonas sp. M18 was identified, which consisted of lasl and lasR genes encoding LuxI-LuxR type regulator. Several functions of the las system from strain M18 were investigated in this study. The chromosomal inactivation of either lasl or lasR by recombination increased the production of both pyoluteorin (Pit) and phenazine-1-carboxylic acid (PCA) by 4-5 fold and 2-3 fold over that of the wild type atrein of M18, respectively. Production of both antibiotics was restored to wild-type levels after in trans complementation with the wild-type lasl or lasR gene. Expression of the translational fusions pltA'-'lacZand phzA'-'lacZfurther confirmed the negative effect of lasl or lasR on both biosynthetic operons, and it was also demonstrated that the las system was related to the ability of swarming motility and the inhibition of cell growth.

  1. Las-like quorum-sensing system negatively regulates both pyoluteorin and phenazine-1-carboxylic acid production in Pseudomonas sp. M18

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    A las-like quorum-sensing system in Pseudomonas sp. M18 was identified, which consisted of lasI and lasR genes encoding LuxI-LuxR type regulator. Several functions of the las system from strain M18 were investigated in this study. The chromosomal inactivation of either lasI or lasR by recombination increased the production of both pyoluteorin (Plt) and phenazine-1-carboxylic acid (PCA) by 4-5 fold and 2-3 fold over that of the wild type strain of M18, respectively. Production of both antibiotics was restored to wild-type levels after in trans complementation with the wild-type lasI or lasR gene. Expression of the translational fusions pltA’-’lacZ and phzA’-’lacZ further confirmed the negative effect of lasI or lasR on both biosynthetic operons, and it was also demonstrated that the las system was related to the ability of swarming motility and the inhibition of cell growth.

  2. A genetically engineered whole-cell pigment-based bacterial biosensing system for quantification of N-butyryl homoserine lactone quorum sensing signal.

    Science.gov (United States)

    Yong, Yang-Chun; Zhong, Jian-Jiang

    2009-09-15

    N-acyl homoserine lactone (AHL) is a widely conserved quorum sensing (QS) signal of gram-negative bacteria and has received attention in fighting against human diseases and environmental pollution. However, a method for quantifying AHL is lacking although it is urgently required for diagnosis and bioprocess manipulation. This work screened out an aromatics degrader Pseudomonas aeruginosa for biosensing system development, which produced a blue-green pigment regulated by the RhlI-RhlR QS system. By taking advantage of the recognition of N-butyryl homoserine lactone (BHL, the signal molecule of RhlI-RhlR QS system and an AHL) by the product of rhlR, a new whole-cell biosensor P. aeruginosa Delta rhlIR/pYC-rhlR (rhlI(-)rhlR(++)) was developed. It was constructed through abolishing its BHL production by in-frame deletion of rhlIR and over-expressing rhlR by introducing a multi-copy plasmid pYC-rhlR into Delta rhlIR. By using the pigment production which responded to exogenous BHL as biosensor output, BHL quantification in samples was simply done spectrophotometrically. Under optimum conditions, the calibration curve had the limit of detection (LOD), the 50% activation/effect concentration, the limit of quantification (LOQ), and the quantitative detection range of 1.3 nM, 2.77+/-0.45 microM, 5.7 nM and 0.11-49.7 microM, respectively. The biosensor output was stable, culture samples could be stored 10 days under -20 degrees C, and this sensing system was resistant to interferences by toxic aromatic pollutants. It was successfully applied to environmental samples even without extraction. The new whole-cell biosensing system provided a simple, stable, toxic pollutants-tolerant, and cost-effective tool for quantitative investigation of the QS signals' role in environmental processes.

  3. Global analysis of the Burkholderia thailandensis quorum sensing-controlled regulon.

    Science.gov (United States)

    Majerczyk, Charlotte; Brittnacher, Mitchell; Jacobs, Michael; Armour, Christopher D; Radey, Mathew; Schneider, Emily; Phattarasokul, Somsak; Bunt, Richard; Greenberg, E Peter

    2014-04-01

    Burkholderia thailandensis contains three acyl-homoserine lactone quorum sensing circuits and has two additional LuxR homologs. To identify B. thailandensis quorum sensing-controlled genes, we carried out transcriptome sequencing (RNA-seq) analyses of quorum sensing mutants and their parent. The analyses were grounded in the fact that we identified genes coding for factors shown previously to be regulated by quorum sensing among a larger set of quorum-controlled genes. We also found that genes coding for contact-dependent inhibition were induced by quorum sensing and confirmed that specific quorum sensing mutants had a contact-dependent inhibition defect. Additional quorum-controlled genes included those for the production of numerous secondary metabolites, an uncharacterized exopolysaccharide, and a predicted chitin-binding protein. This study provides insights into the roles of the three quorum sensing circuits in the saprophytic lifestyle of B. thailandensis, and it provides a foundation on which to build an understanding of the roles of quorum sensing in the biology of B. thailandensis and the closely related pathogenic Burkholderia pseudomallei and Burkholderia mallei.

  4. The AHL- and BDSF-dependent quorum sensing systems control specific and overlapping sets of genes in Burkholderia cenocepacia H111.

    Directory of Open Access Journals (Sweden)

    Nadine Schmid

    Full Text Available Quorum sensing in Burkholderia cenocepacia H111 involves two signalling systems that depend on different signal molecules, namely N-acyl homoserine lactones (AHLs and the diffusible signal factor cis-2-dodecenoic acid (BDSF. Previous studies have shown that AHLs and BDSF control similar phenotypic traits, including biofilm formation, proteolytic activity and pathogenicity. In this study we mapped the BDSF stimulon by RNA-Seq and shotgun proteomics analysis. We demonstrate that a set of the identified BDSF-regulated genes or proteins are also controlled by AHLs, suggesting that the two regulons partially overlap. The detailed analysis of two mutually regulated operons, one encoding three lectins and the other one encoding the large surface protein BapA and its type I secretion machinery, revealed that both AHLs and BDSF are required for full expression, suggesting that the two signalling systems operate in parallel. In accordance with this, we show that both AHLs and BDSF are required for biofilm formation and protease production.

  5. Characterisation of two quorum sensing systems in the endophytic Serratia plymuthica strain G3: differential control of motility and biofilm formation according to life-style

    Directory of Open Access Journals (Sweden)

    Li Jun

    2011-02-01

    Full Text Available Abstract Background N-acylhomoserine lactone (AHL-based quorum sensing (QS systems have been described in many plant-associated Gram-negative bacteria to control certain beneficial phenotypic traits, such as production of biocontrol factors and plant growth promotion. However, the role of AHL-mediated signalling in the endophytic strains of plant-associated Serratia is still poorly understood. An endophytic Serratia sp. G3 with biocontrol potential and high levels of AHL signal production was isolated from the stems of wheat and the role of QS in this isolate was determined. Results Strain G3 classified as Serratia plymuthica based on 16S rRNA was subjected to phylogenetic analysis. Using primers to conserved sequences of luxIR homologues from the Serratia genus, splIR and spsIR from the chromosome of strain G3 were cloned and sequenced. AHL profiles from strain G3 and Escherichia coli DH5α expressing splI or spsI from recombinant plasmids were identified by liquid chromatography-tandem mass spectrometry. This revealed that the most abundant AHL signals produced by SplI in E. coli were N-3-oxo-hexanoylhomoserine lactone (3-oxo-C6-HSL, N-3-oxo-heptanoylhomoserine lactone (3-oxo-C7-HSL, N-3-hydroxy-hexanoylhomoserine lactone (3-hydroxy-C6-HSL, N-hexanoylhomoserine lactone (C6-HSL, and N-heptanoyl homoserine lactone (C7-HSL; whereas SpsI was primarily responsible for the synthesis of N-butyrylhomoserine lactone (C4-HSL and N-pentanoylhomoserine lactone (C5-HSL. Furthermore, a quorum quenching analysis by heterologous expression of the Bacillus A24 AiiA lactonase in strain G3 enabled the identification of the AHL-regulated biocontrol-related traits. Depletion of AHLs with this lactonase resulted in altered adhesion and biofilm formation using a microtiter plate assay and flow cells coupled with confocal laser scanning microscopy respectively. This was different from the closely related S. plymuthica strains HRO-C48 and RVH1, where biofilm formation

  6. Truncated Autoinducing Peptides as Antagonists of Staphylococcus lugdunensis Quorum Sensing.

    Science.gov (United States)

    Gordon, Christopher P; Olson, Shondra D; Lister, Jessica L; Kavanaugh, Jeffrey S; Horswill, Alexander R

    2016-10-13

    Competitive quorum sensing (QS) antagonism offers a novel strategy for attenuating current multidrug resistant staphylococcal infections. To this end, a series of 10 truncated analogues based on the parent autoinducing peptides (AIPs) of Staphylococcus lugdunensis (groups I and II) and Staphylococcus epidermidis (groups I-III) were sequentially assessed against a newly developed Staphylococcus lugdunensis group I QS reporter strain. The truncated analogues based upon Staphylococcus lugdunensis AIP-1 (1) and AIP-2 (2) displayed respective IC50 values of 0.2 ± 0.01 μM and 0.3 ± 0.01 μM, while the truncated analogue of the Staphylococcus epidermidis AIP-1 (3) elicited an IC50 value of 2.7 ± 0.1 μM. These findings demonstrate the potential of cognate and "crosstalk" competitive quorum sensing inhibition using truncated AIPs as a means of attenuating staphylococcal infections in species beyond Staphylococcus aureus.

  7. Quorum Sensing Inhibitory Activity of Giganteone A from Myristica cinnamomea King against Escherichia coli Biosensors.

    Science.gov (United States)

    Sivasothy, Yasodha; Krishnan, Thiba; Chan, Kok-Gan; Abdul Wahab, Siti Mariam; Othman, Muhamad Aqmal; Litaudon, Marc; Awang, Khalijah

    2016-03-21

    Malabaricones A-C (1-3) and giganteone A (4) were isolated from the bark of Myristica cinnamomea King. Their structures were elucidated and characterized by means of NMR and MS spectral analyses. These isolates were evaluated for their anti-quorum sensing activity using quorum sensing biosensors, namely Escherichia coli [pSB401] and Escherichia coli [pSB1075], whereby the potential of giganteone A (4) as a suitable anti-quorum sensing agent was demonstrated.

  8. Quorum Sensing Inhibitory Activity of Giganteone A from Myristica cinnamomea King against Escherichia coli Biosensors

    Directory of Open Access Journals (Sweden)

    Yasodha Sivasothy

    2016-03-01

    Full Text Available Malabaricones A–C (1–3 and giganteone A (4 were isolated from the bark of Myristica cinnamomea King. Their structures were elucidated and characterized by means of NMR and MS spectral analyses. These isolates were evaluated for their anti-quorum sensing activity using quorum sensing biosensors, namely Escherichia coli [pSB401] and Escherichia coli [pSB1075], whereby the potential of giganteone A (4 as a suitable anti-quorum sensing agent was demonstrated.

  9. Quorum Sensing and Synchronization in Populations of Coupled Chemical Oscillators

    Science.gov (United States)

    Taylor, Annette F.; Tinsley, Mark R.; Showalter, Kenneth

    2013-12-01

    Experiments and simulations of populations of coupled chemical oscillators, consisting of catalytic particles suspended in solution, provide insights into density-dependent dynamics displayed by many cellular organisms. Gradual synchronization transitions, the "switching on" of activity above a threshold number of oscillators (quorum sensing) and the formation of synchronized groups (clusters) of oscillators have been characterized. Collective behavior is driven by the response of the oscillators to chemicals emitted into the surrounding solution.

  10. Synthetic polymers for simultaneous bacterial sequestration and quorum sense interference.

    Science.gov (United States)

    Xue, Xuan; Pasparakis, George; Halliday, Nigel; Winzer, Klaus; Howdle, Steven M; Cramphorn, Christopher J; Cameron, Neil R; Gardner, Paul M; Davis, Benjamin G; Fernández-Trillo, Francisco; Alexander, Cameron

    2011-10-10

    Double agents: dual-action polymers are able to sequester rapidly the marine organism Vibrio harveyi from suspension, while at the same time quenching bacterial quorum sense (QS) signals. The potency of the polymers is assessed by cell aggregation experiments and competitive binding assays against a QS signal precursor, and their effect on bacterial behavior is shown by means of bioluminescence. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. In silico and experimental methods revealed highly diverse bacteria with quorum sensing and aromatics biodegradation systems--a potential broad application on bioremediation.

    Science.gov (United States)

    Huang, Yili; Zeng, Yanhua; Yu, Zhiliang; Zhang, Jing; Feng, Hao; Lin, Xiuchun

    2013-11-01

    Phylogenetic overlaps between aromatics-degrading bacteria and acyl-homoserine-lactone (AHL) or autoinducer (AI) based quorum-sensing (QS) bacteria were evident in literatures; however, the diversity of bacteria with both activities had never been finely described. In-silico searching in NCBI genome database revealed that more than 11% of investigated population harbored both aromatic ring-hydroxylating-dioxygenase (RHD) gene and AHL/AI-synthetase gene. These bacteria were distributed in 10 orders, 15 families, 42 genus and 78 species. Horizontal transfers of both genes were common among them. Using enrichment and culture dependent method, 6 Sphingomonadales and 4 Rhizobiales with phenanthrene- or pyrene-degrading ability and AHL-production were isolated from marine, wetland and soil samples. Thin-layer-chromatography and gas-chromatography-mass-spectrum revealed that these Sphingomonads produced various AHL molecules. This is the first report of highly diverse bacteria that harbored both aromatics-degrading and QS systems. QS regulation may have broad impacts on aromatics biodegradation, and would be a new angle for developing bioremediation technology.

  12. Quorum Sensing Influences Burkholderia thailandensis Biofilm Development and Matrix Production.

    Science.gov (United States)

    Tseng, Boo Shan; Majerczyk, Charlotte D; Passos da Silva, Daniel; Chandler, Josephine R; Greenberg, E Peter; Parsek, Matthew R

    2016-10-01

    Members of the genus Burkholderia are known to be adept at biofilm formation, which presumably assists in the survival of these organisms in the environment and the host. Biofilm formation has been linked to quorum sensing (QS) in several bacterial species. In this study, we characterized Burkholderia thailandensis biofilm development under flow conditions and sought to determine whether QS contributes to this process. B. thailandensis biofilm formation exhibited an unusual pattern: the cells formed small aggregates and then proceeded to produce mature biofilms characterized by "dome" structures filled with biofilm matrix material. We showed that this process was dependent on QS. B. thailandensis has three acyl-homoserine lactone (AHL) QS systems (QS-1, QS-2, and QS-3). An AHL-negative strain produced biofilms consisting of cell aggregates but lacking the matrix-filled dome structures. This phenotype was rescued via exogenous addition of the three AHL signals. Of the three B. thailandensis QS systems, we show that QS-1 is required for proper biofilm development, since a btaR1 mutant, which is defective in QS-1 regulation, forms biofilms without these dome structures. Furthermore, our data show that the wild-type biofilm biomass, as well as the material inside the domes, stains with a fucose-binding lectin. The btaR1 mutant biofilms, however, are negative for fucose staining. This suggests that the QS-1 system regulates the production of a fucose-containing exopolysaccharide in wild-type biofilms. Finally, we present data showing that QS ability during biofilm development produces a biofilm that is resistant to dispersion under stress conditions. The saprophyte Burkholderia thailandensis is a close relative of the pathogenic bacterium Burkholderia pseudomallei, the causative agent of melioidosis, which is contracted from its environmental reservoir. Since most bacteria in the environment reside in biofilms, B. thailandensis is an ideal model organism for

  13. Boolean network model of the Pseudomonas aeruginosa quorum sensing circuits.

    Science.gov (United States)

    Dallidis, Stylianos E; Karafyllidis, Ioannis G

    2014-09-01

    To coordinate their behavior and virulence and to synchronize attacks against their hosts, bacteria communicate by continuously producing signaling molecules (called autoinducers) and continuously monitoring the concentration of these molecules. This communication is controlled by biological circuits called quorum sensing (QS) circuits. Recently QS circuits and have been recognized as an alternative target for controlling bacterial virulence and infections without the use of antibiotics. Pseudomonas aeruginosa is a Gram-negative bacterium that infects insects, plants, animals and humans and can cause acute infections. This bacterium has three interconnected QS circuits that form a very complex and versatile QS system, the operation of which is still under investigation. Here we use Boolean networks to model the complete QS system of Pseudomonas aeruginosa and we simulate and analyze its operation in both synchronous and asynchronous modes. The state space of the QS system is constructed and it turned out to be very large, hierarchical, modular and scale-free. Furthermore, we developed a simulation tool that can simulate gene knock-outs and study their effect on the regulons controlled by the three QS circuits. The model and tools we developed will give to life scientists a deeper insight to this complex QS system.

  14. Computer-aided identification of recognized drugs as Pseudomonas aeruginosa quorum-sensing inhibitors

    DEFF Research Database (Denmark)

    Yang, Liang; Rybtke, Morten Theil; Jakobsen, Tim Holm

    2009-01-01

    Attenuation of Pseudomonas aeruginosa virulence by the use of small-molecule quorum-sensing inhibitors (referred to as the antipathogenic drug principle) is likely to play a role in future treatment strategies for chronic infections. In this study, structure-based virtual screening was used...... in a search for putative quorum-sensing inhibitors from a database comprising approved drugs and natural compounds. The database was built from compounds which showed structural similarities to previously reported quorum-sensing inhibitors, the ligand of the P. aeruginosa quorum-sensing receptor Las...

  15. RND efflux pump and its interrelationship with quorum sensing system%RND家族外排泵及其与微生物群体感应系统的相互关系

    Institute of Scientific and Technical Information of China (English)

    梁志彬; 陈豫梅; 陈昱帆; 程莹莹; 张炼辉

    2016-01-01

    抗生素耐药性一直是细菌病害防治的难题,药物外排泵过量表达是细菌耐药性形成的重要机制之一。在革兰氏阴性细菌中,RND(Resistance-nodulation-cell division)家族外排泵在耐药性中发挥着重要作用,近年来的研究表明,依赖于小分子信号物质进行调控的群体感应系统与RND外排泵家族之间存在紧密的相互作用关系。本文在介绍RND家族外排泵的结构、转运机理和群体感应系统的类型及调控方式的基础上,剖析了群体感应系统对RND外排泵的调控机理以及RND外排泵对群体感应系统信号分子转运的影响。深入研究RND家族外排泵与群体感应系统之间的相互依赖、相互制约关系有利于阐明RND家族外排泵的调控机理,并有可能为克服微生物耐药性问题提供新的思路。%Antibiotic resistance has become a serious concern in treatment of bacterial infections. Overexpression of efflux pump is one of the important mechanisms in antibiotic resistance. In Gram negative bacteria, RND (Resistance-nodulation-cell division) superfamily efflux pump plays a vital important role in antibiotics resistance. Recent research progress unveils an intriguing interrelationship between RND efflux pump and the bacterial quorum sensing system, whose regulation is dependent on small signal molecules. This article reviews the latest findings on the structure and transport mechanism of RND efflux pump, as well as the general features and regulatory mechanisms of quorum sensing, with a special focus on the role and mechanism of quorum sensing system in regulation of RND efflux pump, and the influence of efflux pump on quorum sensing signal transportation. Further investigation of the interrelationship between RND efflux pumps and the bacterial quorum sensing systems is critical for elucidation of the regulatory mechanisms that govern the expression of the RND efflux pumps genes, and may also provide useful

  16. Functions and regulation of quorum-sensing in Agrobacterium tumefaciens

    Directory of Open Access Journals (Sweden)

    Denis eFaure

    2014-01-01

    Full Text Available In Agrobacterium tumefaciens, horizontal transfer and vegetative replication of oncogenic Ti plasmids involve a cell-to-cell communication process called quorum-sensing (QS. The determinants of the QS-system belong to the LuxR/LuxI class. The LuxI-like protein TraI synthesizes N-acyl-homoserine lactone molecules which act as diffusible QS-signals. Beyond a threshold concentration, these molecules bind and activate the LuxR-like transcriptional regulator TraR, thereby initiating the QS-regulatory pathway. For the last twenty years, A. tumefaciens has stood as a prominent model in the understanding of the LuxR/LuxI type of QS systems. A number of studies also unveiled features which are unique to A. tumefaciens QS, some of them being directly related to the phytopathogenic lifestyle of the bacteria. In this review we will present the current knowledge of QS in A. tumefaciens at both the genetic and molecular levels. We will also describe how interactions with plant host modulate the QS pathway of A. tumefaciens, and discuss what could be the advantages for the agrobacteria to use such a tightly regulated QS-system to disseminate the Ti plasmids.

  17. Virulence and in planta movement of Xanthomonas hortorum pv. pelargonii are affected by the diffusible signal factor (DSF)-dependent quorum sensing system.

    Science.gov (United States)

    Barel, Victoria; Chalupowicz, Laura; Barash, Isaac; Sharabani, Galit; Reuven, Michal; Dror, Orit; Burdman, Saul; Manulis-Sasson, Shulamit

    2015-09-01

    Xanthomonas hortorum pv. pelargonii (Xhp), the causal agent of bacterial blight in pelargonium, is the most threatening bacterial disease of this ornamental worldwide. To gain an insight into the regulation of virulence in Xhp, we have disrupted the quorum sensing (QS) genes, which mediate the biosynthesis and sensing of the diffusible signal factor (DSF). Mutations in rpfF (encoding the DSF synthase) and rpfC (encoding the histidine sensor kinase of the two-component system RfpC/RpfG) and overexpression of rpfF showed a significant reduction in incidence and severity of the disease on pelargonium. Confocal laser scanning microscopy images of inoculated plants with a green fluorescent protein (GFP)-labelled wild-type strain showed that the pathogen is homogeneously dispersed in the lumen of xylem vessels, reaching the apex and invading the intercellular spaces of the leaf mesophyll tissue within 21 days. In contrast, the rpfF and rpfC knockout mutants, as well as the rpfF-overexpressing strain, remained confined to the vicinity of the inoculation site. The rpfF and rpfC mutants formed large incoherent aggregates in the xylem vessels that might interfere with upward movement of the bacterium within the plant. Both mutants also formed extended aggregates under in vitro conditions, whereas the wild-type strain formed microcolonies. Expression levels of putative virulence genes in planta were substantially reduced within 48 h after inoculation with the QS mutants when compared with the wild-type. The results presented indicate that an optimal DSF concentration is crucial for successful colonization and virulence of Xhp in pelargonium.

  18. Quorum Sensing Inhibiting Activity of Streptomyces coelicoflavus Isolated from Soil.

    Science.gov (United States)

    Hassan, Ramadan; Shaaban, Mona I; Abdel Bar, Fatma M; El-Mahdy, Areej M; Shokralla, Shadi

    2016-01-01

    Quorum sensing (QS) systems communicate bacterial population and stimulate microbial pathogenesis through signaling molecules. Inhibition of QS signals potentially suppresses microbial infections. Antimicrobial properties of Streptomyces have been extensively studied, however, less is known about quorum sensing inhibitory (QSI) activities of Streptomyces. This study explored the QSI potential of Streptomyces isolated from soil. Sixty-five bacterial isolates were purified from soil samples with morphological characteristics of Streptomyces. The three isolates: S6, S12, and S17, exhibited QSI effect by screening with the reporter, Chromobacterium violaceum. Isolate S17 was identified as Streptomyces coelicoflavus by sequencing of the hypervariable regions (V1-V6) of 16S rRNA and was assigned gene bank number KJ855087. The QSI effect of the cell-free supernatant of isolate S17 was not abolished by proteinase K indicating the non-enzymatic activity of QSI components of S17. Three major compounds were isolated and identified, using spectroscopic techniques (1D, 2D NMR, and Mass spectrometry), as behenic acid (docosanoic acid), borrelidin, and 1H-pyrrole-2-carboxylic acid. 1H-pyrrole-2-carboxylic acid inhibited QS and related virulence factors of Pseudomonas aeruginosa PAO1 including; elastase, protease, and pyocyanin without affecting Pseudomonas viability. At the molecular level, 1H-pyrrole-2-carboxylic acid suppressed the expression of QS genes (lasI, lasR, lasA, lasB, rhlI, rhlR, pqsA, and pqsR). Moreover, QSI activity of S17 was assessed under different growth conditions and ISP2 medium supplemented with glucose 0.4% w/v and adjusted at pH 7, showed the highest QSI action. In conclusion, 1H-pyrrole-2-carboxylic acid, one of the major metabolites of Streptomyces isolate S17, inhibited QS and virulence determinants of P. aeruginosa PAO1. The findings of the study open the scope to exploit the in vivo efficacy of this active molecule as anti-pathogenic and anti

  19. Quorum sensing inhibiting activity of Streptomyces coelicoflavus isolated from soil

    Directory of Open Access Journals (Sweden)

    Hassan eRamadan

    2016-05-01

    Full Text Available Quorum sensing (QS systems communicate bacterial population and stimulate microbial pathogenesis through signaling molecules. Inhibition of QS signals potentially suppresses microbial infections. Antimicrobial properties of Streptomyces have been extensively studied, however, less is known about quorum sensing inhibitory (QSI activities of Streptomyces. This study explored the QSI potential of Streptomyces isolated from soil. Sixty-five bacterial isolates were purified from soil samples with morphological characteristics of Streptomyces. The three isolates: S6, S12, and S17, exhibited QSI effect by screening with the reporter, Chromobacterium violaceum. Isolate S17 was identified as Streptomyces coelicoflavus by sequencing of the hypervariable regions (V1-V6 of 16S rRNA and was assigned gene bank number KJ855087. The QSI effect of the cell-free supernatant of isolate S17 was not abolished by proteinase K indicating the non-enzymatic activity of QSI components of S17. Three major compounds were isolated and identified, using spectroscopic techniques (1D, 2D NMR and Mass spectrometry, as behenic acid (docosanoic acid, borrelidin and 1H-pyrrole-2-carboxylic acid. 1H-pyrrole-2-carboxylic acid inhibited QS and related virulence factors of Pseudomonas aeruginosa PAO1 including; elastase, protease and pyocyanin without affecting Pseudomonas viability. At the molecular level, 1H-pyrrole-2-carboxylic acid suppressed the expression of QS genes (lasI, lasR, lasA, lasB, rhlI, rhlR, pqsA and pqsR. Moreover, QSI activity of S17 was assessed under different growth conditions and ISP2 medium supplemented with glucose 0.4% w/v and adjusted at pH 7, showed the highest QSI action. In conclusion, 1H-pyrrole-2-carboxylic acid, one of the major metabolites of Streptomyces isolate S17, inhibited QS and virulence determinants of P. aeruginosa PAO1. The findings of the study open the scope to exploit the in vivo efficacy of this active molecule as anti-pathogenic and

  20. Quorum Sensing in Some Representative Species of Halomonadaceae

    Directory of Open Access Journals (Sweden)

    Inmaculada Llamas

    2013-03-01

    Full Text Available Cell-to-cell communication, or quorum-sensing (QS, systems are employed by bacteria for promoting collective behaviour within a population. An analysis to detect QS signal molecules in 43 species of the Halomonadaceae family revealed that they produced N-acyl homoserine lactones (AHLs, which suggests that the QS system is widespread throughout this group of bacteria. Thin-layer chromatography (TLC analysis of crude AHL extracts, using Agrobacterium tumefaciens NTL4 (pZLR4 as biosensor strain, resulted in different profiles, which were not related to the various habitats of the species in question. To confirm AHL production in the Halomonadaceae species, PCR and DNA sequencing approaches were used to study the distribution of the luxI-type synthase gene. Phylogenetic analysis using sequence data revealed that 29 of the species studied contained a LuxI homolog. Phylogenetic analysis showed that sequences from Halomonadaceae species grouped together and were distinct from other members of the Gammaproteobacteria and also from species belonging to the Alphaproteobacteria and Betaproteobacteria.

  1. Drosophila host model reveals new enterococcus faecalis quorum-sensing associated virulence factors.

    Science.gov (United States)

    Teixeira, Neuza; Varahan, Sriram; Gorman, Matthew J; Palmer, Kelli L; Zaidman-Remy, Anna; Yokohata, Ryoji; Nakayama, Jiro; Hancock, Lynn E; Jacinto, António; Gilmore, Michael S; de Fátima Silva Lopes, Maria

    2013-01-01

    Enterococcus faecalis V583 is a vancomycin-resistant clinical isolate which belongs to the hospital-adapted clade, CC2. This strain harbours several factors that have been associated with virulence, including the fsr quorum-sensing regulatory system that is known to control the expression of GelE and SprE proteases. To discriminate between genes directly regulated by Fsr, and those indirectly regulated as the result of protease expression or activity, we compared gene expression in isogenic mutants of V583 variously defective in either Fsr quorum sensing or protease expression. Quorum sensing was artificially induced by addition of the quorum signal, GBAP, exogenously in a controlled manner. The Fsr regulon was found to be restricted to five genes, gelE, sprE, ef1097, ef1351 and ef1352. Twelve additional genes were found to be dependent on the presence of GBAP-induced proteases. Induction of GelE and SprE by GBAP via Fsr resulted in accumulation of mRNA encoding lrgAB, and this induction was found to be lytRS dependent. Drosophila infection was used to discern varying levels of toxicity stemming from mutations in the fsr quorum regulatory system and the genes that it regulates, highlighting the contribution of LrgAB and bacteriocin EF1097 to infection toxicity. A contribution of SprE to infection toxicity was also detected. This work brought to light new players in E. faecalis success as a pathogen and paves the way for future studies on host tolerance mechanisms to infections caused by this important nosocomial pathogen.

  2. RNAseq-based Transcriptome Analysis of Burkholderia glumae Quorum Sensing.

    Science.gov (United States)

    Kim, Sunyoung; Park, Jungwook; Kim, Ji Hyeon; Lee, Jongyun; Bang, Bongjun; Hwang, Ingyu; Seo, Young-Su

    2013-09-01

    Burkholderia glumae causes rice grain rot and sheath rot by producing toxoflavin, the expression of which is regulated by quorum sensing (QS). The QS systems of B. glumae rely on N-octanoyl homoserine lactone, synthesized by TofI and its cognate receptor TofR, to activate the genes for toxoflavin biosynthesis and an IclR-type transcriptional regulator gene, qsmR. To understand genome-wide transcriptional profiling of QS signaling, we employed RNAseq of the wild-type B. glumae BGR1 with QS-defective mutant, BGS2 (BGR1 tofI::Ω) and QS-dependent transcriptional regulator mutant, BGS9 (BGR1 qsmR::Ω). A comparison of gene expression profiling among the wild-type BGR1 and the two mutants before and after QS onset as well as gene ontology (GO) enrichment analysis from differential expressed genes (DEGs) revealed that genes involved in motility were highly enriched in TofI-dependent DEGs, whereas genes for transport and DNA polymerase were highly enriched in QsmR-dependent DEGs. Further, a combination of pathways with these DEGs and phenotype analysis of mutants pointed to a couple of metabolic processes, which are dependent on QS in B. glumae, that were directly or indirectly related with bacterial motility. The consistency of observed bacterial phenotypes with GOs or metabolic pathways in QS-regulated genes implied that integration RNAseq with GO enrichment or pathways would be useful to study bacterial physiology and phenotypes.

  3. Local and global consequences of flow on bacterial quorum sensing.

    Science.gov (United States)

    Kim, Minyoung Kevin; Ingremeau, François; Zhao, Aishan; Bassler, Bonnie L; Stone, Howard A

    2016-01-11

    Bacteria use a chemical communication process called quorum sensing (QS) to control collective behaviours such as pathogenesis and biofilm formation(1,2). QS relies on the production, release and group-wide detection of signal molecules called autoinducers. To date, studies of bacterial pathogenesis in well-mixed cultures have revealed virulence factors and the regulatory circuits controlling them, including the overarching role of QS(3). Although flow is ubiquitous to nearly all living systems(4), much less explored is how QS influences pathogenic traits in scenarios that mimic host environments, for example, under fluid flow and in complex geometries. Previous studies(5-7) have shown that sufficiently strong flow represses QS. Nonetheless, it is not known how QS functions under constant or intermittent flow, how it varies within biofilms or as a function of position along a confined flow, or how surface topography (grooves, crevices, pores) influence QS-mediated communication. We explore these questions using two common pathogens, Staphylococcus aureus and Vibrio cholerae. We identify conditions where flow represses QS and other conditions where QS is activated despite flow, including characterizing geometric and topographic features that influence the QS response. Our studies highlight that, under flow, genetically identical cells do not exhibit phenotypic uniformity with respect to QS in space and time, leading to complex patterns of pathogenesis and colonization. Understanding the ramifications of spatially and temporally non-uniform QS responses in realistic environments will be crucial for successful deployment of synthetic pro- and anti-QS strategies.

  4. Quorum sensing in CD4+ T cell homeostasis: a hypothesis and a model.

    Directory of Open Access Journals (Sweden)

    Afonso R.M. Almeida

    2012-05-01

    Full Text Available Homeostasis of lymphocyte numbers is believed to be due to competition between cellular populations for a common niche of restricted size, defined by the combination of interactions and trophic factors required for cell survival. Here we propose a new mechanism: homeostasis of lymphocyte numbers could also be achieved by the ability of lymphocytes to perceive the density of their own populations. Such a mechanism would be reminiscent of the primordial quorum sensing systems used by bacteria, in which some bacteria sense the accumulation of bacterial metabolites secreted by other elements of the population, allowing them to count the number of cells present and adapt their growth accordingly. We propose that homeostasis of CD4+ T cell numbers may occur via a quorum-sensing-like mechanism, where IL-2 is produced by activated CD4+ T cells and sensed by a population of CD4+ Treg cells that expresses the high-affinity IL-2Rα-chain and can regulate the number of activated IL-2-producing CD4+ T cells and the total CD4+T cell population. In other words, CD4+ T cell populations can restrain their growth by monitoring the number of activated cells, thus preventing uncontrolled lymphocyte proliferation during immune responses. We hypothesize that malfunction of this quorum-sensing mechanism may lead to uncontrolled T cell activation and autoimmunity. Finally, we present a mathematical model that describes the role of IL-2 and quorum-sensing mechanisms in CD4+ T cell homeostasis during an immune response.

  5. Gene dosage compensation calibrates four regulatory RNAs to control Vibrio cholerae quorum sensing

    DEFF Research Database (Denmark)

    Svenningsen, Sine L; Tu, Kimberly C; Bassler, Bonnie L

    2009-01-01

    Quorum sensing is a mechanism of cell-to-cell communication that allows bacteria to coordinately regulate gene expression in response to changes in cell-population density. At the core of the Vibrio cholerae quorum-sensing signal transduction pathway reside four homologous small RNAs (sRNAs), named...

  6. A mathematical model of quorum sensing regulated EPS production in biofilm communities.

    Science.gov (United States)

    Frederick, Mallory R; Kuttler, Christina; Hense, Burkhard A; Eberl, Hermann J

    2011-04-10

    Biofilms are microbial communities encased in a layer of extracellular polymeric substances (EPS). The EPS matrix provides several functional purposes for the biofilm, such as protecting bacteria from environmental stresses, and providing mechanical stability. Quorum sensing is a cell-cell communication mechanism used by several bacterial taxa to coordinate gene expression and behaviour in groups, based on population densities. We mathematically model quorum sensing and EPS production in a growing biofilm under various environmental conditions, to study how a developing biofilm impacts quorum sensing, and conversely, how a biofilm is affected by quorum sensing-regulated EPS production. We investigate circumstances when using quorum-sensing regulated EPS production is a beneficial strategy for biofilm cells. We find that biofilms that use quorum sensing to induce increased EPS production do not obtain the high cell populations of low-EPS producers, but can rapidly increase their volume to parallel high-EPS producers. Quorum sensing-induced EPS production allows a biofilm to switch behaviours, from a colonization mode (with an optimized growth rate), to a protection mode. A biofilm will benefit from using quorum sensing-induced EPS production if bacteria cells have the objective of acquiring a thick, protective layer of EPS, or if they wish to clog their environment with biomass as a means of securing nutrient supply and outcompeting other colonies in the channel, of their own or a different species.

  7. Attenuation of quorum sensing-regulated behaviour by Tinospora cordifolia extract & identification of its active constituents

    OpenAIRE

    Viraj C Gala; Nithya R John; Bhagwat, Ashok M.; Ajit G Datar; Kharkar, Prashant S.; Desai, Krutika B.

    2016-01-01

    Background & objectives: The pathogenicity of the nosocomial pathogens, Pseudomonas aeruginosa and Acinetobacter baumannii is regulated by their quorum sensing (QS) systems. The objective of the present study was to examine the effect of the cold ethyl acetate extract of Tinospora cordifolia stem on virulence and biofilm development in the wild type and clinical strains of P. aeruginosa and A. baumannii. The study was further aimed to identify the probable active constituents in the plant ext...

  8. Identification of Four New agr Quorum Sensing-Interfering Cyclodepsipeptides from a Marine Photobacterium

    DEFF Research Database (Denmark)

    Kjærulff, Louise; Nielsen, Anita; Månsson, Maria

    2013-01-01

    , including the known pyrrothine antibiotic holomycin and a wide range of peptides, from diketopiperazines to cyclodepsipeptides of 500–900 Da. Purification of components from the pellet fraction led to the isolation and structure elucidation of four new cyclodepsipeptides, ngercheumicin F, G, H, and I....... The ngercheumicins interfered with expression of virulence genes known to be controlled by the agr quorum sensing system of Staphylococcus aureus, although to a lesser extent than the previously described solonamides from the same strain of Photobacterium....

  9. Genome-wide dissection of the quorum sensing signalling pathway in Trypanosoma brucei.

    Science.gov (United States)

    Mony, Binny M; MacGregor, Paula; Ivens, Alasdair; Rojas, Federico; Cowton, Andrew; Young, Julie; Horn, David; Matthews, Keith

    2014-01-30

    The protozoan parasites Trypanosoma brucei spp. cause important human and livestock diseases in sub-Saharan Africa. In mammalian blood, two developmental forms of the parasite exist: proliferative 'slender' forms and arrested 'stumpy' forms that are responsible for transmission to tsetse flies. The slender to stumpy differentiation is a density-dependent response that resembles quorum sensing in microbial systems and is crucial for the parasite life cycle, ensuring both infection chronicity and disease transmission. This response is triggered by an elusive 'stumpy induction factor' (SIF) whose intracellular signalling pathway is also uncharacterized. Laboratory-adapted (monomorphic) trypanosome strains respond inefficiently to SIF but can generate forms with stumpy characteristics when exposed to cell-permeable cAMP and AMP analogues. Exploiting this, we have used a genome-wide RNA interference library screen to identify the signalling components driving stumpy formation. In separate screens, monomorphic parasites were exposed to 8-(4-chlorophenylthio)-cAMP (pCPT-cAMP) or 8-pCPT-2'-O-methyl-5'-AMP to select cells that were unresponsive to these signals and hence remained proliferative. Genome-wide Ion Torrent based RNAi target sequencing identified cohorts of genes implicated in each step of the signalling pathway, from purine metabolism, through signal transducers (kinases, phosphatases) to gene expression regulators. Genes at each step were independently validated in cells naturally capable of stumpy formation, confirming their role in density sensing in vivo. The putative RNA-binding protein, RBP7, was required for normal quorum sensing and promoted cell-cycle arrest and transmission competence when overexpressed. This study reveals that quorum sensing signalling in trypanosomes shares similarities to fundamental quiescence pathways in eukaryotic cells, its components providing targets for quorum-sensing interference-based therapeutics.

  10. Quorum sensing determines the choice of antiphage defense strategy in Vibrio anguillarum

    DEFF Research Database (Denmark)

    Tan, Demeng; Svenningsen, Sine Lo; Middelboe, Mathias

    2015-01-01

    of the outcome of phage-bacterial encounters in the fish pathogen Vibrio anguillarum is bacterial cell-cell communication, known as quorum sensing. Specifically, V. anguillarum PF430-3 cells locked in the low-cell-density state (ΔvanT mutant) express high levels of the phage receptor OmpK, resulting in a high...... susceptibility to phage KVP40, but achieve protection from infection by enhanced biofilm formation. By contrast, cells locked in the high-cell-density state (ΔvanΟ mutant) are almost completely unsusceptible due to quorum-sensing-mediated downregulation of OmpK expression. The phenotypes of the two quorum-sensing......-acylhomoserine lactone quorum-sensing signals in the culture medium, and (iii) survives mainly by one of these two defense mechanisms, rather than by genetic mutation to phage resistance. Taken together, our results demonstrate that V. anguillarum employs quorum-sensing information to choose between two complementary...

  11. Bacterial quorum sensing: its role in virulence and possibilities for its control.

    Science.gov (United States)

    Rutherford, Steven T; Bassler, Bonnie L

    2012-11-01

    Quorum sensing is a process of cell-cell communication that allows bacteria to share information about cell density and adjust gene expression accordingly. This process enables bacteria to express energetically expensive processes as a collective only when the impact of those processes on the environment or on a host will be maximized. Among the many traits controlled by quorum sensing is the expression of virulence factors by pathogenic bacteria. Here we review the quorum-sensing circuits of Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, and Vibrio cholerae. We outline these canonical quorum-sensing mechanisms and how each uniquely controls virulence factor production. Additionally, we examine recent efforts to inhibit quorum sensing in these pathogens with the goal of designing novel antimicrobial therapeutics.

  12. The impact of quorum sensing and swarming motility on Pseudomonas aeruginosa biofilm formation is nutritionally conditional

    DEFF Research Database (Denmark)

    Shrout, J.D.; Chopp, D.L.; Just, C.L.

    2006-01-01

    The role of quorum sensing in Pseudomonas aeruginosa biofilm formation is unclear. Some researchers have shown that quorum sensing is important for biofilm development, while others have indicated it has little or no role. In this study, the contribution of quorum sensing to biofilm development...... was found to depend upon the nutritional environment. Depending upon the carbon source, quorum-sensing mutant strains (lasIrhlI and lasRrhlR) either exhibited a pronounced defect early in biofilm formation or formed biofilms identical to the wild-type strain. Quorum sensing was then shown to exert its...... nutritionally conditional control of biofilm development through regulation of swarming motility. Examination of pilA and fliM mutant strains further supported the role of swarming motility in biofilm formation. These data led to a model proposing that the prevailing nutritional conditions dictate...

  13. Hybrid Quadrupole-Orbitrap mass spectrometry for quantitative measurement of quorum sensing inhibition.

    Science.gov (United States)

    Todd, Daniel A; Zich, David B; Ettefagh, Keivan A; Kavanaugh, Jeffrey S; Horswill, Alexander R; Cech, Nadja B

    2016-08-01

    Drug resistant bacterial infections cause significant morbidity and mortality worldwide, and new strategies are needed for the treatment of these infections. The anti-virulence approach, which targets non-essential virulence factors in bacteria, has been proposed as one way to combat the problem of antibiotic resistance. Virulence in methicillin-resistant Staphylococcus aureus (MRSA) and many other Gram-positive bacterial pathogens is controlled by the quorum sensing system. Thus, there is excellent therapeutic potential for compounds that target this system. With this project, we have developed and validated a novel approach for measuring quorum sensing inhibition in vitro. Ultraperformance liquid chromatography coupled to mass spectrometry (UPLC-MS) was employed to directly measure one of the important outputs of the quorum sensing system in MRSA, auto-inducing peptide I (AIP I) in bacterial cultures. The method for AIP detection was validated and demonstrated limits of detection and quantification of range of 0.0035μM and 0.10μM, respectively. It was shown that the known quorum sensing inhibitor ambuic acid inhibited AIP I production by a clinically relevant strain of MRSA, with an IC50 value of 2.6±0.2μM. The new method performed similarly to previously published methods using GFP reporter assays, but has the advantage of being applicable without the need for engineering of a reporter strain. Additionally, the mass spectrometry-based method could be applicable in situations where interference by the inhibitor prevents the application of fluorescence-based methods.

  14. Lack of AHL-based quorum sensing in Pseudomonas fluorescens isolated from milk

    Directory of Open Access Journals (Sweden)

    Maurilio L. Martins

    2014-09-01

    Full Text Available Numerous bacteria coordinate gene expression in response to small signalling molecules in many cases known as acylhomoserine lactones (AHLs, which accumulate as a function of cell density in a process known as quorum sensing. This work aimed to determine if phenotypes that are important to define microbial activity in foods such as biofilm formation, swarming motility and proteolytic activity of two Pseudomonas fluorescens strains, isolated from refrigerated raw milk, are influenced by AHL molecules. The tested P. fluorescens strains did not produce AHL molecules in none of the evaluated media. We found that biofilm formation was dependent on the culture media, but it was not influenced by AHLs. Our results indicate that biofilm formation, swarming motility and proteolytic activity of the tested P. fluorescens strains are not regulated by acyl-homoserine lactones. It is likely that AHL-dependent quorum sensing system is absent from these strains.

  15. Lack of AHL-based quorum sensing in Pseudomonas fluorescens isolated from milk

    Science.gov (United States)

    Martins, Maurilio L.; Pinto, Uelinton M.; Riedel, Kathrin; Vanetti, Maria C.D.; Mantovani, Hilário C.; de Araújo, Elza F.

    2014-01-01

    Numerous bacteria coordinate gene expression in response to small signalling molecules in many cases known as acylhomoserine lactones (AHLs), which accumulate as a function of cell density in a process known as quorum sensing. This work aimed to determine if phenotypes that are important to define microbial activity in foods such as biofilm formation, swarming motility and proteolytic activity of two Pseudomonas fluorescens strains, isolated from refrigerated raw milk, are influenced by AHL molecules. The tested P. fluorescens strains did not produce AHL molecules in none of the evaluated media. We found that biofilm formation was dependent on the culture media, but it was not influenced by AHLs. Our results indicate that biofilm formation, swarming motility and proteolytic activity of the tested P. fluorescens strains are not regulated by acyl-homoserine lactones. It is likely that AHL-dependent quorum sensing system is absent from these strains. PMID:25477941

  16. Repellent and Anti-quorum Sensing Activity of Six Aromatic Plants Occurring in Colombia.

    Science.gov (United States)

    Cervantes-Ceballos, Leonor; Caballero-Gallardo, Karina; Olivero-Verbel, Jesus

    2015-10-01

    Essential oils (EOs) are widely used as biopesticides and to control bacterial infections. This study describes the ability of six EOs isolated from plants cultivated in Colombia to perform as repellents against Ulomoides dermestoides and as quorum sensing (QS) inhibitors. EOs from Aloysia triphylla, Cymbopogon nardus, Lippia origanoides, Hyptis suaveolens, Swinglea glutinosa and Eucalyptus globulus were repellents classified as Class IV, IV, IV, III, II, and II, respectively, whereas the commercial repellent IR3535 only reached Class II after 2 h exposure. All EOs presented small, but significant inhibitory properties against the QS system in Escherichia coli (pJBA132) at 25 μg/mL after 4 h exposure. These data suggest evaluated EOs from Colombia are sustainable, promising new sources of natural repellents and could be important as anti-quorum sensing molecules.

  17. Dynamical quorum sensing: Population density encoded in cellular dynamics

    Science.gov (United States)

    De Monte, Silvia; d'Ovidio, Francesco; Danø, Sune; Sørensen, Preben Graae

    2007-01-01

    Mutual synchronization by exchange of chemicals is a mechanism for the emergence of collective dynamics in cellular populations. General theories exist on the transition to coherence, but no quantitative, experimental demonstration has been given. Here, we present a modeling and experimental analysis of cell-density-dependent glycolytic oscillations in yeast. We study the disappearance of oscillations at low cell density and show that this phenomenon occurs synchronously in all cells and not by desynchronization, as previously expected. This study identifies a general scenario for the emergence of collective cellular oscillations and suggests a quorum-sensing mechanism by which the cell density information is encoded in the intracellular dynamical state. PMID:18003917

  18. Impact of quorum sensing on the quality of fermented foods

    DEFF Research Database (Denmark)

    Johansen, Pernille; Jespersen, Lene

    2017-01-01

    The quality of fermented food highly dependents on the microorganisms involved, their metabolic activities and interactions. Recently, focus has been on quorum sensing (QS) being a cell density-dependent mechanism allowing adaptive responses. Specific QS molecules in prokaryotes and eukaryotes......, respectively, mediate the transcriptional changes. For food-borne microorganisms QS regulated traits include biofilm formation, acid stress tolerance, bacteriocin production, competence, adhesion, morphological switches and oriented growth. QS has been reported for microorganisms involved in the production...... of a number of different fermented foods such as fermented vegetables, sourdough, dairy products, wine, and so on suggesting that QS plays a role in the fermentation of these fermented foods....

  19. Spatial dispersal of bacterial colonies induces a dynamical transition from local to global quorum sensing

    Science.gov (United States)

    Yusufaly, Tahir I.; Boedicker, James Q.

    2016-12-01

    Bacteria communicate using external chemical signals called autoinducers (AI) in a process known as quorum sensing (QS). QS efficiency is reduced by both limitations of AI diffusion and potential interference from neighboring strains. There is thus a need for predictive theories of how spatial community structure shapes information processing in complex microbial ecosystems. As a step in this direction, we apply a reaction-diffusion model to study autoinducer signaling dynamics in a single-species community as a function of the spatial distribution of colonies in the system. We predict a dynamical transition between a local quorum sensing (LQS) regime, with the AI signaling dynamics primarily controlled by the local population densities of individual colonies, and a global quorum sensing (GQS) regime, with the dynamics being dependent on collective intercolony diffusive interactions. The crossover between LQS to GQS is intimately connected to a trade-off between the signaling network's latency, or speed of activation, and its throughput, or the total spatial range over which all the components of the system communicate.

  20. 细菌群体感应研究进展%Research Progress on Bacteria Quorum Sensing

    Institute of Scientific and Technical Information of China (English)

    许玉彬; 张颖; 王淼; 王少伟; 王刚

    2013-01-01

    从细菌群体感应系统的分类、群体感应与农业生产及生物薄膜形成的关系等方面对近年来细菌群体感应的研究进展进行综述,并对群体感应研究的前景进行展望,以期为细菌群体感应在农业生产特别是植物病害防治中的应用研究提供参考。%T he classification of the quorum sensing system in the gram-negative and gram-positive bacteria ,the relationships between bacterial quorum sensing and agriculture manufacture as well as biofilm formation were reviewed .The prospect of the quorum sensing research in the bacteria w as also discussed .

  1. The Vibrio campbellii quorum sensing signals have a different impact on virulence of the bacterium towards different crustacean hosts.

    Science.gov (United States)

    Pande, Gde Sasmita Julyantoro; Natrah, Fatin Mohd Ikhsan; Sorgeloos, Patrick; Bossier, Peter; Defoirdt, Tom

    2013-12-27

    Pathogenic bacteria communicate with small signal molecules in a process called quorum sensing, and they often use different signal molecules to regulate virulence gene expression. Vibrio campbellii, one of the major pathogens of aquatic organisms, regulates virulence gene expression by a three channel quorum sensing system. Here we show that although they use a common signal transduction cascade, the signal molecules have a different impact on the virulence of the bacterium towards different hosts, i.e. the brine shrimp Artemia franciscana and the commercially important giant freshwater prawn Macrobrachium rosenbergii. These results suggest that the use of multiple types of signal molecules to regulate virulence gene expression is one of the features that allow bacteria to infect different hosts. Our findings emphasize that it is highly important to study the efficacy of quorum sensing inhibitors as novel biocontrol agents under conditions that are as close as possible to the clinical situation.

  2. The symbiotic biofilm of Sinorhizobium fredii SMH12, necessary for successful colonization and symbiosis of Glycine max cv Osumi, is regulated by Quorum Sensing systems and inducing flavonoids via NodD1.

    Directory of Open Access Journals (Sweden)

    Francisco Pérez-Montaño

    Full Text Available Bacterial surface components, especially exopolysaccharides, in combination with bacterial Quorum Sensing signals are crucial for the formation of biofilms in most species studied so far. Biofilm formation allows soil bacteria to colonize their surrounding habitat and survive common environmental stresses such as desiccation and nutrient limitation. This mode of life is often essential for survival in bacteria of the genera Mesorhizobium, Sinorhizobium, Bradyrhizobium, and Rhizobium. The role of biofilm formation in symbiosis has been investigated in detail for Sinorhizobium meliloti and Bradyrhizobium japonicum. However, for S. fredii this process has not been studied. In this work we have demonstrated that biofilm formation is crucial for an optimal root colonization and symbiosis between S. fredii SMH12 and Glycine max cv Osumi. In this bacterium, nod-gene inducing flavonoids and the NodD1 protein are required for the transition of the biofilm structure from monolayer to microcolony. Quorum Sensing systems are also required for the full development of both types of biofilms. In fact, both the nodD1 mutant and the lactonase strain (the lactonase enzyme prevents AHL accumulation are defective in soybean root colonization. The impairment of the lactonase strain in its colonization ability leads to a decrease in the symbiotic parameters. Interestingly, NodD1 together with flavonoids activates certain quorum sensing systems implicit in the development of the symbiotic biofilm. Thus, S. fredii SMH12 by means of a unique key molecule, the flavonoid, efficiently forms biofilm, colonizes the legume roots and activates the synthesis of Nod factors, required for successfully symbiosis.

  3. Coprinopsis cinerea intracellular lactonases hydrolyze quorum sensing molecules of Gram-negative bacteria.

    Science.gov (United States)

    Stöckli, Martina; Lin, Chia-Wei; Sieber, Ramon; Plaza, David F; Ohm, Robin A; Künzler, Markus

    2017-05-01

    Biofilm formation on fungal hyphae and production of antifungal molecules are strategies of bacteria in their competition with fungi for nutrients. Since these strategies are often coordinated and under control of quorum sensing by the bacteria, interference with this bacterial communication system can be used as a counter-strategy by the fungi in this competition. Hydrolysis of N-acyl-homoserine lactones (HSL), a quorum sensing molecule used by Gram-negative bacteria, by fungal cultures has been demonstrated. However, the enzymes that are responsible for this activity, have not been identified. In this study, we identified and characterized two paralogous HSL hydrolyzing enzymes from the coprophilous fungus Coprinopsis cinerea. The C. cinerea HSL lactonases belong to the metallo-β-lactamase family and show sequence homology to and a similar biochemical activity as the well characterized lactonase AiiA from Bacillus thuringiensis. We show that the fungal lactonases, similar to the bacterial enzymes, are kept intracellularly and act as a sink for the bacterial quorum sensing signals both in C. cinerea and in Saccharomyces cerevisiae expressing C. cinerea lactonases, due to the ability of these signal molecules to diffuse over the fungal cell wall and plasma membrane. The two isogenes coding for the C. cinerea HSL lactonases are arranged in the genome as a tandem repeat and expressed preferentially in vegetative mycelium. The occurrence of orthologous genes in genomes of other basidiomycetes appears to correlate with a saprotrophic lifestyle. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Rule-based regulatory and metabolic model for Quorum sensing in P. aeruginosa.

    Science.gov (United States)

    Schaadt, Nadine S; Steinbach, Anke; Hartmann, Rolf W; Helms, Volkhard

    2013-08-21

    In the pathogen P. aeruginosa, the formation of virulence factors is regulated via Quorum sensing signaling pathways. Due to the increasing number of strains that are resistant to antibiotics, there is a high interest to develop novel antiinfectives. In the combat of resistant bacteria, selective blockade of the bacterial cell-to-cell communication (Quorum sensing) has gained special interest as anti-virulence strategy. Here, we modeled the las, rhl, and pqs Quorum sensing systems by a multi-level logical approach to analyze how enzyme inhibitors and receptor antagonists effect the formation of autoinducers and virulence factors. Our rule-based simulations fulfill the behavior expected from literature considering the external level of autoinducers. In the presence of PqsBCD inhibitors, the external HHQ and PQS levels are indeed clearly reduced. The magnitude of this effect strongly depends on the inhibition level. However, it seems that the pyocyanin pathway is incomplete. To match experimental observations we suggest a modified network topology in which PqsE and PqsR acts as receptors and an autoinducer as ligand that up-regulate pyocyanin in a concerted manner. While the PQS biosynthesis is more appropriate as target to inhibit the HHQ and PQS formation, blocking the receptor PqsR that regulates the biosynthesis reduces the pyocyanin level stronger.

  5. Autocrine Signaling and Quorum Sensing: Extreme Ends of a Common Spectrum.

    Science.gov (United States)

    Doğaner, Berkalp A; Yan, Lawrence K Q; Youk, Hyun

    2016-04-01

    'Secrete-and-sense cells' can communicate by secreting a signaling molecule while also producing a receptor that detects the molecule. The cell can potentially 'talk' to itself ('self-communication') or talk to neighboring cells with the same receptor ('neighbor communication'). The predominant forms of secrete-and-sense cells are self-communicating 'autocrine cells', which are largely found in animals, and neighbor-communicating 'quorum sensing cells', which are mostly associated with bacteria. While assumed to function independently of one another, recent studies have discovered quorum-sensing organs and autocrine-signaling microbes. Moreover, similar types of genetic circuit control many autocrine and quorum-sensing cells. Here, we outline these recent findings and explain how autocrine and quorum sensing are two sides of a many-sided 'dice' created by the versatile secrete-and-sense cell.

  6. Identification of Pathways Critical to Quorum Sensing and Virulence Induction

    Energy Technology Data Exchange (ETDEWEB)

    Ognibene, Ted J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Young, N. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Holtz-Morris, A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Daley, P. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2009-02-27

    Quorum sensing is a mode of intercellular communication between bacteria that allows them to collectively regulate behavior such as virulence, sporulation, motility and biofilm formation. It is mediated by bacterially synthesized, diffusible, signaling molecules (autoinducers) that increase in concentration as a bacterial population expands until a critical threshold concentration is reached. However, in most bacterial species that produce autoinducer molecules, the physiologic concentration of these molecules is unknown. Moreover, many bacterial species, including Y. pestis, produce an array of quorum sensing molecules and the physiologic concentration of each individual type of autoinducer molecule is not known. There is a need to accurately and precisely quantitate these molecules, as it may be that different types of autoinducer molecules have different effects on virulence in the bacterium. We focused our efforts on the construction of a platform to identify and quantitate autoinducer molecules using FTICR, 14C isotope labeling and accelerator mass spectrometry (AMS). Specifically, we focused on autoinducer-1 type molecules, acylhomoserine lactone (HSL), derived from S-adenosylmethionine (SAM).

  7. Flexible dynamics of two quorum-sensing coupled repressilators

    Science.gov (United States)

    Hellen, Edward H.; Volkov, Evgeny

    2017-02-01

    Genetic oscillators play important roles in cell life regulation. The regulatory efficiency usually depends strongly on the emergence of stable collective dynamic modes, which requires designing the interactions between genetic networks. We investigate the dynamics of two identical synthetic genetic repressilators coupled by an additional plasmid which implements quorum sensing (QS) in each network thereby supporting global coupling. In a basic genetic ring oscillator network in which three genes inhibit each other in unidirectional manner, QS stimulates the transcriptional activity of chosen genes providing for competition between inhibitory and stimulatory activities localized in those genes. The "promoter strength", the Hill cooperativity coefficient of transcription repression, and the coupling strength, i.e., parameters controlling the basic rates of genetic reactions, were chosen for extensive bifurcation analysis. The results are presented as a map of dynamic regimes. We found that the remarkable multistability of the antiphase limit cycle and stable homogeneous and inhomogeneous steady states exists over broad ranges of control parameters. We studied the antiphase limit cycle stability and the evolution of irregular oscillatory regimes in the parameter areas where the antiphase cycle loses stability. In these regions we observed developing complex oscillations, collective chaos, and multistability between regular limit cycles and complex oscillations over uncommonly large intervals of coupling strength. QS coupling stimulates the appearance of intrachaotic periodic windows with spatially symmetric and asymmetric partial limit cycles which, in turn, change the type of chaos from a simple antiphase character into chaos composed of pieces of the trajectories having alternating polarity. The very rich dynamics discovered in the system of two identical simple ring oscillators may serve as a possible background for biological phenotypic diversification, as well

  8. Synthetic analogs of bacterial quorum sensors

    Energy Technology Data Exchange (ETDEWEB)

    Iyer, Rashi (Los Alamos, NM); Ganguly, Kumkum (Los Alamos, NM); Silks, Louis A. (Los Alamos, NM)

    2011-12-06

    Bacterial quorum-sensing molecule analogs having the following structures: ##STR00001## and methods of reducing bacterial pathogenicity, comprising providing a biological system comprising pathogenic bacteria which produce natural quorum-sensing molecule; providing a synthetic bacterial quorum-sensing molecule having the above structures and introducing the synthetic quorum-sensing molecule into the biological system comprising pathogenic bacteria. Further is provided a method of targeted delivery of an antibiotic, comprising providing a synthetic quorum-sensing molecule; chemically linking the synthetic quorum-sensing molecule to an antibiotic to produce a quorum-sensing molecule-antibiotic conjugate; and introducing the conjugate into a biological system comprising pathogenic bacteria susceptible to the antibiotic.

  9. Identification and characterization of an N-acylhomoserine lactone-dependent quorum-sensing system in Pseudomonas putida strain IsoF

    DEFF Research Database (Denmark)

    Steidle, A.; Allesen-Holm, M.; Riedel, K.

    2002-01-01

    similar to proteins of the LuxI-LuxR family, an open reading frame (ORF) located in the intergenic region between ppuI and ppuR with significant homology to rsaL from Pseudomonas aeruginosa, and a gene, designated ppuA, present upstream of ppuR, the deduced amino acid sequence of which shows similarity...... to long-chain fatty acid coenzyme A ligases from various organisms. Using a transcriptional ppuA:luxAB fusion we demonstrate that expression of ppu,4 is AHL dependent. Furthermore, transcription of the AHL synthase ppuI is shown to be subject to quorum-sensing regulation, creating a positive feedback loop...

  10. Quorum Sensing Activity of Enterobacter asburiae Isolated from Lettuce Leaves

    Directory of Open Access Journals (Sweden)

    Kok-Gan Chan

    2013-10-01

    Full Text Available Bacterial communication or quorum sensing (QS is achieved via sensing of QS signaling molecules consisting of oligopeptides in Gram-positive bacteria and N-acyl homoserine lactones (AHL in most Gram-negative bacteria. In this study, Enterobacteriaceae isolates from Batavia lettuce were screened for AHL production. Enterobacter asburiae, identified by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS was found to produce short chain AHLs. High resolution triple quadrupole liquid chromatography mass spectrometry (LC/MS analysis of the E. asburiae spent supernatant confirmed the production of N-butanoyl homoserine lactone (C4-HSL and N–hexanoyl homoserine lactone (C6-HSL. To the best of our knowledge, this is the first report of AHL production by E. asburiae.

  11. Non-native acylated homoserine lactones reveal that LuxIR quorum sensing promotes symbiont stability.

    Science.gov (United States)

    Studer, Sarah V; Schwartzman, Julia A; Ho, Jessica S; Geske, Grant D; Blackwell, Helen E; Ruby, Edward G

    2014-08-01

    Quorum sensing, a group behaviour coordinated by a diffusible pheromone signal and a cognate receptor, is typical of bacteria that form symbioses with plants and animals. LuxIR-type N-acyl L-homoserine (AHL) quorum sensing is common in Gram-negative Proteobacteria, and many members of this group have additional quorum-sensing networks. The bioluminescent symbiont Vibrio fischeri encodes two AHL signal synthases: AinS and LuxI. AinS-dependent quorum sensing converges with LuxI-dependent quorum sensing at the LuxR regulatory element. Both AinS- and LuxI-mediated signalling are required for efficient and persistent colonization of the squid host, Euprymna scolopes. The basis of the mutualism is symbiont bioluminescence, which is regulated by both LuxI- and AinS-dependent quorum sensing, and is essential for maintaining a colonization of the host. Here, we used chemical and genetic approaches to probe the dynamics of LuxI- and AinS-mediated regulation of bioluminescence during symbiosis. We demonstrate that both native AHLs and non-native AHL analogues can be used to non-invasively and specifically modulate induction of symbiotic bioluminescence via LuxI-dependent quorum sensing. Our data suggest that the first day of colonization, during which symbiont bioluminescence is induced by LuxIR, is a critical period that determines the stability of the V. fischeri population once symbiosis is established.

  12. The ppuI-rsaL-ppuR quorum-sensing system regulates cellular motility, pectate lyase activity, and virulence in potato opportunistic pathogen Pseudomonas sp. StFLB209.

    Science.gov (United States)

    Kato, Taro; Morohoshi, Tomohiro; Someya, Nobutaka; Ikeda, Tsukasa

    2015-01-01

    Pseudomonas sp. StFLB209 was isolated from potato leaf as an N-acylhomoserine lactone (AHL)-producing bacterium and showed a close phylogenetic relationship with P. cichorii, a known plant pathogen. Although there are no reports of potato disease caused by pseudomonads in Japan, StFLB209 was pathogenic to potato leaf. In this study, we reveal the complete genome sequence of StFLB209, and show that the strain possesses a ppuI-rsaL-ppuR quorum-sensing system, the sequence of which shares a high similarity with that of Pseudomonas putida. Disruption of ppuI results in a loss of AHL production as well as remarkable reduction in motility. StFLB209 possesses strong pectate lyase activity and causes maceration on potato tuber and leaf, which was slightly reduced in the ppuI mutant. These results suggest that the quorum-sensing system is well conserved between StFLB209 and P. putida and that the system is essential for motility, full pectate lyase activity, and virulence in StFLB209.

  13. Quorum sensing mechanism in lactic acid bacteria

    Directory of Open Access Journals (Sweden)

    Hatice Yılmaz - Yıldıran

    2015-04-01

    and detection occurs as a consecution it is hard to understand their QS mechanism. In this review, connection between QS mechanism and some characteristics of lactic acid bacteria are evaluated such as concordance with its host, inhibition of pathogen development and colonization in gastrointestinal system, bacteriocin production, acid and bile resistance, adhesion to epithelium cells. Understanding QS mechanism of lactic acid bacteria will be useful to design metabiotics which is defined as novel probiotics.

  14. Inhibition of Quorum Sensing in Staphylococcus spp.

    Science.gov (United States)

    Brackman, Gilles; Coenye, Tom

    2015-01-01

    The Gram-positive, facultative anaerobic coccus-shaped bacteria of the genus Staphylococcus are among the most important causative agents of acute and chronic bacterial infections in humans as well as in animals. Treatment of Staphylococcus infections has become increasingly challenging due to the growing problem of antibiotic resistance. For this reason innovative antimicrobials with novel targets and modes of action are needed. Since the discovery that QS is used by Staphylococcus spp. to coordinate the expression of several genes involved in virulence, biofilm formation and pathogenicity, QS inhibition has gained increasing attention as an alternative anti-pathogenic strategy. A major advantage compared with antibiotic therapy is that QSIs are used in concentrations that do not affect bacterial growth. For this reason, it is expected that these compounds would exert less pressure towards the development of resistance. However, some important points still need to be addressed. Although several inhibitors have proven to be active antipathogenic agents in vitro and in several in vivo models, it is still unknown whether these compounds will also be useful in humans. Furthermore, several fundamental mechanisms by which the different QS systems in Staphylococcus spp. exert their regulatory functions and how they are inhibited by QSIs are still poorly understood. In order to achieve real-life applications with QSIs, these challenges should be addressed and more research will be needed. In this article, we will discuss the different QS systems present in Staphylococcus spp., how they are used to control virulence and biofilm formation and how they can be blocked.

  15. Dynamical quorum-sensing in oscillators coupled through an external medium

    Science.gov (United States)

    Schwab, David J.; Baetica, Ania; Mehta, Pankaj

    2012-11-01

    Many biological and physical systems exhibit population-density-dependent transitions to synchronized oscillations in a process often termed “dynamical quorum sensing”. Synchronization frequently arises through chemical communication via signaling molecules distributed through an external medium. We study a simple theoretical model for dynamical quorum sensing: a heterogenous population of limit-cycle oscillators diffusively coupled through a common medium. We show that this model exhibits a rich phase diagram with four qualitatively distinct physical mechanisms that can lead to a loss of coherent population-level oscillations, including a novel mechanism arising from effective time-delays introduced by the external medium. We derive a single pair of analytic equations that allow us to calculate phase boundaries as a function of population density and show that the model reproduces many of the qualitative features of recent experiments on Belousov-Zhabotinsky catalytic particles as well as synthetically engineered bacteria.

  16. Proteomics of the bacterial cross-talk by quorum sensing.

    Science.gov (United States)

    Di Cagno, Raffaella; De Angelis, Maria; Calasso, Maria; Gobbetti, Marco

    2011-01-01

    Words such as language and behavior are frequently used to depict "quorum sensing" (QS) in the literature. Simplifying the concept, language and cross-talk between bacteria, and between bacteria and animal or plants hosts determine the behavior (e.g., beneficial or pathogenic effects). Genomics and transcriptomics were the principal approaches used to study the multiple mechanisms of QS. Nevertheless, sequencing of genomes paved the way for another approach which consists on comparative and functional proteomics. This review aims at describing how the proteomic dictionary translates: (i) the languages (N-acyl-L-homoserine lactones, AHL; autoinducing peptide, AIP; autoinducer-2, AI-2) used by bacteria to communicate; (ii) signals of QS which induce various phenotypes (e.g., virulence, biofilm maturation); (iii) cross-talk between lactic acid bacteria within various food ecosystems (e.g. sourdough and fermented milk); (iv) probiotic messages at intra- and inter-species and interkingdom levels; and (v) words for quorum quenching (QQ). Proteomics is an indispensible discipline to elucidate the mechanisms of regulation of the multitude of language signals which diffuse through different microbial communities.

  17. Quorum sensing en la asociación beneficiosa de las bacterias con las plantas

    Directory of Open Access Journals (Sweden)

    Marcia M. Rojas Badía

    2012-06-01

    Full Text Available Título en ingles: Quorum sensing in beneficial plant-bacteria associations ResumenSe conoce que el quorum sensing es un atributo común de muchas especies bacterianas y que puede ser un carácter universal de las bacterias. Actualmente se están describiendo a un paso más rápido nuevas señales y nuevos sistemas de regulación por quorum sensing y se han desarrollado las investigaciones acerca de la comunicación célula-célula en bacterias basada en el mecanismo de quorum sensing. En los ambientes naturales existen muchas bacterias que viven juntas y utilizan varias clases de moléculas señales. Dentro de las señales especie específicas predominan las acilhomoserín lactonas (AHLs, pero ya se han descrito una amplia diversidad de moléculas involucradas en la señalización célula-célula. Numerosos bioensayos y sistemas sensores se han desarrollado para la detección, caracterización y cuantificación de las AHLs. Se han obtenido evidencias de la acción de estas moléculas señales en la colonización de la rizosfera, el swarming, las interacciones simbióticas y la capacidad de interrumpir el proceso de señalización de otras bacterias que convivan en el mismo ambiente. Todas estas potencialidades de las bacterias que involucran el mecanismo de quorum sensing, pudieran ser utilizadas para fortalecerla acción estimuladora del crecimiento vegetal y el control biológico de patógenos en los agroecosistemas sostenibles. Palabras clave: comunicación celular; PGPB; control biológico; moléculas señal AbstractThe quorum sensing is a common attribute in some bacterial species. Currently, several signals and new regulation systems are describing and the researchers are very interested in the cell-cell communication based on quorum sensing mechanism. In the natural environments several bacteria are living together, then several types of signal molecules are using. The acylhomoserines lactones (AHLs, are predominant, but a wide range

  18. Effect of solid retention time on membrane fouling in membrane bioreactor: from the perspective of quorum sensing and quorum quenching.

    Science.gov (United States)

    Yu, Huarong; Xu, Guoren; Qu, Fangshu; Li, Guibai; Liang, Heng

    2016-09-01

    Solid retention time (SRT) is one of the most important operational parameters in membrane bioreactor (MBR), which significantly influences membrane fouling. It is widely recognized that SRT mainly changes biomass characteristics, and then, influences membrane fouling. Effect of SRT on quorum sensing (QS) in MBR, which could also influence fouling by coordinating biofilm formation, has not been reported. In this study, fouling, QS, soluble microbial products (SMP), and extracellular polymer substances (EPS) in MBRs operated under SRTs of 4, 10, and 40 days were investigated. The results showed that as SRT increased, the abundance of quorum quenching (QQ) bacteria increased, the quorum signal degradation activity of activated sludge increased, the concentrations of signal molecules in MBR decreased, the excretion of SMP and EPS decreased, and thus membrane biofouling was alleviated. Therefore, besides altering the biomass physiochemical properties, SRT also changed the balance between QS and QQ in MBR, and in this way, influenced membrane biofouling.

  19. 具有群体感应系统微藻共栖细菌的筛选及抑藻活性的研究%SCREENING OF MICROALGAE ASSOCIATED BACTERIA WITH QUORUM SENSING SYSTEM AND THEIR ALGICIDAL ACTIVITY

    Institute of Scientific and Technical Information of China (English)

    徐鲁燕; 郑立; 韩笑天; 崔志松; 郭秀春; 李馨子

    2012-01-01

    以从海洋微藻中分离到的206株共栖细菌为材料,采用生物传感器法筛选具有群体感应系统的细菌,根据16SrRNA基因对它们进行了分子生物学鉴定和系统发育学分析。利用气相质谱联用法(GC.MS)检测群体感应信号分子酰基高丝氨酸内酯类化合物(AHLs)的种类;采用细胞活体荧光测定方法,研究了这类共栖细菌对微藻生长的抑制作用。结果表明,在分离到的206株微藻共栖细菌中有11株具有群体感应系统,它们分属于3类海洋细菌的系统分支:仪.Proteobacteria、y-Proteobacteria和Gram’细菌,通过GC.MS检测确定11株共栖细菌都含有信号分子C8.HSL,部分含有C6.HSL和C14-HSL,其中9株细菌具有抑藻活性,其代谢产物分别对东海原甲藻、棕囊藻、海链藻和赤潮异湾藻的生长具有不同程度的抑制作用。%Two hundred and six associated bacteria strains were isolated from marine microalgae. The bacteria with quorum sensing system were screened by biosensor method. And the identification and phylogenetic analysis of these bacteria were carried out by molecular method based on their 16S rRNA gene. Acylhomoserine lactones (AHLs), as the quorum sensing signals, were detected in the extracts of bacteria strains with quorum sensing system by gas chromatography mass spectrometry (GC-MS), as well as the algicidal activities were analyzed by viable cell fluorescence detection method. Results showed that 11 among the 206 strains had quorum sensing system and they belonged to three phylogenetic branches: a-Proteobacteria, y-Proteobacteria and Gram+ bacteria. GC-MS analysis showed that all of the 11 screened strains contained the quorum sensing signal of C8-HSL, and some of them also contained C6-HSL and C 14-HSL. The algicidal activity study showed that 9 strains had inhibition effects in different degrees against four red tide microalgae including Prorocentrum donghaiense

  20. Quorum-quenching limits quorum-sensing exploitation by signal-negative invaders

    Science.gov (United States)

    Tannières, Mélanie; Lang, Julien; Barnier, Claudie; Shykoff, Jacqui A.; Faure, Denis

    2017-01-01

    Some bacteria produce and perceive quorum-sensing (QS) signals that coordinate several behaviours, including the costly processes that are exoenzyme production and plasmid transfer. In the case of plasmid transfer, the emergence of QS signal-altered invaders and their policing are poorly documented. In Agrobacterium tumefaciens, the virulence Ti-plasmid encodes both synthesis and sensing of QS-signals, which promote its transfer from a donor to a recipient cell. Here, we reported that QS-altered A. tumefaciens mutants arose during experimental evolution. All showed improved growth compared to their ancestor. Genome sequencing revealed that, though some had lost the Ti-plasmid, most were defective for QS-signal synthesis and Ti-plasmid conjugation (traR mutations) and one exhibited a QS-signal exploitation behaviour, using signal produced by other cells to enhance its own Ti-plasmid transfer. We explored mechanisms that can limit this QS-hijacking. We showed that the A. tumefaciens capacity to inactivate QS-signals by expressing QS-degrading enzyme could attenuate dissemination of the QS signal-negative Ti-plasmids. This work shows that enzymatic QS-disruption whether encoded by the QS-producing Ti-plasmid itself, by a companion plasmid in the same donor cells, or by one in the recipient cells, in all cases can serve as a mechanism for controlling QS exploitation by QS signal-negative mutants. PMID:28054641

  1. Quorum-quenching limits quorum-sensing exploitation by signal-negative invaders

    Science.gov (United States)

    Tannières, Mélanie; Lang, Julien; Barnier, Claudie; Shykoff, Jacqui A.; Faure, Denis

    2017-01-01

    Some bacteria produce and perceive quorum-sensing (QS) signals that coordinate several behaviours, including the costly processes that are exoenzyme production and plasmid transfer. In the case of plasmid transfer, the emergence of QS signal-altered invaders and their policing are poorly documented. In Agrobacterium tumefaciens, the virulence Ti-plasmid encodes both synthesis and sensing of QS-signals, which promote its transfer from a donor to a recipient cell. Here, we reported that QS-altered A. tumefaciens mutants arose during experimental evolution. All showed improved growth compared to their ancestor. Genome sequencing revealed that, though some had lost the Ti-plasmid, most were defective for QS-signal synthesis and Ti-plasmid conjugation (traR mutations) and one exhibited a QS-signal exploitation behaviour, using signal produced by other cells to enhance its own Ti-plasmid transfer. We explored mechanisms that can limit this QS-hijacking. We showed that the A. tumefaciens capacity to inactivate QS-signals by expressing QS-degrading enzyme could attenuate dissemination of the QS signal-negative Ti-plasmids. This work shows that enzymatic QS-disruption whether encoded by the QS-producing Ti-plasmid itself, by a companion plasmid in the same donor cells, or by one in the recipient cells, in all cases can serve as a mechanism for controlling QS exploitation by QS signal-negative mutants.

  2. Realization of morphing logic gates in a repressilator with quorum sensing feedback

    Science.gov (United States)

    Agrawal, Vidit; Kang, Shivpal Singh; Sinha, Sudeshna

    2014-03-01

    We demonstrate how a genetic ring oscillator network with quorum sensing feedback can operate as a robust logic gate. Specifically we show how a range of logic functions, namely AND/NAND, OR/NOR and XOR/XNOR, can be realized by the system, thus yielding a versatile unit that can morph between different logic operations. We further demonstrate the capacity of this system to yield complementary logic operations in parallel. Our results then indicate the computing potential of this biological system, and may lead to bio-inspired computing devices.

  3. Realization of Morphing Logic Gates in a Repressilator with Quorum Sensing Feedback

    CERN Document Server

    Agrawal, Vidit; Sinha, Sudeshna

    2013-01-01

    We demonstrate how a genetic ring oscillator network with quorum sensing feedback can operate as a robust logic gate. Specifically we show how a range of logic functions, namely AND/NAND, OR/NOR and XOR/XNOR, can be realized by the system, thus yielding a versatile unit that can morph between different logic operations. We further demonstrate the capacity of this system to yield complementary logic operations in parallel. Our results then indicate the computing potential of this biological system, and may lead to bio-inspired computing devices.

  4. Acyl-Homoserine Lactone Quorum Sensing in the Roseobacter Clade

    Directory of Open Access Journals (Sweden)

    Jindong Zan

    2014-01-01

    Full Text Available Members of the Roseobacter clade are ecologically important and numerically abundant in coastal environments and can associate with marine invertebrates and nutrient-rich marine snow or organic particles, on which quorum sensing (QS may play an important role. In this review, we summarize current research progress on roseobacterial acyl-homoserine lactone-based QS, particularly focusing on three relatively well-studied representatives, Phaeobacter inhibens DSM17395, the marine sponge symbiont Ruegeria sp. KLH11 and the dinoflagellate symbiont Dinoroseobacter shibae. Bioinformatic survey of luxI homologues revealed that over 80% of available roseobacterial genomes encode at least one luxI homologue, reflecting the significance of QS controlled regulatory pathways in adapting to the relevant marine environments. We also discuss several areas that warrant further investigation, including studies on the ecological role of these diverse QS pathways in natural environments.

  5. Flexible Dynamics of Two Quorum Sensing Coupled Repressilators

    CERN Document Server

    Hellen, Edward H

    2016-01-01

    Genetic oscillators play important roles in cell life regulation. The regulatory efficiency usually depends strongly on the emergence of stable collective dynamic modes, which requires designing the interactions between genetic networks. We investigate the dynamics of two identical synthetic genetic repressilators coupled by an additional plasmid which implements quorum sensing (QS) in each network thereby supporting global coupling. In a basic genetic ring oscillator network in which three genes inhibit each other in unidirectional manner, QS stimulates the transcriptional activity of chosen genes providing for competition between inhibitory and stimulatory activities localized in those genes. The "promoter strength", the Hill cooperativity coefficient of transcription repression, and the coupling strength, i.e., parameters controlling the basic rates of genetic reactions, were chosen for extensive bifurcation analysis. The results are presented as a map of dynamic regimes. We found that the remarkable multi...

  6. Synchronization and quorum sensing in a swarm of humanoid robots

    CERN Document Server

    Bechon, Patrick

    2012-01-01

    With the advent of inexpensive simple humanoid robots, new classes of robotic questions can be considered experimentally. One of these is collective behavior of groups of humanoid robots, and in particular robot synchronization and swarming. The goal of this work is to robustly synchronize a group of humanoid robots, and to demonstrate the approach experimentally on a choreography of 8 robots. We aim to be robust to network latencies, and to allow robots to join or leave the group at any time (for example a fallen robot should be able to stand up to rejoin the choreography). Contraction theory is used to allow each robot in the group to synchronize to a common virtual oscillator, and quorum sensing strategies are exploited to fit within the available bandwidth. The humanoids used are Nao's, developed by Aldebaran Robotics.

  7. Acyl-homoserine lactone quorum sensing: from evolution to application.

    Science.gov (United States)

    Schuster, Martin; Sexton, D Joseph; Diggle, Stephen P; Greenberg, E Peter

    2013-01-01

    Quorum sensing (QS) is a widespread process in bacteria that employs autoinducing chemical signals to coordinate diverse, often cooperative activities such as bioluminescence, biofilm formation, and exoenzyme secretion. Signaling via acyl-homoserine lactones is the paradigm for QS in Proteobacteria and is particularly well understood in the opportunistic pathogen Pseudomonas aeruginosa. Despite thirty years of mechanistic research, empirical studies have only recently addressed the benefits of QS and provided support for the traditional assumptions regarding its social nature and its role in optimizing cell-density-dependent group behaviors. QS-controlled public-goods production has served to investigate principles that explain the evolution and stability of cooperation, including kin selection, pleiotropic constraints, and metabolic prudence. With respect to medical application, appreciating social dynamics is pertinent to understanding the efficacy of QS-inhibiting drugs and the evolution of resistance. Future work will provide additional insight into the foundational assumptions of QS and relate laboratory discoveries to natural ecosystems.

  8. Quorum Sensing Activity of Hafnia alvei Isolated from Packed Food

    Directory of Open Access Journals (Sweden)

    Jia-Yi Tan

    2014-04-01

    Full Text Available Quorum sensing (QS is a mechanism adopted by bacteria to regulate expression of genes according to population density. N-acylhomoserine lactones (AHLs are a type of QS signalling molecules commonly found in Gram-negative bacteria which have been reported to play a role in microbial spoilage of foods and pathogenesis. In this study, we isolated an AHL-producing Hafnia alvei strain (FB1 from spherical fish pastes. Analysis via high resolution triple quadrupole liquid chromatography/mass spectrometry (LC/MS on extracts from the spent supernatant of H. alvei FB1 revealed the existence of two short chain AHLs: N-(3-oxohexanoyl homoserine lactone (3-oxo-C6-HSL and N-(3-oxo- octanoyl homoserine lactone (3-oxo-C8-HSL. To our knowledge, this is the first report of the production of AHLs, especially 3-oxo-C8-HSL, by H. alvei.

  9. Bacterial quorum sensing: functional features and potential applications in biotechnology.

    Science.gov (United States)

    Mangwani, Neelam; Dash, Hirak Ranjan; Chauhan, Ashvini; Das, Surajit

    2012-01-01

    Quorum sensing (QS) represents an exceptional pattern of cell-to-cell communication in bacteria using self-synthesized signalling molecules known as autoinducers. Various features regulated by QS in bacteria include virulence, biofilm formation, sporulation, genetic competence and bioluminescence, among others. Other than the diverse signalling properties of autoinducers, there are non-signalling properties also associated with these signalling molecules which make them potential antimicrobial agents and metal chelators. Additionally, QS signal antagonism has also been shown to be a promising alternative for blocking pathogenic diseases. Besides, QS has impressive design features useful in tissue engineering and biosensor technology. Although many aspects of QS are well understood, several other features remain largely unknown, especially in biotechnology applications. This review focuses on the functional features and potential applications of QS signalling molecules in biotechnology.

  10. Insights into the Quorum Sensing Regulon of the Acidophilic Acidithiobacillus ferrooxidans Revealed by Transcriptomic in the Presence of an Acyl Homoserine Lactone Superagonist Analog.

    Science.gov (United States)

    Mamani, Sigde; Moinier, Danielle; Denis, Yann; Soulère, Laurent; Queneau, Yves; Talla, Emmanuel; Bonnefoy, Violaine; Guiliani, Nicolas

    2016-01-01

    While a functional quorum sensing system has been identified in the acidophilic chemolithoautotrophic Acidithiobacillus ferrooxidans ATCC 23270(T) and shown to modulate cell adhesion to solid substrates, nothing is known about the genes it regulates. To address the question of how quorum sensing controls biofilm formation in A. ferrooxidans (T), the transcriptome of this organism in conditions in which quorum sensing response is stimulated by a synthetic superagonist AHL (N-acyl homoserine lactones) analog has been studied. First, the effect on biofilm formation of a synthetic AHL tetrazolic analog, tetrazole 9c, known for its agonistic QS activity, was assessed by fluorescence and electron microscopy. A fast adherence of A. ferrooxidans (T) cells on sulfur coupons was observed. Then, tetrazole 9c was used in DNA microarray experiments that allowed the identification of genes regulated by quorum sensing signaling, and more particularly, those involved in early biofilm formation. Interestingly, afeI gene, encoding the AHL synthase, but not the A. ferrooxidans quorum sensing transcriptional regulator AfeR encoding gene, was shown to be regulated by quorum sensing. Data indicated that quorum sensing network represents at least 4.5% (141 genes) of the ATCC 23270(T) genome of which 42.5% (60 genes) are related to biofilm formation. Finally, AfeR was shown to bind specifically to the regulatory region of the afeI gene at the level of the palindromic sequence predicted to be the AfeR binding site. Our results give new insights on the response of A. ferrooxidans to quorum sensing and on biofilm biogenesis.

  11. Modulating Vibrio cholerae quorum-sensing-controlled communication using autoinducer-loaded nanoparticles.

    Science.gov (United States)

    Lu, Hoang D; Spiegel, Alina C; Hurley, Amanda; Perez, Lark J; Maisel, Katharina; Ensign, Laura M; Hanes, Justin; Bassler, Bonnie L; Semmelhack, Martin F; Prud'homme, Robert K

    2015-04-08

    The rise of bacterial antibiotic resistance has created a demand for alternatives to traditional antibiotics. Attractive possibilities include pro- and anti-quorum sensing therapies that function by modulating bacterial chemical communication circuits. We report the use of Flash NanoPrecipitation to deliver the Vibrio cholerae quorum-sensing signal CAI-1 ((S)-3-hydroxytridecan-4-one) in a water dispersible form as nanoparticles. The particles activate V. cholerae quorum-sensing responses 5 orders of magnitude higher than does the identically administered free CAI-1 and are diffusive across in vivo delivery barriers such as intestinal mucus. This work highlights the promise of combining quorum-sensing strategies with drug delivery approaches for the development of next-generation medicines.

  12. Bacteria clustering by polymers induces the expression of quorum-sensing-controlled phenotypes

    Science.gov (United States)

    Lui, Leong T.; Xue, Xuan; Sui, Cheng; Brown, Alan; Pritchard, David I.; Halliday, Nigel; Winzer, Klaus; Howdle, Steven M.; Fernandez-Trillo, Francisco; Krasnogor, Natalio; Alexander, Cameron

    2013-12-01

    Bacteria deploy a range of chemistries to regulate their behaviour and respond to their environment. Quorum sensing is one method by which bacteria use chemical reactions to modulate pre-infection behaviour such as surface attachment. Polymers that can interfere with bacterial adhesion or the chemical reactions used for quorum sensing are therefore a potential means to control bacterial population responses. Here, we report how polymeric ‘bacteria sequestrants’, designed to bind to bacteria through electrostatic interactions and therefore inhibit bacterial adhesion to surfaces, induce the expression of quorum-sensing-controlled phenotypes as a consequence of cell clustering. A combination of polymer and analytical chemistry, biological assays and computational modelling has been used to characterize the feedback between bacteria clustering and quorum sensing signalling. We have also derived design principles and chemical strategies for controlling bacterial behaviour at the population level.

  13. Synthesis of (R)-norbgugaine and its potential as quorum sensing inhibitor against Pseudomonas aeruginosa

    Digital Repository Service at National Institute of Oceanography (India)

    Majik, M.S.; Naik, D.; Bhat, C.; Tilve, S.; Tilvi, S.; DeSouza, L.

    and cat hydrogenation as the key steps and its biological studies are reported for the first time. The synthesized norbgugaine was evaluated for inhibition of quorum sensing mediated virulence factors (motility, biofilm formation, pyocyanin pigmentation...

  14. Bacteria clustering by polymers induces the expression of quorum-sensing-controlled phenotypes.

    Science.gov (United States)

    Lui, Leong T; Xue, Xuan; Sui, Cheng; Brown, Alan; Pritchard, David I; Halliday, Nigel; Winzer, Klaus; Howdle, Steven M; Fernandez-Trillo, Francisco; Krasnogor, Natalio; Alexander, Cameron

    2013-12-01

    Bacteria deploy a range of chemistries to regulate their behaviour and respond to their environment. Quorum sensing is one method by which bacteria use chemical reactions to modulate pre-infection behaviour such as surface attachment. Polymers that can interfere with bacterial adhesion or the chemical reactions used for quorum sensing are therefore a potential means to control bacterial population responses. Here, we report how polymeric 'bacteria sequestrants', designed to bind to bacteria through electrostatic interactions and therefore inhibit bacterial adhesion to surfaces, induce the expression of quorum-sensing-controlled phenotypes as a consequence of cell clustering. A combination of polymer and analytical chemistry, biological assays and computational modelling has been used to characterize the feedback between bacteria clustering and quorum sensing signalling. We have also derived design principles and chemical strategies for controlling bacterial behaviour at the population level.

  15. Peptides as Quorum Sensing Molecules: Measurement Techniques and Obtained Levels In vitro and In vivo

    Science.gov (United States)

    Verbeke, Frederick; De Craemer, Severine; Debunne, Nathan; Janssens, Yorick; Wynendaele, Evelien; Van de Wiele, Christophe; De Spiegeleer, Bart

    2017-01-01

    The expression of certain bacterial genes is regulated in a cell-density dependent way, a phenomenon called quorum sensing. Both Gram-negative and Gram-positive bacteria use this type of communication, though the signal molecules (auto-inducers) used by them differ between both groups: Gram-negative bacteria use predominantly N-acyl homoserine lacton (AHL) molecules (autoinducer-1, AI-1) while Gram-positive bacteria use mainly peptides (autoinducer peptides, AIP or quorum sensing peptides). These quorum sensing molecules are not only involved in the inter-microbial communication, but can also possibly cross-talk directly or indirectly with their host. This review summarizes the currently applied analytical approaches for quorum sensing identification and quantification with additionally summarizing the experimentally found in vivo concentrations of these molecules in humans. PMID:28446863

  16. Dynamical quorum sensing and synchronization in collections of excitable and oscillatory catalytic particles

    Science.gov (United States)

    Tinsley, M. R.; Taylor, A. F.; Huang, Z.; Wang, F.; Showalter, K.

    2010-06-01

    We present experimental studies of interacting excitable and oscillatory catalytic particles in well-stirred and spatially distributed systems. A number of distinct paths to synchronized oscillatory behavior are described. We present an example of a Kuramoto type transition in a well-stirred system with a collective rhythm emerging on increasing the number density of oscillatory particles. Groups of spatially distributed oscillatory particles become entrained to a common frequency by organizing centers. Quorum sensing type transitions are found in populations of globally and locally coupled excitable particles, with a sharp transition from steady state to fully synchronized behavior at a critical density or group size.

  17. Mathematical analysis of a quorum sensing induced biofilm dispersal model and numerical simulation of hollowing effects.

    Science.gov (United States)

    Emerenini, Blessing O; Sonner, Stefanie; Eberl, Hermann J

    2017-06-01

    We analyze a mathematical model of quorum sensing induced biofilm dispersal. It is formulated as a system of non-linear, density-dependent, diffusion-reaction equations. The governing equation for the sessile biomass comprises two non-linear diffusion effects, a degeneracy as in the porous medium equation and fast diffusion. This equation is coupled with three semi-linear diffusion-reaction equations for the concentrations of growth limiting nutrients, autoinducers, and dispersed cells. We prove the existence and uniqueness of bounded non-negative solutions of this system and study the behavior of the model in numerical simulations, where we focus on hollowing effects in established biofilms.

  18. Bacteria clustering by polymers induces the expression of quorum sense controlled phenotypes

    OpenAIRE

    Lui, Leong T.; Xue, Xuan; Sui, Cheng; Brown, Alan; Pritchard, David I.; Halliday, Nigel; Winzer, Klaus; Howdle, Stephen M.; Fernandez-Trillo, Francisco; Krasnogor, Natalio; Alexander, Cameron

    2013-01-01

    Bacteria deploy a range of chemistries to regulate their behaviour and respond to their environment. Quorum sensing is one mean by which bacteria use chemical reactions to modulate pre-infection behaviour such as surface attachment. Polymers that can interfere with bacterial adhesion or the chemical reactions used for quorum sensing are thus a potential means to control bacterial population responses. Here we report how polymeric “bacteria sequestrants”, designed to bind to bacteria through e...

  19. KARAKTERISASI BAKTERI ANTI QUORUM SENSING (AQS) SEBAGAI PENGHAMBAT VIRULENSI PENYAKIT PADA IKAN LELE DUMBO (Clarias gariepinus)

    OpenAIRE

    Hessy Novita; Iman Rusmana; Munti Yuhana; Fachriyan Hasmi Pasaribu

    2015-01-01

    Penyakit bakterial adalah salah satu penyebab kerugian besar di bidang akuakultur. Faktor virulensi bakteri penyakit umumnya diekspresikan oleh gen-gen virulen yang diregulasi dengan sistem Quorum Sensing. Tujuan dari penelitian ini adalah untuk mendapatkan isolat bakteri yang memiliki potensi sebagai Anti Quorum Sensing (AQS) yang dapat menghambat faktor virulensi bakteri patogen penyebab penyakit pada ikan lele dumbo (Clarias gariepinus). Isolasi bakteri dilakukan dari sedimen, organ pencer...

  20. Death and Survival in Streptococcus mutans: Differing Outcomes of a Quorum-Sensing Signalling Peptide

    Directory of Open Access Journals (Sweden)

    Vincent eLeung

    2015-10-01

    Full Text Available Bacteria are considered ‘social’ organisms able to communicate with one another using small hormone-like molecules (pheromones in a process called quorum-sensing. These signalling molecules increase in concentration as a function of bacterial cell density. For most human pathogens, quorum-sensing is critical for virulence and biofilm formation, and the opportunity to interfere with bacterial quorum-sensing could provide a sophisticated means for manipulating the composition of pathogenic biofilms, and possibly eradicating the infection. Streptococcus mutans is a well-characterized resident of the dental plaque biofilm, and is the major pathogen of dental caries (tooth decay. In S. mutans, its CSP quorum-sensing signalling peptide does not act as a classical quorum-sensing signal by accumulating passively in proportion to cell density. In fact, particular stresses such as those encountered in the oral cavity, induces the production of the CSP pheromone, suggesting that the pheromone most probably functions as a stress-inducible alarmone by triggering the signalling to the bacterial population to initiate an adaptive response that results in different phenotypic outcomes. This mini-review discusses two different CSP-induced phenotypes, bacterial ‘suicide’ and dormancy, and the underlying mechanisms by which S. mutans utilizes the same quorum-sensing signalling peptide to regulate two opposite phenotypes.

  1. Flavonoids Suppress Pseudomonas aeruginosa Virulence through Allosteric Inhibition of Quorum-sensing Receptors.

    Science.gov (United States)

    Paczkowski, Jon E; Mukherjee, Sampriti; McCready, Amelia R; Cong, Jian-Ping; Aquino, Christopher J; Kim, Hahn; Henke, Brad R; Smith, Chari D; Bassler, Bonnie L

    2017-03-10

    Quorum sensing is a process of cell-cell communication that bacteria use to regulate collective behaviors. Quorum sensing depends on the production, detection, and group-wide response to extracellular signal molecules called autoinducers. In many bacterial species, quorum sensing controls virulence factor production. Thus, disrupting quorum sensing is considered a promising strategy to combat bacterial pathogenicity. Several members of a family of naturally produced plant metabolites called flavonoids inhibit Pseudomonas aeruginosa biofilm formation by an unknown mechanism. Here, we explore this family of molecules further, and we demonstrate that flavonoids specifically inhibit quorum sensing via antagonism of the autoinducer-binding receptors, LasR and RhlR. Structure-activity relationship analyses demonstrate that the presence of two hydroxyl moieties in the flavone A-ring backbone are essential for potent inhibition of LasR/RhlR. Biochemical analyses reveal that the flavonoids function non-competitively to prevent LasR/RhlR DNA binding. Administration of the flavonoids to P. aeruginosa alters transcription of quorum sensing-controlled target promoters and suppresses virulence factor production, confirming their potential as anti-infectives that do not function by traditional bacteriocidal or bacteriostatic mechanisms. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Individual and combined roles of the master regulators AphA and LuxR in control of the Vibrio harveyi quorum-sensing regulon.

    Science.gov (United States)

    van Kessel, Julia C; Rutherford, Steven T; Shao, Yi; Utria, Alan F; Bassler, Bonnie L

    2013-02-01

    Bacteria use a chemical communication process called quorum sensing to control transitions between individual and group behaviors. In the Vibrio harveyi quorum-sensing circuit, two master transcription factors, AphA and LuxR, coordinate the quorum-sensing response. Here we show that AphA regulates 167 genes, LuxR regulates 625 genes, and they coregulate 77 genes. LuxR strongly controls genes at both low cell density and high cell density, suggesting that it is the major quorum-sensing regulator. In contrast, AphA is absent at high cell density and acts to fine-tune quorum-sensing gene expression at low cell density. We examined two loci as case studies of coregulation by AphA and LuxR. First, AphA and LuxR directly regulate expression of the genes encoding the quorum-regulatory small RNAs Qrr2, Qrr3, and Qrr4, the consequence of which is a specifically timed transition between the individual and the group life-styles. Second, AphA and LuxR repress type III secretion system genes but at different times and to different extents. The consequence of this regulation is that type III secretion is restricted to a peak at mid-cell density. Thus, the asymmetric production of AphA and LuxR coupled with differences in their strengths and timing of target gene regulation generate a precise temporal pattern of gene expression.

  3. Plausible Drug Targets in the Streptococcus mutans Quorum Sensing Pathways to Combat Dental Biofilms and Associated Risks.

    Science.gov (United States)

    Kaur, Gurmeet; Rajesh, Shrinidhi; Princy, S Adline

    2015-12-01

    Streptococcus mutans, a Gram positive facultative anaerobe, is one among the approximately seven hundred bacterial species to exist in human buccal cavity and cause dental caries. Quorum sensing (QS) is a cell-density dependent communication process that respond to the inter/intra-species signals and elicit responses to show behavioral changes in the bacteria to an aggressive forms. In accordance to this phenomenon, the S. mutans also harbors a Competing Stimulating Peptide (CSP)-mediated quorum sensing, ComCDE (Two-component regulatory system) to regulate several virulence-associated traits that includes the formation of the oral biofilm (dental plaque), genetic competence and acidogenicity. The QS-mediated response of S. mutans adherence on tooth surface (dental plaque) imparts antibiotic resistance to the bacterium and further progresses to lead a chronic state, known as periodontitis. In recent years, the oral streptococci, S. mutans are not only recognized for its cariogenic potential but also well known to worsen the infective endocarditis due to its inherent ability to colonize and form biofilm on heart valves. The review significantly appreciate the increasing complexity of the CSP-mediated quorum-sensing pathway with a special emphasis to identify the plausible drug targets within the system for the development of anti-quorum drugs to control biofilm formation and associated risks.

  4. Engineering quorum sensing signaling of Pseudomonas for enhanced wastewater treatment and electricity harvest: A review.

    Science.gov (United States)

    Yong, Yang-Chun; Wu, Xiang-Yang; Sun, Jian-Zhong; Cao, Ying-Xiu; Song, Hao

    2015-12-01

    Cell-cell communication that enables synchronized population behaviors in microbial communities dictates various biological processes. It is of great interest to unveil the underlying mechanisms of fine-tuning cell-cell communication to achieve environmental and energy applications. Pseudomonas is a ubiquitous microbe in environments that had wide applications in bioremediation and bioenergy generation. The quorum sensing (QS, a generic cell-cell communication mechanism) systems of Pseudomonas underlie the aromatics biodegradation, denitrification and electricity harvest. Here, we reviewed the recent progresses of the genetic strategies in engineering QS circuits to improve efficiency of wastewater treatment and the performance of microbial fuel cells. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. The acyl-homoserine lactone-type quorum-sensing system modulates cell motility and virulence of Erwinia chrysanthemi pv. zeae.

    Science.gov (United States)

    Hussain, Mumtaz B B M; Zhang, Hai-Bao; Xu, Jin-Ling; Liu, Qiongguang; Jiang, Zide; Zhang, Lian-Hui

    2008-02-01

    Erwinia chrysanthemi pv. zeae is one of the Erwinia chrysanthemi pathovars that infects on both dicotyledons and monocotyledons. However, little is known about the molecular basis and regulatory mechanisms of its virulence. By using a transposon mutagenesis approach, we cloned the genes coding for an E. chrysanthemi pv. zeae synthase of acyl-homoserine lactone (AHL) quorum-sensing signals (expI(Ecz)) and a cognate response regulator (expR(Ecz)). Chromatography analysis showed that expI(Ecz) encoded production of the AHL signal N-(3-oxo-hexanoyl)-homoserine lactone (OHHL). Null mutation of expI(Ecz) in the E. chrysanthemi pv. zeae strain EC1 abolished AHL production, increased bacterial swimming and swarming motility, disabled formation of multicell aggregates, and attenuated virulence of the pathogen on potato tubers. The mutation also marginally reduced the inhibitory activity of E. chrysanthemi pv. zeae on rice seed germination. The mutant phenotypes were rescued by either exogenous addition of AHL signal or in trans expression of expI(Ecz). These data demonstrate that the AHL-type QS signal plays an essential role in modulation of E. chrysanthemi pv. zeae cell motility and the ability to form multicell aggregates and is involved in regulation of bacterial virulence.

  6. Exposure to static magnetic field stimulates quorum sensing circuit in luminescent Vibrio strains of the Harveyi clade.

    Science.gov (United States)

    Talà, Adelfia; Delle Side, Domenico; Buccolieri, Giovanni; Tredici, Salvatore Maurizio; Velardi, Luciano; Paladini, Fabio; De Stefano, Mario; Nassisi, Vincenzo; Alifano, Pietro

    2014-01-01

    In this study, the evidence of electron-dense magnetic inclusions with polyhedral shape in the cytoplasm of Harveyi clade Vibrio strain PS1, a bioluminescent bacterium living in symbiosis with marine organisms, led us to investigate the behavior of this bacterium under exposure to static magnetic fields ranging between 20 and 2000 Gauss. When compared to sham-exposed, the light emission of magnetic field-exposed bacteria growing on solid medium at 18°C ±0.1°C was increased up to two-fold as a function of dose and growth phase. Stimulation of bioluminescence by magnetic field was more pronounced during the post-exponential growth and stationary phase, and was lost when bacteria were grown in the presence of the iron chelator deferoxamine, which caused disassembly of the magnetic inclusions suggesting their involvement in magnetic response. As in luminescent Vibrio spp. bioluminescence is regulated by quorum sensing, possible effects of magnetic field exposure on quorum sensing were investigated. Measurement of mRNA levels by reverse transcriptase real time-PCR demonstrated that luxR regulatory gene and luxCDABE operon coding for luciferase and fatty acid reductase complex were significantly up-regulated in magnetic field-exposed bacteria. In contrast, genes coding for a type III secretion system, whose expression was negatively affected by LuxR, were down-regulated. Up-regulation of luxR paralleled with down-regulation of small RNAs that mediate destabilization of luxR mRNA in quorum sensing signaling pathways. The results of experiments with the well-studied Vibrio campbellii strain BB120 (originally classified as Vibrio harveyi) and derivative mutants unable to synthesize autoinducers suggest that the effects of magnetic fields on quorum sensing may be mediated by AI-2, the interspecies quorum sensing signal molecule.

  7. Acyl-homoserine lactone-based quorum sensing and quorum quenching hold promise to determine the performance of biological wastewater treatments: An overview.

    Science.gov (United States)

    Huang, Jinhui; Shi, Yahui; Zeng, Guangming; Gu, Yanling; Chen, Guiqiu; Shi, Lixiu; Hu, Yi; Tang, Bi; Zhou, Jianxin

    2016-08-01

    Quorum sensing (QS) is a communication process between cells, in which bacteria secrete and sense the specific chemicals, and regulate gene expression in response to population density. Quorum quenching (QQ) blocks QS system, and inhibits gene expression mediating bacterial behaviors. Given the extensive research of acyl-homoserine lactone (AHL) signals, existences and effects of AHL-based QS and QQ in biological wastewater treatments are being subject to high concern. This review summarizes AHL structure, synthesis mode, degradation mechanisms, analytical methods, environmental factors, AHL-based QS and QQ mechanisms. The existences and roles of AHL-based QS and QQ in biomembrane processes, activated sludge processes and membrane bioreactors are summarized and discussed, and corresponding exogenous regulation strategy by selective enhancement of AHL-based QS or QQ coexisting in biological wastewater treatments is suggested. Such strategies including the addition of AHL signals, AHL-producing bacteria as well as quorum quenching enzyme or bacteria can effectively improve wastewater treatment performance without killing or limiting bacterial survival and growth. This review will present the theoretical and practical cognition for bacterial AHL-based QS and QQ, suggest the feasibility of exogenous regulation strategies in biological wastewater treatments, and provide useful information to scientists and engineers who work in this field.

  8. Control of acetic acid fermentation by quorum sensing via N-acylhomoserine lactones in Gluconacetobacter intermedius.

    Science.gov (United States)

    Iida, Aya; Ohnishi, Yasuo; Horinouchi, Sueharu

    2008-04-01

    A number of gram-negative bacteria regulate gene expression in a cell density-dependent manner by quorum sensing via N-acylhomoserine lactones (AHLs). Gluconacetobacter intermedius NCI1051, a gram-negative acetic acid bacterium, produces three different AHLs, N-decanoyl-l-homoserine lactone, N-dodecanoyl-L-homoserine lactone, and an N-dodecanoyl-L-homoserine lactone with a single unsaturated bond in its acyl chain, as determined by liquid chromatography-tandem mass spectrometry. Two genes encoding an AHL synthase and a cognate regulator were cloned from strain NCI1051 and designated ginI and ginR, respectively. Disruption of ginI or ginR abolished AHL production, indicating that NCI1051 contains a single set of quorum-sensing genes. Transcriptional analysis showed that ginI is activated by GinR, which is consistent with the finding that there is an inverted repeat whose nucleotide sequence is similar to the sequence bound by members of the LuxR family at position -45 with respect to the transcriptional start site of ginI. A single gene, designated ginA, located just downstream of ginI is transcribed by read-through from the GinR-inducible ginI promoter. A ginA mutant, as well as the ginI and ginR mutants, grew more rapidly in medium containing 2% (vol/vol) ethanol and accumulated acetic acid at a higher rate with a greater final yield than parental strain NCI1051. In addition, these mutants produced larger amounts of gluconic acid than the parental strain. These data demonstrate that the GinI/GinR quorum-sensing system in G. intermedius controls the expression of ginA, which in turn represses oxidative fermentation, including acetic acid and gluconic acid fermentation.

  9. The Agr-like quorum-sensing system regulates sporulation and production of enterotoxin and beta2 toxin by Clostridium perfringens type A non-food-borne human gastrointestinal disease strain F5603.

    Science.gov (United States)

    Li, Jihong; Chen, Jianming; Vidal, Jorge E; McClane, Bruce A

    2011-06-01

    Clostridium perfringens type A strains producing enterotoxin (CPE) cause one of the most common bacterial food-borne illnesses, as well as many cases of non-food-borne human gastrointestinal disease. Recent studies have shown that an Agr-like quorum-sensing system controls production of chromosomally encoded alpha-toxin and perfringolysin O by C. perfringens, as well as sporulation by Clostridium botulinum and Clostridium sporogenes. The current study explored whether the Agr-like quorum-sensing system also regulates sporulation and production of two plasmid-encoded toxins (CPE and beta2 toxin) that may contribute to the pathogenesis of non-food-borne human gastrointestinal disease strain F5603. An isogenic agrB null mutant was inhibited for production of beta2 toxin during vegetative growth and in sporulating culture, providing the first evidence that, in C. perfringens, this system can control production of plasmid-encoded toxins as well as chromosomally encoded toxins. This mutant also showed reduced production of alpha-toxin and perfringolysin O during vegetative growth. Importantly, when cultured in sporulation medium, the mutant failed to efficiently form spores and was blocked for CPE production. Complementation partially or fully reversed all phenotypic changes in the mutant, confirming that they were specifically due to inactivation of the agr locus. Western blots suggest that this loss of sporulation and sporulation-specific CPE production for the agrB null mutant involves, at least in part, Agr-mediated regulation of production of Spo0A and alternative sigma factors, which are essential for C. perfringens sporulation.

  10. Research progress of quorum-sensing systems in biofilm of pseudomonas aeruginosa%铜绿假单胞菌生物被膜密度感知系统分子机制的研究进展

    Institute of Scientific and Technical Information of China (English)

    李聪然; 钱皎; 王睿

    2007-01-01

    铜绿假单胞菌通过形成生物被膜(biofilm,BBF)能够持续地将浮游的细菌保护起来便于细菌繁殖,是慢性或持续性感染的原因之一.密度感知系统(quorum-sensing systems,QSS)通过细胞-细胞间的信号传递在生物被膜形成中起到重要的作用.本文将就QSS系统在铜绿假单胞菌的BBF形成中的分子机制进行综述.

  11. Mutacins related to quorum sensing system and the analysis of their functions%密度感应相关性变链素及其作用分析

    Institute of Scientific and Technical Information of China (English)

    霍永标

    2011-01-01

    细菌素是由某些细菌在代谢过程中产生的一类具有抗菌活性的蛋白质或多肽,变异链球菌产生的细菌素称为变链素.变链素可能与口腔生物膜中变异链球菌的致龋性及其在牙面的定植有关.目前已有多种变链素被分离、纯化并完成了基因序列和氨基酸序列的测定,变链素与密度感应调控系统的关系及在新型抗菌制剂研发中的应用价值已受到人们关注.本文就密度感应相关变链素及其作用的研究现状作一综述.%Bacteriocins are antibacterial proteins or polypeptides directly produced by some bacteria during their metabolic process. Streptococcus mutants also produce bacteriocin which named mutacin. Mutacins are probably relevant to the cariogenic characters and colonization of the Streptococcus mutants. Researchers pay close attention to the potential application on new antimicrobial by studying about mutacins. Many mutacins have been isolated and purified, some of which are related to quorum sensing regulation system. Furthermore, the gene sequences and amino acid sequences of these mutacins are also determined. This review summarizes the function of mutacins that related to the quorum sensing system.

  12. 细菌QS系统LuxS功能研究进展%Current status on function of bacterial LuxS in quorum sensing system-A

    Institute of Scientific and Technical Information of China (English)

    陈伟

    2011-01-01

    Quorum sens!ng is a process, during which bacteria cells make use of some small diffisible molecules to communicate and coordinate diverse behaviors in response to cell density. The only QS system existed in both Grampositive and Gram-negative bacteria associates the production of autoinducer-2(AI-2). The synthase of AI-2, LuxS, is widely distributed among the bacteria,which suggests that AI-2 be a language for interspecies communication. However,LuxS is also an integral component of the activated methyl cycle in bacteria. Recently,LuxS-based QS system has been intensively studied and the results showed that the function of LuxS is various. We summarized the function of bacterial LuxS in QS system in the recent years, especially in the synthesis of AI-3 (a novel autoindueer), the activation of type 3 secretion system(T3SS) ,and the cross-talk between pathogens and hosts, in order to understand further bacterial communication and offer a strategy for the development of novel antimicrobial drugs.%群感效应(Quorum sensing,QS)是细菌细胞间利用可扩散的小分子物质进行信息交流的过程,以响应群体密度从而产生各种各样的协调性行为。在革兰氏阳性菌与阴性菌中同时存在的唯一个QS系统就是涉及自诱导物-2(Autoindueer-2,AI-2)的合成机制。AI-2合成酶LuxS广泛存在于细菌中,说明AI-2是细菌种间交流的语言。然而,LuxS本身也是活性甲基循环(Activated methylcycle,AMC)的固有组分。近几年来,人们对基于LuxS的QS系统进行了广泛地研究,发现LuxS的功

  13. Flavones as Quorum Sensing Inhibitors Identified by a Newly Optimized Screening Platform Using Chromobacterium violaceum as Reporter Bacteria.

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    Skogman, Malena E; Kanerva, Sonja; Manner, Suvi; Vuorela, Pia M; Fallarero, Adyary

    2016-09-10

    Quorum sensing (QS) is the process by which bacteria produce and detect signal molecules to coordinate their collective behavior. This intercellular communication is a relevant target for anti-biofilm therapies. Here we have optimized a screening-applicable assay to search for new quorum sensing inhibitors from natural compound libraries. In this system, QS is correlated with the production of violacein, which is directly controlled by the LuxI/LuxR system in Chromobacterium violaceum ATCC 31532. The parallel use of C. violaceum Tn5-mutant CV026, which depends on auto-inducer addition, allows simultaneous discrimination of compounds that act as quenchers of the AHL signal (quorum quenchers). The incorporation of a redox stain into the platform allowed further distinction between QS inhibitors, quorum quenchers and antibacterial compounds. A pilot screening was performed with 465 natural and synthetic flavonoids. All the most active compounds were flavones and they displayed potencies (IC50) in the range of 3.69 to 23.35 μM. These leads were particularly promising as they inhibited the transition from microcolonies into mature biofilms from Escherichia coli and Pseudomonas aeruginosa strains. This approach can be very effective in identifying new antimicrobials posing lesser risks of resistance.

  14. Reversible non-genetic phenotypic heterogeneity in bacterial quorum sensing.

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    Pradhan, Binod B; Chatterjee, Subhadeep

    2014-05-01

    Bacteria co-ordinate their social behaviour in a density-dependent manner by production of diffusible signal molecules by a process known as quorum sensing (QS). It is generally assumed that in homogenous environments and at high cell density, QS synchronizes cells in the population to perform collective social tasks in unison which maximize the benefit at the inclusive fitness of individuals. However, evolutionary theory predicts that maintaining phenotypic heterogeneity in performing social tasks is advantageous as it can serve as a bet-hedging survival strategy. Using Pseudomonas syringae and Xanthomonas campestris as model organisms, which use two diverse classes of QS signals, we show that two distinct subpopulations of QS-responsive and non-responsive cells exist in the QS-activated population. Addition of excess exogenous QS signal does not significantly alter the distribution of QS-responsive and non-responsive cells in the population. We further show that progeny of cells derived from these subpopulations also exhibited heterogeneous distribution patterns similar to their respective parental strains. Overall, these results support the model that bacteria maintain QS-responsive and non-responsive subpopulations at high cell densities in a bet-hedging strategy to simultaneously perform functions that are both positively and negatively regulated by QS to improve their fitness in fluctuating environments.

  15. Bacterial quorum sensing and nitrogen cycling in rhizosphere soil

    Energy Technology Data Exchange (ETDEWEB)

    DeAngelis, K.M.; Lindow, S.E.; Firestone, M.K.

    2008-10-01

    Plant photosynthate fuels carbon-limited microbial growth and activity, resulting in increased rhizosphere nitrogen (N)-mineralization. Most soil organic N is macromolecular (chitin, protein, nucleotides); enzymatic depolymerization is likely rate-limiting for plant N accumulation. Analyzing Avena (wild oat) planted in microcosms containing sieved field soil, we observed increased rhizosphere chitinase and protease specific activities, bacterial cell densities, and dissolved organic nitrogen (DON) compared to bulk soil. Low-molecular weight DON (<3000 Da) was undetectable in bulk soil but comprised 15% of rhizosphere DON. Extracellular enzyme production in many bacteria requires quorum sensing (QS), cell-density dependent group behavior. Because proteobacteria are considered major rhizosphere colonizers, we assayed the proteobacterial QS signals acyl-homoserine lactones (AHLs), which were significantly increased in the rhizosphere. To investigate the linkage between soil signaling and N cycling, we characterized 533 bacterial isolates from Avena rhizosphere: 24% had chitinase or protease activity and AHL production; disruption of QS in 7 of 8 eight isolates disrupted enzyme activity. Many {alpha}-Proteobacteria were newly found with QS-controlled extracellular enzyme activity. Enhanced specific activities of N-cycling enzymes accompanied by bacterial density-dependent behaviors in rhizosphere soil gives rise to the hypothesis that QS could be a control point in the complex process of rhizosphere N-mineralization.

  16. The fitness burden imposed by synthesising quorum sensing signals.

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    Ruparell, A; Dubern, J F; Ortori, C A; Harrison, F; Halliday, N M; Emtage, A; Ashawesh, M M; Laughton, C A; Diggle, S P; Williams, P; Barrett, D A; Hardie, K R

    2016-09-12

    It is now well established that bacterial populations utilize cell-to-cell signaling (quorum-sensing, QS) to control the production of public goods and other co-operative behaviours. Evolutionary theory predicts that both the cost of signal production and the response to signals should incur fitness costs for producing cells. Although costs imposed by the downstream consequences of QS have been shown, the cost of QS signal molecule (QSSM) production and its impact on fitness has not been examined. We measured the fitness cost to cells of synthesising QSSMs by quantifying metabolite levels in the presence of QSSM synthases. We found that: (i) bacteria making certain QSSMs have a growth defect that exerts an evolutionary cost, (ii) production of QSSMs negatively correlates with intracellular concentrations of QSSM precursors, (iii) the production of heterologous QSSMs negatively impacts the production of a native QSSM that shares common substrates, and (iv) supplementation with exogenously added metabolites partially rescued growth defects imposed by QSSM synthesis. These data identify the sources of the fitness costs incurred by QSSM producer cells, and indicate that there may be metabolic trade-offs associated with QS signaling that could exert selection on how signaling evolves.

  17. Synchronization and quorum sensing in an ensemble of indirectly coupled chaotic oscillators

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    Li, Bing-Wei; Fu, Chenbo; Zhang, Hong; Wang, Xingang

    2012-10-01

    The fact that the elements in some realistic systems are influenced by each other indirectly through a common environment has stimulated a new surge of studies on the collective behavior of coupled oscillators. Most of the previous studies, however, consider only the case of coupled periodic oscillators, and it remains unknown whether and to what extent the findings can be applied to the case of coupled chaotic oscillators. Here, using the population density and coupling strength as the tuning parameters, we explore the synchronization and quorum sensing behaviors in an ensemble of chaotic oscillators coupled through a common medium, in which some interesting phenomena are observed, including the appearance of the phase synchronization in the process of progressive synchronization, the various periodic oscillations close to the quorum sensing transition, and the crossover of the critical population density at the transition. These phenomena, which have not been reported for indirectly coupled periodic oscillators, reveal a corner of the rich dynamics inherent in indirectly coupled chaotic oscillators, and are believed to have important implications to the performance and functionality of some realistic systems.

  18. Spontaneous quorum sensing mutation modulates electroactivity of Pseudomonas aeruginosa PA14.

    Science.gov (United States)

    Berger, Carola; Rosenbaum, Miriam A

    2017-10-01

    Pseudomonas aeruginosa is able to interact with the anode of a bioelectrochemical system through redox active phenazines. Earlier studies showed that this interaction is strain and carbon source dependent. With a spontaneously formed ΔlasR mutant of P. aeruginosa PA14 and the wildtype, we investigated the connection between the complex quorum sensing network and current production. Depending on the carbon source, phenazine production and subsequently current generation are effected differently in these two populations. In glucose-fed cultures, the lack of the LasR regulator led to a shift in phenazine concentration, relative composition, and time profiles. In contrast, with the common fermentation product 2,3-butanediol as carbon substrate, no phenazine production was detected for the ΔlasR mutant. For the wildtype, this carbon source is known to induce phenazine synthesis and elevated current production. This work supports the earlier hypothesis of a signaling link between 2,3-butanediol and the quorum-sensing regulatory system and extends this hypothesis to predict a lasR-dependent interaction. The wildtype and mutant population were also evaluated in direct competition, showing strong initial dominance of the wildtype but a higher survival rate of the ΔlasR mutant in later stages of growth. We found no evidence for strong social interactions between these two subpopulations. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Novel Sinorhizobium meliloti quorum sensing positive and negative regulatory feedback mechanisms respond to phosphate availability.

    Science.gov (United States)

    McIntosh, Matthew; Meyer, Stefan; Becker, Anke

    2009-12-01

    The Sin quorum sensing system of Sinorhizobium meliloti depends upon at least three genes, sinR, sinI and expR, and N-acyl homoserine lactones (AHLs) as signals to regulate multiple processes in its free-living state in the rhizosphere and in the development towards symbiosis with its plant host. In this study, we have characterized novel mechanisms of transcription control through which the system regulates itself. At low AHL levels a positive feedback loop activates expression of sinI (AHL synthase), resulting in amplification of AHL levels. At high AHL levels, expression of sinI is reduced by a negative feedback loop. These feedback mechanisms are mediated by the LuxR-type regulators ExpR and SinR. Expression of sinR and expR is regulated by ExpR in the presence of AHLs. A novel ExpR binding site in the promoter of sinR is responsible for the reduction of expression of this gene. In addition, expression of sinR, upon which sinI expression is dependent, is induced by phoB during growth under phosphate-limiting conditions. This indicates that this response ensures quorum sensing in phosphate-restricted growth.

  20. Early activation of quorum sensing in Pseudomonas aeruginosa reveals the architecture of a complex regulon

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    Schuster Martin

    2007-08-01

    Full Text Available Abstract Background Quorum-sensing regulation of gene expression in Pseudomonas aeruginosa is complex. Two interconnected acyl-homoserine lactone (acyl-HSL signal-receptor pairs, 3-oxo-dodecanoyl-HSL-LasR and butanoyl-HSL-RhlR, regulate more than 300 genes. The induction of most of the genes is delayed during growth of P. aeruginosa in complex medium, cannot be advanced by addition of exogenous signal, and requires additional regulatory components. Many of these late genes can be induced by addition of signals early by using specific media conditions. While several factors super-regulate the quorum receptors, others may co-regulate target promoters or may affect expression posttranscriptionally. Results To better understand the contributions of super-regulation and co-regulation to quorum-sensing gene expression, and to better understand the general structure of the quorum sensing network, we ectopically expressed the two receptors (in the presence of their cognate signals and another component that affects quorum sensing, the stationary phase sigma factor RpoS, early in growth. We determined the effect on target gene expression by microarray and real-time PCR analysis. Our results show that many target genes (e.g. lasB and hcnABC are directly responsive to receptor protein levels. Most genes (e.g. lasA, lecA, and phnAB, however, are not significantly affected, although at least some of these genes are directly regulated by quorum sensing. The majority of promoters advanced by RhlR appeared to be regulated directly, which allowed us to build a RhlR consensus sequence. Conclusion The direct responsiveness of many quorum sensing target genes to receptor protein levels early in growth confirms the role of super-regulation in quorum sensing gene expression. The observation that the induction of most target genes is not affected by signal or receptor protein levels indicates that either target promoters are co-regulated by other transcription factors

  1. AinS quorum sensing regulates the Vibrio fischeri acetate switch.

    Science.gov (United States)

    Studer, Sarah V; Mandel, Mark J; Ruby, Edward G

    2008-09-01

    The marine bacterium Vibrio fischeri uses two acyl-homoserine lactone (acyl-HSL) quorum-sensing systems. The earlier signal, octanoyl-HSL, produced by AinS, is required for normal colonization of the squid Euprymna scolopes and, in culture, is necessary for a normal growth yield. In examining the latter requirement, we found that during growth in a glycerol/tryptone-based medium, wild-type V. fischeri cells initially excrete acetate but, in a metabolic shift termed the acetate switch, they subsequently utilize the acetate, removing it from the medium. In contrast, an ainS mutant strain grown in this medium does not remove the excreted acetate, which accumulates to lethal levels. The acetate switch is characterized by the induction of acs, the gene encoding acetyl coenzyme A (acetyl-CoA) synthetase, leading to uptake of the excreted acetate. Wild-type cells induce an acs transcriptional reporter 25-fold, coincident with the disappearance of the extracellular acetate; in contrast, the ainS mutant did not display significant induction of the acs reporter. Supplementation of the medium of an ainS mutant with octanoyl-HSL restored normal levels of acs induction and acetate uptake. Additional mutant analyses indicated that acs regulation was accomplished through the regulator LitR but was independent of the LuxIR quorum-signaling pathway. Importantly, the acs mutant of V. fischeri has a competitive defect when colonizing the squid, indicating the importance of proper control of acetate metabolism in the light of organ symbiosis. This is the first report of quorum-sensing control of the acetate switch, and it indicates a metabolic connection between acetate utilization and cell density.

  2. Sub-MICs of Mentha piperita essential oil and menthol inhibits AHL mediated quorum sensing and biofilm of Gram negative bacteria

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    Fohad Mabood Husain

    2015-05-01

    Full Text Available Bacterial quorum sensing (QS is a density dependent communication system that regulates the expression of certain genes including production of virulence factors in many pathogens. Bioactive plant extract/compounds inhibiting QS regulated gene expression may be a potential candidate as antipathogenic drug. In this study anti-QS activity of peppermint (Mentha piperita oil was first tested using the Chromobacterium violaceum CVO26 biosensor. Further, the findings of the present investigation revealed that peppermint oil at sub-MICs strongly interfered with acyl homoserine lactone (AHL regulated virulence factors and biofilm formation in Pseudomonas aeruginosa and Aeromonas hydrophila. The result of molecular docking analysis attributed the quorum sensing inhibitory activity exhibited by peppermint oil to menthol. Assessment of ability of menthol to interfere with quorum sensing systems of various Gram-negative pathogens comprising diverse AHL molecules revealed that it reduced the AHL dependent production of violacein, virulence factors and biofilm formation indicating broad-spectrum anti-QS activity. Using two E. coli biosensors, MG4/pKDT17 and pEAL08-2, we also confirmed that menthol inhibited both the las and pqs quorum sensing systems. Further, findings of the in vivo studies with menthol on nematode model Caenorhabditis elegans showed significantly enhanced survival of the nematode. Our data identified menthol as a novel broad spectrum quorum sensing inhibitor.

  3. Study on the influence of quorum sensing on fish spoilage%群体感应对鱼类腐败的影响研究

    Institute of Scientific and Technical Information of China (English)

    顾清清; 王彦波

    2012-01-01

    Quorum sensing (QS) is the phenomenon in response to a certain content of the diffusible chemical signal molecules (auto inducers), which was produced by members of bacteria. Nowadays, quorum sensing has been one of the most important research fields in life sciences. Thus, this review presented the mechanisms of fish spoilage and the correlation with quorum sensing system based on kinds of signal molecules found in quorum sensing system. In addition, the influence of quorum sensing system on fish corruption was also discussed. The aim of this review is to provide a theoretical basis for the preservation and shelflife of fish and the research and development of novel preservative.%群体感应是指细菌产生可扩散的化学信号分子(自诱导物),当化学信号分子到达一定浓度时引起的感应现象,目前已经成为生命科学相关研究的热点之一.文章在综合分析群体感应系统及其信号分子的种类基础上,讨论了鱼类腐败的原因及群体感应系统对鱼类腐败的影响,旨在为鱼类贮藏保鲜,延长货架期及寻求新的防腐剂奠定一定的理论基础.

  4. Quorum sensing in veterinary pathogens: mechanisms, clinical importance and future perspectives.

    Science.gov (United States)

    Boyen, F; Eeckhaut, V; Van Immerseel, F; Pasmans, F; Ducatelle, R; Haesebrouck, F

    2009-03-30

    Under certain circumstances the individuals of a bacterial population may find advantages in acting together and making "collective decisions". This phenomenon is better known as quorum sensing. When the concentration of signal molecules produced by the surrounding bacteria exceeds a certain threshold, the bacterial population acts as a single organism, collectively expressing virulence genes, biofilm forming genes, etc. Several mechanisms of quorum sensing are discussed, each with its distinct signal molecules and respective receptors. Some of these mechanisms are restricted to sensing intraspecies signalling, but interspecies and even interkingdom signalling have also been described. Several veterinary pathogens such as Staphylococcus aureus, Staphylococcus pseudintermedius, Pseudomonas aeruginosa and Salmonella Typhimurium use quorum sensing as a means to optimize virulence gene expression and host colonization. Therefore, targeting of the QS mechanisms may provide a novel strategy for combating bacterial infections, also in veterinary medicine.

  5. Interspecific quorum sensing mediates the resuscitation of viable but nonculturable vibrios.

    Science.gov (United States)

    Ayrapetyan, Mesrop; Williams, Tiffany C; Oliver, James D

    2014-04-01

    Entry and exit from dormancy are essential survival mechanisms utilized by microorganisms to cope with harsh environments. Many bacteria, including the opportunistic human pathogen Vibrio vulnificus, enter a form of dormancy known as the viable but nonculturable (VBNC) state. VBNC cells can resuscitate when suitable conditions arise, yet the molecular mechanisms facilitating resuscitation in most bacteria are not well understood. We discovered that bacterial cell-free supernatants (CFS) can awaken preexisting dormant vibrio populations within oysters and seawater, while CFS from a quorum sensing mutant was unable to produce the same resuscitative effect. Furthermore, the quorum sensing autoinducer AI-2 could induce resuscitation of VBNC V. vulnificus in vitro, and VBNC cells of a mutant unable to produce AI-2 were unable to resuscitate unless the cultures were supplemented with exogenous AI-2. The quorum sensing inhibitor cinnamaldehyde delayed the resuscitation of wild-type VBNC cells, confirming the importance of quorum sensing in resuscitation. By monitoring AI-2 production by VBNC cultures over time, we found quorum sensing signaling to be critical for the natural resuscitation process. This study provides new insights into the molecular mechanisms stimulating VBNC cell exit from dormancy, which has significant implications for microbial ecology and public health.

  6. A Model of Rapid Radicalization Behavior Using Agent-Based Modeling and Quorum Sensing

    Science.gov (United States)

    Schwartz, Noah; Drucker, Nick; Campbell, Kenyth

    2012-01-01

    Understanding the dynamics of radicalization, especially rapid radicalization, has become increasingly important to US policy in the past several years. Traditionally, radicalization is considered a slow process, but recent social and political events demonstrate that the process can occur quickly. Examining this rapid process, in real time, is impossible. However, recreating an event using modeling and simulation (M&S) allows researchers to study some of the complex dynamics associated with rapid radicalization. We propose to adapt the biological mechanism of quorum sensing as a tool to explore, or possibly explain, rapid radicalization. Due to the complex nature of quorum sensing, M&S allows us to examine events that we could not otherwise examine in real time. For this study, we employ Agent Based Modeling (ABM), an M&S paradigm suited to modeling group behavior. The result of this study was the successful creation of rapid radicalization using quorum sensing. The Battle of Mogadishu was the inspiration for this model and provided the testing conditions used to explore quorum sensing and the ideas behind rapid radicalization. The final product has wider applicability however, using quorum sensing as a possible tool for examining other catalytic rapid radicalization events.

  7. Quorum-Sensing Kinetics in Saccharomyces cerevisiae: A Symphony of ARO Genes and Aromatic Alcohols.

    Science.gov (United States)

    Avbelj, Martina; Zupan, Jure; Kranjc, Luka; Raspor, Peter

    2015-09-30

    The kinetics of quorum sensing in Saccharomyces cerevisiae were studied using a mini-fermentation platform. The quorum-sensing molecules were monitored using our previous HPLC approach that is here supported by quantitative real-time PCR analysis of the quorum-sensing genes. We thus initially confirm correlations between peak production rates of the monitored quorum-sensing molecules 2-phenylethanol, tryptophol, and tyrosol and peak expression of the genes responsible for their synthesis: ARO8, ARO9, and ARO10. This confirms the accuracy of our previously implemented kinetic model, thus favoring its use in further studies in this field. We also show that the quorum-sensing kinetics are precisely dependent on the population growth phase and that tyrosol production is also regulated by cell concentration, which has not been reported previously. Additionally, we show that during wine fermentation, ethanol stress reduces the production of 2-phenylethanol, tryptophol, and tyrosol, which opens new challenges in the control of wine fermentation.

  8. Quorum sensing activity of Serratia fonticola strain RB-25 isolated from an ex-landfill site.

    Science.gov (United States)

    Ee, Robson; Lim, Yan-Lue; Tee, Kok-Keng; Yin, Wai-Fong; Chan, Kok-Gan

    2014-03-12

    Quorum sensing is a unique bacterial communication system which permits bacteria to synchronize their behaviour in accordance with the population density. The operation of this communication network involves the use of diffusible autoinducer molecules, termed N-acylhomoserine lactones (AHLs). Serratia spp. are well known for their use of quorum sensing to regulate the expression of various genes. In this study, we aimed to characterized the AHL production of a bacterium designated as strain RB-25 isolated from a former domestic waste landfill site. It was identified as Serratia fonticola using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry analysis and this was confirmed by 16S ribosomal DNA sequencing. High resolution triple quadrupole liquid chromatography-mass spectrometry analysis of S. fonticola strain RB-25 spent culture supernatant indicated the existence of three AHLs namely: N-butyryl-L-homoserine lactone (C4-HSL), N-hexanoyl-L-homoserine lactone (C6-HSL) and N-(3-oxohexanoyl) homoserine-lactone (3-oxo-C6 HSL). This is the first report of the production of these AHLs in S. fonticola.

  9. Quorum Sensing Activity of Serratia fonticola Strain RB-25 Isolated from an Ex-landfill Site

    Directory of Open Access Journals (Sweden)

    Robson Ee

    2014-03-01

    Full Text Available Quorum sensing is a unique bacterial communication system which permits bacteria to synchronize their behaviour in accordance with the population density. The operation of this communication network involves the use of diffusible autoinducer molecules, termed N-acylhomoserine lactones (AHLs. Serratia spp. are well known for their use of quorum sensing to regulate the expression of various genes. In this study, we aimed to characterized the AHL production of a bacterium designated as strain RB-25 isolated from a former domestic waste landfill site. It was identified as Serratia fonticola using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF mass spectrometry analysis and this was confirmed by 16S ribosomal DNA sequencing. High resolution triple quadrupole liquid chromatography-mass spectrometry analysis of S. fonticola strain RB-25 spent culture supernatant indicated the existence of three AHLs namely: N-butyryl-L-homoserine lactone (C4-HSL, N-hexanoyl-L-homoserine lactone (C6-HSL and N-(3-oxohexanoyl homoserine-lactone (3-oxo-C6 HSL. This is the first report of the production of these AHLs in S. fonticola.

  10. PepO, a CovRS-controlled endopeptidase, disrupts Streptococcus pyogenes quorum sensing.

    Science.gov (United States)

    Wilkening, Reid V; Chang, Jennifer C; Federle, Michael J

    2016-01-01

    Group A Streptococcus (GAS, Streptococcus pyogenes) is a human-restricted pathogen with a capacity to both colonize asymptomatically and cause illnesses ranging from pharyngitis to necrotizing fasciitis. An understanding of how and when GAS switches between genetic programs governing these different lifestyles has remained an enduring mystery and likely requires carefully tuned environmental sensors to activate and silence genetic schemes when appropriate. Herein, we describe the relationship between the Control of Virulence (CovRS, CsrRS) two-component system and the Rgg2/3 quorum-sensing pathway. We demonstrate that responses of CovRS to the stress signals Mg(2+) and a fragment of the antimicrobial peptide LL-37 result in modulated activity of pheromone signaling of the Rgg2/3 pathway through a means of proteolysis of SHP peptide pheromones. This degradation is mediated by the cytoplasmic endopeptidase PepO, which is the first identified enzymatic silencer of an RRNPP-type quorum-sensing pathway. These results suggest that under conditions in which the virulence potential of GAS is elevated (i.e. enhanced virulence gene expression), cellular responses mediated by the Rgg2/3 pathway are abrogated and allow individuals to escape from group behavior. These results also indicate that Rgg2/3 signaling is instead functional during non-virulent GAS lifestyles.

  11. Composition, anti-quorum sensing and antimicrobial activity of essential oils from Lippia alba

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    Jesus Olivero-Verbel

    2014-09-01

    Full Text Available Many Gram-negative pathogens have the ability to produce N-acylhomoserine lactones (AHLs as signal molecules for quorum sensing (QS. This cell-cell communication system allows them to coordinate gene expression and regulate virulence. Strategies to inhibit QS are promising for the control of infectious diseases or antibiotic resistant bacterial pathogens. The aim of the present study was to evaluate the anti-quorum sensing (anti-QS and antibacterial potential of five essential oils isolated from Lippia alba on the Tn-5 mutant of Chromobacterium violaceum CV026, and on the growth of the gram-positive bacteria S. aureus ATCC 25923. The anti-QS activity was detected through the inhibition of the QS-controlled violacein pigment production by the sensor bacteria. Results showed that two essential oils from L. alba, one containing the greatest geranial:neral and the other the highest limonene:carvone concentrations, were the most effective QS inhibitors. Both oils also had small effects on cell growth. Moreover, the geranial/neral chemotype oil also produced the maximum zone of growth inhibition against S. aureus ATCC 25923. These data suggest essential oils from L. alba have promising properties as QS modulators, and present antibacterial activity on S. aureus.

  12. Quorum Sensing Inhibition and Structure-Activity Relationships of β-Keto Esters.

    Science.gov (United States)

    Forschner-Dancause, Stephanie; Poulin, Emily; Meschwitz, Susan

    2016-07-25

    Traditional therapeutics to treat bacterial infections have given rise to multi-drug resistant pathogens, which pose a major threat to human and animal health. In several pathogens, quorum sensing (QS)-a cell-cell communication system in bacteria-controls the expression of genes responsible for pathogenesis, thus representing a novel target in the fight against bacterial infections. Based on the structure of the autoinducers responsible for QS activity and other QS inhibitors, we hypothesize that β-keto esters with aryl functionality could possess anti-QS activity. A panel of nineteen β-keto ester analogs was tested for the inhibition of bioluminescence (a QS-controlled phenotype) in the marine pathogen Vibrio harveyi. Initial screening demonstrated the need of a phenyl ring at the C-3 position for antagonistic activity. Further additions to the phenyl ring with 4-substituted halo groups or a 3- or 4-substituted methoxy group resulted in the most active compounds with IC50 values ranging from 23 µM to 53 µM. The compounds additionally inhibit green fluorescent protein production by E. coli JB525. Evidence is presented that aryl β-keto esters may act as antagonists of bacterial quorum sensing by competing with N-acyl homoserine lactones for receptor binding. Expansion of the β-keto ester panel will enable us to obtain more insight into the structure-activity relationships needed to allow for the development of novel anti-virulence agents.

  13. Mini Review of Phytochemicals and Plant Taxa with Activity as Microbial Biofilm and Quorum Sensing Inhibitors

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    Chieu Anh Kim Ta

    2015-12-01

    Full Text Available Microbial biofilms readily form on many surfaces in nature including plant surfaces. In order to coordinate the formation of these biofilms, microorganisms use a cell-to-cell communication system called quorum sensing (QS. As formation of biofilms on vascular plants may not be advantageous to the hosts, plants have developed inhibitors to interfere with these processes. In this mini review, research papers published on plant-derived molecules that have microbial biofilm or quorum sensing inhibition are reviewed with the objectives of determining the biosynthetic classes of active compounds, their biological activity in assays, and their families of occurrence and range. The main findings are the identification of plant phenolics, including benzoates, phenyl propanoids, stilbenes, flavonoids, gallotannins, proanthocyanidins and coumarins as important inhibitors with both activities. Some terpenes including monoterpenes, sesquiterpenes, diterpenes and triterpenes also have anti-QS and anti-biofilm activities. Relatively few alkaloids were reported. Quinones and organosulfur compounds, especially from garlic, were also active. A common feature is the polar nature of these compounds. Phytochemicals with these activities are widespread in Angiosperms in temperate and tropical regions, but gymnosperms, bryophytes and pteridophytes were not represented.

  14. Quorum Sensing Inhibition and Structure–Activity Relationships of β-Keto Esters

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    Stephanie Forschner-Dancause

    2016-07-01

    Full Text Available Traditional therapeutics to treat bacterial infections have given rise to multi-drug resistant pathogens, which pose a major threat to human and animal health. In several pathogens, quorum sensing (QS—a cell-cell communication system in bacteria—controls the expression of genes responsible for pathogenesis, thus representing a novel target in the fight against bacterial infections. Based on the structure of the autoinducers responsible for QS activity and other QS inhibitors, we hypothesize that β-keto esters with aryl functionality could possess anti-QS activity. A panel of nineteen β-keto ester analogs was tested for the inhibition of bioluminescence (a QS-controlled phenotype in the marine pathogen Vibrio harveyi. Initial screening demonstrated the need of a phenyl ring at the C-3 position for antagonistic activity. Further additions to the phenyl ring with 4-substituted halo groups or a 3- or 4-substituted methoxy group resulted in the most active compounds with IC50 values ranging from 23 µM to 53 µM. The compounds additionally inhibit green fluorescent protein production by E. coli JB525. Evidence is presented that aryl β-keto esters may act as antagonists of bacterial quorum sensing by competing with N-acyl homoserine lactones for receptor binding. Expansion of the β-keto ester panel will enable us to obtain more insight into the structure–activity relationships needed to allow for the development of novel anti-virulence agents.

  15. Composition, anti-quorum sensing and antimicrobial activity of essential oils from Lippia alba.

    Science.gov (United States)

    Olivero-Verbel, Jesus; Barreto-Maya, Ana; Bertel-Sevilla, Angela; Stashenko, Elena E

    2014-01-01

    Many Gram-negative pathogens have the ability to produce N-acylhomoserine lactones (AHLs) as signal molecules for quorum sensing (QS). This cell-cell communication system allows them to coordinate gene expression and regulate virulence. Strategies to inhibit QS are promising for the control of infectious diseases or antibiotic resistant bacterial pathogens. The aim of the present study was to evaluate the anti-quorum sensing (anti-QS) and antibacterial potential of five essential oils isolated from Lippia alba on the Tn-5 mutant of Chromobacterium violaceum CV026, and on the growth of the gram-positive bacteria S. aureus ATCC 25923. The anti-QS activity was detected through the inhibition of the QS-controlled violacein pigment production by the sensor bacteria. Results showed that two essential oils from L. alba, one containing the greatest geranial:neral and the other the highest limonene:carvone concentrations, were the most effective QS inhibitors. Both oils also had small effects on cell growth. Moreover, the geranial/neral chemotype oil also produced the maximum zone of growth inhibition against S. aureus ATCC 25923. These data suggest essential oils from L. alba have promising properties as QS modulators, and present antibacterial activity on S. aureus.

  16. Deciphering the role of coumarin as a novel quorum sensing inhibitor suppressing virulence phenotypes in bacterial pathogens.

    Science.gov (United States)

    Gutiérrez-Barranquero, José A; Reen, F Jerry; McCarthy, Ronan R; O'Gara, Fergal

    2015-04-01

    The rapid unchecked rise in antibiotic resistance over the last few decades has led to an increased focus on the need for alternative therapeutic strategies for the treatment and clinical management of microbial infections. In particular, small molecules that can suppress microbial virulence systems independent of any impact on growth are receiving increased attention. Quorum sensing (QS) is a cell-to-cell signalling communication system that controls the virulence behaviour of a broad spectrum of bacterial pathogens. QS systems have been proposed as an effective target, particularly as they control biofilm formation in pathogens, a key driver of antibiotic ineffectiveness. In this study, we identified coumarin, a natural plant phenolic compound, as a novel QS inhibitor, with potent anti-virulence activity in a broad spectrum of pathogens. Using a range of biosensor systems, coumarin was active against short, medium and long chain N-acyl-homoserine lactones, independent of any effect on growth. To determine if this suppression was linked to anti-virulence activity, key virulence systems were studied in the nosocomial pathogen Pseudomonas aeruginosa. Consistent with suppression of QS, coumarin inhibited biofilm, the production of phenazines and swarming motility in this organism potentially linked to reduced expression of the rhlI and pqsA quorum sensing genes. Furthermore, coumarin significantly inhibited biofilm formation and protease activity in other bacterial pathogens and inhibited bioluminescence in Aliivibrio fischeri. In light of these findings, coumarin would appear to have potential as a novel quorum sensing inhibitor with a broad spectrum of action.

  17. Herbs, Spices and Medicinal Plants Used In Hispanic Traditional Medicine Can Decrease Quorum Sensing Dependent Virulence in Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    V Huerta

    2008-06-01

    Full Text Available Summary: Inhibition of quorum sensing (QS, a cell density dependent regulation of bacterial virulent gene expression by autoinducers (AI is an attractive strategy for the discovery of novel antimicrobials and overcome antibiotic resistance. Pseudomonas aeruginosa (PAO1, an opportunistic pathogen in immune compromised patients is under the regulation of the LasR-RhlR system for its QS mediated development of virulence. Natural products have recently become a promising source for deriving molecules that can potentially inhibit quorum sensing.  Herbs, Spices and Medicinal Plants (HSMP used in Hispanic cultures have been used for treating common ailments for many centuries. However, few studies have investigated its QS related antivirulent activities. Our objective was to determine the ability of 25 popular Hispanic HSMP on the expression of QS regulated virulence factors in PAO1. Effect of these extracts on QS mediated PAO1 virulent factors pyocyanin, elastase, and total proteolytic activity were quantified by standard protocols. Results indicated that several extracts reduced pyocyanin synthesis, with some extracts completely inhibiting its formation and secretion. The extracts that decreased the pyocyanin formation also decreased the expression and activity of elastase and other proteolytic enzymes important for the virulence. We observed that HSMP from Central/South American countries can inhibit QS dependent and independent virulent processes in PA-O1. Further research into the exact mechanism of action can lead to better understanding and discovery of new category of drugs and strategies for the management of PAO1 infections and antimicrobial resistance.   Industrial relevance: Quorum sensing is an important process involved in bacterial survival and infections, recent research has focused on the development of therapeutic agents which prevent or manage bacterial pathogenesis by inhibiting bacterial QS. Inhibition of quorum sensing offers an

  18. Agaricus Blazei Hot Water Extract Shows Anti Quorum Sensing Activity in the Nosocomial Human PathogenPseudomonas Aeruginosa

    NARCIS (Netherlands)

    Sokovic, M.; Ciric, A.; Glamoclija, J.; Nicolic, M.; Griensven, van L.J.L.D.

    2014-01-01

    The edible mushroom Agaricus blazei Murill is known to induce protective immunomodulatory action against a variety of infectious diseases. In the present study we report potential anti-quorum sensing properties of A. blazei hot water extract. Quorum sensing (QS) plays an important role in virulence,

  19. The impact of quorum sensing on the virulence of Aeromonas hydrophila and Aeromonas salmonicida towards burbot (Lota lota L.) larvae.

    Science.gov (United States)

    Natrah, F M I; Alam, Md Iftakharul; Pawar, Sushant; Harzevili, A Shiri; Nevejan, Nancy; Boon, Nico; Sorgeloos, Patrick; Bossier, Peter; Defoirdt, Tom

    2012-09-14

    In this study, the link between quorum sensing in Aeromonas spp. and its virulence towards burbot (Lota lota) was investigated. High mortality occurred in burbot juveniles challenged with Aeromonas salmonicida HN-00, but not in juveniles challenged with Aeromonas hydrophila AH-1N. Meanwhile, both A. hydrophila AH-1N and A. salmonicida HN-00 were virulent towards larvae. The effect of quorum sensing on the virulence of A. hydrophila AH-1N towards burbot larvae was further investigated using quorum sensing mutants (N-(butyryl)-L-homoserine lactone production and receptor mutants). Challenge with these mutants resulted in higher survival of burbot larvae when compared to challenge with the wild type, and the addition of the signal molecule N-butyryl-L-homoserine lactone restored the virulence of the quorum sensing production mutant. Moreover, quorum sensing inhibitors protected the burbot larvae from both Aeromonas strains. Finally, the freshwater micro-algae Chlorella saccharophila and Chlamydomonas reinhardtii, which are able to interfere with quorum sensing, also protected burbot from the pathogens. However, QS interference was unlikely to be the only mechanism. This study revealed that the virulence of Aeromonas spp. towards burbot is regulated by quorum sensing and that quorum sensing inhibitors and micro-algae are promising biocontrol agents.

  20. Identification of poultry meat-derived fatty acids functioning as quorum sensing signal inhibitors of autoinducer-2 (AI-2)

    Science.gov (United States)

    Autoinducer-2 (AI-2) is a compound that plays a key role in bacterial cell-to-cell communication (quorum sensing). Previous research has shown certain food matrices inhibit this signaling compound. Using the reporter strain, Vibrio harveyi BB170, quorum sensing inhibitors contained in poultry meat...

  1. Herbs, Spices and Medicinal Plants Used In Hispanic Traditional Medicine Can Decrease Quorum Sensing Dependent Virulence in Pseudomonas aeruginosa

    OpenAIRE

    V Huerta; Mihalik, K; S H Crixell; D A Vattem

    2008-01-01

    Summary: Inhibition of quorum sensing (QS), a cell density dependent regulation of bacterial virulent gene expression by autoinducers (AI) is an attractive strategy for the discovery of novel antimicrobials and overcome antibiotic resistance. Pseudomonas aeruginosa (PAO1), an opportunistic pathogen in immune compromised patients is under the regulation of the LasR-RhlR system for its QS mediated development of virulence. Natural products have recently become a promising source for deriving mo...

  2. Identification of quorum sensing signal molecules and oligolignols associated with watermark disease in willow (Salix sp.).

    Science.gov (United States)

    Huvenne, Hanneke; Goeminne, Geert; Maes, Martine; Messens, Eric

    2008-09-01

    The bacterium Brenneria salicis is the causal agent of watermark disease in willow. This work shows the importance of in situ studies and high-resolution separation of biological samples with ultrahigh performance liquid chromatography combined with ion trap mass spectrometry to unambiguously identify molecular compounds associated with this disease. Approximately 40 oligolignols accumulated in wood sap of watermark diseased willow, and are indicative for degradation of the xylem cell wall, of which 15 were structurally assigned based on an earlier study. Many bacteria are known to produce and release quorum sensing signal molecules that switch on the expression of specific, sometimes pathogenic functions. Two quorum sensing signal molecules, N-(3-oxohexanoyl)-l-homoserine lactone and N-(hexanoyl)-l-homoserine lactone, were present in 4/1 ratios in diseased wood and in high-density in vitro cultures of B. salicis at 0.13-1.2 microM concentrations, and absent in healthy wood and in low-density in vitro cultures of B. salicis. Although it is not a proof, it can be an indication for involvement of quorum sensing in B. salicis pathogenesis. Cyclic dipeptides were present at high concentrations in high-density in vitro cultures of B. salicis, but not in situ, and were found not to be involved in quorum sensing signaling, therefore, the attribution of quorum signal properties to cyclic dipeptides isolated from in vitro cultures of pathogenic bacteria should be reconsidered.

  3. Classroom Activities to Engage Students and Promote Critical Thinking about Genetic Regulation of Bacterial Quorum Sensing

    Directory of Open Access Journals (Sweden)

    Kimberly Aebli

    2016-05-01

    Full Text Available We developed an interactive activity to mimic bacterial quorum sensing, and a classroom worksheet to promote critical thinking about genetic regulation of the lux operon. The interactive quorum sensing activity engages students and provides a direct visualization of how population density functions to influence light production in bacteria. The worksheet activity consists of practice problems that require students to apply basic knowledge of the lux operon in order to make predictions about genetic complementation experiments, and students must evaluate how genetic mutations in the lux operon affect gene expression and overall phenotype. The worksheet promotes critical thinking and problem solving skills, and emphasizes the roles of diffusible signaling molecules, regulatory proteins, and structural proteins in quorum sensing.

  4. The Effect of Magnetic Fields on the Quorum Sensing-Regulated Luminescence of Vibrio fischeri

    Science.gov (United States)

    Barron, Addie; Hagen, Steve; Son, Minjun

    2015-03-01

    Quorum sensing (QS) is a mechanism by which bacteria communicate through the secretion and detection of extracellular signaling molecules known as autoinducers. This research focuses on the quorum sensing regulated bioluminescence of Vibrio fischeri, a marine bacterium that lives in symbiosis with certain fish and squid species. Previous studies of V. harveyi, a close relative of V. fisheri, indicate that a strong magnetic field has a positive effect on V.harveyi bioluminescence. However the effect of magnetic fields on quorum sensing-regulated luminescence is in general poorly understood. We grew V. fischeri in solid and liquid growth media, subject to strong static magnetic fields, and imaged the bioluminescence over a period of forty-eight hours. Luminescence patterns were analyzed in both the spatial and time dimensions. We find no indication that a magnetic field influences Vibrio fischeri luminescence either positively or negatively. This research was funded by the Grant Number NSF DMR-1156737.

  5. Anti-Quorum Sensing Potential of Potato Rhizospheric Bacteria

    Directory of Open Access Journals (Sweden)

    Adeleh Sobhanipour

    2017-01-01

    Full Text Available The occurrence of antibiotic-resistant pathogenic bacteria is becoming a serious problem. The rise of multiresistance strains has forced the pharmaceutical industry to come up with new generation of more effective and potent antibiotics, therefore creating development of antivirulence compounds. Due to extensive usage of cell-to-cell bacterial communication (QS systems to monitor the production of virulence factors, disruption of QS system results in creation of a promising strategy for the control of bacterial infection. Numerous natural quorum quenching (QQ agents have been identified. In addition, many microorganisms are capable of producing smaller molecular QS inhibitors and/or macromolecular QQ enzymes. In present survey, anti QS activity of 1280 rhizosphere bacteria was assessed using the Pectobacterium carotovorum as AHL-donor and Chromobacterium violaceum CV026 as biosensor system. The results showed that 61 strains had highly AHL-degrading activity. Both Lux I and Lux R activity were affected by some isolates, suggesting that the rhizobacteria target both QS signal and receptor. These soil microorganisms with their anti-QS activity have the potential to be novel therapeutic agents for reducing virulence and pathogenicity of antibiotic resistant bacteria.

  6. Negative regulation of bacterial quorum sensing tunes public goods cooperation.

    Science.gov (United States)

    Gupta, Rashmi; Schuster, Martin

    2013-11-01

    Bacterial quorum sensing (QS) often coordinates the expression of other, generally more costly public goods involved in virulence and nutrient acquisition. In many Proteobacteria, the basic QS circuitry consists of a synthase that produces a diffusible acyl-homoserine lactone and a cognate receptor that activates public goods expression. In some species, the circuitry also contains negative regulators that have the potential to modulate the timing and magnitude of activation. In this study, we experimentally investigated the contribution of this regulatory function to the evolutionary stability of public goods cooperation in the opportunistic pathogen Pseudomonas aeruginosa. We compared fitness and public goods expression rates of strains lacking either qteE or qscR, each encoding a distinct negative regulator, with those of the wild-type parent and a signal-blind receptor mutant under defined growth conditions. We found that (1) qteE and qscR mutations behave virtually identically and have a stronger effect on the magnitude than on the timing of expression, (2) high expression in qteE and qscR mutants imposes a metabolic burden under nutrient conditions that advance induction and (3) high expression in qteE and qscR mutants increases population growth when QS is required, but also permits invasion by both wild-type and receptor mutant strains. Our data indicate that negative regulation of QS balances the costs and benefits of public goods by attenuating expression after transition to the induced state. As the cells cannot accurately assess the amount of cooperation needed, such bet-hedging would be advantageous in changing parasitic and nonparasitic environments.

  7. Quorum sensing: a non-conventional target for antibiotic discovery.

    Science.gov (United States)

    Naik, Varsha; Mahajan, Girish

    2013-10-01

    Quorum sensing (QS) is known to regulate different functions viz. pathogenesis, biofilm formation, and host colonization, along with other functions by regulating bacterial virulence determinants. Therefore, QS is deemed to be an interesting target to modulate pathogenesis. Also, there have been global reports of continuous emergence of antibiotic-resistant microbes; hence, an alternative treatment that compliments antibiotic activity is highly desirable. One such approach is to look for QS inhibitors, which can quench the virulence phenotypes exerted by pathogenic bacteria and compliment antibiotic treatment. In the present study, Pseudomonas aeruginosa strain was used as the model organism which produces three pigments viz. pyocyanin, pyoverdin and pyorubin. Pyocyanin synthesis is reported to be QS dependent and is one of the virulence factors of P. aeruginosa. Hence, we envisage inhibition of pyocyanin pigment would indicate QS inhibition (QSI). Auto-inducers like N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL/3-oxo-C12-HSL) and N-butyryl-L- homoserine lactone (BHL/C4-HSL) were used to enhance the pyocyanin pigment production by the model strain at different doses and time points. BHL, at 25 microM was found to be a better inducer of pyocyanin. Tannic acid (TA) was tested to suppress this pigment synthesis and it was found to be effective when assessed at different time points. About 5.12 mg/mL TA was found to be the optimum concentration at which pyocyanin was inhibited by 77.3%. Thus, we confirm that TA can be used as a QSI, either in its purest form or in the crude form found in various plant species, and could be considered for development to compliment antibiotic therapy.

  8. Inhibition of marine biofouling by bacterial quorum sensing inhibitors

    Science.gov (United States)

    Dobretsov, Sergey; Teplitski, Max; Bayer, Mirko; Gunasekera, Sarath; Proksch, Peter; Paul, Valerie J

    2012-01-01

    Seventy eight natural products from chemical libraries containing compounds from marine organisms (sponges, algae, fungi, tunicates and cyanobacteria) and terrestrial plants, were screened for the inhibition of bacterial quorum sensing (QS) using a reporter strain Chromobacterium violaceum CV017. About half of the natural products did not show any QS inhibition. Twenty four percent of the tested compounds inhibited QS of the reporter without causing toxicity. The QS inhibitory activities of the most potent and abundant compounds were further investigated using the LuxR-based reporter E. coli pSB401 and the LasR-based reporter E. coli pSB1075. Midpacamide and tenuazonic acid were toxic to the tested reporters. QS-dependent luminescence of the LasR-based reporter, which is normally induced by N-3-oxo-dodecanoyl-L-homoserine lactone, was reduced by demethoxy encecalin and hymenialdisin at concentrations 46.6 μM and 15μM, respectively. Hymenialdisin, demethoxy encecalin, microcolins A and B and kojic acid inhibited responses of the LuxR-based reporter induced by N-3-oxo-hexanoyl-L-homoserine lactone at concentrations 40.2 μM, 2.2 μM, 1.5 μM, 15 μM and 36 μM, respectively. The ability to prevent microfouling by one of the compounds screened in this study (kojic acid; final concentrations 330 μM and 1 mM) was tested in a controlled mesocosm experiment. Kojic acid inhibited formation of microbial communities on glass slides, decreasing the densities of bacteria and diatoms in comparison with the control lacking kojic acid. The study suggests that natural products with QS inhibitory properties can be used for controlling biofouling communities. PMID:21882898

  9. Structure-based discovery and experimental verification of novel AI-2 quorum sensing inhibitors against Vibrio harveyi.

    Science.gov (United States)

    Li, Minyong; Ni, Nanting; Chou, Han-Ting; Lu, Chung-Dar; Tai, Phang C; Wang, Binghe

    2008-08-01

    Quorum sensing has been implicated in the control of pathologically relevant bacterial behavior such as secretion of virulence factors, biofilm formation, sporulation, and swarming motility. The AI-2 quorum sensing pathway is found in both gram-positive and gram-negative bacteria. Therefore, antagonizing AI-2 quorum sensing is a possible approach to modifying bacterial behaviour. However, efforts in developing inhibitors of AI-2-mediated quorum sensing are especially lacking. High-throughput virtual screening using the V. harveyi LuxP crystal structure identified two compounds that were found to antagonize AI-2-mediated quorum sensing in V. harveyi without cytotoxicity. The sulfone functionality of these inhibitors was identified as critical to their ability to mimic the natural ligand in their interactions with Arg 215 and Arg 310 of the active site.

  10. Quorum sensing in human pathogens%病原菌群体感应系统的研究进展

    Institute of Scientific and Technical Information of China (English)

    钱妩燕; 江涛

    2012-01-01

    群体感应是细菌间依赖细胞密度的一种信息传递方式.细菌通过合成、分泌信号分子感知细菌群体密度,从而控制整个细菌群体行为.目前已在许多革兰阴性菌、革兰阳性菌和真菌中发现群体感应系统,对群体感应系统信号分子结构、信号传导通路进行大量研究后,发现其与细菌生物膜形成、生成分泌毒力因子密切相关.本文就以典型的铜绿假单胞菌、金黄色葡萄球菌、哈氏弧菌、白色念珠菌为例,对群体感应系统相关机制及研究进展予以综述.%Quorum sensing is a density-dependent cell-signaling m(cc)hanism,driven by secreted signaling molecules called autoinducer. Communication enables population of cells to synchronize gene expression.Thus,quorum sensing allows groups of bacteria to act in union by perception of bacterial population density.A number of quorum sensing systems have been found in gram-negative bacteria,grampositive bacteria and fungi,which are commonly associated with biofilm formation and virulence. This review focuses on the lasted mechanism of quorum sensing system based on typical pathogen,including Pseudomonas aeruginosa,Staphylococcus aureus,Vibrio harveyi and Candida albicans.

  11. Amphypterygium adstringens anacardic acid mixture inhibits quorum sensing-controlled virulence factors of Chromobacterium violaceum and Pseudomonas aeruginosa.

    Science.gov (United States)

    Castillo-Juárez, Israel; García-Contreras, Rodolfo; Velázquez-Guadarrama, Norma; Soto-Hernández, Marcos; Martínez-Vázquez, Mariano

    2013-10-01

    Quorum sensing (QS) is a process of bacterial cell-cell communication that controls a large number of systems affecting pathogenicity. Interrupting this communication system can provide nonvirulent pathogenic bacteria. The aim of this study was to evaluate the anti-quorum sensing (anti-QS) potential of an anacardic acids mixture isolated from Amphipterygium adstringens, a medicinal plant known as "cuachalalate", to prevent the onset of bacterial infections as an alternate to antibiotics. Initially we investigated the anti-QS activity of A. adstringens hexane extract (HE) by the inhibition of violacein production in Chromobacterium violaceum. From the active HE, an anacardic acid mixture (AAM) was obtained. The anti-quorum sensing activity of AAM was investigated by the rhamnolipid and pyocyanin production constraint as well as decrease of elastase activity, all being quorum sensing-controlled virulence factors expressed in the pathogenic bacteria Pseudomonas aeruginosa. HE induced a 91.6% of inhibition of the violecin production at 55 μg/mL concentration, whereas AAM showed 94% of inhibition at 166 μg/mL. In both cases, inhibition of violacein production did not affect the viability of the bacterium. AAM inhibited pyocyanin (86% at 200 μg/mL) and rhamnolipid (91% at 500 μg/mL) production in a dose/response form and decrease the elastase (75% at 500 μg/mL) activity in P. aeruginosa without affecting its development. Because an anacardic acids mixture isolated from A. adstringens demonstrated anti-QS, it could be further exploited for novel molecules to treat the emerging infections of antibiotic-resistant bacterial pathogens. Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.

  12. Dynamical quorum sensing and clustering dynamics in a population of spatially distributed active rotators

    Science.gov (United States)

    Sakaguchi, Hidetsugu; Maeyama, Satomi

    2013-02-01

    A model of clustering dynamics is proposed for a population of spatially distributed active rotators. A transition from excitable to oscillatory dynamics is induced by the increase of the local density of active rotators. It is interpreted as dynamical quorum sensing. In the oscillation regime, phase waves propagate without decay, which generates an effectively long-range interaction in the clustering dynamics. The clustering process becomes facilitated and only one dominant cluster appears rapidly as a result of the dynamical quorum sensing. An exact localized solution is found to a simplified model equation, and the competitive dynamics between two localized states is studied numerically.

  13. Inhibition of quorum sensing in Pseudomonas aeruginosa biofilm bacteria by a halogenated furanone compound

    DEFF Research Database (Denmark)

    Hentzer, Morten; Riedel, Kathrin; Rasmussen, Thomas B;

    2002-01-01

    Novel molecular tools have been constructed which allow for in situ detection of N-acyl homoserine lactone (AHL)-mediated quorum sensing in Pseudomonas aeruginosa biofilms. The reporter responds to AHL activation of LasR by expression of an unstable version of the green-fluorescent protein (Gfp...... macroalga Delisea pulchra, is capable of interfering with AHL-mediated quorum sensing in P. aeruginosa. It is demonstrated that the furanone compound specifically represses expression of a PlasB-gfp reporter fusion without affecting growth or protein synthesis. In addition, it reduces the production...

  14. Inhibition of quorum sensing in Pseudomonas aeruginosa biofilm bacteria by a halogenated furanone compound

    DEFF Research Database (Denmark)

    Hentzer, Morten; Riedel, K.; Rasmussen, Thomas Bovbjerg

    2002-01-01

    Novel molecular tools have been constructed which allow for in situ detection of N-acyl homoserine lactone (AHL)-mediated quorum sensing in Pseudomonas aeruginosa biofilms. The reporter responds to AHL activation of LasR lay expression of an unstable version of the green-fluorescent protein (Gfp......). Gfp-based reporter technology has been applied for non-destructive, single-cell-level detection of quorum sensing in laboratory-based P. aeruginosa biofilms. It is reported that a synthetic halogenated furanone compound, which is a derivative of the secondary metabolites produced by the Australian...

  15. Response of Salmonella Typhi to bile-generated oxidative stress: implication of quorum sensing and persister cell populations.

    Science.gov (United States)

    Walawalkar, Yogesh D; Vaidya, Yatindra; Nayak, Vijayashree

    2016-11-01

    Salmonella Typhi can chronically persist within the gallbladder of patients suffering from gallbladder diseases. This study, intended to improve our understanding of bacterial mechanisms underlying bile adaptation, revealed that bile, which is a bactericidal agent, led to the generation of reactive oxygen species in S Typhi. Salmonella Typhi in response showed a significant increase in the production of anti-oxidative enzymes, namely superoxide dismutase and catalase. The work reports that the quorum-sensing (QS) system of S Typhi regulates the level of these enzymes during oxidative stress. In support of these observations, the quorum-sensing mutant of S Typhi was found to be sensitive to bile with significantly lower levels of anti-oxidant enzymes compared to other clinical isolates. Furthermore the addition of exogenous cell-free extracts (CFEs) of S Typhi containing the quorum-sensing signalling molecule significantly increased the levels of these enzymes within the mutant. Interestingly the CFE addition did not significantly restore the biofilm-forming ability of the mutant strain when compared with the wild-type. In the presence of ciprofloxacin and ampicillin, S Typhi formed persister cells which increased >3-fold in the presence of bile. Thus the QS-system of S Typhi aids in oxidative stress management, and enhanced persister cell populations could assist chronic bacterial persistence within the gallbladder.

  16. Choosing an Appropriate Infection Model to Study Quorum Sensing Inhibition in Pseudomonas Infections

    Directory of Open Access Journals (Sweden)

    Evelina Papaioannou

    2013-09-01

    Full Text Available Bacteria, although considered for decades to be antisocial organisms whose sole purpose is to find nutrients and multiply are, in fact, highly communicative organisms. Referred to as quorum sensing, cell-to-cell communication mechanisms have been adopted by bacteria in order to co-ordinate their gene expression. By behaving as a community rather than as individuals, bacteria can simultaneously switch on their virulence factor production and establish successful infections in eukaryotes. Understanding pathogen-host interactions requires the use of infection models. As the use of rodents is limited, for ethical considerations and the high costs associated with their use, alternative models based on invertebrates have been developed. Invertebrate models have the benefits of low handling costs, limited space requirements and rapid generation of results. This review presents examples of such models available for studying the pathogenicity of the Gram-negative bacterium Pseudomonas aeruginosa. Quorum sensing interference, known as quorum quenching, suggests a promising disease-control strategy since quorum-quenching mechanisms appear to play important roles in microbe-microbe and host-pathogen interactions. Examples of natural and synthetic quorum sensing inhibitors and their potential as antimicrobials in Pseudomonas-related infections are discussed in the second part of this review.

  17. Choosing an appropriate infection model to study quorum sensing inhibition in Pseudomonas infections.

    Science.gov (United States)

    Papaioannou, Evelina; Utari, Putri Dwi; Quax, Wim J

    2013-09-23

    Bacteria, although considered for decades to be antisocial organisms whose sole purpose is to find nutrients and multiply are, in fact, highly communicative organisms. Referred to as quorum sensing, cell-to-cell communication mechanisms have been adopted by bacteria in order to co-ordinate their gene expression. By behaving as a community rather than as individuals, bacteria can simultaneously switch on their virulence factor production and establish successful infections in eukaryotes. Understanding pathogen-host interactions requires the use of infection models. As the use of rodents is limited, for ethical considerations and the high costs associated with their use, alternative models based on invertebrates have been developed. Invertebrate models have the benefits of low handling costs, limited space requirements and rapid generation of results. This review presents examples of such models available for studying the pathogenicity of the Gram-negative bacterium Pseudomonas aeruginosa. Quorum sensing interference, known as quorum quenching, suggests a promising disease-control strategy since quorum-quenching mechanisms appear to play important roles in microbe-microbe and host-pathogen interactions. Examples of natural and synthetic quorum sensing inhibitors and their potential as antimicrobials in Pseudomonas-related infections are discussed in the second part of this review.

  18. Quorum sensing influences Vibrio harveyi growth rates in a manner not fully accounted for by the marker effect of bioluminescence.

    Directory of Open Access Journals (Sweden)

    Zeena E Nackerdien

    Full Text Available BACKGROUND: The light-emitting Vibrios provide excellent material for studying the interaction of cellular communication with growth rate because bioluminescence is a convenient marker for quorum sensing. However, the use of bioluminescence as a marker is complicated because bioluminescence itself may affect growth rate, e.g. by diverting energy. METHODOLOGY/PRINCIPAL FINDINGS: The marker effect was explored via growth rate studies in isogenic Vibrio harveyi (Vh strains altered in quorum sensing on the one hand, and bioluminescence on the other. By hypothesis, growth rate is energy limited: mutants deficient in quorum sensing grow faster because wild type quorum sensing unleashes bioluminescence and bioluminescence diverts energy. Findings reported here confirm a role for bioluminescence in limiting Vh growth rate, at least under the conditions tested. However, the results argue that the bioluminescence is insufficient to explain the relationship of growth rate and quorum sensing in Vh. A Vh mutant null for all genes encoding the bioluminescence pathway grew faster than wild type but not as fast as null mutants in quorum sensing. Vh quorum sensing mutants showed altered growth rates that do not always rank with their relative increase or decrease in bioluminescence. In addition, the cell-free culture fluids of a rapidly growing Vibrio parahaemolyticus (Vp strain increased the growth rate of wild type Vh without significantly altering Vh's bioluminescence. The same cell-free culture fluid increased the bioluminescence of Vh quorum mutants. CONCLUSIONS/SIGNIFICANCE: The effect of quorum sensing on Vh growth rate can be either positive or negative and includes both bioluminescence-dependent and independent components. Bioluminescence tends to slow growth rate but not enough to account for the effects of quorum sensing on growth rate.

  19. 基于LuxS的群体感应系统在乳酸茵共培养中的研究%Resent Progresses on LuxS-Mediated Quorum Sensing System in Co-culture Among Latic Acid Bacteria

    Institute of Scientific and Technical Information of China (English)

    张腾; 贺银凤

    2012-01-01

    群体感应是微生物调控群体行为的重要方式,基于LuxS的群体感应系统广泛存在于各种属细菌中。AI一2作为LuxS系统的信号分子,在细胞交流中起到关键作用。LuxS系统在多种乳酸菌共同作用完成发酵任务以及某些乳酸菌行使益生功能中发挥了重要作用。文中综述了AI一2的合成途径、转导方式并重点阐述LuxS系统对乳酸菌共培养过程中蛋白表达和基因转录的影响。对LuxS系统进行深入研究,必将进一步揭示多种乳酸菌共同发酵以及其完成益生功能的机理,为从分子水平调控乳酸菌的发酵和益生行为提供了可能。%Quorum sensing is an important way for bacteria to control its group behaviors. LuxS-mediated quorum sensing widely exists in many species of bacteria. AI-2 used as autoinducer of LuxS-mediated system plays an impor- tant role in cell to cell communication. LuxS-mediated system makes a significant effect on fermentation process con- trolled by multiple latic acid bacteria (LAB). This paper reviews the way of AI-2 synthesis and transduction. We will also focus on the changes of protein expression and gene transcription regulated by LuxS-mediated system under the condition of co-culture among LABs. Researching in LuxS-mediated system will further reveal the mechanism of multiple LABs jointly working in fermentation and make it possible to control sourdough LABs' group behaviors in the mo- lecular level.

  20. Function analysis of luxS gene relating to quorum sensing system in Enterococcus faecalis%粪肠球菌群体感应系统luxS基因的研究

    Institute of Scientific and Technical Information of China (English)

    邵长林; 孙忠科; 尚伟; 袁静; 廖祥儒

    2011-01-01

    Objective To study the function of luxS gene relating to quorum sensing system and synthesize AI-2 signaling molecules in vitro and to further explore the LuxS/AI-2 dependent quorum sensing system in Enterococcus faecalis. Methods First, Vibrio harveyi BB170 was used as a reporter strain to detect the AI-2 activity of culture supernatants from E. Faecalis. Secondly, luxS and pfs genes were amplified from E. Faecalis and compared with the amino acid sequences. Then,the two genes were inserted into pGEX-4T-l expression vector, transformed into Escherichia coli BL2l( DE3 ) for expression and purification. Finally, AI-2 was synthesized in vitro with S-adenosylhomocysteine( SAH ) as a substrate and the purified proteins or cell proteins from E. Coli as catalytic enzymes for the reaction. Results Three strains of E. Faecalis were all able to secrete the active AI-2 signaling molecules. A high LuxS protein homology was analyzed among E. Faecalis, V. Harveyi, Salmonella typhimurium and E. Coli. The active AI-2 molecules could be synthesized by SAH with purified proteins or cell proteins from E. Coli. Conclusion LuxS/AI-2 dependent quorum sensing system is found in E. Faecalis and the luxS gene is required for AI-2 production.%目的 研究粪肠球菌群体感应系统luxS基因的功能并体外合成AI-2信号分子,为研究粪肠球菌LuxS/AI-2依赖的群体感应系统提供依据.方法 以哈氏弧菌BB170作为报告菌株,检测3株粪肠球菌培养上清的AI-2活性,然后从粪肠球菌中扩增出luxS和pfs基因,测序和比对氨基酸序列,并将两基因插入到pGEX-4T-1表达载体中,转化至大肠杆菌BL21(DE3)中实现表达与纯化,进而以S-腺苷高半胱氨酸为底物、纯化的蛋白或构建的大肠杆菌菌体蛋白为反应酶,体外合成AI-2.结果 3株粪肠球菌均能够分泌有活性的AI-2信号分子;LuxS蛋白序列分析发现其与哈氏弧菌、沙门菌、大肠杆菌具有高度同源性;SAH均可以与纯化的蛋白

  1. Identification of poultry meat-derived fatty acids functioning as quorum sensing signal inhibitors to autoinducer-2 (AI-2).

    Science.gov (United States)

    Widmer, K W; Soni, K A; Hume, M E; Beier, R C; Jesudhasan, P; Pillai, S D

    2007-11-01

    Autoinducer-2 (AI-2) is a compound that plays a key role in bacterial cell-to-cell communication (quorum sensing). Previous research has shown certain food matrices inhibit this signaling compound. Using the reporter strain, Vibrio harveyi BB170, quorum-sensing inhibitors contained in poultry meat wash (PMW) samples were characterized by molecular weight and hydrophobic properties using liquid chromatography systems. Most fractions that demonstrated AI-2 inhibition were 13.7 kDa or less, and had hydrophobic properties. Hexane was used to extract inhibitory compounds from a PMW preparation and the extract was further separated by gas chromatography (GC). Several fatty acids were identified and quantified. Linoleic acid, oleic acid, palmitic acid, and stearic acid were each tested for inhibition at 0.1, 1, and 10 mM concentrations. All samples expressed AI-2 inhibition (ranging from approximately 25% to 99%). Fatty acids, combined in concentrations equivalent to those determined by GC analysis, expressed inhibition at 59.5%, but higher combined concentrations (10- and 100-fold) had inhibition at 84.4% and 69.5%, respectively. The combined fatty acids (100-fold) did not demonstrate a substantial decrease in colony plate counts, despite presenting high AI-2 inhibition. These fatty acids, through modulating quorum sensing by inhibition, may offer a unique means to control foodborne pathogens and reduce microbial spoilage.

  2. Structure and Inhibition of Quorum Sensing Target from Streptococcus pneumoniae

    Energy Technology Data Exchange (ETDEWEB)

    Singh,V.; Shi, W.; Almo, S.; Evans, G.; Furneaux, R.; Tyler, P.; Painter, G.; Lenz, D.; Mee, S.; et al.

    2006-01-01

    Streptococcus pneumoniae 5'-methylthioadenosine/S-adenosylhomocysteine hydrolase (MTAN) catalyzes the hydrolytic deadenylation of its substrates to form adenine and 5-methylthioribose or S-ribosylhomocysteine (SRH). MTAN is not found in mammals but is involved in bacterial quorum sensing. MTAN gene disruption affects the growth and pathogenicity of bacteria, making it a target for antibiotic design. Kinetic isotope effects and computational studies have established a dissociative S{sub N}1 transition state for Escherichia coli MTAN, and transition state analogues resembling the transition state are powerful inhibitors of the enzyme [Singh, V., Lee, J. L., Nunez, S., Howell, P. L., and Schramm, V. L. (2005) Biochemistry 44, 11647-11659]. The sequence of MTAN from S. pneumoniae is 40% identical to that of E. coli MTAN, but S. pneumoniae MTAN exhibits remarkably distinct kinetic and inhibitory properties. 5'-Methylthio-Immucillin-A (MT-ImmA) is a transition state analogue resembling an early S{sub N}1 transition state. It is a weak inhibitor of S. pneumoniae MTAN with a K{sub i} of 1.0 {mu}M. The X-ray structure of S. pneumoniae MTAN with MT-ImmA indicates a dimer with the methylthio group in a flexible hydrophobic pocket. Replacing the methyl group with phenyl (PhT-ImmA), tolyl (p-TolT-ImmA), or ethyl (EtT-ImmA) groups increases the affinity to give K{sub i} values of 335, 60, and 40 nM, respectively. DADMe-Immucillins are geometric and electrostatic mimics of a fully dissociated transition state and bind more tightly than Immucillins. MT-DADMe-Immucillin-A inhibits with a K{sub i} value of 24 nM, and replacing the 5'-methyl group with p-Cl-phenyl (p-Cl-PhT-DADMe-ImmA) gave a K{sub i}* value of 0.36 nM. The inhibitory potential of DADMe-Immucillins relative to the Immucillins supports a fully dissociated transition state structure for S. pneumoniae MTAN. Comparison of active site contacts in the X-ray crystal structures of E. coli and S. pneumoniae

  3. Bacterial behaviors associated with the quorum-sensing peptide pheromone ('alarmone') in streptococci.

    Science.gov (United States)

    Dufour, Delphine; Lévesque, Céline M

    2013-05-01

    Streptococci are among the predominant bacterial species living in the human body. They are normally harmless bacteria, but have the ability to cause diverse infections, ranging from mild (e.g., tooth decay and sore throat) to life-threatening (e.g., endocarditis and meningitis). Streptococci have evolved various means of coping with the deleterious effects of environmental stressors and avoiding the host immune system. Recently, several studies have shown that streptococci colonizing the mouth and upper respiratory tract are able to mount complex stress responses in order to persist and successfully survive competition in their ecological niche. Using a small quorum-sensing peptide pheromone acting as a stress-inducible 'alarmone', oral streptococci synchronize the gene expression of a specific group of cells to coordinate important biological activities.

  4. Pseudomonas cremoricolorata Strain ND07 Produces N-acyl Homoserine Lactones as Quorum Sensing Molecules

    Directory of Open Access Journals (Sweden)

    Nina Yusrina Muhamad Yunos

    2014-06-01

    Full Text Available Quorum sensing (QS is a bacterial cell-to-cell communication system controlling QS-mediated genes which is synchronized with the population density. The regulation of specific gene activity is dependent on the signaling molecules produced, namely N-acyl homoserine lactones (AHLs. We report here the identification and characterization of AHLs produced by bacterial strain ND07 isolated from a Malaysian fresh water sample. Molecular identification showed that strain ND07 is clustered closely to Pseudomonas cremoricolorata. Spent culture supernatant extract of P. cremoricolorata strain ND07 activated the AHL biosensor Chromobacterium violaceum CV026. Using high resolution triple quadrupole liquid chromatography-mass spectrometry, it was confirmed that P. cremoricolorata strain ND07 produced N-octanoyl-l-homoserine lactone (C8-HSL and N-decanoyl-l-homoserine lactone (C10-HSL. To the best of our knowledge, this is the first documentation on the production of C10-HSL in P. cremoricolorata strain ND07.

  5. Antibiotic-mediated selection of quorum-sensing-negative Staphylococcus aureus

    DEFF Research Database (Denmark)

    Paulander, Wilhelm Erik Axel; Varming, Anders Nissen; Bæk, Kristoffer Torbjørn

    2012-01-01

    , agr deficiency correlates with increased duration of and mortality due to bacteremia during antibiotic treatment and with a higher frequency of glycopeptide resistance than in agr-carrying strains. Our results provide an explanation for the frequent isolation of agr-defective strains from hospital...... of glycopeptide resistance greater than those of other strains. We show here that agr-negative strains have a fitness advantage over agr-positive strains in the presence of sublethal concentrations of some antibiotics and that the fitness defect of agr-positive cells is caused by antibiotic-mediated expression......Staphylococcus aureus is a human commensal that at times turns into a serious bacterial pathogen causing life-threatening infections. For the delicate control of virulence, S. aureus employs the agr quorum-sensing system that, via the intracellular effector molecule RNAIII, regulates virulence gene...

  6. Rosmarinic acid is a homoserine lactone mimic produced by plants that activates a bacterial quorum-sensing regulator.

    Science.gov (United States)

    Corral-Lugo, Andrés; Daddaoua, Abdelali; Ortega, Alvaro; Espinosa-Urgel, Manuel; Krell, Tino

    2016-01-05

    Quorum sensing is a bacterial communication mechanism that controls genes, enabling bacteria to live as communities, such as biofilms. Homoserine lactone (HSL) molecules function as quorum-sensing signals for Gram-negative bacteria. Plants also produce previously unidentified compounds that affect quorum sensing. We identified rosmarinic acid as a plant-derived compound that functioned as an HSL mimic. In vitro assays showed that rosmarinic acid bound to the quorum-sensing regulator RhlR of Pseudomonas aeruginosa PAO1 and competed with the bacterial ligand N-butanoyl-homoserine lactone (C4-HSL). Furthermore, rosmarinic acid stimulated a greater increase in RhlR-mediated transcription in vitro than that of C4-HSL. In P. aeruginosa, rosmarinic acid induced quorum sensing-dependent gene expression and increased biofilm formation and the production of the virulence factors pyocyanin and elastase. Because P. aeruginosa PAO1 infection induces rosmarinic acid secretion from plant roots, our results indicate that rosmarinic acid secretion is a plant defense mechanism to stimulate a premature quorum-sensing response. P. aeruginosa is a ubiquitous pathogen that infects plants and animals; therefore, identification of rosmarinic acid as an inducer of premature quorum-sensing responses may be useful in agriculture and inform human therapeutic strategies.

  7. Synthesis of new 3-and 4-substituted analogues of acyl homoserine lactone quorum sensing autoinducers

    DEFF Research Database (Denmark)

    Olsen, Jacob Alsbæk; Severinsen, Rune Eg; Rasmussen, Thomas Bovbjerg

    2002-01-01

    The quorum sensing mechanism in Gram-negative bacteria uses small intercellular signal molecules, N-acyl-homoserine lactones (AHLs), to control transcription of specific genes in relation to population density. In this communication, we describe the parallel synthesis of new AHL analogues, in which...

  8. Synthesis of new 3- and 4-substituted analogues of acyl homoserine lactone quorum sensing autoinducers

    DEFF Research Database (Denmark)

    Olsen, J. A.; Severinsen, R.; Rasmussen, T. B.

    2002-01-01

    The quorum sensing mechanism in Gram-negative bacteria uses small intercellular signal molecules, N-acyl-homoserine lactones (AHLs), to control transcription of specific genes in relation to population density. In this communication, we describe the parallel synthesis of new AHL analogues, in which...

  9. Going beyond the Control of Quorum-Sensing to Combat Biofilm Infections.

    Science.gov (United States)

    Abraham, Wolf-Rainer

    2016-01-09

    Most bacteria attach to surfaces where they form a biofilm, cells embedded in a complex matrix of polymers. Cells in biofilms are much better protected against noxious agents than free-living cells. As a consequence it is very difficult to control pathogens with antibiotics in biofilm infections and novel targets are urgently needed. One approach aims at the communication between cells to form and to maintain a biofilm, a process called quorum-sensing. Water soluble small-sized molecules mediate this process and a number of antagonists of these compounds have been found. In this review natural compounds and synthetic drugs which do not interfere with the classical quorum-sensing compounds are discussed. For some of these compounds the targets are still not known, but others interfere with the formation of exopolysaccharides, virulence factors, or cell wall synthesis or they start an internal program of biofilm dispersal. Some of their targets are more conserved among pathogens than the receptors for quorum sensing autoinducers mediating quorum-sensing, enabling a broader application of the drug. The broad spectrum of mechanisms, the diversity of bioactive compounds, their activity against several targets, and the conservation of some targets among bacterial pathogens are promising aspects for several clinical applications of this type of biofilm-controlling compound in the future.

  10. Melnikov method to a bacteria-immunity model with bacterial quorum sensing mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Zhonghua [School of Sciences, Xi' an University of Science and Technology, Xi' an 710054 (China)], E-mail: wwwzhonghua@sohu.com; Peng Jigen [Research Center for Applied Mathematics, Xi' an Jiaotong University, Xi' an 710049 (China); Zhang Juan [Department of Mathematics, North China Electric Power University, Beijing 102206 (China)

    2009-04-15

    A bacteria-immunity model with bacterial quorum sensing is formulated, which describes the competition between bacteria and immune cells. After periodic perturbation and a series of coordinate transformations, the model is brought into a standard form, and which is amenable to Melnikov method. By the method, the existences of chaotic motion and homoclinic bifurcations are proved.

  11. Quorum Sensing Regulation of Adhesion in Serratia Marcescens MG1 is surface dependent

    DEFF Research Database (Denmark)

    Labbate, M.; Zhu, H.; Thung, L.;

    2007-01-01

    Serratia marcescens is an opportunistic pathogen and a major cause of ocular infections. In previous studies of S. marcescens MG1, we showed that biofilm maturation and sloughing were regulated by N-acyl homoserine lactone (AHL)-based quorum sensing (QS). Because of the importance of adhesion...

  12. A Mathematical model to investigate quorum sensing regulation and its heterogenecity in pseudomonas syringae on leaves

    Science.gov (United States)

    The bacterium Pseudomonas syringae is a plant-pathogen, which through quorum sensing (QS), controls virulence. In this paper, by means of mathematical modeling, we investigate QS of this bacterium when living on leaf surfaces. We extend an existing stochastic model for the formation of Pseudomonas s...

  13. A spatial model of the evolution of quorum sensing regulating bacteriocin production

    NARCIS (Netherlands)

    Czaran, T.L.; Hoekstra, R.F.

    2007-01-01

    Like any form of cooperative behavior, quorum sensing (QS) in bacteria is potentially vulnerable to cheating, the occurrence of individuals that contribute less but still profit from the benefits provided by others. In this paper, we explore the evolutionary stability of QS as a regulatory mechanism

  14. Choosing an appropriate infection model to study quorum sensing inhibition in Pseudomonas infections

    NARCIS (Netherlands)

    Papaioannou, Evelina; Utari, Putri Dwi; Quax, Wim J.

    2013-01-01

    Bacteria, although considered for decades to be antisocial organisms whose sole purpose is to find nutrients and multiply are, in fact, highly communicative organisms. Referred to as quorum sensing, cell-to-cell communication mechanisms have been adopted by bacteria in order to co-ordinate their gen

  15. Kinetic Model for Signal Binding to the Quorum Sensing Regulator LasR

    DEFF Research Database (Denmark)

    Claussen, Anetta; Jakobsen, Tim Holm; Bjarnsholt, Thomas;

    2013-01-01

    of the active LasR quorum-sensing regulator was studied in an Escherichia coli background as a function of signal molecule concentration. The functional activity of the regulator was monitored via a GFP reporter fusion to lasB expressed from the native lasB promoter. The new data shows that the active form...

  16. Protoanemonin: a natural quorum sensing inhibitor that selectively activates iron starvation response

    NARCIS (Netherlands)

    Fazzini, R.A.; Skindersoe, M.; Bielecki, M.; Puchalka, J.; Givskov, M.; Martins Dos Santos, V.A.P.

    2013-01-01

    Many Gram-negative bacteria employ cell-to-cell communication mediated by N-acyl homoserine lactones (quorum sensing) to control expression of a wide range of genes including, but not limited to, genes encoding virulence factors. Outside the laboratory, the bacteria live in complex communities where

  17. Going beyond the Control of Quorum-Sensing to Combat Biofilm Infections

    Directory of Open Access Journals (Sweden)

    Wolf-Rainer Abraham

    2016-01-01

    Full Text Available Most bacteria attach to surfaces where they form a biofilm, cells embedded in a complex matrix of polymers. Cells in biofilms are much better protected against noxious agents than free-living cells. As a consequence it is very difficult to control pathogens with antibiotics in biofilm infections and novel targets are urgently needed. One approach aims at the communication between cells to form and to maintain a biofilm, a process called quorum-sensing. Water soluble small-sized molecules mediate this process and a number of antagonists of these compounds have been found. In this review natural compounds and synthetic drugs which do not interfere with the classical quorum-sensing compounds are discussed. For some of these compounds the targets are still not known, but others interfere with the formation of exopolysaccharides, virulence factors, or cell wall synthesis or they start an internal program of biofilm dispersal. Some of their targets are more conserved among pathogens than the receptors for quorum sensing autoinducers mediating quorum-sensing, enabling a broader application of the drug. The broad spectrum of mechanisms, the diversity of bioactive compounds, their activity against several targets, and the conservation of some targets among bacterial pathogens are promising aspects for several clinical applications of this type of biofilm-controlling compound in the future.

  18. Quorum-sensing-directed protein expression in Serratia proteamaculans B5a

    DEFF Research Database (Denmark)

    Christensen, Allan Beck; Riedel, Kathrin; Eberl, Leo

    2003-01-01

    N-Acyl-L-homoserine-lactone-producing Serratia species are frequently encountered in spoiling foods of vegetable and protein origin. The role of quorum sensing in the food spoiling properties of these bacteria is currently being investigated. A set of luxR luxI homologous genes encoding a putative...

  19. A spatial model of the evolution of quorum sensing regulating bacteriocin production

    NARCIS (Netherlands)

    Czaran, T.L.; Hoekstra, R.F.

    2007-01-01

    Like any form of cooperative behavior, quorum sensing (QS) in bacteria is potentially vulnerable to cheating, the occurrence of individuals that contribute less but still profit from the benefits provided by others. In this paper, we explore the evolutionary stability of QS as a regulatory mechanism

  20. Vibrio vulnificus produces quorum sensing signals of the AHL-class

    DEFF Research Database (Denmark)

    Valiente, E.; Bruhn, Jesper Bartholin; Nielsen, Kristian Fog

    2009-01-01

    Vibrio vulnificus is an aquatic pathogenic bacterium that can cause vibriosis in humans and fish. The species is subdivided into three biotypes with the fish-virulent strains belonging to biotype 2. The quorum sensing (QS) phenomenon mediated by furanosyl borate diester or autoinducer 2 (AI-2) ha...

  1. Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Jensen, Peter Østrup; Rasmussen, Thomas B;

    2005-01-01

    The opportunistic human pathogen Pseudomonas aeruginosa is the predominant micro-organism of chronic lung infections in cystic fibrosis patients. P. aeruginosa colonizes the lungs by forming biofilm microcolonies throughout the lung. Quorum sensing (QS) renders the biofilm bacteria highly tolerant...

  2. A broad range quorum sensing inhibitor working through sRNA inhibition

    DEFF Research Database (Denmark)

    Jakobsen, Tim H.; Warming, Anders N.; Vejborg, Rebecca M.

    2017-01-01

    For the last decade, chemical control of bacterial virulence has received considerable attention. Ajoene, a sulfur-rich molecule from garlic has been shown to reduce expression of key quorum sensing regulated virulence factors in the opportunistic pathogen Pseudomonas aeruginosa. Here we show tha...

  3. Ligand Binding Kinetics of the Quorum Sensing Regulator PqsR

    DEFF Research Database (Denmark)

    Welch, Martin; Hodgkinson, James T.; Gross, Jeremy;

    2013-01-01

    The Pseudomonas aeruginosa quinolone signal (PQS) is a quorum sensing molecule that plays an important role in regulating the virulence of this organism. We have purified the ligand binding domain of the receptor PqsRLBD for PQS and have used Förster resonance energy transfer fluorimetry...

  4. Regulation of pqs quorum sensing via catabolite repression control in Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Zhang, Lianbo; Gao, Qingguo; Chen, Wanying;

    2013-01-01

    that the Pseudomonas aeruginosa catabolite repression control protein regulates the Pseudomonas quinolone signal quorum sensing, which further controls synthesis of virulence factor pyocyanin, biofilm formation and survival during infection models. Our study suggests that deregulation of the catabolite repression by P...

  5. Inhibition of quorum sensing in Pseudomonas aeruginosa biofilm bacteria by a halogenated furanone compound

    DEFF Research Database (Denmark)

    Hentzer, Morten; Riedel, K.; Rasmussen, Thomas Bovbjerg

    2002-01-01

    ). Gfp-based reporter technology has been applied for non-destructive, single-cell-level detection of quorum sensing in laboratory-based P. aeruginosa biofilms. It is reported that a synthetic halogenated furanone compound, which is a derivative of the secondary metabolites produced by the Australian...

  6. A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation.

    Science.gov (United States)

    O'Loughlin, Colleen T; Miller, Laura C; Siryaporn, Albert; Drescher, Knut; Semmelhack, Martin F; Bassler, Bonnie L

    2013-10-29

    Quorum sensing is a chemical communication process that bacteria use to regulate collective behaviors. Disabling quorum-sensing circuits with small molecules has been proposed as a potential strategy to prevent bacterial pathogenicity. The human pathogen Pseudomonas aeruginosa uses quorum sensing to control virulence and biofilm formation. Here, we analyze synthetic molecules for inhibition of the two P. aeruginosa quorum-sensing receptors, LasR and RhlR. Our most effective compound, meta-bromo-thiolactone (mBTL), inhibits both the production of the virulence factor pyocyanin and biofilm formation. mBTL also protects Caenorhabditis elegans and human lung epithelial cells from killing by P. aeruginosa. Both LasR and RhlR are partially inhibited by mBTL in vivo and in vitro; however, RhlR, not LasR, is the relevant in vivo target. More potent antagonists do not exhibit superior function in impeding virulence. Because LasR and RhlR reciprocally control crucial virulence factors, appropriately tuning rather than completely inhibiting their activities appears to hold the key to blocking pathogenesis in vivo.

  7. A qrr noncoding RNA deploys four different regulatory mechanisms to optimize quorum-sensing dynamics.

    Science.gov (United States)

    Feng, Lihui; Rutherford, Steven T; Papenfort, Kai; Bagert, John D; van Kessel, Julia C; Tirrell, David A; Wingreen, Ned S; Bassler, Bonnie L

    2015-01-15

    Quorum sensing is a cell-cell communication process that bacteria use to transition between individual and social lifestyles. In vibrios, homologous small RNAs called the Qrr sRNAs function at the center of quorum-sensing pathways. The Qrr sRNAs regulate multiple mRNA targets including those encoding the quorum-sensing regulatory components luxR, luxO, luxM, and aphA. We show that a representative Qrr, Qrr3, uses four distinct mechanisms to control its particular targets: the Qrr3 sRNA represses luxR through catalytic degradation, represses luxM through coupled degradation, represses luxO through sequestration, and activates aphA by revealing the ribosome binding site while the sRNA itself is degraded. Qrr3 forms different base-pairing interactions with each mRNA target, and the particular pairing strategy determines which regulatory mechanism occurs. Combined mathematical modeling and experiments show that the specific Qrr regulatory mechanism employed governs the potency, dynamics, and competition of target mRNA regulation, which in turn, defines the overall quorum-sensing response.

  8. Type 2 quorum sensing monitoring, inhibition and biofilm formation in marine microrganisms.

    Science.gov (United States)

    Liaqat, Iram; Bachmann, Robert Thomas; Edyvean, Robert G J

    2014-03-01

    The quorum sensing (QS) dependent behaviour of micro-organisms, in particular expression of virulence genes, biofilm formation and dispersal, have provided impetus for investigating practical approaches to interfere with microbial QS. This study tests Halomonas pacifica and Marinobacter hydrocarbonoclasticus, two halophilic marine micro-organism, for their AI-2 dependent QS signalling and the effect of two well-known quorum-sensing inhibitors (QSIs), patulin and penicillic acid, on biofilm formation. We report, for the first time, the successful amplification of a putative luxS gene in H. pacifica using degenerated primers and AI-2 dependent QS as well as inhibition using QSIs. Penicillic acid had a strong inhibitory effect on AI-2 induction of H. pacifica at non-growth inhibitory concentrations, while patulin has an adverse effect only at the highest concentration (25 μM). QSIs effect on biofilm forming capability was isolate specific, with maximum inhibition at 25 μM of patulin in H. pacifica. In M. hydrocarbonoclasticus, no adverse effects were noted at any tested concentration of either QSIs. Detection of bioluminescence and the presence of a putative luxS gene provide biochemical and genetic evidence for the production of a signalling molecule(s) which is the essential first step in characterizing H. pacifica QS. This study highlights the importance of AI-2 dependent QS in a marine setting, not previously reported. It further suggests that QSI compounds must be selected in the specific system in which they are to function, and they cannot easily be transferred from one QS system to another.

  9. Interference of quorum sensing in Pseudomonas syringae by bacterial epiphytes that limit iron availability.

    Science.gov (United States)

    Dulla, Glenn F J; Krasileva, Ksenia V; Lindow, Steven E

    2010-06-01

    Leaf surfaces harbour bacterial epiphytes that are capable of influencing the quorum sensing (QS) system, density determination through detection of diffusible signal molecules, of the plant-pathogen Pseudomonas syringae pv. syringae (Pss) which controls expression of extracellular polysaccharide production, motility and other factors contributing to virulence to plants. Approximately 11% of the bacterial epiphytes recovered from a variety of plants produced a diffusible factor capable of inhibiting the QS system of Pss as indicated by suppression of ahlI. Blockage of QS by these interfering strains correlated strongly with their ability to limit iron availability to Pss. A direct relationship between the ability of isogenic Escherichia coli strains to sequester iron via their production of different siderophores and their ability to suppress QS in Pss was also observed. Quorum sensing induction was inversely related to iron availability in culture media supplemented with iron chelators or with FeCl(3). Co-inoculation of interfering strains with Pss onto leaves increased the number of resultant disease lesions over twofold compared with that on plants inoculated with Pss alone. Transposon-generated mutants of interfering strains in which QS inhibition was blocked did not increase disease when co-inoculated with Pss. Increased disease incidence was also not observed when a non-motile mutant of Pss was co-inoculated onto plants with QS interfering bacteria suggesting that these strains enhanced the motility of Pss in an iron-dependent manner, leading to an apparent increase in virulence of this pathogen. Considerable cross-talk mediated by iron scavenging apparently occurs on plants, thereby altering the behaviour of bacteria such as Pss that exhibit important QS-dependent traits in this habitat.

  10. Immune Subversion and Quorum-Sensing Shape the Variation in Infectious Dose among Bacterial Pathogens

    Science.gov (United States)

    Gama, João Alves; Abby, Sophie S.; Vieira-Silva, Sara; Dionisio, Francisco; Rocha, Eduardo P. C.

    2012-01-01

    Many studies have been devoted to understand the mechanisms used by pathogenic bacteria to exploit human hosts. These mechanisms are very diverse in the detail, but share commonalities whose quantification should enlighten the evolution of virulence from both a molecular and an ecological perspective. We mined the literature for experimental data on infectious dose of bacterial pathogens in humans (ID50) and also for traits with which ID50 might be associated. These compilations were checked and complemented with genome analyses. We observed that ID50 varies in a continuous way by over 10 orders of magnitude. Low ID50 values are very strongly associated with the capacity of the bacteria to kill professional phagocytes or to survive in the intracellular milieu of these cells. Inversely, high ID50 values are associated with motile and fast-growing bacteria that use quorum-sensing based regulation of virulence factors expression. Infectious dose is not associated with genome size and shows insignificant phylogenetic inertia, in line with frequent virulence shifts associated with the horizontal gene transfer of a small number of virulence factors. Contrary to previous proposals, infectious dose shows little dependence on contact-dependent secretion systems and on the natural route of exposure. When all variables are combined, immune subversion and quorum-sensing are sufficient to explain two thirds of the variance in infectious dose. Our results show the key role of immune subversion in effective human infection by small bacterial populations. They also suggest that cooperative processes might be important for successful infection by bacteria with high ID50. Our results suggest that trade-offs between selection for population growth-related traits and selection for the ability to subvert the immune system shape bacterial infectiousness. Understanding these trade-offs provides guidelines to study the evolution of virulence and in particular the micro-evolutionary paths

  11. Quorum sensing and microbial drug resistance%群体感应与微生物耐药性

    Institute of Scientific and Technical Information of China (English)

    陈昱帆; 刘诗胤; 梁志彬; 吕明发; 周佳暖; 张炼辉

    2016-01-01

    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。%Microbial drug resistance has become a serious problem of global concern, and the evolution and regulatory mechanisms of microbial drug resistance has become a hotspot of research in recent years. Recent studies showed that certain microbial resistance mechanisms are regulated by quorum sensing system. Quorum sensing is a ubiquitous cell-cell communication system in the microbial world, which associates with cell density. High-density microbial cells produce sufficient amount of small signal molecules, activating a range of downstream cellular processes including virulence and drug resistance mechanisms, which increases bacterial drug tolerance and causes infections on host organisms. In this review, the general mechanisms of microbial drug resistance and quorum-sensing systems are summarized with a focus on the association of quorum sensing and chemical signaling systems with microbial drug resistance mechanisms, including biofilm formation and drug efflux pump. The potential use of quorum quenching as a new strategy to control microbial resistance is also discussed.

  12. Identification of a quorum sensing pheromone posttranslationally farnesylated at the internal tryptophan residue from Bacillus subtilis subsp. natto.

    Science.gov (United States)

    Hayashi, Shunsuke; Usami, Syohei; Nakamura, Yuta; Ozaki, Koki; Okada, Masahiro

    2015-01-01

    Bacillus subtilis subsp. natto produces poly-γ-glutamic acid under the control of quorum sensing. We identified ComXnatto pheromone as the quorum-sensing pheromone with an amino acid sequence of Lys-Trp-Pro-Pro-Ile-Glu and the tryptophan residue posttranslationally modified by a farnesyl group. ComXnatto pheromone is unique in the sense that the 5th tryptophan residue from the C-terminal is farnesylated.

  13. Quorum Quenching of Nitrobacter winogradskyi Suggests that Quorum Sensing Regulates Fluxes of Nitrogen Oxide(s) during Nitrification

    Science.gov (United States)

    Giguere, Andrew T.; Bottomley, Peter J.

    2016-01-01

    ABSTRACT Quorum sensing (QS) is a widespread process in bacteria used to coordinate gene expression with cell density, diffusion dynamics, and spatial distribution through the production of diffusible chemical signals. To date, most studies on QS have focused on model bacteria that are amenable to genetic manipulation and capable of high growth rates, but many environmentally important bacteria have been overlooked. For example, representatives of proteobacteria that participate in nitrification, the aerobic oxidation of ammonia to nitrate via nitrite, produce QS signals called acyl-homoserine lactones (AHLs). Nitrification emits nitrogen oxide gases (NO, NO2, and N2O), which are potentially hazardous compounds that contribute to global warming. Despite considerable interest in nitrification, the purpose of QS in the physiology/ecology of nitrifying bacteria is poorly understood. Through a quorum quenching approach, we investigated the role of QS in a well-studied AHL-producing nitrite oxidizer, Nitrobacter winogradskyi. We added a recombinant AiiA lactonase to N. winogradskyi cultures to degrade AHLs to prevent their accumulation and to induce a QS-negative phenotype and then used mRNA sequencing (mRNA-Seq) to identify putative QS-controlled genes. Our transcriptome analysis showed that expression of nirK and nirK cluster genes (ncgABC) increased up to 19.9-fold under QS-proficient conditions (minus active lactonase). These data led to us to query if QS influenced nitrogen oxide gas fluxes in N. winogradskyi. Production and consumption of NOx increased and production of N2O decreased under QS-proficient conditions. Quorum quenching transcriptome approaches have broad potential to identify QS-controlled genes and phenotypes in organisms that are not genetically tractable.

  14. Rational design and synthesis of new quorum-sensing inhibitors derived from acylated homoserine lactones and natural products from garlic

    DEFF Research Database (Denmark)

    Persson, T.; Rasmussen, Thomas Bovbjerg; Skindersoe, M.

    2005-01-01

    with similarity both to sulfides 10a-s and to bioactive structures from garlic. Design and biological screening of all compounds presented in this work targeted inhibition of quorum-sensing comprising competitive inhibition of transcriptional regulators LuxR and LasR. The design was based on critical interactions...... within the binding-site and structural motifs in molecular components isolated from garlic, 7 and 8, shown to be quorum-sensing inhibitors but not antibiotics. A potent quorum-sensing inhibitor N-(heptylsulfanylacetyl)-L-homoserine lactone (10c) was identified. Together with data collected for the other...

  15. Switch of SpnR function from activating to inhibiting quorum sensing by its exogenous addition

    Energy Technology Data Exchange (ETDEWEB)

    Takayama, Yuriko [Department of Innovation Systems Engineering, Graduate School of Engineering, Utsunomiya University, 7-1-2 Yoto, Utsunomiya, Tochigi 321-8585 (Japan); CREST, Japan Science and Technology Agency, 7-1-2 Yoto, Utsunomiya, Tochigi 321-8585 (Japan); Kato, Norihiro, E-mail: katon@cc.utsunomiya-u.ac.jp [CREST, Japan Science and Technology Agency, 7-1-2 Yoto, Utsunomiya, Tochigi 321-8585 (Japan); Department of Material and Environmental Chemistry, Graduate School of Engineering, Utsunomiya University, 7-1-2 Yoto, Utsunomiya, Tochigi 321-8585 (Japan)

    2016-09-02

    The opportunistic human pathogen Serratia marcescens AS-1 produces the N-hexanoylhomoserine lactone (C6HSL) receptor SpnR, a homologue of LuxR from Vibrio fischeri, which activates pig clusters to produce the antibacterial prodigiosin. In this study, we attempted to artificially regulate quorum sensing (QS) by changing the role of SpnR in N-acylhomoserine lactone (AHL)-mediated QS. SpnR was obtained as a fusion protein tagged with maltose-binding protein (MBP) from overexpression in Escherichia coli, and its specific affinity to C6HSL was demonstrated by quartz crystal microbalance analysis and AHL-bioassay with Chromobacterium violaceum CV026. Prodigiosin production was effectively inhibited by externally added MBP-SpnR in both wild-type AS-1 and the AHL synthase-defective mutant AS-1(ΔspnI). For the mutant, the induced amount of prodigiosin was drastically reduced to approximately 4% with the addition of 18 μM MBP-SpnR to the liquid medium, indicating 81% trapping of C6HSL. A system for inhibiting QS can be constructed by adding exogenous AHL receptor to the culture broth to keep the concentration of free AHL low, whereas intracellular SpnR naturally functions as the activator in response to QS. - Highlights: • Quorum sensing (QS) regulates the expression of some bacterial genes. • We added an AHL receptor to culture media to inhibit QS in Serratia marcescens AS-1. • The exogenous receptor effectively bound C6HSL and inhibited QS. • This approach can be used to artificially regulate AHL-mediated QS.

  16. Phenotypic and genotypic characterisation of Burkholderia cenocepacia J2315 mutants affected in homoserine lactone and diffusible signal factor-based quorum sensing systems suggests interplay between both types of systems.

    Directory of Open Access Journals (Sweden)

    Claudia Udine

    Full Text Available Many putative virulence factors of Burkholderia cenocepacia are controlled by various quorum sensing (QS circuits. These QS systems either use N-acyl homoserine lactones (AHL or cis-2-dodecenoic acid ("Burkholderia diffusible signal factor", BDSF as signalling molecules. Previous work suggested that there is little cross-talk between both types of systems. We constructed mutants in B. cenocepacia strain J2315, in which genes encoding CepI (BCAM1870, CciI (BCAM0239a and the BDSF synthase (BCAM0581 were inactivated, and also constructed double (ΔcepIΔBCAM0581, ΔcciIΔBCAM0581 and ΔcepIΔcciI mutants and a triple (ΔcepIΔcciIΔBCAM0581 mutant. Subsequently we investigated phenotypic properties (antibiotic susceptibility, biofilm formation, production of AHL and BDSF, protease activity and virulence in Caenorhabditis elegans and measured gene expression in these mutants, and this in the presence and absence of added BDSF, AHL or both. The triple mutant was significantly more affected in biofilm formation, antimicrobial susceptibility, virulence in C. elegans, and protease production than either the single or double mutants. The ΔBCAM0581 mutant and the ΔcepIΔBCAM0581 and ΔcciIΔBCAM0581 double mutants produced significantly less AHL compared to the WT strain and the ΔcepI and ΔcciI single mutant, respectively. The expression of cepI and cciI in ΔBCAM0581, was approximately 3-fold and 7-fold (p<0.05 lower than in the WT, respectively. The observed differences in AHL production, expression of cepI and cciI and QS-controlled phenotypes in the ΔBCAM0581 mutant could (at least partially be restored by addition of BDSF. Our data suggest that, in B. cenocepacia J2315, AHL and BDSF-based QS systems co-regulate the same set of genes, regulate different sets of genes that are involved in the same phenotypes and/or that the BDSF system controls the AHL-based QS system. As the expression of the gene encoding the C6-HSL synthase CciI (and to a

  17. How ants use quorum sensing to estimate the average quality of a fluctuating resource.

    Science.gov (United States)

    Franks, Nigel R; Stuttard, Jonathan P; Doran, Carolina; Esposito, Julian C; Master, Maximillian C; Sendova-Franks, Ana B; Masuda, Naoki; Britton, Nicholas F

    2015-07-08

    We show that one of the advantages of quorum-based decision-making is an ability to estimate the average value of a resource that fluctuates in quality. By using a quorum threshold, namely the number of ants within a new nest site, to determine their choice, the ants are in effect voting with their feet. Our results show that such quorum sensing is compatible with homogenization theory such that the average value of a new nest site is determined by ants accumulating within it when the nest site is of high quality and leaving when it is poor. Hence, the ants can estimate a surprisingly accurate running average quality of a complex resource through the use of extraordinarily simple procedures.

  18. Modulation of Quorum Sensing in Acylhomoserine Lactone-Producing or -Degrading Tobacco Plants Leads to Alteration of Induced Systemic Resistance Elicited by the Rhizobacterium Serratia marcescens 90-166.

    Science.gov (United States)

    Ryu, Choong-Min; Choi, Hye Kyung; Lee, Chi-Ho; Murphy, John F; Lee, Jung-Kee; Kloepper, Joseph W

    2013-06-01

    Numerous root-associated bacteria (rhizobacteria) are known to elicit induced systemic resistance (ISR) in plants. Bacterial cell-density-dependent quorum sensing (QS) is thought to be important for ISR. Here, we investigated the role of QS in the ISR elicited by the rhizobacterium, Serratia marcescens strain 90-166, in tobacco. Since S. marcescens 90-166 produces at least three QS signals, QS-mediated ISR in strain 90-166 has been difficult to understand. Therefore, we investigated the ISR capacity of two transgenic tobacco (Nicotiana tabacum) plants that contained either bacterial acylhomoserine lactone-producing (AHL) or -degrading (AiiA) genes in conjunction with S. marcescens 90-166 to induce resistance against bacterial and viral pathogens. Root application of S. marcescens 90-166 increased ISR to the bacterial pathogens, Pectobacterium carotovorum subsp. carotovorum and Pseudomonas syringae pv. tabaci, in AHL plants and decreased ISR in AiiA plants. In contrast, ISR to Cucumber mosaic virus was reduced in AHL plants treated with S. marcescens 90-166 but enhanced in AiiA plants. Taken together, these data indicate that QS-dependent ISR is elicited by S. marcescens 90-166 in a pathogen-dependent manner. This study provides insight into QS-dependent ISR in tobacco elicited by S. marcescens 90-166.

  19. Modulation of Quorum Sensing in Acylhomoserine Lactone-Producing or -Degrading Tobacco Plants Leads to Alteration of Induced Systemic Resistance Elicited by the Rhizobacterium Serratia marcescens 90-166

    Directory of Open Access Journals (Sweden)

    Choong-Min Ryu

    2013-06-01

    Full Text Available Numerous root-associated bacteria (rhizobacteria are known to elicit induced systemic resistance (ISR in plants. Bacterial cell-density-dependent quorum sensing (QS is thought to be important for ISR. Here, we investigated the role of QS in the ISR elicited by the rhizobacterium, Serratia marcescens strain 90–166, in tobacco. Since S. marcescens 90–166 produces at least three QS signals, QS-mediated ISR in strain 90–166 has been difficult to understand. Therefore, we investigated the ISR capacity of two transgenic tobacco (Nicotiana tabacum plants that contained either bacterial acylhomoserine lactone-producing (AHL or -degrading (AiiA genes in conjunction with S. marcescens 90–166 to induce resistance against bacterial and viral pathogens. Root application of S. marcescens 90–166 increased ISR to the bacterial pathogens, Pectobacterium carotovorum subsp. carotovorum and Pseudomonas syringae pv. tabaci, in AHL plants and decreased ISR in AiiA plants. In contrast, ISR to Cucumber mosaic virus was reduced in AHL plants treated with S. marcescens 90–166 but enhanced in AiiA plants. Taken together, these data indicate that QS-dependent ISR is elicited by S. marcescens 90–166 in a pathogen-dependent manner. This study provides insight into QS-dependent ISR in tobacco elicited by S. marcescens 90–166.

  20. 铜绿假单胞菌中群体感应系统的研究进展%Research progress of quorum sensing in Pseudomonas aeruginosa

    Institute of Scientific and Technical Information of China (English)

    杨帆; 张乐; 盛哈蕾; 张克斌

    2012-01-01

    Quorum sensing is a kind of signaling pathway for communication among bacteria cells. Bacteria can monitor their population density and regulate hunderds of genes expression by detecting small diffusible molecules. The P. Aeruginosa quorum sensing circuitry is comprised of two complete systems (LasR/LasI and Rhll/RhlR) and one orphan 4-quinolone signalling system. This paper reviews the regulation mechanism and it's potential application of quorum sensing systems of P. Aeruginosa.%群体感应系统(quorum sensing)是一种细菌细胞与细胞间的信号传递系统.细菌通过可扩散的小分子信号分子感知细胞群体的密度,从而引起一些特定基因在细菌群体中的协调表达.铜绿假单胞菌中的QS系统包括LasI/LasR和RhlI/RhlR两条主要的信号系统和喹诺酮信号系统.本文系统地介绍了铜绿假单胞菌中QS系统的研究现状和相关应用.

  1. An age-dependent model to analyse the evolutionary stability of bacterial quorum sensing.

    Science.gov (United States)

    Mund, A; Kuttler, C; Pérez-Velázquez, J; Hense, B A

    2016-09-21

    Bacterial communication is enabled through the collective release and sensing of signalling molecules in a process called quorum sensing. Cooperative processes can easily be destabilized by the appearance of cheaters, who contribute little or nothing at all to the production of common goods. This especially applies for planktonic cultures. In this study, we analyse the dynamics of bacterial quorum sensing and its evolutionary stability under two levels of cooperation, namely signal and enzyme production. The model accounts for mutation rates and switches between planktonic and biofilm state of growth. We present a mathematical approach to model these dynamics using age-dependent colony models. We explore the conditions under which cooperation is stable and find that spatial structuring can lead to long-term scenarios such as coexistence or bistability, depending on the non-linear combination of different parameters like death rates and production costs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Secondary metabolites produced by marine streptomyces as antibiofilm and quorum-sensing inhibitor of uropathogen Proteus mirabilis.

    Science.gov (United States)

    Younis, Khansa Mohammed; Usup, Gires; Ahmad, Asmat

    2016-03-01

    Quorum-sensing regulates bacterial biofilm formation and virulence factors, thereby making it an interesting target for attenuating pathogens. In this study, we investigated anti-biofilm and anti-quorum-sensing compounds from secondary metabolites of halophiles marine streptomyces against urinary catheter biofilm forming Proteus mirabilis without effect on growth viability. A total of 40 actinomycetes were isolated from samples collected from different places in Iraq including marine sediments and soil samples. Fifteen isolates identified as streptomyces and their supernatant screened as anti-quorum-sensing by inhibiting quorum-sensing regulated prodigiosin biosynthesis of Serratia marcescens strain Smj-11 as a reporter strain. Isolate Sediment Lake Iraq (sdLi) showed potential anti-quorum-sensing activity. Out of 35 clinical isolates obtained from Urinary catheter used by patient at the Universiti Kebangsaan Malaysia Medical Center, 22 isolates were characterized and identified as Proteus mirabilis. Isolate Urinary Catheter B4 (UCB4) showed the highest biofilm formation with highest resistance to used antibiotic and was chosen for further studies. Ethyl acetate secondary metabolites extract was produced from sdLi isolate. First, we determined the Minimum Inhibitory Concentration (MIC) of sdLi crude extract against UCB4 isolate, and all further experiments used concentrations below the MIC. Tests of subinhibitory concentrations of sdLi crude extract showed good inhibition against UCB4 isolate biofilm formation on urinary catheter and cover glass using Scanning electron microscopy and light microscopy respectively. The influence of sub-MIC of sdLi crude extract was also found to attenuate the quorum sensing (QS)-dependent factors such as hemolysin activity, urease activity, pH value, and motility of UCB4 isolate. Evidence is presented that these nontoxic secondary metabolites may act as antagonists of bacterial quorum sensing by competing with quorum-sensing signals

  3. 群体感应在水产养殖中的应用前景%Quorum-sensing in aquaculture: application and perspective

    Institute of Scientific and Technical Information of China (English)

    宋协法; 孙颉

    2012-01-01

    群体感应,也被称为“细胞间的交流”,是细菌通过化学信号的传递进行彼此交流的一种方式。本文介绍了群体感应的机理和类型以及信号分子的检测方法,并结合实际情况,对其在水产养殖领域的应用前景进行了探讨,以期为群体感应在水产养殖中的应用提供理论依据。%Quorum-sensing, also known as "communication among cells", is a way of bacteria communicating with each other by chemical signals. By introducing quorum-sensing system and its detection methods, we drew the conclusion that the application of quorum-sensing would have great development and practical values in aquaculture. The paper mainly introduced the application trend of quorum-sensing in aquaculture.

  4. QUORUM SENSING SYSTEMS OF MARINE VIBRIOS AND THEIR SIGNAL INTERFERENCE%几种海洋弧菌的密度感应系统及其信号干扰

    Institute of Scientific and Technical Information of China (English)

    白方方; 张晓华; 韩茵; 陈吉祥

    2007-01-01

    @@ 密度感应(quorum sensing,QS)是细菌通过感受种群密度的变化而控制特定基因表达的一种机制(Miller et al.,2001).密度感应细菌可以产生和释放特定的化学信号分子,称为自诱导分子(autoinducer,AI),其浓度随着细菌密度的增加而增加.

  5. 枯草芽孢杆菌的群体感应信号系统及其在环境领域的应用前景%Quorum sensing signal system of Bacillus subtilis and its application prospect in the environment

    Institute of Scientific and Technical Information of China (English)

    陈瑞; 王大力; 林志芬; 尹大强

    2012-01-01

    The present paper would like to introduce the biological features and main applications of Bacillus subtilis in brief and elaborate its quorum sensing system in a thorough-going way. As is known, Bacillus subtilis quorum sensing tends to display its function during the growth of late logarithmic and stationary stage, in which it is possible for its sensitive molecules to get synthesized in between their cells and then would be brought out to the extracellular ones through the ATP-binding cassette. As is shown, the main signaling molecules may represent the ComX phermone and competence and sporulation factors in the process of quorum sensing in Bacillus subtilis . We have already made a review over the ways of their generation, the characteristic features and the likely roles in the regulation of quorum sensing system respectively. Since ComX pheromone is the main promoter for the development of gene' s mobility when it has accumulated to a certain extent in the extracellular structures with the increasing number of bacteria, and their function of competence and sporulation factor are closely related to their intracellular concentration. Generally speaking, the low concentration of competence and sporulation factor in the intracellular structures tend to promote the development of mobility, which in turn is likely to spore formation of high concentration due to the deterioration of nutritional conditions. And, it is for this reason, Bacillus subtilis can widely be used for degradation of pollutants in the field of environmental protection and sustainable maintenance through toxicity testing checking as strain of gram-positive bacteria in fighting against toxicity, though it has not been clear for its behavior. Quorum sensing is a very important regulatory mechanism during the growth of Bacillus subtilis, however, current studies are mainly focused on exploring the theoretical problems about the quorum sensing mechanism with scarce report on its applications. It is

  6. 细菌群体感应抑制剂的研究进展%Research Progress on Bacterial Quorum Sensing Inhibitors

    Institute of Scientific and Technical Information of China (English)

    孙琦; 梁经纬; 王琳; 张廷剑; 孟繁浩

    2016-01-01

    在菌群生长过程中,细菌能不断产生化学信号分子并分泌到周围环境中,当信号分子的数量达到一定阈值时,可调控菌体相关基因的表达如生物膜的形成、生物发光等,以适应环境的变化,这种现象称为细菌群体感应(quorum sensing,QS)。细菌群体感应抑制剂(quorum sensing inhibitor,QSI)以细菌的群体感应为靶点,只针对病原菌的群体感应系统起抑制作用,并不杀死体内的正常细菌或干扰其正常生命活动,为人类提供了一种新型抗菌途径。综述了细菌群体感应信号分子的调控系统和细菌群体感应抑制剂的研究进展。%Bacteria can produce chemical signal molecules and secret them into the surrounding environment during their growth processes.When the number of signal molecules reaches to a certain threshold,the related genes expression,such as biofilm formation or bioluminescent,will be regulated,in order to adapt to such envi-ronmental changes.This phenomenon is called bacterial quorum sensing(QS).Using bacterial quorum sensing as a target,bacterial quorum sensing inhibitors(QSI)make pathogens lose pathogenicity by blocking the expres-sion of harmful genes,whilst do not kill the normal bacteria or interfere with the normal physiological activity of bacteria,which providing a new antibacterial way for mankind.Research progress on signal molecules regula-tion system of bacterial quorum sensing system and bacterial quorum sensing inhibitors are reviewed in this paper.

  7. Anti-quorum Sensing and Anti-biofilm Activity of Delftia tsuruhatensis Extract by Attenuating the Quorum Sensing-Controlled Virulence Factor Production in Pseudomonas aeruginosa.

    Science.gov (United States)

    Singh, Vijay K; Mishra, Avinash; Jha, Bhavanath

    2017-01-01

    Multidrug-resistance bacteria commonly use cell-to-cell communication that leads to biofilm formation as one of the mechanisms for developing resistance. Quorum sensing inhibition (QSI) is an effective approach for the prevention of biofilm formation. A Gram-negative bacterium, Delftia tsuruhatensis SJ01, was isolated from the rhizosphere of a species of sedge (Cyperus laevigatus) grown along the coastal-saline area. The isolate SJ01 culture and bacterial crude extract showed QSI activity in the biosensor plate containing the reference strain Chromobacterium violaceum CV026. A decrease in the violacein production of approximately 98% was detected with the reference strain C. violaceum CV026. The bacterial extract (strain SJ01) exhibited anti-quorum sensing activity and inhibited the biofilm formation of clinical isolates wild-type Pseudomonas aeruginosa PAO1 and P. aeruginosa PAH. A non-toxic effect of the bacterial extract (SJ01) was detected on the cell growth of the reference strains as P. aeruginosa viable cells were present within the biofilm. It is hypothesized that the extract (SJ01) may change the topography of the biofilm and thus prevent bacterial adherence on the biofilm surface. The extract also inhibits the motility, virulence factors (pyocyanin and rhamnolipid) and activity (elastase and protease) in P. aeruginosa treated with SJ01 extract. The potential active compound present was identified as 1,2-benzenedicarboxylic acid, diisooctyl ester. Microarray and transcript expression analysis unveiled differential expression of quorum sensing regulatory genes. The key regulatory genes, LasI, LasR, RhlI, and RhlR were down-regulated in the P. aeruginosa analyzed by quantitative RT-PCR. A hypothetical model was generated of the transcriptional regulatory mechanism inferred in P. aeruginosa for quorum sensing, which will provide useful insight to develop preventive strategies against the biofilm formation. The potential active compound identified, 1

  8. A high-throughput screen for quorum-sensing inhibitors that target acyl-homoserine lactone synthases.

    Science.gov (United States)

    Christensen, Quin H; Grove, Tyler L; Booker, Squire J; Greenberg, E Peter

    2013-08-20

    Many Proteobacteria use N-acyl-homoserine lactone (acyl-HSL) quorum sensing to control specific genes. Acyl-HSL synthesis requires unique enzymes that use S-adenosyl methionine as an acyl acceptor and amino acid donor. We developed and executed an enzyme-coupled high-throughput cell-free screen to discover acyl-HSL synthase inhibitors. The three strongest inhibitors were equally active against two different acyl-HSL synthases: Burkholderia mallei BmaI1 and Yersinia pestis YspI. Two of these inhibitors showed activity in whole cells. The most potent compound behaves as a noncompetitive inhibitor with a Ki of 0.7 µM and showed activity in a cell-based assay. Quorum-sensing signal synthesis inhibitors will be useful in attempts to understand acyl-HSL synthase catalysis and as a tool in studies of quorum-sensing control of gene expression. Because acyl-HSL quorum-sensing controls virulence of some bacterial pathogens, anti-quorum-sensing chemicals have been sought as potential therapeutic agents. Our screen and identification of acyl-HSL synthase inhibitors serve as a basis for efforts to target quorum-sensing signal synthesis as an antivirulence approach.

  9. Staphylococcus aureus RNAIII and Its Regulon Link Quorum Sensing, Stress Responses, Metabolic Adaptation, and Regulation of Virulence Gene Expression.

    Science.gov (United States)

    Bronesky, Delphine; Wu, Zongfu; Marzi, Stefano; Walter, Philippe; Geissmann, Thomas; Moreau, Karen; Vandenesch, François; Caldelari, Isabelle; Romby, Pascale

    2016-09-08

    Staphylococcus aureus RNAIII is one of the main intracellular effectors of the quorum-sensing system. It is a multifunctional RNA that encodes a small peptide, and its noncoding parts act as antisense RNAs to regulate the translation and/or the stability of mRNAs encoding transcriptional regulators, major virulence factors, and cell wall metabolism enzymes. In this review, we explain how regulatory proteins and RNAIII are embedded in complex regulatory circuits to express virulence factors in a dynamic and timely manner in response to stress and environmental and metabolic changes.

  10. Classifying the Topology of AHL-Driven Quorum Sensing Circuits in Proteobacterial Genomes

    Directory of Open Access Journals (Sweden)

    Sándor Pongor

    2012-04-01

    Full Text Available Virulence and adaptability of many Gram-negative bacterial species are associated with an N-acylhomoserine lactone (AHL gene regulation mechanism called quorum sensing (QS. The arrangement of quorum sensing genes is variable throughout bacterial genomes, although there are unifying themes that are common among the various topological arrangements. A bioinformatics survey of 1,403 complete bacterial genomes revealed characteristic gene topologies in 152 genomes that could be classified into 16 topological groups. We developed a concise notation for the patterns and show that the sequences of LuxR regulators and LuxI autoinducer synthase proteins cluster according to the topological patterns. The annotated topologies are deposited online with links to sequences and genome annotations at http://bacteria.itk.ppke.hu/QStopologies/.

  11. The art of antibacterial warfare: Deception through interference with quorum sensing-mediated communication.

    Science.gov (United States)

    Rampioni, Giordano; Leoni, Livia; Williams, Paul

    2014-08-01

    Almost a century on from the discovery of penicillin, the war against bacterial infection still rages compounded by the emergence of strains resistant to virtually every clinically approved antibiotic and the dearth of new antibacterial agents entering the clinic. Consequently there is renewed interest in drugs which attenuate virulence rather than bacterial growth. Since the metaphors of warfare are often used to describe the battle between pathogen and host, we will describe in such a context, the molecular communication (quorum sensing) mechanisms used by bacteria to co-ordinate virulence at the population level. Recent progress in exploiting this information through the design of anti-virulence deception strategies that disrupt quorum sensing through signal molecule inactivation, inhibition of signal molecule biosynthesis or the blockade of signal transduction and their advantages and disadvantages are considered.

  12. [The effect of topology of quorum sensing-related genes in Pectobacterium atrosepticumon their expression].

    Science.gov (United States)

    Gogoleva, N E; Shlykova, L V; Gorshkov, V Iu; Daminova, A G; Gogolev, Iu V

    2014-01-01

    In prokaryotic genomes, the neighboring genes are often located on the complementary DNA strands and adjoin each other by their 5'- or 3'-ends or even overlap by their open reading frames. It was suggested that such gene topology hasfunctional purpose providing the regulation of their expression. For those genes that overlap by their coding 3'-termini this assumption has not been confirmed experimentally. In a broad group of bacteria that belong to proteobacteria such a convergent gene arrangement is typical for functionally connected quorum sensing-related genes "P" and "R" that encode synthases of N-acyl homoserine lactones and their sensors, respectively. In the present study on the example of overlapping quorum sensing-related genes of plant pathogenic bacterium Pectobacterium atrosepticum SCRI1043--expI and expR it was shown that the topology of these genes determines the regula- tion of their expression.

  13. Atividade anti-quorum sensing de extratos de grumixama (Eugenia brasiliensis) e pitanga (Eugenia uniflora l.).

    OpenAIRE

    RODRIGUES,Adeline Conceição

    2015-01-01

    Pinto, Uelinton Manoel Muitas bactérias regulam a expressão gênica em resposta a sinais difusíveis produzidos de forma dependente da densidade celular, em um processo denominado quorum sensing. Esse processo ocorre por meio da produção, liberação e detecção de moléculas sinalizadoras. Os fenótipos regulados pelo quorum sensing estão envolvidos nos processos de virulência, esporulação, motilidade, produção de enzimas, bioluminescência, produção de pigmentos, entre outros. A interrupção de q...

  14. Detection of Quorum Sensing Signals in Gram-Negative Bacteria by Using Reporter Strain CV026

    Directory of Open Access Journals (Sweden)

    Ahmad Humayan KABIR

    2010-12-01

    Full Text Available Quorum sensing signals are referred to as acylated homoserine lactones (AHL that are mainly found in Gram-negative bacteria. It implies the ability of certain bacteria of producing different AHL molecules. The bacteria Pseudomonas aureofaciens and Xenorhabdus nematophila were cultured in Luria-Bertani (LB10 media and CV026 was used as a reporter strain to detect the presence of AHLs produced by the cultured bacteria. In this study, the reporter strain has revealed the quorum sensing ability of P. aureofaciens and X. nematophila by producing the purple pigment violacein in the supply of external AHLs molecules. Thin layer chromatography (TLC bioassay having four controls was conducted to detect specific AHL molecule supplied by P. aureofaciens and X. nematophila. The specific AHL molecule was observed to be migrated according to their polarity on the TLC plate.

  15. Discovery of a quorum sensing modulator pharmacophore by 3D small-molecule microarray screening

    DEFF Research Database (Denmark)

    Marsden, David M; Nicholson, Rebecca L; Skindersoe, Mette E

    2010-01-01

    ligand-binding domains of the LuxR homolog CarR from Erwinia carotovora subsp. carotovora. The 3D microarray platform was used to discover the biologically active chloro-pyridine pharmacophore, which was validated using a fluorometric ligand binding assay and ITC. Analogs containing the chloro......The screening of large arrays of drug-like small-molecules was traditionally a time consuming and resource intensive task. New methodology developed within our laboratories provides an attractive low cost, 3D microarray-assisted screening platform that could be used to rapidly assay thousands...... of compounds. As a proof-of-principle the platform was exploited to screen a number of quorum sensing analogs. Quorum sensing is used by bacterium to initiate and spread infection; in this context its modulation may have significant clinical value. 3D microarray slides were probed with fluorescently labeled...

  16. Bacterial Secretant from Pseudomonas aeruginosa Dampens Inflammasome Activation in a Quorum Sensing-Dependent Manner

    Science.gov (United States)

    Yang, Jungmin; Lee, Kang-Mu; Park, Sangjun; Cho, Yoeseph; Lee, Eunju; Park, Jong-Hwan; Shin, Ok Sarah; Son, Junghyun; Yoon, Sang Sun; Yu, Je-Wook

    2017-01-01

    Inflammasome signaling can contribute to host innate immune defense against bacterial pathogens such as Pseudomonas aeruginosa. However, bacterial evasion of host inflammasome activation is still poorly elucidated. Quorum sensing (QS) is a bacterial communication mechanism that promotes coordinated adaptation by triggering expression of a wide range of genes. QS is thought to strongly contribute to the virulence of P. aeruginosa, but the molecular impact of bacterial QS on host inflammasome defense is completely unknown. Here, we present evidence that QS-related factors of the bacterial secretant (BS) from P. aeruginosa can dampen host inflammasome signaling in mouse bone marrow-derived macrophages. We found that BS from QS-defective ΔlasR/rhlR mutant, but not from wild-type (WT) P. aeruginosa, induces robust activation of the NLRC4 inflammasome. P. aeruginosa-released flagellin mediates this inflammasome activation by ΔlasR/rhlR secretant, but QS-regulated bacterial proteases in the WT BS impair extracellular flagellin to attenuate NLRC4 inflammasome activation. P. aeruginosa-secreted proteases also degrade inflammasome components in the extracellular space to inhibit the propagation of inflammasome-mediated responses. Furthermore, QS-regulated virulence factor pyocyanin and QS autoinducer 3-oxo-C12-homoserine lactone directly suppressed NLRC4- and even NLRP3-mediated inflammasome assembly and activation. Taken together, our data indicate that QS system of P. aeruginosa facilitates bacteria to evade host inflammasome-dependent sensing machinery. PMID:28396663

  17. Quorum sensing signals affect spoilage of refrigerated large yellow croaker (Pseudosciaena crocea) by Shewanella baltica.

    Science.gov (United States)

    Zhu, Junli; Zhao, Aifei; Feng, Lifang; Gao, Haichun

    2016-01-18

    In this work we investigated the specific spoilage organism (SSO) of large yellow croaker (Pseudosciaena crocea) stored at 4°C and role of quorum sensing (QS) system of SSO isolated from the spoiled fish. According to microbial count and 16S rRNA gene of the isolated pure strains, Shewanella, mainly Shewanella baltica and Shewanella putrefaciens, was predominant genera at the end of shelf-life of P. crocea. Among Shewanella isolates, S.baltica02 was demonstrated as SSO in spoilage potential characteristics by inoculation into sterile fish juice using sensory and chemical analyses. Autoinducer 2 and two cyclic dipeptides (DKPs) including cyclo-(l-Pro-l-Leu) and cyclo-(l-Pro-l-Phe), no any AHLs, were detected in cell-free S. baltica culture. Interestingly, S.baltica02 had the highest QS activity among three spoilers of S. baltica. The production of biofilm, trimethylamines (TMA) and putrescine in these spoilers significantly increased in the presence of cyclo-(l-Pro-l-Leu), rather than cyclo-(l-Pro-l-Phe) and 4,5-dihydroxy-2,3-pentanedione (the AI-2 precursor, DPD). In accordance with the effect of signal molecules on the spoilage phenotype, exposure to exogenous cyclo-(l-Pro-l-Leu) was also showed to up-regulate the transcription levels of luxR, torA and ODC, and no effect of luxS indicated that S. baltica could sense cyclo-(l-Pro-l-Leu). In the fish homogenate, exogenous cyclo-(l-Pro-l-Leu) shortened lag phase durations and enhanced growth rates of the dominant bacteria, H2S producing bacteria, under refrigerated storage, while exogenous DPD retarded growth of competing bacteria, such as Enterobacteriaceae. Meanwhile, cyclo-(l-Pro-l-Leu) also promoted the accumulation of metabolites on the spoilage process of homogenate. S.baltica02 luxS mutant preliminarily proved that AI-2 might not play a signaling role in the spoilage. The present study suggested that the spoilage potential of S. baltica in P. crocea might be regulated by DKP-based quorum sensing.

  18. 食品腐败中细菌群体感应现象的研究进展%Advances on bacterial quorum sensing in food spoilage

    Institute of Scientific and Technical Information of China (English)

    李学鹏; 陈桂芳; 仪淑敏; 朱军莉; 李婷婷; 李春; 励建荣

    2015-01-01

    微生物作用是引起食品腐败变质的主要因素之一.研究表明,细菌群体感应在该过程中起着重要作用.文中介绍了群体感应现象的产生机制与研究前沿,重点以牛奶和奶制品、肉和肉制品、水产品和果蔬4类食品体系为例分析了细菌群体感应现象在食品腐败中的作用,最后对开发以群体感应抑制剂为新型防腐剂的食品保藏新策略进行了论述,以期在为从群体感应角度研究食品腐败机制及保鲜方法提供理论依据.%Microbial activities is one of the major factors of food deterioration.The studies showed that bacterial quorum sensing plays an important role on food spoilage.This article summarized the mechanism for generation of quorum sensing system and its related researches.In particularly,the effect of bacterial quorum sensing on spoilage of foods,such as milk and milk products,meat and meat products,aquatic products,fruits and vegetables,was analyzed.Furthermore,the new strategy for food preservation based on quorum sensing inhibitors was briefly discussed.This paper will provide the theoretical basis for the study of food deterioration mechanism and the development of preservation methods derived from quorum sensing.

  19. A cell-based model for quorum sensing in heterogeneous bacterial colonies.

    Science.gov (United States)

    Melke, Pontus; Sahlin, Patrik; Levchenko, Andre; Jönsson, Henrik

    2010-06-17

    Although bacteria are unicellular organisms, they have the ability to act in concert by synthesizing and detecting small diffusing autoinducer molecules. The phenomenon, known as quorum sensing, has mainly been proposed to serve as a means for cell-density measurement. Here, we use a cell-based model of growing bacterial microcolonies to investigate a quorum-sensing mechanism at a single cell level. We show that the model indeed predicts a density-dependent behavior, highly dependent on local cell-clustering and the geometry of the space where the colony is evolving. We analyze the molecular network with two positive feedback loops to find the multistability regions and show how the quorum-sensing mechanism depends on different model parameters. Specifically, we show that the switching capability of the network leads to more constraints on parameters in a natural environment where the bacteria themselves produce autoinducer than compared to situations where autoinducer is introduced externally. The cell-based model also allows us to investigate mixed populations, where non-producing cheater cells are shown to have a fitness advantage, but still cannot completely outcompete producer cells. Simulations, therefore, are able to predict the relative fitness of cheater cells from experiments and can also display and account for the paradoxical phenomenon seen in experiments; even though the cheater cells have a fitness advantage in each of the investigated groups, the overall effect is an increase in the fraction of producer cells. The cell-based type of model presented here together with high-resolution experiments will play an integral role in a more explicit and precise comparison of models and experiments, addressing quorum sensing at a cellular resolution.

  20. Intracellular screen to identify metagenomic clones that induce or inhibit a quorum-sensing biosensor.

    Science.gov (United States)

    Williamson, Lynn L; Borlee, Bradley R; Schloss, Patrick D; Guan, Changhui; Allen, Heather K; Handelsman, Jo

    2005-10-01

    The goal of this study was to design and evaluate a rapid screen to identify metagenomic clones that produce biologically active small molecules. We built metagenomic libraries with DNA from soil on the floodplain of the Tanana River in Alaska. We extracted DNA directly from the soil and cloned it into fosmid and bacterial artificial chromosome vectors, constructing eight metagenomic libraries that contain 53,000 clones with inserts ranging from 1 to 190 kb. To identify clones of interest, we designed a high throughput "intracellular" screen, designated METREX, in which metagenomic DNA is in a host cell containing a biosensor for compounds that induce bacterial quorum sensing. If the metagenomic clone produces a quorum-sensing inducer, the cell produces green fluorescent protein (GFP) and can be identified by fluorescence microscopy or captured by fluorescence-activated cell sorting. Our initial screen identified 11 clones that induce and two that inhibit expression of GFP. The intracellular screen detected quorum-sensing inducers among metagenomic clones that a traditional overlay screen would not. One inducing clone carries a LuxI homologue that directs the synthesis of an N-acyl homoserine lactone quorum-sensing signal molecule. The LuxI homologue has 62% amino acid sequence identity to its closest match in GenBank, AmfI from Pseudomonas fluorescens, and is on a 78-kb insert that contains 67 open reading frames. Another inducing clone carries a gene with homology to homocitrate synthase. Our results demonstrate the power of an intracellular screen to identify functionally active clones and biologically active small molecules in metagenomic libraries.

  1. The role of quorum sensing in the pathogenicity of the cunning aggressor Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Givskov, Michael Christian

    2007-01-01

    that bacteria preferentially live in communities in the form of primitive organisms in which the behavior of individual cells is coordinated by cell-cell communication, known as quorum sensing (QS). Bacteria use QS for regulation of the processes involved in their interaction with each other, their environment...... in the protective mechanisms of P. aeruginosa and show how disruption of the QS can be used as an approach to control this cunning aggressor....

  2. Production of Tyrosol by Candida albicans Biofilms and Its Role in Quorum Sensing and Biofilm Development▿

    OpenAIRE

    Alem, M.A.S.; Oteef, M.D.Y.; Flowers, T; Douglas, L J

    2006-01-01

    Tyrosol and farnesol are quorum-sensing molecules produced by Candida albicans which accelerate and block, respectively, the morphological transition from yeasts to hyphae. In this study, we have investigated the secretion of tyrosol by C. albicans and explored its likely role in biofilm development. Both planktonic (suspended) cells and biofilms of four C. albicans strains, including three mutants with defined defects in the Efg 1 and Cph 1 morphogenetic signaling pathways, synthesized extra...

  3. Bacillus marcorestinctum sp. nov., a Novel Soil Acylhomoserine Lactone Quorum-Sensing Signal Quenching Bacterium

    OpenAIRE

    Xianzhen Li; Bo Zhu; Nuo Li; Fang Chen; Yan Han

    2010-01-01

    A Gram-positive, facultatively anaerobic, endospore-forming and rod-shaped bacterium was isolated from soil samples and designated strain LQQ. This organism strongly quenches the acylhomoserine lactone quorum-sensing signal. The LQQ strain exhibits phenotypic characteristics consistent with its classification in the genus Bacillus. It is positive in catalase and no special growth factor is needed. It uses glucose as sole carbon source. The DNA G + C content is 39.8 mol %. The closest relative...

  4. 变形链球菌ComCDE密度感应参与不同菌种的竞争%Quorum sensing system is involved in bacteriocin production and bacterial competition of Streptococcus mutans

    Institute of Scientific and Technical Information of China (English)

    张恺; 凌均棨; 刘佳; 霍丽珺; 麦俊妮

    2012-01-01

    目的 研究口腔变形链球菌( S.mutans )ComCDE密度感应系统参与血链球菌(S.sanguinis)的相互竞争作用.方法 采用LIVE\\DEAD BacLightTM荧光染色结合激光共聚焦显微镜,观察变形链球菌(简称变链菌)在CSP信号肽诱导下群体细菌自身死亡变化;通过荧光定量反转录聚合酶链反应(RT-PCR)测定细菌素以及细菌素免疫蛋白相关基因表达变化,分析变链菌ComCDE系统参与菌群生存竞争的调控机制.结果 在细菌竞争中,变形链球菌△comC、△comD 、△comE突变株失去不同菌种间的竞争力,无法抑制相邻Ssanguinis的正常生长;只有野生株保持竞争力,抑制相邻S.sanguinis生长,形成缺陷菌环.CSP信号肽诱导下,变链菌群体死菌/活菌率增高58.1%(P<0.05);细菌素及免疫蛋白相关SMU.151、SMU.423、SMU.1913c基因分别升高23.3倍(P=0.00)、15.9倍(P<0.05)、19.3倍(P<0.05).结论 变形链球菌ComCDE密度感应系统调控变链菌的变链素及免疫蛋白产生、参与不同菌种间竞争生存.%Objective To study the role of ComCDE quorum sensing system of Streptococcus mutans (S.mutans) in bacteriocin production and bacterial competition.Methods Growth competition between S.mutans and Streptococcus sanguis (S.sanguis) was analyzed through the bacterial competition assay.Cellular growth and death of S.mutans with and without CSP peptide was monitored by using the laser confocal microscopy and LIVE/DEAD BacLightTM staining.Bacteriocin and bacteriocin immunity protein related gene expression was determined by real-time RT-PCR.Results Competition assay showed that S.mutans △comC,△comD,and △comE mutant lost the ability of competition,and they could not suppress the normal growth of S.sanguinis,while S.mutans UA159 wild type strain inhibited the normal growth of the adjacent S.sanguinis.In the presence of CSP peptide,the ratio of Dead/live cells of S.mutans UA159 was increased 58.1% (P < 0.05),and

  5. Physiological framework for the regulation of quorum sensing-dependent public goods in Pseudomonas aeruginosa.

    Science.gov (United States)

    Mellbye, Brett; Schuster, Martin

    2014-03-01

    Many bacteria possess cell density-dependent quorum-sensing (QS) systems that often regulate cooperative secretions involved in host-microbe or microbe-microbe interactions. These secretions, or "public goods," are frequently coregulated by stress and starvation responses. Here we provide a physiological rationale for such regulatory complexity in the opportunistic pathogen Pseudomonas aeruginosa. Using minimal-medium batch and chemostat cultures, we comprehensively characterized specific growth rate-limiting macronutrients as key triggers for the expression of extracellular enzymes and metabolites directly controlled by the las and rhl QS systems. Expression was unrelated to cell density, depended on the secreted product's elemental composition, and was induced only when the limiting nutrient was not also a building block of the product; rhl-dependent products showed the strongest response, caused by the largely las-independent induction of the regulator RhlR and its cognate signal. In agreement with the prominent role of the rhl system, slow growth inverted the las-to-rhl signal ratio, previously considered a characteristic distinguishing between planktonic and biofilm lifestyles. Our results highlight a supply-driven, metabolically prudent regulation of public goods that minimizes production costs and thereby helps stabilize cooperative behavior. Such regulation would be beneficial for QS-dependent public goods that act broadly and nonspecifically, and whose need cannot always be accurately assessed by the producing cell. Clear differences in the capacities of the las and rhl systems to integrate starvation signals help explain the existence of multiple QS systems in one cell.

  6. From deep-sea volcanoes to human pathogens: a conserved quorum-sensing signal in Epsilonproteobacteria.

    Science.gov (United States)

    Pérez-Rodríguez, Ileana; Bolognini, Marie; Ricci, Jessica; Bini, Elisabetta; Vetriani, Costantino

    2015-05-01

    Chemosynthetic Epsilonproteobacteria from deep-sea hydrothermal vents colonize substrates exposed to steep thermal and redox gradients. In many bacteria, substrate attachment, biofilm formation, expression of virulence genes and host colonization are partly controlled via a cell density-dependent mechanism involving signal molecules, known as quorum sensing. Within the Epsilonproteobacteria, quorum sensing has been investigated only in human pathogens that use the luxS/autoinducer-2 (AI-2) mechanism to control the expression of some of these functions. In this study we showed that luxS is conserved in Epsilonproteobacteria and that pathogenic and mesophilic members of this class inherited this gene from a thermophilic ancestor. Furthermore, we provide evidence that the luxS gene is expressed--and a quorum-sensing signal is produced--during growth of Sulfurovum lithotrophicum and Caminibacter mediatlanticus, two Epsilonproteobacteria from deep-sea hydrothermal vents. Finally, we detected luxS transcripts in Epsilonproteobacteria-dominated biofilm communities collected from deep-sea hydrothermal vents. Taken together, our findings indicate that the epsiloproteobacterial lineage of the LuxS enzyme originated in high-temperature geothermal environments and that, in vent Epsilonproteobacteria, luxS expression is linked to the production of AI-2 signals, which are likely produced in situ at deep-sea vents. We conclude that the luxS gene is part of the ancestral epsilonproteobacterial genome and represents an evolutionary link that connects thermophiles to human pathogens.

  7. KARAKTERISASI BAKTERI ANTI QUORUM SENSING (AQS SEBAGAI PENGHAMBAT VIRULENSI PENYAKIT PADA IKAN LELE DUMBO (Clarias gariepinus

    Directory of Open Access Journals (Sweden)

    Hessy Novita

    2015-03-01

    Full Text Available Penyakit bakterial adalah salah satu penyebab kerugian besar di bidang akuakultur. Faktor virulensi bakteri penyakit umumnya diekspresikan oleh gen-gen virulen yang diregulasi dengan sistem Quorum Sensing. Tujuan dari penelitian ini adalah untuk mendapatkan isolat bakteri yang memiliki potensi sebagai Anti Quorum Sensing (AQS yang dapat menghambat faktor virulensi bakteri patogen penyebab penyakit pada ikan lele dumbo (Clarias gariepinus. Isolasi bakteri dilakukan dari sedimen, organ pencernaan dan air kolam ikan lele dumbo dari Parung, Ciampea, dan Gunung Sindur, Bogor, Jawa Barat. Sebanyak 347 isolat bakteri berhasil diisolasi, dan sebanyak 68 (19% isolat di antaranya mempunyai aktivitas AQS dengan empat isolat yang berpotensi sebagai bakteri AQS yaitu: TS 1 dan TS 2, TA 23, dan TY 33. Empat isolat tersebut teridentifikasi berdasarkan sekuen 16S rRNA sebagai Bacillus amyloliquefaciens, Lysinnibacillus sphaericus, Lysinnibacillus fusiformis, dan Bacillus cereus dengan persentase kemiripan masing-masing 93%, 99%, dan 100%. Berdasarkan analisa gen AHL (Acyl Homoserine Lactone laktonase (aiiA, keempat isolat tersebut menghasilkan enzim AHL. Hasil studi ini menunjukkan bahwa isolat bakteri hasil isolasi dari kolam ikan lele dumbo dapat menghambat mekanisme Quorum Sensing bakteri patogen ikan dengan mendegradasi autoinduser-nya yang berupa AHL.

  8. Control of Acetic Acid Fermentation by Quorum Sensing via N-Acylhomoserine Lactones in Gluconacetobacter intermedius▿ †

    Science.gov (United States)

    Iida, Aya; Ohnishi, Yasuo; Horinouchi, Sueharu

    2008-01-01

    A number of gram-negative bacteria regulate gene expression in a cell density-dependent manner by quorum sensing via N-acylhomoserine lactones (AHLs). Gluconacetobacter intermedius NCI1051, a gram-negative acetic acid bacterium, produces three different AHLs, N-decanoyl-l-homoserine lactone, N-dodecanoyl-l-homoserine lactone, and an N-dodecanoyl-l-homoserine lactone with a single unsaturated bond in its acyl chain, as determined by liquid chromatography-tandem mass spectrometry. Two genes encoding an AHL synthase and a cognate regulator were cloned from strain NCI1051 and designated ginI and ginR, respectively. Disruption of ginI or ginR abolished AHL production, indicating that NCI1051 contains a single set of quorum-sensing genes. Transcriptional analysis showed that ginI is activated by GinR, which is consistent with the finding that there is an inverted repeat whose nucleotide sequence is similar to the sequence bound by members of the LuxR family at position −45 with respect to the transcriptional start site of ginI. A single gene, designated ginA, located just downstream of ginI is transcribed by read-through from the GinR-inducible ginI promoter. A ginA mutant, as well as the ginI and ginR mutants, grew more rapidly in medium containing 2% (vol/vol) ethanol and accumulated acetic acid at a higher rate with a greater final yield than parental strain NCI1051. In addition, these mutants produced larger amounts of gluconic acid than the parental strain. These data demonstrate that the GinI/GinR quorum-sensing system in G. intermedius controls the expression of ginA, which in turn represses oxidative fermentation, including acetic acid and gluconic acid fermentation. PMID:18245283

  9. Isovaleryl-homoserine lactone, an unusual branched-chain quorum-sensing signal from the soybean symbiont Bradyrhizobium japonicum.

    Science.gov (United States)

    Lindemann, Andrea; Pessi, Gabriella; Schaefer, Amy L; Mattmann, Margrith E; Christensen, Quin H; Kessler, Aline; Hennecke, Hauke; Blackwell, Helen E; Greenberg, E Peter; Harwood, Caroline S

    2011-10-01

    Many species of Proteobacteria communicate by using LuxI-LuxR-type quorum-sensing systems that produce and detect acyl-homoserine lactone (acyl-HSL) signals. Most of the known signals are straight-chain fatty acyl-HSLs, and evidence indicates that LuxI homologs prefer fatty acid-acyl carrier protein (ACP) over fatty acyl-CoA as the acyl substrate for signal synthesis. Two related LuxI homologs, RpaI and BtaI from Rhodopseudomonas palustris and photosynthetic stem-nodulating bradyrhizobia, direct production of the aryl-HSLs p-coumaroyl-HSL and cinnamoyl-HSL, respectively. Here we report that BjaI from the soybean symbiont Bradyrhizobium japonicum USDA110 is closely related to RpaI and BtaI and catalyzes the synthesis of isovaleryl-HSL (IV-HSL), a branched-chain fatty acyl-HSL. We show that IV-HSL induces expression of bjaI, and in this way IV-HSL functions like many other acyl-HSL quorum-sensing signals. Purified histidine-tagged BjaI was an IV-HSL synthase, which was active with isovaleryl-CoA but not detectably so with isovaleryl-ACP. This suggests that the RpaI-BtaI-BjaI subfamily of acyl-HSL synthases may use CoA- rather than ACP-linked substrates for acyl-HSL synthesis. The bjaI-linked bjaR(1) gene is involved in the response to IV-HSL, and BjaR(1) is sensitive to IV-HSL at concentrations as low as 10 pM. Low but sufficient levels of IV-HSL (about 5 nM) accumulate in B. japonicum culture fluid. The low levels of IV-HSL synthesis have likely contributed to the fact that the quorum-sensing signal from this bacterium has not been described elsewhere.

  10. Mapping quorum sensing onto neural networks to understand collective decision making in heterogeneous microbial communities

    Science.gov (United States)

    Yusufaly, Tahir I.; Boedicker, James Q.

    2017-08-01

    Microbial communities frequently communicate via quorum sensing (QS), where cells produce, secrete, and respond to a threshold level of an autoinducer (AI) molecule, thereby modulating gene expression. However, the biology of QS remains incompletely understood in heterogeneous communities, where variant bacterial strains possess distinct QS systems that produce chemically unique AIs. AI molecules bind to ‘cognate’ receptors, but also to ‘non-cognate’ receptors found in other strains, resulting in inter-strain crosstalk. Understanding these interactions is a prerequisite for deciphering the consequences of crosstalk in real ecosystems, where multiple AIs are regularly present in the same environment. As a step towards this goal, we map crosstalk in a heterogeneous community of variant QS strains onto an artificial neural network model. This formulation allows us to systematically analyze how crosstalk regulates the community’s capacity for flexible decision making, as quantified by the Boltzmann entropy of all QS gene expression states of the system. In a mean-field limit of complete cross-inhibition between variant strains, the model is exactly solvable, allowing for an analytical formula for the number of variants that maximize capacity as a function of signal kinetics and activation parameters. An analysis of previous experimental results on the Staphylococcus aureus two-component Agr system indicates that the observed combination of variant numbers, gene expression rates and threshold concentrations lies near this critical regime of parameter space where capacity peaks. The results are suggestive of a potential evolutionary driving force for diversification in certain QS systems.

  11. Quorum Sensing in Populations of Spatially Extended Chaotic Oscillators Coupled Indirectly via a Heterogeneous Environment

    Science.gov (United States)

    Li, Bing-Wei; Cao, Xiao-Zhi; Fu, Chenbo

    2017-05-01

    Many biological and chemical systems could be modeled by a population of oscillators coupled indirectly via a dynamical environment. Essentially, the environment by which the individual element communicates with each other is heterogeneous. Nevertheless, most of previous works considered the homogeneous case only. Here we investigated the dynamical behaviors in a population of spatially distributed chaotic oscillators immersed in a heterogeneous environment. Various dynamical synchronization states (such as oscillation death, phase synchronization, and complete synchronized oscillation) as well as their transitions were explored. In particular, we uncovered a non-traditional quorum sensing transition: increasing the population density leaded to a transition from oscillation death to synchronized oscillation at first, but further increasing the density resulted in degeneration from complete synchronization to phase synchronization or even from phase synchronization to desynchronization. The underlying mechanism of this finding was attributed to the dual roles played by the population density. What's more, by treating the environment as another component of the oscillator, the full system was then effectively equivalent to a locally coupled system. This fact allowed us to utilize the master stability functions approach to predict the occurrence of complete synchronization oscillation, which agreed with that from the direct numerical integration of the system. The potential candidates for the experimental realization of our model were also discussed.

  12. Advances in the research of LuxR family protein in quorum-sensing system of gram-negative bacteria%革兰阴性菌群体感应系统中LuxR家族蛋白的研究进展

    Institute of Scientific and Technical Information of China (English)

    陈征; 向军

    2016-01-01

    Quorum sensing (QS) is a cell-density-dependent method for information transmission among bacteria,as well as a mechanism for the bacteria to adapt to environment.LuxR family protein plays a key role in gram-negative bacterial QS system as a kind of transcription regulators and participates in a variety of biological behaviors with LuxI protein and signal molecules,such as bioluminescence,biofilm formation,virulence factors production,and so on.The advances in the research of LuxR family protein in QS system of gram-negative bacteria were summarized in this review.

  13. Research progress on quorum sensing of Aspergilus flavus%黄曲霉群体感应研究进展

    Institute of Scientific and Technical Information of China (English)

    李彩艳; 梁志宏; 黄昆仑

    2015-01-01

    曲霉属真菌(Aspergillus)如黄曲霉、寄生曲霉侵染玉米、花生等富含油脂的作物种子后产生的黄曲霉毒素(aflatoxin)具有强致癌作用,严重威胁食品安全和人类健康。群体感应(quorum sensing, QS)曾经认为只存在于细菌中,但是在真菌中也存在 QS系统,菌体的形态建成和次级代谢产物的产生都与细胞的群体密度有关。黄曲霉拥有类似群体感应的机制,菌核到分生孢子的转换受细胞密度和脂肪氧合酶调控。氧脂素作为信号分子通过密度依赖机制可抑制或促进黄曲霉的生长及黄曲霉毒素的生物合成,本文综述了黄曲霉群体感应及信号通路的研究进展,旨在从群体感应的角度抑制黄曲霉毒素的产生,为微生物与食品安全的研究提供指导。%Aspergillus spp such as A. flavus and A. parasiticus can infect oil-rich crop seeds and subsequently lead to aflatoxin contamination, which has an important impact on economic loss and health risk. Although once thought to exist only in bacteria, QS systems are now well established in fungi. Recently it has been shown that A. flavus possesses a quorum-sensing-like mechanism, where a sclerotia-to-conidia transition is governed by cell density and lipoxygenase activity. Oxylipins can inhibit or stimulate fungal development and aflatoxin production via a density-dependent mechanism as a kind of signal .This paper reviewed the research progress on quorum sensing and signaling pathways of A. flavus and was aimed to inhibit the generation of aflatoxin from the perspective of quorum sensing, providing a guidance for the research of microorganism and food safety.

  14. Surface enhanced Raman scattering for detection of Pseudomonas aeruginosa quorum sensing compounds

    Science.gov (United States)

    Thrift, Will; Bhattacharjee, Arunima; Darvishzadeh-Varcheie, Mahsa; Lu, Ying; Hochbaum, Allon; Capolino, Filippo; Whiteson, Katrine; Ragan, Regina

    2015-08-01

    Pseudomonas aeruginosa (PA), a biofilm forming bacterium, commonly affects cystic fibrosis, burn victims, and immunocompromised patients. PA produces pyocyanin, an aromatic, redox active, secondary metabolite as part of its quorum sensing signaling system activated during biofilm formation. Surface enhanced Raman scattering (SERS) sensors composed of Au nanospheres chemically assembled into clusters on diblock copolymer templates were fabricated and the ability to detect pyocyanin to monitor biofilm formation was investigated. Electromagnetic full wave simulations of clusters observed in scanning electron microcopy images show that the localized surface plasmon resonance wavelength is 696 nm for a dimer with a gap spacing of 1 nm in an average dielectric environment of the polymer and analyte; the local electric field enhancement is on the order of 400 at resonance, relative to free space. SERS data acquired at 785 nm excitation from a monolayer of benzenethiol on fabricated samples was compared with Raman data of pure benzenethiol and enhancement factors as large as 8×109 were calculated that are consistent with simulated field enhancements. Using this system, the limit of detection of pyocyanin in pure gradients was determined to be 10 parts per billion. In SERS data of the supernatant from the time dependent growth of PA shaking cultures, pyocyanin vibrational modes were clearly observable during the logarithmic growth phase corresponding to activation of genes related to biofilm formation. These results pave the way for the use of SERS sensors for the early detection of biofilm formation, leading to reduced healthcare costs and better patient outcomes.

  15. Exploiting quorum sensing interfering strategies in gram-negative bacteria for the enhancement of environmental applications

    Directory of Open Access Journals (Sweden)

    Weiwei eZhang

    2016-01-01

    Full Text Available Quorum sensing (QS is a widespread intercellular form of communication to coordinate physiological processes and cooperative activities of bacteria at the population level, and it depends on the production, secretion, and detection of small diffusible autoinducers, such as acyl-homoserine lactones (AHLs, auto-inducing oligo-peptides (AIPs and autoinducer 2. In this review, the function of QS autoinducers of gram-negative bacteria in different aspects of wastewater treatment systems is examined. Based on research primarily performed over the past ten years, QS involvement in the formation of biofilm and aerobic granules and changes of the microbial community and degradation/transformation pathways is discussed. In particular, the QS pathway in the role of bacterial infections and disease prevention in aquaculture is addressed. Interference of QS autoinducer-regulated pathways is considered potential treatment for a variety of environmentally related problems. This review is expected to serve as a stepping stone for further study and development strategies based on the mediation of QS-regulated pathways to enhance applications in both wastewater treatment systems and aquaculture.

  16. Quorum Sensing Regulation of Competence and Bacteriocins in Streptococcus pneumoniae and mutans

    Science.gov (United States)

    Shanker, Erin; Federle, Michael J.

    2017-01-01

    The human pathogens Streptococcus pneumoniae and Streptococcus mutans have both evolved complex quorum sensing (QS) systems that regulate the production of bacteriocins and the entry into the competent state, a requirement for natural transformation. Natural transformation provides bacteria with a mechanism to repair damaged genes or as a source of new advantageous traits. In S. pneumoniae, the competence pathway is controlled by the two-component signal transduction pathway ComCDE, which directly regulates SigX, the alternative sigma factor required for the initiation into competence. Over the past two decades, effectors of cellular killing (i.e., fratricides) have been recognized as important targets of the pneumococcal competence QS pathway. Recently, direct interactions between the ComCDE and the paralogous BlpRH pathway, regulating bacteriocin production, were identified, further strengthening the interconnections between these two QS systems. Interestingly, a similar theme is being revealed in S. mutans, the primary etiological agent of dental caries. This review compares the relationship between the bacteriocin and the competence QS pathways in both S. pneumoniae and S. mutans, and hopes to provide clues to regulatory pathways across the genus Streptococcus as a potential tool to efficiently investigate putative competence pathways in nontransformable streptococci. PMID:28067778

  17. AHL-type quorum sensing and its regulation on symplasmata formation in Pantoea agglomerans YS19.

    Science.gov (United States)

    Jiang, Jing; Wu, Suisui; Wang, Jieru; Feng, Yongjun

    2015-05-01

    Pantoea agglomerans YS19, an endophytic diazotrophic bacterium isolated from rice, is characterized by the formation of multicellular aggregate structure called symplasmata, which not only bestow the strong stress-resistance of the bacterium, but also contribute to the specific adaptation in the endophyte-host association. Acyl-homoserine lactones (AHLs), as the important signal molecule in the quorum sensing (QS) system of gram-negative bacteria, were demonstrated to regulate motility, cell-aggregation, and other bacterial behaviors. Here, the production of AHL by P. agglomerans YS19 and its regulation on the symplasmata formation were studied. It was revealed that the production of AHL by YS19 was initiated at the exponential growth stage and from then on, reached the peak values at the stationary growth stage in LB medium. The AHL was identified as N-3-oxooctanoyl-L-homoserine lactone (OOHL) by MALDI-TOF-MS analysis. The AHL synthesis gene pagI and receptor gene pagR in YS19 were cloned and phylogenetic analysis showed that they were high conservative among strains in species of P. agglomerans. It was revealed that AHL promoted the bacterial growth and symplasmata formation of YS19. Meanwhile, the colonization ability and growth-promoting effect of YS19 on the host plant were also enhanced by AHL. These results strongly suggest the pleiotropic effects of the AHL-type QS system in endophytic life of the strain.

  18. Quorum sensing communication between bacteria and human cells: signals, targets and functions

    Directory of Open Access Journals (Sweden)

    Angelika eHolm

    2014-06-01

    Full Text Available Both direct and long-range interactions between pathogenic Pseudomonas aeruginosa bacteria and their eukaryotic hosts are important in the outcome of infections. For cell-to-cell communication, these bacteria employ the quorum sensing (QS system to pass on information of the density of the bacterial population and collectively switch on virulence factor production, biofilm formation and resistance development. Thus, QS allows bacteria to behave as a community to perform tasks which would be impossible for individual cells, e.g. to overcome defense and immune systems and establish infections in higher organisms. This review highlights these aspects of QS and our own recent research on how P.aeruginosa communicates with human cells using the small QS signal molecules N-acyl homoserine lactones (AHL. We focus on how this conversation changes the behavior and function of neutrophils, macrophages and epithelial cells and on how the signaling machinery in human cells responsible for the recognition of AHL. Understanding the bacteria-host relationships at both cellular and molecular levels is essential for the identification of new targets and for the development of novel strategies to fight bacterial infections in the future.

  19. Solonamide B inhibits quorum sensing and reduces Staphylococcus aureus mediated killing of human neutrophils.

    Science.gov (United States)

    Nielsen, Anita; Månsson, Maria; Bojer, Martin S; Gram, Lone; Larsen, Thomas O; Novick, Richard P; Frees, Dorte; Frøkiær, Hanne; Ingmer, Hanne

    2014-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) continues to be a serious human pathogen, and particularly the spread of community associated (CA)-MRSA strains such as USA300 is a concern, as these strains can cause severe infections in otherwise healthy adults. Recently, we reported that a cyclodepsipeptide termed Solonamide B isolated from the marine bacterium, Photobacterium halotolerans strongly reduces expression of RNAIII, the effector molecule of the agr quorum sensing system. Here we show that Solonamide B interferes with the binding of S. aureus autoinducing peptides (AIPs) to sensor histidine kinase, AgrC, of the agr two-component system. The hypervirulence of USA300 has been linked to increased expression of central virulence factors like α-hemolysin and the phenol soluble modulins (PSMs). Importantly, in strain USA300 Solonamide B dramatically reduced the activity of α-hemolysin and the transcription of psma encoding PSMs with an 80% reduction in toxicity of supernatants towards human neutrophils and rabbit erythrocytes. To our knowledge this is the first report of a compound produced naturally by a Gram-negative marine bacterium that interferes with agr and affects both RNAIII and AgrA controlled virulence gene expression in S. aureus.

  20. Heterogeneous Response to a Quorum-Sensing Signal in the Luminescence of Individual Vibrio fischeri

    Science.gov (United States)

    Pérez, Pablo Delfino; Hagen, Stephen J.

    2010-01-01

    The marine bacterium Vibrio fischeri regulates its bioluminescence through a quorum sensing mechanism: the bacterium releases diffusible small molecules (autoinducers) that accumulate in the environment as the population density increases. This accumulation of autoinducer (AI) eventually activates transcriptional regulators for bioluminescence as well as host colonization behaviors. Although V.fischeri quorum sensing has been extensively characterized in bulk populations, far less is known about how it performs at the level of the individual cell, where biochemical noise is likely to limit the precision of luminescence regulation. We have measured the time-dependence and AI-dependence of light production by individual V.fischeri cells that are immobilized in a perfusion chamber and supplied with a defined concentration of exogenous AI. We use low-light level microscopy to record and quantify the photon emission from the cells over periods of several hours as they respond to the introduction of AI. We observe an extremely heterogeneous response to the AI signal. Individual cells differ widely in the onset time for their luminescence and in their resulting brightness, even in the presence of high AI concentrations that saturate the light output from a bulk population. The observed heterogeneity shows that although a given concentration of quorum signal may determine the average light output from a population of cells, it provides far weaker control over the luminescence output of each individual cell. PMID:21103327

  1. Ecological feedback in quorum-sensing microbial populations can induce heterogeneous production of autoinducers

    Science.gov (United States)

    Bauer, Matthias; Knebel, Johannes; Lechner, Matthias; Pickl, Peter; Frey, Erwin

    2017-01-01

    Autoinducers are small signaling molecules that mediate intercellular communication in microbial populations and trigger coordinated gene expression via ‘quorum sensing’. Elucidating the mechanisms that control autoinducer production is, thus, pertinent to understanding collective microbial behavior, such as virulence and bioluminescence. Recent experiments have shown a heterogeneous promoter activity of autoinducer synthase genes, suggesting that some of the isogenic cells in a population might produce autoinducers, whereas others might not. However, the mechanism underlying this phenotypic heterogeneity in quorum-sensing microbial populations has remained elusive. In our theoretical model, cells synthesize and secrete autoinducers into the environment, up-regulate their production in this self-shaped environment, and non-producers replicate faster than producers. We show that the coupling between ecological and population dynamics through quorum sensing can induce phenotypic heterogeneity in microbial populations, suggesting an alternative mechanism to stochastic gene expression in bistable gene regulatory circuits. DOI: http://dx.doi.org/10.7554/eLife.25773.001 PMID:28741470

  2. 假单胞菌Quorum sensing调控体系%Regulation on Quorum Sensing in Pseudomonas

    Institute of Scientific and Technical Information of China (English)

    张玲华; 冯莉; 田兴山

    2006-01-01

    群体感应(Quorum sensing,QS)是近来受到广泛关注的一种细菌群体行为调控机制,通过感应一些信号分子如酰基高丝氨酸环内酯(acyl-homoserine lactone,AHL)来判断菌群密度和周围环境变化,假单胞菌中同样也有AHL信号分子,当信号达到一定的浓度阈值时,能启动菌体中相关基因的表达来适应环境中的变化,从而调节菌体的群体行为(如致病性及群体生长调节).众多报道说明了假单胞菌的群体感应调节系统是由一些全面的调节子所调控的.本文系统介绍了假单胞菌群体感应调控系统,并分析假单胞菌在该系统中复杂的应答反应.

  3. Methylobacterium-plant interaction genes regulated by plant exudate and quorum sensing molecules

    Directory of Open Access Journals (Sweden)

    Manuella Nóbrega Dourado

    2013-12-01

    Full Text Available Bacteria from the genus Methylobacterium interact symbiotically (endophytically and epiphytically with different plant species. These interactions can promote plant growth or induce systemic resistance, increasing plant fitness. The plant colonization is guided by molecular communication between bacteria-bacteria and bacteria-plants, where the bacteria recognize specific exuded compounds by other bacteria (e.g. homoserine molecules and/or by the plant roots (e.g. flavonoids, ethanol and methanol, respectively. In this context, the aim of this study was to evaluate the effect of quorum sensing molecules (N-acyl-homoserine lactones and plant exudates (including ethanol in the expression of a series of bacterial genes involved in Methylobacterium-plant interaction. The selected genes are related to bacterial metabolism (mxaF, adaptation to stressful environment (crtI, phoU and sss, to interactions with plant metabolism compounds (acdS and pathogenicity (patatin and phoU. Under in vitro conditions, our results showed the differential expression of some important genes related to metabolism, stress and pathogenesis, thereby AHL molecules up-regulate all tested genes, except phoU, while plant exudates induce only mxaF gene expression. In the presence of plant exudates there is a lower bacterial density (due the endophytic and epiphytic colonization, which produce less AHL, leading to down regulation of genes when compared to the control. Therefore, bacterial density, more than plant exudate, influences the expression of genes related to plant-bacteria interaction.

  4. Bioinformatic Prediction of Gene Functions Regulated by Quorum Sensing in the Bioleaching Bacterium Acidithiobacillus ferrooxidans

    Directory of Open Access Journals (Sweden)

    Alvaro Banderas

    2013-08-01

    Full Text Available The biomining bacterium Acidithiobacillus ferrooxidans oxidizes sulfide ores and promotes metal solubilization. The efficiency of this process depends on the attachment of cells to surfaces, a process regulated by quorum sensing (QS cell-to-cell signalling in many Gram-negative bacteria. At. ferrooxidans has a functional QS system and the presence of AHLs enhances its attachment to pyrite. However, direct targets of the QS transcription factor AfeR remain unknown. In this study, a bioinformatic approach was used to infer possible AfeR direct targets based on the particular palindromic features of the AfeR binding site. A set of Hidden Markov Models designed to maintain palindromic regions and vary non-palindromic regions was used to screen for putative binding sites. By annotating the context of each predicted binding site (PBS, we classified them according to their positional coherence relative to other putative genomic structures such as start codons, RNA polymerase promoter elements and intergenic regions. We further used the Multiple EM for Motif Elicitation algorithm (MEME to further filter out low homology PBSs. In summary, 75 target-genes were identified, 34 of which have a higher confidence level. Among the identified genes, we found afeR itself, zwf, genes encoding glycosyltransferase activities, metallo-beta lactamases, and active transport-related proteins. Glycosyltransferases and Zwf (Glucose 6-phosphate-1-dehydrogenase might be directly involved in polysaccharide biosynthesis and attachment to minerals by At. ferrooxidans cells during the bioleaching process.

  5. Anti-Quorum Sensing Potential of Crude Kigelia africana Fruit Extracts

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    Hafizah Y. Chenia

    2013-02-01

    Full Text Available The increasing incidence of multidrug-resistant pathogens has stimulated the search for novel anti-virulence compounds. Although many phytochemicals show promising antimicrobial activity, their power lies in their anti-virulence properties. Thus the quorum sensing (QS inhibitory activity of four crude Kigelia africana fruit extracts was assessed qualitatively and quantitatively using the Chromobacterium violaceum and Agrobacterium tumefaciens biosensor systems. Inhibition of QS-controlled violacein production in C. violaceum was assayed using the qualitative agar diffusion assay as well as by quantifying violacein inhibition using K. africana extracts ranging from 0.31–8.2 mg/mL. Qualitative modulation of QS activity was investigated using the agar diffusion double ring assay. All four extracts showed varying levels of anti-QS activity with zones of violacein inhibition ranging from 9–10 mm. The effect on violacein inhibition was significant in the following order: hexane > dichloromethane > ethyl acetate > methanol. Inhibition was concentration-dependent, with the ≥90% inhibition being obtained with ≥1.3 mg/mL of the hexane extract. Both LuxI and LuxR activity were affected by crude extracts suggesting that the phytochemicals target both QS signal and receptor. K. africana extracts with their anti-QS activity, have the potential to be novel therapeutic agents, which might be important in reducing virulence and pathogenicity of drug-resistant bacteria in vivo.

  6. Virulence Inhibitors from Brazilian Peppertree Block Quorum Sensing and Abate Dermonecrosis in Skin Infection Models

    Science.gov (United States)

    Muhs, Amelia; Lyles, James T.; Parlet, Corey P.; Nelson, Kate; Kavanaugh, Jeffery S.; Horswill, Alexander R.; Quave, Cassandra L.

    2017-01-01

    Widespread antibiotic resistance is on the rise and current therapies are becoming increasingly limited in both scope and efficacy. Methicillin-resistant Staphylococcus aureus (MRSA) represents a major contributor to this trend. Quorum sensing controlled virulence factors include secreted toxins responsible for extensive damage to host tissues and evasion of the immune system response; they are major contributors to morbidity and mortality. Investigation of botanical folk medicines for wounds and infections led us to study Schinus terebinthifolia (Brazilian Peppertree) as a potential source of virulence inhibitors. Here, we report the inhibitory activity of a flavone rich extract “430D-F5” against all S. aureus accessory gene regulator (agr) alleles in the absence of growth inhibition. Evidence for this activity is supported by its agr-quenching activity (IC50 2–32 μg mL−1) in transcriptional reporters, direct protein outputs (α-hemolysin and δ-toxin), and an in vivo skin challenge model. Importantly, 430D-F5 was well tolerated by human keratinocytes in cell culture and mouse skin in vivo; it also demonstrated significant reduction in dermonecrosis following skin challenge with a virulent strain of MRSA. This study provides an explanation for the anti-infective activity of peppertree remedies and yields insight into the potential utility of non-biocide virulence inhibitors in treating skin infections. PMID:28186134

  7. Virulence Inhibitors from Brazilian Peppertree Block Quorum Sensing and Abate Dermonecrosis in Skin Infection Models.

    Science.gov (United States)

    Muhs, Amelia; Lyles, James T; Parlet, Corey P; Nelson, Kate; Kavanaugh, Jeffery S; Horswill, Alexander R; Quave, Cassandra L

    2017-02-10

    Widespread antibiotic resistance is on the rise and current therapies are becoming increasingly limited in both scope and efficacy. Methicillin-resistant Staphylococcus aureus (MRSA) represents a major contributor to this trend. Quorum sensing controlled virulence factors include secreted toxins responsible for extensive damage to host tissues and evasion of the immune system response; they are major contributors to morbidity and mortality. Investigation of botanical folk medicines for wounds and infections led us to study Schinus terebinthifolia (Brazilian Peppertree) as a potential source of virulence inhibitors. Here, we report the inhibitory activity of a flavone rich extract "430D-F5" against all S. aureus accessory gene regulator (agr) alleles in the absence of growth inhibition. Evidence for this activity is supported by its agr-quenching activity (IC50 2-32 μg mL(-1)) in transcriptional reporters, direct protein outputs (α-hemolysin and δ-toxin), and an in vivo skin challenge model. Importantly, 430D-F5 was well tolerated by human keratinocytes in cell culture and mouse skin in vivo; it also demonstrated significant reduction in dermonecrosis following skin challenge with a virulent strain of MRSA. This study provides an explanation for the anti-infective activity of peppertree remedies and yields insight into the potential utility of non-biocide virulence inhibitors in treating skin infections.

  8. Single cell analysis of Vibrio harveyi uncovers functional heterogeneity in response to quorum sensing signals

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    Anetzberger Claudia

    2012-09-01

    Full Text Available Abstract Background Vibrio harveyi and closely related species are important pathogens in aquaculture. A complex quorum sensing cascade involving three autoinducers controls bioluminescence and several genes encoding virulence factors. Single cell analysis of a V. harveyi population has already indicated intercellular heterogeneity in the production of bioluminescence. This study was undertaken to analyze the expression of various autoinducer-dependent genes in individual cells. Results Here we used reporter strains bearing promoter::gfp fusions to monitor the induction/repression of three autoinducer-regulated genes in wild type conjugates at the single cell level. Two genes involved in pathogenesis - vhp and vscP, which code for an exoprotease and a component of the type III secretion system, respectively, and luxC (the first gene in the lux operon were chosen for analysis. The lux operon and the exoprotease gene are induced, while vscP is repressed at high cell density. As controls luxS and recA, whose expression is not dependent on autoinducers, were examined. The responses of the promoter::gfp fusions in individual cells from the same culture ranged from no to high induction. Importantly, simultaneous analysis of two autoinducer induced phenotypes, bioluminescence (light detection and exoproteolytic activity (fluorescence of a promoter::gfp fusion, in single cells provided evidence for functional heterogeneity within a V. harveyi population. Conclusions Autoinducers are not only an indicator for cell density, but play a pivotal role in the coordination of physiological activities within the population.

  9. Quorum Sensing Activity of a Kluyvera sp. Isolated from a Malaysian Waterfall

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    Nina Yusrina Muhamad Yunos

    2014-05-01

    Full Text Available In many species of bacteria, the quorum sensing mechanism is used as a unique communication system which allows them to regulate gene expression and behavior in accordance with their population density. N-Acylhomoserine lactones (AHLs are known as diffusible autoinducer molecules involved in this communication network. This finding aimed to characterize the production of AHL of a bacterial strain ND04 isolated from a Malaysian waterfall. Strain ND04 was identified as Kluyvera sp. as confirmed by molecular analysis of its 16S ribosomal RNA gene sequence. Kluyvera sp. is closely related to the Enterobacteriaceae family. Chromobacterium violaceum CV026 was used as a biosensor to detect the production of AHL by strain ND04. High resolution triple quadrupole liquid chromatography-mass spectrometry analysis of strain ND04 showed our isolate produced two AHLs which are N-(3-oxohexanoylhomoserine lactone (3-oxo-C6 HSL and N-3-oxo-octanoyl-L-homoserine lactone (3-oxo-C8 HSL.

  10. Chemical probes of quorum sensing: from compound development to biological discovery.

    Science.gov (United States)

    Welsh, Michael A; Blackwell, Helen E

    2016-09-01

    Bacteria can utilize chemical signals to coordinate the expression of group-beneficial behaviors in a method of cell-cell communication called quorum sensing (QS). The discovery that QS controls the production of virulence factors and biofilm formation in many common pathogens has driven an explosion of research aimed at both deepening our fundamental understanding of these regulatory networks and developing chemical agents that can attenuate QS signaling. The inherently chemical nature of QS makes studying these pathways with small molecule tools a complementary approach to traditional microbiology techniques. Indeed, chemical tools are beginning to yield new insights into QS regulation and provide novel strategies to inhibit QS. Here, we review the most recent advances in the development of chemical probes of QS systems in Gram-negative bacteria, with an emphasis on the opportunistic pathogen Pseudomonas aeruginosa We first describe reports of novel small molecule modulators of QS receptors and QS signal synthases. Next, in several case studies, we showcase how chemical tools have been deployed to reveal new knowledge of QS biology and outline lessons for how researchers might best target QS to combat bacterial virulence. To close, we detail the outstanding challenges in the field and suggest strategies to overcome these issues.

  11. Synthetic Quorum Sensing and Induced Aggregation in Model Microcapsule Colonies with Repressilator Feedback

    Science.gov (United States)

    Shum, Henry; Yashin, Victor; Balazs, Anna

    We model a system of synthetic microcapsules that communicate chemically by releasing nanoparticles or signaling molecules. These signaling species bind to receptors on the shells of capsules and modulate the target shell's permeability, thereby controlling nanoparticle release from the target capsule. Using the repressilator regulatory network motif, whereby three species suppress the production of the next in a cyclic fashion, we show that large amplitude oscillations in nanoparticle release can emerge when many capsules are close together. This exemplifies quorum sensing, which is the ability of cells to gauge their population density and collectively initiate a new behavior once a critical density is reached. We present a physically realizable model in which the oscillations exhibited in crowded populations induce aggregation of the microcapsules, mimicking complex biological behavior of the slime mold Dictyostelium discoideum with only simple, synthetic components. We also show that the clusters can be dispersed and reformed repeatedly and controllably by addition of chemical stimuli, demonstrating possible applications in creating reconfigurable or programmable materials.

  12. Screening of certain medicinal plants from India for their anti-quorum sensing activity.

    Science.gov (United States)

    Zahin, Maryam; Hasan, Sameena; Aqil, Farrukh; Khan, Mohd Sajjad Ahmad; Husain, Fohad Mabood; Ahmad, Iqbal

    2010-12-01

    Discovery of quorum sensing (QS) system to coordinate virulence and biofilm formation in bacterial pathogens has triggered search for safe, stable and non-toxic anti-QS compounds from natural products. Ethanolic extracts of 24 Indian medicinal plants were tested by agar well and disc diffusion assay for anti-QS activity using Chromobacterium violaceum (CV12472 and CVO26) reporter strains. AHL from C. violaceum CV31532 was isolated and partially purified for its use in CVO26 based bioassay. Effect on swarming-motility of Pseudomonas aeruginosa (PAO1) was also recorded at sub-MIC concentrations of extracts. Of the 24 medicinal plants screened Hemidesmus indicus (L.) Schult (root), Holarrhena antidysenterica (Roth) A.DC. (bark), Mangifera indica L. (seed) Punica granatum L. (pericarp) and Psoralea corylifolia L. (seed) demonstrated varying level of inhibition of violacein production in the reporter strains. Moreover, a significant reduction in swarms was recorded over control. The inhibition of violacein production and swarming motility may be due to direct or indirect interference on QS by active constituents or the interactive effect of different phytocompounds present in the extracts. These plant extracts may be selected for activity guided fractionation to identify and characterize the active principle.

  13. Epigallocatechin gallate from Camellia sinensis L. (Kuntze is a potential quorum sensing inhibitor in Chromobacterium violaceum

    Directory of Open Access Journals (Sweden)

    Joemar C. Taganna

    2008-06-01

    Full Text Available The problem on the widespread occurrence of antibiotic resistant strains of bacteria calls for novel methods of control of bacterial activity. One of the new viable alternatives to antibiotics is the use of substances that inhibit quorum sensing (QS – a bacterial communication system that has been known to regulate the expression of virulence genes during infection. In this study, epigallocatechin gallate (EGCG from green tea, Camellia sinensis L. (Kuntze was tested for its ability to inhibit QS in a test organism, Chromobacterium violaceum. This microorganism produces a violet-colored substance, violacein, through QS. This study aimed to detect inhibition of QS-regulated violacein production in C. violaceum by EGCG and to determine the dynamics of QS inhibition relative to the concentration of EGCG. The effect of increasing concentration of EGCG on both violacein production and cell density of treated and untreated C. violaceum was determined in a 96-well-microplate format and read at 570nm and 620nm for violacein production and growth, respectively. The results show that addition of EGCG increased the growth of the organism while there is concentration-dependent decrease in the QS-controlled production of violacein. This study thus establishes that EGCG is a potential QS inhibitor and can be further studied and developed for its use as an anti-pathogenic but non-toxic drug.

  14. [Biofilm caused by fungi--structure, quorum sensing, morphogenetic changes, resistance to drugs].

    Science.gov (United States)

    Nowak, Magdalena; Kurnatowski, Piotr

    2009-01-01

    Formation of fungal biofilms in patients with implanted biomedical prosthesis constitutes very serious clinical problems. The biofilm can lead to dysfunction of implanted material and can be a reservoir for chronic and systemic infections. Numerous investigations demonstrated differences in quantity and structure of biofilms that had been formed by various species of fungi belonged to Candida genus. Stages of biofilm formations had been examined carefully in in vitro conditions. Biofilm formation begin with adhesion of fungi to the surface, microcolonies are formed subsequently. At the end of the process, extracellular material is excreted, and its formula, that is various in different fungi Candida species, contribute to its resistance to antifungal drugs. Farnesol and tyrosol are two quorum-sensing molecules. They are acting inversely, regulating formation of "germ tubes" and influencing morphogenetic conversion between yeast and filamentous forms, which plays a very important role in pathogenicity and formation of biofilm. Drug resistance of fungi from Candida has been shown to create a very important clinical problem. Many experiments in vitro confirm significantly lower activity of antifungal drugs toward Candida biofilm than toward Candida, in the form of planctonic cells. Surprisingly, some non-steroidal anti-inflammatory drugs can inhibit biofilm formation.

  15. RpoN Regulates Virulence Factors of Pseudomonas aeruginosa via Modulating the PqsR Quorum Sensing Regulator.

    Science.gov (United States)

    Cai, Zhao; Liu, Yang; Chen, Yicai; Yam, Joey Kuok Hoong; Chew, Su Chuen; Chua, Song Lin; Wang, Ke; Givskov, Michael; Yang, Liang

    2015-11-30

    The alternative sigma factor RpoN regulates many cell functions, such as motility, quorum sensing, and virulence in the opportunistic pathogen Pseudomonas aeruginosa (P. aeruginosa). P. aeruginosa often evolves rpoN-negative variants during the chronic infection in cystic fibrosis patients. It is unclear how RpoN interacts with other regulatory mechanisms to control virulence of P. aeruginosa. In this study, we show that RpoN modulates the function of PqsR, a quorum sensing receptor regulating production of virulence factors including the phenazine pyocyanin. The ∆rpoN mutant is able to synthesize 4-quinolone signal molecule HHQ but unable to activate PqsR and Pseudomonas quinolone signal (pqs) quorum sensing. The ∆rpoN mutant produces minimal level of pyocyanin and is unable to produce the anti-staphylococcal agents. Providing pqsR in trans in the ∆rpoN mutant restores its pqs quorum sensing and virulence factor production to the wild-type level. Our study provides evidence that RpoN has a regulatory effect on P. aeruginosa virulence through modulating the function of the PqsR quorum sensing regulator.

  16. RpoN Regulates Virulence Factors of Pseudomonas aeruginosa via Modulating the PqsR Quorum Sensing Regulator

    Directory of Open Access Journals (Sweden)

    Zhao Cai

    2015-11-01

    Full Text Available The alternative sigma factor RpoN regulates many cell functions, such as motility, quorum sensing, and virulence in the opportunistic pathogen Pseudomonas aeruginosa (P. aeruginosa. P. aeruginosa often evolves rpoN-negative variants during the chronic infection in cystic fibrosis patients. It is unclear how RpoN interacts with other regulatory mechanisms to control virulence of P. aeruginosa. In this study, we show that RpoN modulates the function of PqsR, a quorum sensing receptor regulating production of virulence factors including the phenazine pyocyanin. The ∆rpoN mutant is able to synthesize 4-quinolone signal molecule HHQ but unable to activate PqsR and Pseudomonas quinolone signal (pqs quorum sensing. The ∆rpoN mutant produces minimal level of pyocyanin and is unable to produce the anti-staphylococcal agents. Providing pqsR in trans in the ∆rpoN mutant restores its pqs quorum sensing and virulence factor production to the wild-type level. Our study provides evidence that RpoN has a regulatory effect on P. aeruginosa virulence through modulating the function of the PqsR quorum sensing regulator.

  17. Functional determinants of the quorum-sensing non-coding RNAs and their roles in target regulation.

    Science.gov (United States)

    Shao, Yi; Feng, Lihui; Rutherford, Steven T; Papenfort, Kai; Bassler, Bonnie L

    2013-07-31

    Quorum sensing is a chemical communication process that bacteria use to control collective behaviours including bioluminescence, biofilm formation, and virulence factor production. In Vibrio harveyi, five homologous small RNAs (sRNAs) called Qrr1-5, control quorum-sensing transitions. Here, we identify 16 new targets of the Qrr sRNAs. Mutagenesis reveals that particular sequence differences among the Qrr sRNAs determine their target specificities. Modelling coupled with biochemical and genetic analyses show that all five of the Qrr sRNAs possess four stem-loops: the first stem-loop is crucial for base pairing with a subset of targets. This stem-loop also protects the Qrr sRNAs from RNase E-mediated degradation. The second stem-loop contains conserved sequences required for base pairing with the majority of the target mRNAs. The third stem-loop plays an accessory role in base pairing and stability. The fourth stem-loop functions as a rho-independent terminator. In the quorum-sensing regulon, Qrr sRNAs-controlled genes are the most rapid to respond to quorum-sensing autoinducers. The Qrr sRNAs are conserved throughout vibrios, thus insights from this work could apply generally to Vibrio quorum sensing.

  18. Chemical probes for competitive profiling of the quorum sensing signal synthase PqsD of Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Michaela Prothiwa

    2016-12-01

    Full Text Available The human pathogen Pseudomonas aeruginosa uses the pqs quorum sensing system to coordinate the production of its broad spectrum of virulence factors to facilitate colonization and infection of its host. Hereby, the enzyme PqsD is a virulence related quorum sensing signal synthase that catalyzes the central step in the biosynthesis of the Pseudomonas quinolone signals HHQ and PQS. We developed a library of cysteine reactive chemical probes with an alkyne handle for fluorescence tagging and report the selective and highly sensitive in vitro labelling of the active site cysteine of this important enzyme. Interestingly, only one type of probe, with a reactive α-chloroacetamide was capable of covalently reacting with the active site. We demonstrated the potential of our probes in a competitive labelling platform where we screened a library of synthetic HHQ and PQS analogues with heteroatom replacements and found several inhibitors of probe binding that may represent promising scaffolds for the development of customized PqsD inhibitors as well as a chemical toolbox to investigate the activity and active site specificity of the enzyme.

  19. Effects of allicin on the formation of Pseudomonas aeruginosa biofinm and the production of quorum-sensing controlled virulence factors.

    Science.gov (United States)

    Lihua, Lin; Jianhuit, Wang; Jialini, Yu; Yayin, Li; Guanxin, Liu

    2013-01-01

    The Gram-negative Pseudomonas aeruginosa bacterial pathogen is reputed for its resistance to multiple antibiotics, and this property is strongly associated with the development of biofilms. Bacterial biofilms form by aggregation of microorganisms on a solid surface and secretion of an extracellular polysaccharide substances that acts as a physical protection barrier for the encased bacteria. In addition, the P aeruginosa quorum-sensing system contributes to antibiotic resistance by regulating the expression of several virulence factors, including exotoxin A, elastase, pyoverdin and rhamnolipid. The organosulfur compound allicin, derived from garlic, has been shown to inhibit both surface-adherence of bacteria and production of virulence factors. In this study, the effects of allicin on P aeruginosa biofilm formation and the production of quorum-sensing controlled virulence factors were investigated. The results demonstrated that allicin could inhibit early bacterial adhesion, reduce EPS secretion, and down-regulate virulence factors' production. Collectively, these findings suggest the potential of allicin as a therapeutic agent for controlling P aeruginosa biofilm.

  20. Quorum-sensing system and biofilm formation in Pseudomonas aeruginosa%铜绿假单胞菌群体感应系统与生物膜形成

    Institute of Scientific and Technical Information of China (English)

    杨华; 余加林

    2006-01-01

    群体感应(quorum-sensing,QS)系统是细菌依赖于群体密度的信号交流机制,细菌依靠该机制对外界环境变化作出协调统一的应答.目前对铜绿假单胞菌的QS系统已有较深入的研究,该菌的QS系统由两种相互作用的酰化高丝氨酸内酯(AHL)及非-AHL分子调节系统组成,在转录或转录后水平上对细菌的群体行为作出调节.针对QS系统的抗生素将为治疗细菌生物膜感染带来广阔前景.

  1. Advance in Quorum-Sensing System to Affect Vibrio cholerae Biofilm Formation%霍乱弧菌群体感应系统影响生物膜形成的研究进展

    Institute of Scientific and Technical Information of China (English)

    叶晓敏; 陆春

    2010-01-01

    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.

  2. Quorum quenching activity in cell-free lysate of endophytic bacteria isolated from Pterocarpus santalinus Linn., and its effect on quorum sensing regulated biofilm in Pseudomonas aeruginosa PAO1.

    Science.gov (United States)

    Rajesh, P S; Ravishankar Rai, V

    2014-01-01

    Quorum sensing mechanism allows the microorganisms to resist the antibiotic treatment by forming biofilms. Quorum quenching is one of the mechanisms to control the development of drug resistance in microbes. Endophyte bacteria are beneficial to plant growth as they support the immune system against the pathogen attack. The endophytic bacteria present in Pterocarpus santalinus were screened for the presence of N-acyl homoserine lactones (AHLs) degrading bacteria using biosensor strains and further confirmed by quantifying the violacein production. Cell-free lysate of endophytic bacteria, Bacillus firmus PT18 and Enterobacter asburiae PT39 exhibited potent AHL degrading ability by inhibiting about 80% violacein production in biosensor strain. Furthermore, when the cell-free lysate was applied to Pseudomonas aeruginosa PAO1 and PAO1-JP2 biofilm it resulted in significant (p<0.01) inhibition of biofilm formation. The biofilm inhibition was confirmed by visualization of biofilm slides under fluorescence microscopy, which showed decrease in total biomass formation in treated slides. Isolation and amplification of the gene (aiiA) indicated that the presence of AHL lactonase in cell-free lysate and sequence alignment indicated that AiiA contains a "HXHXDH" zinc-binding motif that is being conserved in several groups of metallohydrolases. Therefore, the study shows the potential of AHLs degradation by AHL lactonase present in cell-free lysate of isolated endophytic bacteria and inhibition of quorum sensing regulated biofilm formation in P. aeruginosa PAO1. Copyright © 2013 Elsevier GmbH. All rights reserved.

  3. Quorum sensing of microalgae associated marine Ponticoccus sp. PD-2 and its algicidal function regulation.

    Science.gov (United States)

    Chi, Wendan; Zheng, Li; He, Changfei; Han, Bin; Zheng, Minggang; Gao, Wei; Sun, Chengjun; Zhou, Gefei; Gao, Xiangxing

    2017-12-01

    Quorum sensing (QS) systems play important roles in regulating many physiological functions of microorganisms, such as biofilm formation, bioluminescence, and antibiotic production. One marine algicidal bacterium, Ponticoccus sp. PD-2, was isolated from the microalga Prorocentrum donghaiense, and its N-acyl-homoserine lactone (AHL)-mediated QS system was verified. In this study, we analyzed the AHLs profile of strain PD-2. Two AHLs, 3-oxo-C8-HSL and 3-oxo-C10-HSL, were detected using a biosensor overlay assay and GC-MS methods. Two complete AHL-QS systems (designated zlaI/R and zlbI/R) were identified in the genome of strain PD-2. When expressed in Escherichia coli, both zlaI and zlbI genes could each produce 3-oxo-C8-HSL and 3-oxo-C10-HSL. Algicidal activity was investigated by evaluating the inhibitory rate (IR) of microalgae growth by measuring the fluorescence of viable cells. We found that the metabolites of strain PD-2 had algicidal activity against its host P. donghaiense (IR 84.81%) and two other red tide microalgae, Phaeocystis globosa (IR 78.91%) and Alexandrium tamarense (IR 67.14%). β-cyclodextrin which binds to AHLs and inhibits the QS system reduced the algicidal activity more than 50%. This indicates that inhibiting the QS system may affect the algicidal metabolites production of strain PD-2. Our study indicated that a QS-regulated algicidal system may play a potential role in the process of red tides disintegration. QS might be a potential way to control red tides.

  4. Prevention of bacterial quorum sensing in aquifer materials and effect on bioclogging

    Science.gov (United States)

    Baveye, P.; Superak, C.; Farris, K.

    2012-12-01

    In aquifer materials that are clogged as a result of the growth and metabolism of bacteria, microscopic observations usually show the bacterial cells to be present in aggregates that tend to be strategically located at constrictions in the pore space, either strained there, or accumulating at these spots for metabolic advantages. Aggregation appears to be fostered by exopolymer production, but can also occur purely as a result of electrostatic interactions. On membranes, research has shown that if bacteria are discouraged from aggregating, for example by eliminating the biochemical means (e.g., "quorum sensing") by which they communicate in order to do so, biofouling of the membranes is significantly delayed and in some cases even largely alleviated. In this context, the goal of the research described in this presentation was to determine if a similar situation might arise when quorum quenchers are added to the liquid injected in columns of fine sand inoculated with various bacterial strains. Traditional saturated hydraulic conductivity and piezometer measurements asre complemented with detailed microscopic observations in the pore space. Perspectives on the possible use of quorum quenchers in practical situations is discussed.

  5. Quorum sensing of pathogenic bacteria and quorum-sensing inhibitors%病原菌的群体感应及其抑制剂的研究进展

    Institute of Scientific and Technical Information of China (English)

    程古月; 郝海红; 戴梦红; 刘振利; 袁宗辉

    2012-01-01

    The emergence of antibiotic-resistant and especially multidrug-resistant pathogenic bacteria intensifies the need to screen new drug targets and develop new antibacterial drugs. Bacteria coordinate their virulent behaviors in a cell density-dependent manner known as quorum sensing (QS). In this process, pathogenic bacteria exchange autoinducers (AIs) to regulate the expression of genes involved in processes such as virulence, adhesion, and biofilm formation. Different types of AIs mediate different QS systems. Preventing the accumulation of AIs or blocking their recognition by signal receptors can reduce the pathogenic processes under QS control. Therefore, quorum-sensing inhibitors (QSIs) may be an effective way to treat bacterial infections, especially those caused by antibiotic-resistant strains. QSIs can be categorized into three classes: nonpeptide small molecules, peptides, and proteins (including quorum-quenching enzymes and antibodies). In addition, competing bacteria and animal hosts can scavenge AIs, thus playing the role of QSIs. QSIs can be screened by natural QSI indicator strains, engineered bacteria, or computer simulation. The continuing study of QS-mediated pathogenic mechanisms will provide new targets for QSIs. The combined use of QSIs and traditional antimicrobials is expected to improve treatment and help prevent the further development of drug resistance.%随着病原菌耐药性特别是多重耐药性的日益严重,抗菌药作用新靶点的发现和新型抗菌药物的研发显得尤为重要.病原菌的致病作用常受到与其群体密度相关的群体感应(quorum-sensing,QS)系统的调控.细菌通过释放和交换自诱导信号分子(autoinducers,AIs)以调控致病相关基因的表达,从而影响细菌的毒力、黏附和生物膜的形成等.不同种类的AIs介导不同的QS系统,阻止AIs的积累或其与受体的识别和结合就可以抑制QS调控的致病基因的表达.因此,QS抑制剂(quorum-sensing

  6. Airway Epithelial Cell Integrity Protects from Cytotoxicity of Pseudomonas aeruginosa Quorum-Sensing Signals.

    Science.gov (United States)

    Losa, Davide; Köhler, Thilo; Bacchetta, Marc; Saab, Joanna Bou; Frieden, Maud; van Delden, Christian; Chanson, Marc

    2015-08-01

    Cell-to-cell communication via gap junctions regulates airway epithelial cell homeostasis and maintains the epithelium host defense. Quorum-sensing molecules produced by Pseudomonas aeruginosa coordinate the expression of virulence factors by this respiratory pathogen. These bacterial signals may also incidentally modulate mammalian airway epithelial cell responses to the pathogen, a process called interkingdom signaling. We investigated the interactions between the P. aeruginosa N-3-oxo-dodecanoyl-L-homoserine lactone (C12) quorum-sensing molecule and human airway epithelial cell gap junctional intercellular communication (GJIC). C12 degradation and its effects on cells were monitored in various airway epithelial cell models grown under nonpolarized and polarized conditions. Its concentration was further monitored in daily tracheal aspirates of colonized intubated patients. C12 rapidly altered epithelial integrity and decreased GJIC in nonpolarized airway epithelial cells, whereas other quorum-sensing molecules had no effect. The effects of C12 were dependent on [Ca(2+)]i and could be prevented by inhibitors of Src tyrosine family and Rho-associated protein kinases. In contrast, polarized airway cells grown on Transwell filters were protected from C12 except when undergoing repair after wounding. In vivo during colonization of intubated patients, C12 did not accumulate, but it paralleled bacterial densities. In vitro C12 degradation, a reaction catalyzed by intracellular paraoxonase 2 (PON2), was impaired in nonpolarized cells, whereas PON2 expression was increased during epithelial polarization. The cytotoxicity of C12 on nonpolarized epithelial cells, combined with its impaired degradation allowing its accumulation, provides an additional pathogenic mechanism for P. aeruginosa infections.

  7. Study of the major essential oil compounds of Coriandrum sativum against Acinetobacter baumannii and the effect of linalool on adhesion, biofilms and quorum sensing.

    Science.gov (United States)

    Alves, Susana; Duarte, Andreia; Sousa, Sónia; Domingues, Fernanda C

    2016-01-01

    Acinetobacter baumannii is a pathogen that has the ability to adhere to surfaces in the hospital environment and to form biofilms which are increasingly resistant to antimicrobial agents. The aim of this work was to study the antimicrobial activity of the major oil compounds of Coriandrum sativum against A. baumannii. The effect of linalool on planktonic cells and biofilms of A. baumannii on different surfaces, as well as its effect on adhesion and quorum sensing was evaluated. From all the compounds evaluated, linalool was the compound with the best antibacterial activity, with minimum inhibitory concentration values between 2 and 8 μl ml(-1). Linalool also inhibited biofilm formation and dispersed established biofilms of A. baumannii, changed the adhesion of A. baumannii to surfaces and interfered with the quorum- sensing system. Thus, linalool could be a promising antimicrobial agent for controlling planktonic cells and biofilms of A. baumannii.

  8. Quorum sensing and virulence of Pseudomonas aeruginosa during lung infection of cystic fibrosis patients.

    Directory of Open Access Journals (Sweden)

    Thomas Bjarnsholt

    Full Text Available Pseudomonas aeruginosa is the predominant microorganism in chronic lung infection of cystic fibrosis patients. The chronic lung infection is preceded by intermittent colonization. When the chronic infection becomes established, it is well accepted that the isolated strains differ phenotypically from the intermittent strains. Dominating changes are the switch to mucoidity (alginate overproduction and loss of epigenetic regulation of virulence such as the Quorum Sensing (QS. To elucidate the dynamics of P. aeruginosa QS systems during long term infection of the CF lung, we have investigated 238 isolates obtained from 152 CF patients at different stages of infection ranging from intermittent to late chronic. Isolates were characterized with regard to QS signal molecules, alginate, rhamnolipid and elastase production and mutant frequency. The genetic basis for change in QS regulation were investigated and identified by sequence analysis of lasR, rhlR, lasI and rhlI. The first QS system to be lost was the one encoded by las system 12 years (median value after the onset of the lung infection with subsequent loss of the rhl encoded system after 17 years (median value shown as deficiencies in production of the 3-oxo-C12-HSL and C4-HSL QS signal molecules respectively. The concomitant development of QS malfunction significantly correlated with the reduced production of rhamnolipids and elastase and with the occurrence of mutations in the regulatory genes lasR and rhlR. Accumulation of mutations in both lasR and rhlR correlated with development of hypermutability. Interestingly, a higher number of mucoid isolates were found to produce C4-HSL signal molecules and rhamnolipids compared to the non-mucoid isolates. As seen from the present data, we can conclude that P. aeruginosa and particularly the mucoid strains do not lose the QS regulation or the ability to produce rhamnolipids until the late stage of the chronic infection.

  9. Attenuation of adhesion, quorum sensing and biofilm mediated virulence of carbapenem resistant Escherichia coli by selected natural plant products.

    Science.gov (United States)

    Thakur, Pallavi; Chawla, Raman; Tanwar, Ankit; Chakotiya, Ankita Singh; Narula, Alka; Goel, Rajeev; Arora, Rajesh; Sharma, Rakesh Kumar

    2016-03-01

    The multi-drug resistance offered by Carbapenem Resistant Escherichia coli (Family: Enterobacteriaceae; Class: Gammaproteobacteria) against third line antibiotics can be attributed towards its ability to develop biofilm. Such process involves adhesion and quorum-sensing induced colonization leading to biomass development. The present study explored the anti-adhesion, anti-quorum sensing and anti-biofilm potential of 05 pre-standardized potent herbals. Berberis aristata (PTRC-2111-A) exhibited maximum potential in all these activities i.e. 91.3% ± 0.05% (Anti-adhesion), 96.06% ± 0.05% (Anti-Quorum sensing) and 51.3% ± 0.07% (Anti-Biofilm formation) respectively. Camellia sinensis (PTRC-31911-A) showed both anti-adhesion (84.1% ± 0.03%) and anti-quorum sensing (90.0%) potential while Holarrhena antidysenterica (PTRC-8111-A) showed only anti-quorum sensing potential as compared to standards/antibiotics. These findings were in line with the molecular docking analysis of phytoligands against Lux S and Pilin receptors. Furthermore, the pairwise correlation analysis of the tested activities with qualitative, quantitative and bioactivity functional descriptors revealed that an increased content of alkaloid, moderate content of flavonoids and decreased content of tannins supported all the three activities. In addition, nitric oxide and superoxide scavenging activity were found to be correlated with anti-quorum sensing activity. The findings indicated clearly that B. aristata (Family: Berberidaceae) and C. sinensis (Family: Theaceae) were potent herbal leads with significant therapeutic potential which further needs to be explored at pre-clinical level in the future.

  10. Collective Behavior of Quorum-Sensing Run-and-Tumble Particles under Confinement

    Science.gov (United States)

    Rein, Markus; Heinß, Nike; Schmid, Friederike; Speck, Thomas

    2016-02-01

    We study a generic model for quorum-sensing bacteria in circular confinement. Every bacterium produces signaling molecules, the local concentration of which triggers a response when a certain threshold is reached. If this response lowers the motility, then an aggregation of bacteria occurs which differs fundamentally from standard motility-induced phase separation due to the long-ranged nature of the concentration of signal molecules. We analyze this phenomenon analytically and by numerical simulations employing two different protocols leading to stationary cluster and ring morphologies, respectively.

  11. Quorum sensing and bacterial virulence%群体感应与细菌毒力

    Institute of Scientific and Technical Information of China (English)

    张晓兵; 府伟灵

    2011-01-01

    @@ 细菌产生自诱导物质(autoinducers,AIs)作为细菌间相互联系的信号分子,其浓度随着细菌的增殖而升高.由于该信号分子能自由通过细胞膜,因此细胞内外的浓度相近.当该信号分子浓度达到一定浓度,就激活细菌胞内的受体,从而改变基因表达,这种现象就是群体感应(quorum sensing,QS).

  12. In vitro screens for quorum sensing inhibitors and in vivo confirmation of their effect

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; van Gennip, Maria; Jakobsen, Tim H

    2010-01-01

    This article will introduce the reader to protocols intended for (i) identification of quorum sensing (QS) inhibitors (QSIs), (ii) characterization of these compounds in vitro and (iii) evaluation of these compounds in animal models. Traditional antimicrobial drugs are designed against planktonic...... bacteria and not against bacterial biofilms. In biofilms, bacteria are highly resistant to otherwise lethal treatments and they communicate with each other, thus enabling coordinated group behavior. For many years, we have focused on interference with cell to cell communication, also known as QS...

  13. Piper nigrum, Piper betle and Gnetum gnemon Natural Food Sources with Anti-Quorum Sensing Properties

    OpenAIRE

    Li Ying Tan; Wai-Fong Yin; Kok-Gan Chan

    2013-01-01

    Various parts of Piper nigrum, Piper betle and Gnetum gnemon are used as food sources by Malaysians. The purpose of this study is to examine the anti-quorum sensing (anti-QS) properties of P. nigrum, P. betle and G. gnemon extracts. The hexane, chloroform and methanol extracts of these plants were assessed in bioassays involving Pseudomonas aeruginosa PA01, Escherichia coli [pSB401], E. coli [pSB1075] and Chromobacterium violaceum CV026. It was found that the extracts of these three plants ha...

  14. How Delisea pulchra furanones affect quorum sensing and swarming motility in Serratia liquefaciens MG1

    DEFF Research Database (Denmark)

    Rasmussen, T B; Manefield, M; Andersen, Jens Bo

    2000-01-01

    Halogenated furanones produced by the benthic marine macroalga Delisea pulchra inhibit swarming motility of Serratia liquefaciens MG1. This study demonstrates that exogenously added furanones control transcription of the quorum sensing regulated gene swrA in competition with the cognate signal...... molecule N:-butanoyl-L-homoserine lactone. This in turn results in reduced production of the surface-active compound serrawettin W2, which is crucial for surface translocation of the differentiated swarm cells. It is demonstrated that furanones interfere with interspecies communication during swarming...

  15. Staphylococcus aureus autoinducer-2 quorum sensing decreases biofilm formation in an icaR-dependent manner

    Directory of Open Access Journals (Sweden)

    Yu Dan

    2012-12-01

    Full Text Available Abstract Background Staphylococcus aureus is an important pathogen that causes biofilm-associated infection in humans. Autoinducer 2 (AI-2, a quorum-sensing (QS signal for interspecies communication, has a wide range of regulatory functions in both Gram-positive and Gram-negative bacteria, but its exact role in biofilm formation in S. aureus remains unclear. Results Here we demonstrate that mutation of the AI-2 synthase gene luxS in S. aureus RN6390B results in increased biofilm formation compared with the wild-type (WT strain under static, flowing and anaerobic conditions and in a mouse model. Addition of the chemically synthesized AI-2 precursor in the luxS mutation strain (ΔluxS restored the WT phenotype. Real-time RT-PCR analysis showed that AI-2 activated the transcription of icaR, a repressor of the ica operon, and subsequently a decreased level of icaA transcription, which was presumably the main reason why luxS mutation influences biofilm formation. Furthermore, we compared the roles of the agr-mediated QS system and the LuxS/AI-2 QS system in the regulation of biofilm formation using the ΔluxS strain, RN6911 and the Δagr ΔluxS strain. Our data indicate a cumulative effect of the two QS systems on the regulation of biofilm formation in S. aureus. Conclusion These findings demonstrate that AI-2 can decrease biofilm formation in S. aureus via an icaR-activation pathway. This study may provide clues for therapy in S. aureus biofilm-associated infection.

  16. Quorum sensing coordinates brute force and stealth modes of infection in the plant pathogen Pectobacterium atrosepticum.

    Directory of Open Access Journals (Sweden)

    Hui Liu

    2008-06-01

    Full Text Available Quorum sensing (QS in vitro controls production of plant cell wall degrading enzymes (PCWDEs and other virulence factors in the soft rotting enterobacterial plant pathogen Pectobacterium atrosepticum (Pba. Here, we demonstrate the genome-wide regulatory role of QS in vivo during the Pba-potato interaction, using a Pba-specific microarray. We show that 26% of the Pba genome exhibited differential transcription in a QS (expI- mutant, compared to the wild-type, suggesting that QS may make a greater contribution to pathogenesis than previously thought. We identify novel components of the QS regulon, including the Type I and II secretion systems, which are involved in the secretion of PCWDEs; a novel Type VI secretion system (T6SS and its predicted substrates Hcp and VgrG; more than 70 known or putative regulators, some of which have been demonstrated to control pathogenesis and, remarkably, the Type III secretion system and associated effector proteins, and coronafacoyl-amide conjugates, both of which play roles in the manipulation of plant defences. We show that the T6SS and a novel potential regulator, VirS, are required for full virulence in Pba, and propose a model placing QS at the apex of a regulatory hierarchy controlling the later stages of disease progression in Pba. Our findings indicate that QS is a master regulator of phytopathogenesis, controlling multiple other regulators that, in turn, co-ordinately regulate genes associated with manipulation of host defences in concert with the destructive arsenal of PCWDEs that manifest the soft rot disease phenotype.

  17. Quorum sensing coordinates brute force and stealth modes of infection in the plant pathogen Pectobacterium atrosepticum.

    Science.gov (United States)

    Liu, Hui; Coulthurst, Sarah J; Pritchard, Leighton; Hedley, Peter E; Ravensdale, Michael; Humphris, Sonia; Burr, Tom; Takle, Gunnhild; Brurberg, May-Bente; Birch, Paul R J; Salmond, George P C; Toth, Ian K

    2008-06-20

    Quorum sensing (QS) in vitro controls production of plant cell wall degrading enzymes (PCWDEs) and other virulence factors in the soft rotting enterobacterial plant pathogen Pectobacterium atrosepticum (Pba). Here, we demonstrate the genome-wide regulatory role of QS in vivo during the Pba-potato interaction, using a Pba-specific microarray. We show that 26% of the Pba genome exhibited differential transcription in a QS (expI-) mutant, compared to the wild-type, suggesting that QS may make a greater contribution to pathogenesis than previously thought. We identify novel components of the QS regulon, including the Type I and II secretion systems, which are involved in the secretion of PCWDEs; a novel Type VI secretion system (T6SS) and its predicted substrates Hcp and VgrG; more than 70 known or putative regulators, some of which have been demonstrated to control pathogenesis and, remarkably, the Type III secretion system and associated effector proteins, and coronafacoyl-amide conjugates, both of which play roles in the manipulation of plant defences. We show that the T6SS and a novel potential regulator, VirS, are required for full virulence in Pba, and propose a model placing QS at the apex of a regulatory hierarchy controlling the later stages of disease progression in Pba. Our findings indicate that QS is a master regulator of phytopathogenesis, controlling multiple other regulators that, in turn, co-ordinately regulate genes associated with manipulation of host defences in concert with the destructive arsenal of PCWDEs that manifest the soft rot disease phenotype.

  18. Interference of quorum sensing in urinary pathogen Serratia marcescens by Anethum graveolens.

    Science.gov (United States)

    Salini, Ramesh; Pandian, Shunmugiah Karutha

    2015-08-01

    Serratia marcescens is an opportunistic turned obligate pathogen frequently associated with urinary tract infections (UTI) and are multidrug resistant at most instances. Quorum sensing (QS) system, a population-dependent global regulatory system, controls the pathogenesis machinery of S. marcescens as it does in other pathogens. In the present study, methanol extract of a common herb and spice, Anethum graveolens (AGME) was assessed for its anti-QS potential against the clinical isolate of S. marcescens. AGME notably reduced the biofilm formation and QS-dependent virulence factors production in a concentration-dependent manner (64-1024 μg mL(-1)). The light and confocal microscopic images clearly evidenced the antibiofilm activity of AGME (256 μg mL(-1)) at its minimal biofilm inhibitory concentration. Besides, in support of biochemical assays, the expression analysis of QS-regulated genes fimC, bsmA and flhD which are crucial for initial adhesion and motility confirmed their downregulation upon exposure to AGME. LC-MS analysis of AGME revealed 3-O-methyl ellagic acid (3-O-ME) as one of its active principles having nearly similar antibiofilm activity and a reduced inhibition of prodigiosin (27%) and protease (15%) compared to AGME [prodigiosin (47%) and protease (50%)]. UFLC analysis revealed that 0.355 mg g(-1) of 3-O-ME was present in the AGME. AGME and the 3-O-ME significantly interfered the QS system of a QS model strain S. marcescens MG1 and its mutant S. marcescens MG44 which in turn corroborates the anti-QS mechanism of AGME.

  19. Induction of Plasmid Conjugation in Bacillus subtilis Is Bistable and Driven by a Direct Interaction of a Rap/Phr Quorum-sensing System with a Master Repressor.

    Science.gov (United States)

    Rösch, Thomas C; Graumann, Peter L

    2015-08-14

    Conjugation of plasmid pLS20 from Bacillus subtilis is limited to a time window between early and late exponential growth. Genetic evidence has suggested that pLS20-encoded protein RcoLS20 represses expression of a large conjugation operon, whereas Rap protein RapLS20 relieves repression. We show that RapLS20 is a true antirepressor protein that forms dimers in vivo and in vitro and that it directly binds to the repressor protein RcoLS20 in a 1:1 stoichiometry. We provide evidence that RapLS20 binds to the helix-turn-helix-containing domain of RcoLS20 in vivo, probably obstructing DNA binding of RcoLS20, as seen in competitive DNA binding experiments. The activity of RapLS20 in turn is counteracted by the addition of the cognate PhrLS20 peptide, which directly binds to the Rap protein and presumably induces a conformational change of the antirepressor. Thus, a Rap protein acts directly as an antirepressor protein during regulation of plasmid conjugation, turning on conjugation, and is counteracted by the PhrLS20 peptide, which, by analogy to known Rap/Phr systems, is secreted and taken back up into the cells, mediating cell density-driven regulation. Finally, we show that this switchlike process establishes a population heterogeneity, where up to 30% of the cells induce transcription of the conjugation operon.

  20. Induction of Plasmid Conjugation in Bacillus subtilis Is Bistable and Driven by a Direct Interaction of a Rap/Phr Quorum-sensing System with a Master Repressor*

    Science.gov (United States)

    Rösch, Thomas C.; Graumann, Peter L.

    2015-01-01

    Conjugation of plasmid pLS20 from Bacillus subtilis is limited to a time window between early and late exponential growth. Genetic evidence has suggested that pLS20-encoded protein RcoLS20 represses expression of a large conjugation operon, whereas Rap protein RapLS20 relieves repression. We show that RapLS20 is a true antirepressor protein that forms dimers in vivo and in vitro and that it directly binds to the repressor protein RcoLS20 in a 1:1 stoichiometry. We provide evidence that RapLS20 binds to the helix-turn-helix-containing domain of RcoLS20 in vivo, probably obstructing DNA binding of RcoLS20, as seen in competitive DNA binding experiments. The activity of RapLS20 in turn is counteracted by the addition of the cognate PhrLS20 peptide, which directly binds to the Rap protein and presumably induces a conformational change of the antirepressor. Thus, a Rap protein acts directly as an antirepressor protein during regulation of plasmid conjugation, turning on conjugation, and is counteracted by the PhrLS20 peptide, which, by analogy to known Rap/Phr systems, is secreted and taken back up into the cells, mediating cell density-driven regulation. Finally, we show that this switchlike process establishes a population heterogeneity, where up to 30% of the cells induce transcription of the conjugation operon. PMID:26112413

  1. QsrO a novel regulator of quorum-sensing and virulence in Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Thilo Köhler

    Full Text Available In Pseudomonas aeruginosa, the production of many secreted virulence factors is controlled by a quorum-sensing (QS circuit, constituted of transcriptional activators (LasR, RhlR, PqsR and their cognate signaling molecules (3-oxo-C12-HSL, C4-HSL, PQS. QS is a cooperative behavior that is beneficial to a population but can be exploited by "QS-cheaters", individuals which do not respond to the QS-signal, but can use public goods produced by QS-cooperators. In order to identify QS-deficient clones we designed a genetic screening based on a lasB-lacZ fusion. We isolated one clone (PT1617 deficient in QS-dependent gene expression and virulence factor production despite wild type lasR, rhlR and pqsR alleles. Whole genome sequencing of PT1617 revealed a 3,552 bp deletion encompassing ORFs PA2228-PA2229-PA2230 and the pslA gene. However, complementation of PT1617 by plasmid-encoded copies of these ORFs, did not restore QS. Unexpectedly, gene expression levels of ORFs PA2228, PA2227 (vqsM and PA2222, located adjacent to the deletion, were 10 to 100 fold higher in mutant PT1617 than in PAO1. When expressed from a constitutive promoter on a plasmid, PA2226, alone was found to be sufficient to confer a QS-negative phenotype on PAO1 as well as on PA14. Co-expression of PA2226 and PA2225 in PAO1 further prevented induction of the type III secretion system. In summary, we have identified a novel genetic locus including ORF2226 termed qsrO (QS-repressing ORF, capable of down-regulating all three known QS-systems in P. aeruginosa.

  2. Development of a mimotope vaccine targeting the Staphylococcus aureus quorum sensing pathway.

    Directory of Open Access Journals (Sweden)

    John P O'Rourke

    Full Text Available A major hurdle in vaccine development is the difficulty in identifying relevant target epitopes and then presenting them to the immune system in a context that mimics their native conformation. We have engineered novel virus-like-particle (VLP technology that is able to display complex libraries of random peptide sequences on a surface-exposed loop in the coat protein without disruption of protein folding or VLP assembly. This technology allows us to use the same VLP particle for both affinity selection and immunization, integrating the power of epitope discovery and epitope mimicry of traditional phage display with the high immunogenicity of VLPs. Previously, we showed that using affinity selection with our VLP platform identifies linear epitopes of monoclonal antibodies and subsequent immunization generates the proper antibody response. To test if our technology could identify immunologic mimotopes, we used affinity selection on a monoclonal antibody (AP4-24H11 that recognizes the Staphylococcus aureus autoinducing peptide 4 (AIP4. AIP4 is a secreted eight amino acid, cyclized peptide produced from the S. aureus accessory gene regulator (agrIV quorum-sensing operon. The agr system coordinates density dependent changes in gene expression, leading to the upregulation of a host of virulence factors, and passive transfer of AP4-24H11 protects against S. aureus agrIV-dependent pathogenicity. In this report, we identified a set of peptides displayed on VLPs that bound with high specificity to AP4-24H11. Importantly, similar to passive transfer with AP4-24H11, immunization with a subset of these VLPs protected against pathogenicity in a mouse model of S. aureus dermonecrosis. These data are proof of principle that by performing affinity selection on neutralizing antibodies, our VLP technology can identify peptide mimics of non-linear epitopes and that these mimotope based VLP vaccines provide protection against pathogens in relevant animal models.

  3. CqsA-CqsS quorum-sensing signal-receptor specificity in Photobacterium angustum.

    Science.gov (United States)

    Ke, Xiaobo; Miller, Laura C; Ng, Wai-Leung; Bassler, Bonnie L

    2014-02-01

    Quorum sensing (QS) is a process of bacterial cell-cell communication that relies on the production, detection and population-wide response to extracellular signal molecules called autoinducers. The QS system commonly found in vibrios and photobacteria consists of the CqsA synthase/CqsS receptor pair. Vibrio cholerae CqsA/S synthesizes and detects (S)-3-hydroxytridecan-4-one (C10-CAI-1), whereas Vibrio harveyi produces and detects a distinct but similar molecule, (Z)-3-aminoundec-2-en-4-one (Ea-C8-CAI-1). To understand the signalling properties of the larger family of CqsA-CqsS pairs, here, we characterize the Photobacterium angustum CqsA/S system. Many photobacterial cqsA genes harbour a conserved frameshift mutation that abolishes CAI-1 production. By contrast, their cqsS genes are intact. Correcting the P. angustum cqsA reading frame restores production of a mixture of CAI-1 moieties, including C8-CAI-1, C10-CAI-1, Ea-C8-CAI-1 and Ea-C10-CAI-1. This signal production profile matches the P. angustum CqsS receptor ligand-detection capability. The receptor exhibits a preference for molecules with 10-carbon tails, and the CqsS Ser(168) residue governs this preference. P. angustum can overcome the cqsA frameshift to produce CAI-1 under particular limiting growth conditions presumably through a ribosome slippage mechanism. Thus, we propose that P. angustum uses CAI-1 signalling for adaptation to stressful environments.

  4. Quorum Sensing in Bacillus thuringiensis Is Required for Completion of a Full Infectious Cycle in the Insect

    Directory of Open Access Journals (Sweden)

    Leyla Slamti

    2014-07-01

    Full Text Available Bacterial cell-cell communication or quorum sensing (QS is a biological process commonly described as allowing bacteria belonging to a same pherotype to coordinate gene expression to cell density. In Gram-positive bacteria, cell-cell communication mainly relies on cytoplasmic sensors regulated by secreted and re-imported signaling peptides. The Bacillus quorum sensors Rap, NprR, and PlcR were previously identified as the first members of a new protein family called RNPP. Except for the Rap proteins, these RNPP regulators are transcription factors that directly regulate gene expression. QS regulates important biological functions in bacteria of the Bacillus cereus group. PlcR was first characterized as the main regulator of virulence in B. thuringiensis and B. cereus. More recently, the PlcR-like regulator PlcRa was characterized for its role in cysteine metabolism and in resistance to oxidative stress. The NprR regulator controls the necrotrophic properties allowing the bacteria to survive in the infected host. The Rap proteins negatively affect sporulation via their interaction with a phosphorelay protein involved in the activation of Spo0A, the master regulator of this differentiation pathway. In this review we aim at providing a complete picture of the QS systems that are sequentially activated during the lifecycle of B. cereus and B. thuringiensis in an insect model of infection.

  5. The hydrocarbon-degrading marine bacterium Cobetia sp. strain MM1IDA2H-1 produces a biosurfactant that interferes with quorum sensing of fish pathogens by signal hijacking.

    Science.gov (United States)

    Ibacache-Quiroga, C; Ojeda, J; Espinoza-Vergara, G; Olivero, P; Cuellar, M; Dinamarca, M A

    2013-07-01

    Biosurfactants are produced by hydrocarbon-degrading marine bacteria in response to the presence of water-insoluble hydrocarbons. This is believed to facilitate the uptake of hydrocarbons by bacteria. However, these diffusible amphiphilic surface-active molecules are involved in several other biological functions such as microbial competition and intra- or inter-species communication. We report the isolation and characterization of a marine bacterial strain identified as Cobetia sp. MM1IDA2H-1, which can grow using the sulfur-containing heterocyclic aromatic hydrocarbon dibenzothiophene (DBT). As with DBT, when the isolated strain is grown in the presence of a microbial competitor, it produces a biosurfactant. Because the obtained biosurfactant was formed by hydroxy fatty acids and extracellular lipidic structures were observed during bacterial growth, we investigated whether the biosurfactant at its critical micelle concentration can interfere with bacterial communication systems such as quorum sensing. We focused on Aeromonas salmonicida subsp. salmonicida, a fish pathogen whose virulence relies on quorum sensing signals. Using biosensors for quorum sensing based on Chromobacterium violaceum and Vibrio anguillarum, we showed that when the purified biosurfactant was mixed with N-acyl homoserine lactones produced by A. salmonicida, quorum sensing was inhibited, although bacterial growth was not affected. In addition, the transcriptional activities of A. salmonicida virulence genes that are controlled by quorum sensing were repressed by both the purified biosurfactant and the growth in the presence of Cobetia sp. MM1IDA2H-1. We propose that the biosurfactant, or the lipid structures interact with the N-acyl homoserine lactones, inhibiting their function. This could be used as a strategy to interfere with the quorum sensing systems of bacterial fish pathogens, which represents an attractive alternative to classical antimicrobial therapies in fish aquaculture.

  6. A chemical biology approach to interrogate quorum-sensing regulated behaviors at the molecular and cellular level.

    Science.gov (United States)

    Lowery, Colin A; Matamouros, Susana; Niessen, Sherry; Zhu, Jie; Scolnick, Jonathan; Lively, Jenny M; Cravatt, Benjamin F; Miller, Samuel I; Kaufmann, Gunnar F; Janda, Kim D

    2013-07-25

    Small molecule probes have been used extensively to explore biologic systems and elucidate cellular signaling pathways. In this study, we use an inhibitor of bacterial communication to monitor changes in the proteome of Salmonella enterica serovar Typhimurium with the aim of discovering unrecognized processes regulated by AI-2-based quorum-sensing (QS), a mechanism of bacterial intercellular communication that allows for the coordination of gene expression in a cell density-dependent manner. In S. typhimurium, this system regulates the uptake and catabolism of intercellular signals and has been implicated in pathogenesis, including the invasion of host epithelial cells. We demonstrate that our QS antagonist is capable of selectively inhibiting the expression of known QS-regulated proteins in S. typhimurium, thus attesting that QS inhibitors may be used to confirm proposed and elucidate previously unidentified QS pathways without relying on genetic manipulation.

  7. Impact of Pseudomonas aeruginosa quorum sensing on biofilm persistence in an in vivo intraperitoneal foreign-body infection model

    DEFF Research Database (Denmark)

    Christensen, Louise D; Moser, Claus; Jensen, Peter Ø

    2007-01-01

    Pseudomonas aeruginosa is an opportunistic human pathogen that causes chronic biofilm-based infections in host organisms. P. aeruginosa employs quorum sensing (QS) to control expression of its virulence, and to establish and maintain chronic infections. Under such conditions, the biofilm mode....... aeruginosa are cleared more rapidly from silicone implants as compared to their wild-type counterparts. Concurrently, treatment with the QS inhibitor furanone C-30 of mice harbouring implants colonized with the wild-type P. aeruginosa resulted in a significantly faster clearing of the implants as compared...... to the placebo-treated group. These results were obtained with both an inbred (BALB/c) and an outbred (NMRI) mouse strain. The present results support a model by which functional QS systems play a pivotal role in the ability of bacteria to resist clearing by the innate immune system and strongly suggest...

  8. ``Quorum sensing'' generated multistability and chaos in a synthetic genetic oscillator

    Science.gov (United States)

    Potapov, I.; Zhurov, B.; Volkov, E.

    2012-06-01

    We model the dynamics of the synthetic genetic oscillator Repressilator equipped with quorum sensing. In addition to a circuit of 3 genes repressing each other in a unidirectional manner, the model includes a phase-repulsive type of the coupling module implemented as the production of a small diffusive molecule—autoinducer (AI). We show that the autoinducer (which stimulates the transcription of a target gene) is responsible for the disappearance of the limit cycle (LC) through the infinite period bifurcation and the formation of a stable steady state (SSS) for sufficiently large values of the transcription rate. We found conditions for hysteresis between the limit cycle and the stable steady state. The parameters' region of the hysteresis is determined by the mRNA to protein lifetime ratio and by the level of transcription-stimulating activity of the AI. In addition to hysteresis, increasing AI-dependent stimulation of transcription may lead to the complex dynamic behavior which is characterized by the appearance of several branches on the bifurcation continuation, containing different regular limit cycles, as well as a chaotic regime. The multistability which is manifested as the coexistence between the stable steady state, limit cycles, and chaos seems to be a novel type of the dynamics for the ring oscillator with the added quorum sensing positive feedback.

  9. Towards Predictive Modeling of Information Processing in Microbial Ecosystems With Quorum-Sensing Interactions

    Science.gov (United States)

    Yusufaly, Tahir; Boedicker, James

    Bacteria communicate using external chemical signals in a process known as quorum sensing. However, the efficiency of this communication is reduced by both limitations on the rate of diffusion over long distances and potential interference from neighboring strains. Therefore, having a framework to quantitatively predict how spatial structure and biodiversity shape information processing in bacterial colonies is important, both for understanding the evolutionary dynamics of natural microbial ecosystems, and for the rational design of synthetic ecosystems with desired computational properties. As a first step towards these goals, we implement a reaction-diffusion model to study the dynamics of a LuxI/LuxR quorum sensing circuit in a growing bacterial population. The spatiotemporal concentration profile of acyl-homoserine lactone (AHL) signaling molecules is analyzed, and used to define a measure of physical and functional signaling network connectivity. From this, we systematically investigate how different initial distributions of bacterial populations influence the subsequent efficiency of collective long-range signal propagation in the population. We compare our results with known experimental data, and discuss limitations and extensions to our modeling framework.-/abstract-

  10. Quality evaluation of synthetic quorum sensing peptides used in R & D

    Institute of Scientific and Technical Information of China (English)

    Frederick Verbeke; Evelien Wynendaele; Sarah Braet; Matthias DHondt; Bart De Spiegeleer

    2015-01-01

    Peptides are becoming an important class of molecules in the pharmaceutical field. Closely related peptide-impurities in peptides are inherent to the synthesis approach and have demonstrated to potentially mask biomedical experimental results. Quorum sensing peptides are attracting high interest in R&D and therefore a representative set of quorum sensing peptides, with a requested purity of at least 95.0%, was evaluated for their purity and nature of related impurities. In-house quality control (QC) revealed a large discrepancy between the purity levels as stated on the supplier’s certificate of analysis and our QC results. By using our QC analysis flowchart, we demonstrated that only 44.0% of the peptides met the required purity. The main compound of one sample was even found to have a different structure compared to the desired peptide. We also found that the majority of the related impurities were lacking amino acid(s) in the desired peptide sequence. Relying on the certificates of analysis as provided by the supplier might have serious consequences for peptide research, and peptide-researchers should implement and maintain a thorough in-house QC.

  11. A quorum-sensing factor in vegetative Dictyostelium discoideum cells revealed by quantitative migration analysis.

    Directory of Open Access Journals (Sweden)

    Laurent Golé

    Full Text Available BACKGROUND: Many cells communicate through the production of diffusible signaling molecules that accumulate and once a critical concentration has been reached, can activate or repress a number of target genes in a process termed quorum sensing (QS. In the social amoeba Dictyostelium discoideum, QS plays an important role during development. However little is known about its effect on cell migration especially in the growth phase. METHODS AND FINDINGS: To investigate the role of cell density on cell migration in the growth phase, we use multisite timelapse microscopy and automated cell tracking. This analysis reveals a high heterogeneity within a given cell population, and the necessity to use large data sets to draw reliable conclusions on cell motion. In average, motion is persistent for short periods of time (t ≤ 5 min, but normal diffusive behavior is recovered over longer time periods. The persistence times are positively correlated with the migrated distances. Interestingly, the migrated distance decreases as well with cell density. The adaptation of cell migration to cell density highlights the role of a secreted quorum sensing factor (QSF on cell migration. Using a simple model describing the balance between the rate of QSF generation and the rate of QSF dilution, we were able to gather all experimental results into a single master curve, showing a sharp cell transition between high and low motile behaviors with increasing QSF. CONCLUSION: This study unambiguously demonstrates the central role played by QSF on amoeboid motion in the growth phase.

  12. Transition state analogs of 5'-methylthioadenosine nucleosidase disrupt quorum sensing.

    Energy Technology Data Exchange (ETDEWEB)

    Gutierrez, J.; Crowder, T; Rinaldo-Matthis, A; Ho, M; Almo, S; Schramm, V

    2009-01-01

    5'-Methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) is a bacterial enzyme involved in S-adenosylmethionine-related quorum sensing pathways that induce bacterial pathogenesis factors. Transition state analogs MT-DADMe-Immucillin-A, EtT-DADMe-Immucillin-A and BuT-DADMe-Immucillin-A are slow-onset, tight-binding inhibitors of Vibrio cholerae MTAN (VcMTAN), with equilibrium dissociation constants of 73, 70 and 208 pM, respectively. Structural analysis of VcMTAN with BuT-DADMe-Immucillin-A revealed interactions contributing to the high affinity. We found that in V. cholerae cells, these compounds are potent MTAN inhibitors with IC50 values of 27, 31 and 6 nM for MT-, EtT- and BuT-DADMe-Immucillin-A, respectively; the compounds disrupt autoinducer production in a dose-dependent manner without affecting growth. MT- and BuT-DADMe-Immucillin-A also inhibited autoinducer-2 production in enterohemorrhagic Escherichia coli O157:H7 with IC{sub 50} values of 600 and 125 nM, respectively. BuT-DADMe-Immucillin-A inhibition of autoinducer-2 production in both strains persisted for several generations and caused reduction in biofilm formation. These results support MTAN's role in quorum sensing and its potential as a target for bacterial anti-infective drug design.

  13. Manipulation of the Quorum Sensing Signal AI-2 Affects the Antibiotic-Treated Gut Microbiota

    Directory of Open Access Journals (Sweden)

    Jessica Ann Thompson

    2015-03-01

    Full Text Available The mammalian gut microbiota harbors a diverse ecosystem where hundreds of bacterial species interact with each other and their host. Given that bacteria use signals to communicate and regulate group behaviors (quorum sensing, we asked whether such communication between different commensal species can influence the interactions occurring in this environment. We engineered the enteric bacterium, Escherichia coli, to manipulate the levels of the interspecies quorum sensing signal, autoinducer-2 (AI-2, in the mouse intestine and investigated the effect upon antibiotic-induced gut microbiota dysbiosis. E. coli that increased intestinal AI-2 levels altered the composition of the antibiotic-treated gut microbiota, favoring the expansion of the Firmicutes phylum. This significantly increased the Firmicutes/Bacteroidetes ratio, to oppose the strong effect of the antibiotic, which had almost cleared the Firmicutes. This demonstrates that AI-2 levels influence the abundance of the major phyla of the gut microbiota, the balance of which is known to influence human health.

  14. Quality evaluation of synthetic quorum sensing peptides used in R&D

    Directory of Open Access Journals (Sweden)

    Frederick Verbeke

    2015-06-01

    Full Text Available Peptides are becoming an important class of molecules in the pharmaceutical field. Closely related peptide-impurities in peptides are inherent to the synthesis approach and have demonstrated to potentially mask biomedical experimental results. Quorum sensing peptides are attracting high interest in R&D and therefore a representative set of quorum sensing peptides, with a requested purity of at least 95.0%, was evaluated for their purity and nature of related impurities. In-house quality control (QC revealed a large discrepancy between the purity levels as stated on the supplier׳s certificate of analysis and our QC results. By using our QC analysis flowchart, we demonstrated that only 44.0% of the peptides met the required purity. The main compound of one sample was even found to have a different structure compared to the desired peptide. We also found that the majority of the related impurities were lacking amino acid(s in the desired peptide sequence. Relying on the certificates of analysis as provided by the supplier might have serious consequences for peptide research, and peptide-researchers should implement and maintain a thorough in-house QC.

  15. Estimation of spatial distribution of quorum sensing signaling in sequencing batch biofilm reactor (SBBR) biofilms.

    Science.gov (United States)

    Wang, Jinfeng; Ding, Lili; Li, Kan; Huang, Hui; Hu, Haidong; Geng, Jinju; Xu, Ke; Ren, Hongqiang

    2017-08-28

    Quorum sensing (QS) signaling, plays a significant role in regulating formation of biofilms in the nature; however, little information about the occurrence and distribution of quorum sensing molecular in the biofilm of carriers has been reported. In this study, distribution of QS signaling molecules (the acylated homoserine lactones-AHLs, and AI-2), extracellular polymeric substances (EPS) and the mechanical properties in sequencing batch biofilm reactor (SBBR) biofilms have been investigated. Using increased centrifugal force, the biofilms were detached into different fractions. The AHLs ranged from 5.2ng/g to 98.3ng/g in different fractions of biofilms, and N-decanoyl-dl-homoserine lactone (C10-HSL) and N-dodecanoyl-dl-homoserine lactone (C12-HSL) in the biofilms obtained at various centrifugal forces displayed significant differences (pbiofilms ranged from 79.2ng/g to 98.3ng/g. Soluble EPS and loosely bound EPS content in the different fractions of biofilms displayed significant positive relationship with the distribution of C12-HSL (r=0.86, pbiofilms were positively related with AHLs with 22.76% was significantly positively (pBiofilm adhesion and compliance was the strongest in the tightly-bound biofilm, the weakest in the supernatant/surface biofilm, which was in accordance with the distribution of C12 HSL(r=0.77, pbiofilm application. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. EFFECTS OF PSYCHOTROPIC DRUGS AS BACTERIAL EFFLUX PUMP INHIBITORS ON QUORUM SENSING REGULATED BEHAVIORS

    Directory of Open Access Journals (Sweden)

    Aynur Aybey

    2014-10-01

    Full Text Available Psychotropic drugs are known to have antimicrobial activity against several groups of microorganisms. The antidepressant agents such as duloxetine, paroxetine, hydroxyzine and venlafaxine are shown to act as efflux pump inhibitors in bacterial cells. In order to the investigation of the effects of psychotropic drugs were determined for clinically significant pathogens by using standart broth microdillusion method. The anti-quorum sensing (anti-QS activity of psychotropic drugs was tested against four test pathogens using the agar well diffusion method. All drugs showed strong inhibitory effect on the growth of S. typhimurium. Additionally, quorum sensing-regulated behaviors of Pseudomonas aeruginosa, including swarming, swimming and twitching motility and alkaline protease production were investigated. Most effective drugs on swarming, swimming and twitching motility and alkaline protease production, respectively, were paroxetine and duloxetine; duloxetine; hydroxyzine and venlafaxine; paroxetine and venlafaxine; venlafaxine. Accordingly, psychotropic drugs were shown strongly anti-QS activity by acting as bacterial efflux pump inhibitors and effection on motility and alkaline protease production of P. aeruginosa.

  17. A Host-Produced Autoinducer-2 Mimic Activates Bacterial Quorum Sensing.

    Science.gov (United States)

    Ismail, Anisa S; Valastyan, Julie S; Bassler, Bonnie L

    2016-04-13

    Host-microbial symbioses are vital to health; nonetheless, little is known about the role crosskingdom signaling plays in these relationships. In a process called quorum sensing, bacteria communicate with one another using extracellular signal molecules called autoinducers. One autoinducer, AI-2, is proposed to promote interspecies bacterial communication, including in the mammalian gut. We show that mammalian epithelia produce an AI-2 mimic activity in response to bacteria or tight-junction disruption. This AI-2 mimic is detected by the bacterial AI-2 receptor, LuxP/LsrB, and can activate quorum-sensing-controlled gene expression, including in the enteric pathogen Salmonella typhimurium. AI-2 mimic activity is induced when epithelia are directly or indirectly exposed to bacteria, suggesting that a secreted bacterial component(s) stimulates its production. Mutagenesis revealed genes required for bacteria to both detect and stimulate production of the AI-2 mimic. These findings uncover a potential role for the mammalian AI-2 mimic in fostering crosskingdom signaling and host-bacterial symbioses.

  18. Quantifying the integration of quorum-sensing signals with single-cell resolution.

    Directory of Open Access Journals (Sweden)

    Tao Long

    2009-03-01

    Full Text Available Cell-to-cell communication in bacteria is a process known as quorum sensing that relies on the production, detection, and response to the extracellular accumulation of signaling molecules called autoinducers. Often, bacteria use multiple autoinducers to obtain information about the vicinal cell density. However, how cells integrate and interpret the information contained within multiple autoinducers remains a mystery. Using single-cell fluorescence microscopy, we quantified the signaling responses to and analyzed the integration of multiple autoinducers by the model quorum-sensing bacterium Vibrio harveyi. Our results revealed that signals from two distinct autoinducers, AI-1 and AI-2, are combined strictly additively in a shared phosphorelay pathway, with each autoinducer contributing nearly equally to the total response. We found a coherent response across the population with little cell-to-cell variation, indicating that the entire population of cells can reliably distinguish several distinct conditions of external autoinducer concentration. We speculate that the use of multiple autoinducers allows a growing population of cells to synchronize gene expression during a series of distinct developmental stages.

  19. Determinants governing ligand specificity of the Vibrio harveyi LuxN quorum-sensing receptor.

    Science.gov (United States)

    Ke, Xiaobo; Miller, Laura C; Bassler, Bonnie L

    2015-01-01

    Quorum sensing is a process of bacterial cell-cell communication that relies on the production, release and receptor-driven detection of extracellular signal molecules called autoinducers. The quorum-sensing bacterium Vibrio harveyi exclusively detects the autoinducer N-((R)-3-hydroxybutanoyl)-L-homoserine lactone (3OH-C4 HSL) via the two-component receptor LuxN. To discover the principles underlying the exquisite selectivity LuxN has for its ligand, we identified LuxN mutants with altered specificity. LuxN uses three mechanisms to verify that the bound molecule is the correct ligand: in the context of the overall ligand-binding site, His210 validates the C3 modification, Leu166 surveys the chain-length and a strong steady-state kinase bias imposes an energetic hurdle for inappropriate ligands to elicit signal transduction. Affinities for the LuxN kinase on and kinase off states underpin whether a ligand will act as an antagonist or an agonist. Mutations that bias LuxN to the agonized, kinase off, state are clustered in a region adjacent to the ligand-binding site, suggesting that this region acts as the switch that triggers signal transduction. Together, our analyses illuminate how a histidine sensor kinase differentiates between ligands and exploits those differences to regulate its signaling activity.

  20. A diketopiperazine factor from Rheinheimera aquimaris QSI02 exhibits anti-quorum sensing activity

    Science.gov (United States)

    Sun, Shiwei; Dai, Xiaoyun; Sun, Jiao; Bu, Xiangguo; Weng, Caihong; Li, Hui; Zhu, Hu

    2016-01-01

    An ethyl acetate (EtOAc) extract isolated from the marine bacterium, Rheinheimera aquimaris QSI02, was found to exhibit anti-quorum sensing (anti-QS) activity. A subsequent bioassay-guided isolation protocol led to the detection of an active diketopiperazine factor, cyclo(Trp-Ser). Biosensor assay data showed that the minimum inhibitory concentration (MIC) of cyclo(Trp-Ser) ranged from 3.2 mg/ml to 6.4 mg/m for several microorganisms, including Escherichia coli, Chromobacterium violaceum CV026, Pseudomonas aeruginosa PA01, Staphylococcus aureus, and Candida albicans. Additionally, sub-MICs of cyclo(Trp-Ser) decreased the QS-regulated violacein production in C. violaceum CV026 by 67%. Furthermore, cyclo(Trp-Ser) can decrease QS-regulated pyocyanin production, elastase activity and biofilm formation in P. aeruginosa PA01 by 65%, 40% and 59.9%, respectively. Molecular docking results revealed that cyclo(Trp-Ser) binds to CviR receptor more rigidly than C6HSL with lower docking energy −8.68 kcal/mol, while with higher binding energy of −8.40 kcal/mol than 3-oxo-C12HSL in LasR receptor. Molecular dynamics simulation suggested that cyclo(Trp-Ser) is more easy to bind to CviR receptor than natural signaling molecule, but opposite in LasR receptor. These results suggest that cyclo(Trp-Ser) can be used as a potential inhibitor to control QS systems of C. violaceum and P. aeruginosa and provide increased the understanding of molecular mechanism that influences QS-regulated behaviors. PMID:28000767

  1. Modulation of Staphylococcus aureus Response to Antimicrobials by the Candida albicans Quorum Sensing Molecule Farnesol.

    Science.gov (United States)

    Kong, Eric F; Tsui, Christina; Kucharíková, Sona; Van Dijck, Patrick; Jabra-Rizk, Mary Ann

    2017-09-11

    In microbial biofilms, microorganisms utilize secreted signaling chemical molecules to coordinate their collective behavior. Farnesol is a quorum-sensing molecule secreted by the fungal species Candida albicans, shown to play a central physiological role during fungal biofilm growth. Our pervious in vitro and in vivo studies characterized an intricate interaction between C. albicans and the bacterial pathogen Staphylococcus aureus, as these species co-exist in biofilm. In this study, we aimed to investigate the impact of farnesol on S. aureus survival, biofilm formation and response to antimicrobials. Results demonstrated that in the presence of exogenously supplemented farnesol, or farnesol secreted by C. albicans in biofilm, S. aureus exhibited significantly enhanced tolerance to antimicrobials. Using gene expression studies, S. aureus mutant strains and chemical inhibitors, the mechanism for the enhanced tolerance was attributed to upregulation of drug efflux pumps. Importantly, we showed that sequential exposure of S. aureus to farnesol generated a phenotype with high resistance to antimicrobials. Based on presence of intracellular reactive oxygen species upon farnesol exposure, we hypothesize that antimicrobial tolerance in S. aureus may be mediated by farnesol-induced oxidative stress triggering the upregulation of efflux pumps, as part of a general stress response system. Hence, in mixed biofilms, C. albicans may influence the pathogenicity of S. aureus through acquisition of a drug tolerant phenotype, with important therapeutic implications. Understanding inter-species signaling in polymicrobial biofilms and the specific drug resistance responses to secreted molecules, may lead to the identification of novel targets for drug development. Copyright © 2017 American Society for Microbiology.

  2. Chitosan nanoparticles enhances the anti-quorum sensing activity of kaempferol.

    Science.gov (United States)

    Ilk, Sedef; Sağlam, Necdet; Özgen, Mustafa; Korkusuz, Feza

    2017-01-01

    Quorum sensing (QS) is a cell density dependent expression of species in bacteria mediated by compounds called autoinducers (AI). Several processes responsible for successful establishment of bacterial infection are mediated by QS. Inhibition of QS is therefore being considered as a new target for antimicrobial chemotherapy. Flavonoid compounds are strong antioxidant and antimicrobial agents but their applications are limited due to their poor dissolution and bioavailability. Our objective was to investigate the effect of kaempferol loaded chitosan nanoparticles on modulating QS mediated by AI in model bioassay test systems. For this purpose, kaempferol loaded nanoparticles were synthesized and characterized in terms of hydrodynamic diameter, hydrogen bonding, amorphous transformation and antioxidant activity. QS inhibition in time dependent manner of nanoparticles was measured in violacein pigment producing using the biosensor strain Chromobacterium violaceum CV026 mediated by AI known as acylated homoserine lactone (AHL). Our results indicated that the average kaempferol loaded chitosan/TPP nanoparticle size and zeta potential were 192.27±13.6nm and +35mV, respectively. The loading and encapsulation efficiency of kaempferol into chitosan/TPP nanoparticles presented higher values between 78 and 93%. Kaempferol loaded chitosan/TPP nanoparticle during the 30 storage days significantly inhibited the production of violacein pigment in Chromobacterium violaceum CV026. The observation that kaempferol encapsulated chitosan nanoparticles can inhibit QS related processes opens up an exciting new strategy for antimicrobial chemotherapy as stable QS-based anti-biofilm agents. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Regulation of Yersina pestis Virulence by AI-2 Mediated Quorum Sensing

    Energy Technology Data Exchange (ETDEWEB)

    Segelke, B; Hok, S; Lao, V; Corzett, M; Garcia, E

    2010-03-29

    The proposed research was motivated by an interest in understanding Y. pestis virulence mechanisms and bacteria cell-cell communication. It is expected that a greater understanding of virulence mechanisms will ultimately lead to biothreat countermeasures and novel therapeutics. Y. pestis is the etiological agent of plague, the most devastating disease in human history. Y. pestis infection has a high mortality rate and a short incubation before mortality. There is no widely available and effective vaccine for Y. pestis and multi-drug resistant strains are emerging. Y. pestis is a recognized biothreat agent based on the wide distribution of the bacteria in research laboratories around the world and on the knowledge that methods exist to produce and aerosolize large amounts of bacteria. We hypothesized that cell-cell communication via signaling molecules, or quorum sensing, by Y. pestis is important for the regulation of virulence factor gene expression during host invasion, though a causative link had never been established. Quorum sensing is a mode of intercellular communication which enables orchestration of gene expression for many bacteria as a function of population density and available evidence suggests there may be a link between quorum sensing and regulation of Y. pesits virulence. Several pathogenic bacteria have been shown to regulate expression of virulence factor genes, including genes encoding type III secretion, via quorum sensing. The Y. pestis genome encodes several cell-cell signaling pathways and the interaction of at least three of these are thought to be involved in one or more modes of host invasion. Furthermore, Y. pestis gene expression array studies carried out at LLNL have established a correlation between expression of known virulence factors and genes involved in processing of the AI-2 quorum sensing signal. This was a basic research project that was intended to provide new insights into bacterial intercellular communication and how it is

  4. The quorum sensing transcriptional regulator TraR has separate binding sites for DNA and the anti-activator

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Zhida; Fuqua, Clay [Department of Molecular and Cellular Biochemistry, 212 S. Hawthorne Dr. Simon Hall 400A, Indiana University, Bloomington, IN 47405 (United States); Chen, Lingling, E-mail: linchen@indiana.edu [Department of Molecular and Cellular Biochemistry, 212 S. Hawthorne Dr. Simon Hall 400A, Indiana University, Bloomington, IN 47405 (United States)

    2012-02-10

    Highlights: Black-Right-Pointing-Pointer Quorum sensing transcription factor TraR is inhibited by forming TraR-TraM complex. Black-Right-Pointing-Pointer K213 is a key DNA binding residue, but not involved in interaction with TraM. Black-Right-Pointing-Pointer Mutations of TraM-interacting TraR residues did not affect DNA-binding of TraR. Black-Right-Pointing-Pointer Mutations of TraR residues reduced the TraR-TraM interaction more than those of TraM. Black-Right-Pointing-Pointer TraM inhibition on DNA-binding of TraR is driven by thermodynamics. -- Abstract: Quorum sensing represents a mechanism by which bacteria control their genetic behaviors via diffusible signals that reflect their population density. TraR, a quorum sensing transcriptional activator in the Rhizobiaceae family, is regulated negatively by the anti-activator TraM via formation of a TraR-TraM heterocomplex. Prior structural analysis suggests that TraM and DNA bind to TraR in distinct sites. Here we combined isothermal titration calorimetry (ITC) and electrophoretic mobility shift assays (EMSA) to investigate roles of TraR residues from Rhizobium sp. NGR234 in binding of both TraM and DNA. We found that K213A mutation of TraR{sub NGR} abolished DNA binding, however, did not alter TraM binding. Mutations of TraM-interfacing TraR{sub NGR} residues decreased the TraR-TraM interaction, but did not affect the DNA-binding activity of TraR{sub NGR}. Thus, our biochemical studies support the independent binding sites on TraR for TraM and DNA. We also found that point mutations in TraR{sub NGR} appeared to decrease the TraR-TraM interaction more effectively than those in TraM{sub NGR}, consistent with structural observations that individual TraR{sub NGR} residues contact with more TraM{sub NGR} residues than each TraM{sub NGR} residues with TraR{sub NGR} residues. Finally, we showed that TraM inhibition on DNA-binding of TraR was driven thermodynamically. We discussed subtle mechanistic differences in Tra

  5. Quorum sensing in Aeromonas salmonicida subsp. achromogenes and the effect of the autoinducer synthase AsaI on bacterial virulence

    DEFF Research Database (Denmark)

    Schwenteit, Johanna; Gram, Lone; Nielsen, Kristian Fog

    2011-01-01

    The Gram-negative fish pathogenic bacterium Aeromonas salmonicida possesses the LuxIRtype quorum sensing (QS) system, termed AsaIR. In this study the role of QS in A. salmonicida subsp. achromogenes virulence and pigment production was investigated. Five wild-type Asa strains induced the N......Ideficient mutant was 20-fold higher than that of the isogenic wt strain and the mean day to death of the mutant was significantly prolonged. Furthermore, the expression of two virulence factors (a toxic protease, AsaP1, and a cytotoxic factor) and a brown pigment were reduced in the mutant. AsaP1 productionwas...... inhibited by synthetic QS inhibitors (N- (propylsulfanylacetyl)-L-homoserine lactone; N-(pentylsulfanylacetyl)-L-homoserine lactone; and N-(heptylsulfanylacetyl)-L-homoserine lactone) at concentrations that did not affect bacterial growth. It is a new finding that the AHL synthase of Aeromonas affects...

  6. Synthetic furanones inhibit quorum-sensing and enhance bacterial clearance in Pseudomonas aeruginosa lung infection in mice

    DEFF Research Database (Denmark)

    Wu, H.; Song, Z.; Hentzer, Morten

    2004-01-01

    Introduction: Antibiotics are used to treat bacterial infections by killing the bacteria or inhibiting their growth, but resistance to antibiotics can develop readily. The discovery that bacterial quorum-sensing regulates bacterial virulence as well as the formation of biofilms opens up new ways...

  7. Alcohol-based quorum sensing plays a role in adhesion and sliding motility of the yeast Debaryomyces hansenii

    DEFF Research Database (Denmark)

    Gori, Klaus; Knudsen, Peter Boldsen; Nielsen, Kristian Fog

    2011-01-01

    The yeast Debaryomyces hansenii was investigated for its production of alcohol-based quorum sensing (QS) molecules including the aromatic alcohols phenylethanol, tyrosol, tryptophol and the aliphatic alcohol farnesol. Debaryomyces hansenii produced phenylethanol and tyrosol, which were primarily ....... © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved....

  8. Thermoregulation of N-acyl homoserine lactone-based quorum sensing in the soft rot bacterium Pectobacterium atrosepticum.

    Science.gov (United States)

    Latour, Xavier; Diallo, Stéphanie; Chevalier, Sylvie; Morin, Danièle; Smadja, Bruno; Burini, Jean-François; Haras, Dominique; Orange, Nicole

    2007-06-01

    The psychrotolerant bacterium Pectobacterium atrosepticum produces four N-acyl homoserine lactones under a wide range of temperatures. Their thermoregulation differs from that of the exoenzyme production, described as being under quorum-sensing control. A mechanism involved in this thermoregulation consists of controlling N-acyl homoserine lactones synthase production at a transcriptional level.

  9. Synthetic furanones inhibit quorum-sensing and enhance bacterial clearance in Pseudomonas aeruginosa lung infection in mice

    DEFF Research Database (Denmark)

    Wu, H; Song, Z; Hentzer, M

    2004-01-01

    INTRODUCTION: Antibiotics are used to treat bacterial infections by killing the bacteria or inhibiting their growth, but resistance to antibiotics can develop readily. The discovery that bacterial quorum-sensing regulates bacterial virulence as well as the formation of biofilms opens up new ways...

  10. AI-2 does not function as a quorum sensing molecule in Campylobacter jejuni during exponential growth in vitro

    NARCIS (Netherlands)

    Holmes, K.; Tavender, T.J.; Winzer, K.; Wells, J.; Hardie, K.

    2009-01-01

    Background - Campylobacter jejuni contains a homologue of the luxS gene shown to be responsible for the production of the signalling molecule autoinducer-2 (AI-2) in Vibrio harveyi and Vibrio cholerae. The aim of this study was to determine whether AI-2 acted as a diffusible quorum sensing signal co

  11. The effect of burdock leaf fraction on adhesion, biofilm formation, quorum sensing and virulence factors of Pseudomonas aeruginosa.

    Science.gov (United States)

    Lou, Z; Wang, H; Tang, Y; Chen, X

    2017-03-01

    This study aimed to evaluate the effect of a fraction of burdock (Arctium lappa L.) leaf on the initial adhesion, biofilm formation, quorum sensing and virulence factors of Pseudomonas aeruginosa. Antibiofilm activity of the burdock leaf fraction was studied by the method of crystal violet staining. When the concentration of the burdock leaf fraction was 2·0 mg ml(-1) , the inhibition rates on biofilm formation of P. aeruginosa were 100%. The burdock leaf fraction was found to inhibit the formation of biofilm by reducing bacterial surface hydrophobicity, decreasing bacterial aggregation ability and inhibiting swarming motility. Interestingly, the burdock leaf fraction inhibited the secretion of quorum-sensing (QS) signalling molecule 3-oxo-C12-HSL and interfered quorum sensing. Moreover, the QS-regulated pyocyanin and elastase were also inhibited. Chemical composition analysis by UPLC-MS showed 11 active compounds in the burdock leaf fraction. The burdock leaf fraction significantly inhibited the formation of biofilm and quorum sensing, as well as significantly decreased the content of virulence factors. This study introduces a natural and effective bacterial biofilm inhibitor, which could also significantly decrease the content of virulence factors and the drug resistance of P. aeruginosa. © 2016 The Society for Applied Microbiology.

  12. Bacterial quorum sensing in an evolutionary perspective%从进化谈细菌细胞间的群体感应信号传递

    Institute of Scientific and Technical Information of China (English)

    陈林; 杨亮; 段康民

    2012-01-01

    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.%In contrast to the individual and nonsocial organism view of bacteria, recent discoveries show that bacteria can communicate and exhibit population behaviour via a system known as quorum sensing. Some bacterial behavious can only be initiated when the cell number reaches a certain level (Quorum sensing, QS). It is generally believed that quorum sensing is used to coordinate cooperative behaviours at the population level; however, many issues exist regarding the evolution or development of such a system. In the present paper, the evolutionary process of bacterial quorum-sensing systems is discussed based on recent events and progresses in this field. As quorum sensing systems are often affected by environmental factors, such as temperature, pH, and nutrient levels, it is hence proposed that the evolution of bacterial cooperation, such as the quorum sensing, is rather a dynamic and ever-changing process which is radically affected by environmental conditions, genetic exchanges, as

  13. Qualitative and quantitative determination of quorum sensing inhibition in vitro

    DEFF Research Database (Denmark)

    Jakobsen, Tim Holm; van Gennip, Maria; Christensen, Louise Dahl

    2011-01-01

    of reporter strains consisting of a lasB-gfp or rhlA-gfp fusion in P. aeruginosa for qualitative and quantitative evaluation of the inhibition of the two major QS pathways, monitored as reduced expression of green fluorescence. By the use of an in vitro flow cell system it is possible to study the QSI...

  14. Glyceryl trinitrate is a novel inhibitor of quorum sensing in ...

    African Journals Online (AJOL)

    cein, water saturated butanol (900 µl) was added followed by vortexing and ..... and even if systemic absorption occurs, GTN has a very short half-life (1 to 3 .... ruginosa sodA and sodB mutants defective in manganese- and iron cofactored ...

  15. The involvement of bacterial quorum sensing in the spoilage of refrigerated Litopenaeus vannamei.

    Science.gov (United States)

    Zhu, Suqin; Wu, Haohao; Zeng, Mingyong; Liu, Zunying; Wang, Ying

    2015-01-02

    Quorum-sensing signals in refrigerated shrimp (Litopenaeus vannamei) undergoing spoilage were examined using bioreporter assays, thin-layer chromatography and gas chromatography-mass spectrometry, and the results revealed the presence of three types of autoinducers including acetylated homoserine lactones (AHLs) (i.e., N-hexanoyl-homoserine lactone, N-oxohexanoyl-homoserine lactone and N-octanoyl-homoserine lactone), autoinducer-2, and cyclic dipeptides (i.e., cyclo-(L-Pro-L-Leu), cyclo-(L-Leu-L-Leu) and cyclo-(L-Pro-L-Phe)). Autoinducer-2, rather than any AHL, was detected in extracts from pure cultures of the specific spoilage organisms (SSO), i.e., Shewanella putrefaciens (SS01) and Shewanella baltica (SA02). As for the cyclic peptides, only SA02 was determined to produce cyclo-(L-Pro-L-Leu). According to the transcription levels of LuxR (the master quorum-sensing regulator) in the SSO in response to exogenous autoinducers, the SSO could sense AHLs and cyclo-(L-Leu-L-Leu), rather than autoinducer-2, cyclo-(L-Leu-L-Leu) and cyclo-(L-Pro-L-Phe). In accordance with the results of LuxR expression, the production of biofilm matrixes and extracellular proteases in the SSO was regulated by exogenous AHLs and cyclo-(L-Pro-L-Leu), rather than 4,5-dihydroxy-2,3-pentanedione (the autoinducer-2 precursor), cyclo-(L-Leu-L-Leu) and cyclo-(L-Pro-L-Phe). Exogenous N-hexanoyl-homoserine lactone and cyclo-(L-Pro-L-Leu) increased the growth rates and population percentages of the SSO in shrimp samples under refrigerated storage, and interestingly, exogenous 4,5-dihydroxy-2,3-pentanedione also increased the population percentages of the SSO in vivo by inhibiting the growth of the competing bacteria. However, according to the levels of TVB-N and the volatile organic components in the shrimp samples, exogenous 4,5-dihydroxy-2,3-pentanedione did not accelerate the shrimp spoilage process as N-hexanoyl-homoserine lactone and cyclo-(L-Pro-L-Leu) did. In summary, our results suggest that

  16. Quorum sensing Inhibitors as anti-pathogenic drugs

    DEFF Research Database (Denmark)

    Rasmussen, Thomas Bovbjerg; Givskov, Michael Christian

    2006-01-01

    as well as elevated tolerance to the activity of the innate immune system. Gram-negative bacteria commonly use N-acyl homoserine lactones (AHL) as QS signal molecules. The use of signal molecule based drugs to attenuate bacterial pathogenecity rather than bacterial growth is attractive for several reasons......, particularly considering the emergence of increasingly antibiotic-resistant bacteria. Compounds capable of this type of interference have been termed anti-pathogenic drugs. A large variety of synthetic AHL analogues and natural products libraries have been screened and a number of QS inhibitors (QSI) have been...

  17. 牙周致病菌密度感应信号系统luxS基因的检测%Detection of luxS gene of quorum sensing signal system in periodontal pathogen

    Institute of Scientific and Technical Information of China (English)

    雷朝锋; 杨禾; 孙昌娟; 苗棣; 徐屹

    2009-01-01

    目的 检测牙周可疑致病菌密度感应信号系统luxS基因,了解其在牙周致病菌中的分布.方法 选取牙龈卟啉单胞菌、伴放线放线杆菌、具核梭杆菌的模式株、参考株及临床分离株作为研究对象,提取DNA,通过聚合酶链反应(PCR)、电泳鉴定和DNA测序,并利用GenBank数据库的Blast检测以上细菌luxS基因的存在情况.结果 电泳鉴定存在目的 条带,测序和Blast检测表明牙龈卟啉单胞菌PCR产物与目的 基因有高度一致性(均为99%以上),具核梭杆菌测序结果 与GenBank数据库的基因相同,伴放线放线杆菌电泳鉴定结果 显示存在目的 条带(750 bp),与参考条带大小一致.结论 本实验引物设计合理,能较好地扩增出牙龈卟啉单胞菌、具核梭杆菌、伴放线放线杆菌各实验菌株的luxS基因,为进一步研究luxS基因的功能奠定了基础.%Objective To detect the presence and distribution of luxS gene in quorum sensing signal system in the periodontal pathogens.Methods The total DNA of Porphyromonas gingivalis(Pg),Fusobacterium nucleatum(Fn),Actinobacillus acitinomycetimcomtans(Aa)were extracted.The presence of luxS was detected by polymerase chain reaction(PCR).The products of PCR were detected by electrophoresis.sequenced and identified by a Blast search of the GenBank database. Results Electrophoresis,sequencing and Blast searching indicated that the PCR products of Pg were highly consistent with the luxS gene in GenBank.The sequencing result of Fn was also identified with the target gene.The PCR product of Aa was the same as reference through electrophoresis.Conclusions Pg,Fn,Aa contain luxS gene.Further studies may be required to investigate the functions of luxS in the periodontal pathogens.

  18. Effects of quorum sensing system lasR/rhlR gene on the expression of Foxp3, TGF-β1 and IL-10 of lung tissue in tracheal intubation model rat with Pseudomonas aeruginosa biofilm infection

    Directory of Open Access Journals (Sweden)

    Qing-qing XIANG

    2016-03-01

    Full Text Available Objective  To investigate the effects of lasR/rhlR gene on Foxp3, TGF-β1 and IL-10 of lung tissue in rat tracheal intubation model with biofilm infection of Pseudomonas aeruginosa (Ps. aer wild strain (PAO1 and quorum sensing (QS deficient strain (ΔlasRΔrhlR. Methods  Twenty-one SD rats were randomly assigned into 3 groups (7 each: ΔlasRΔrhlR-treated group, PAO1-treated group and sterile control group. Biofilms (BF were cultured in vitro, and the BF coated tube (infected respectively with Ps. aer PAO1 strain, ΔlasRΔrhlR strain, or with asepsis was inserted into the trachea to establish the rat model. The rats were sacrificed on the 7th day after intubation. Colony count of lung tissue homogenate (cfu and lung HE staining were performed, and IL-10 content in bronchoalveolar lavage fluid (BALF, TGF-β1 in lung tissue, and the expression of Foxp3 mRNA in lung cells were determined. Results  The bacterial counts were significantly higher in PAO1 and ΔlasRΔrhlR groups than that in sterile control group, and the counts were obviously higher in PAO1 group (10 400.00±6313.70/g lung tissue than that in ΔlasRΔrhlR group (975.00±559.97/g lung tissue, P<0.05. There was no significant pathological changes in lung tissue in sterile control group, while the bronchi and blood vessels in PAO1 group were infiltrated by a large number of inflammatory cells and complicated with alveolar septum thickening and local abscess and necrosis. The pathological changes were milder in ΔlasRΔrhlR group than in PAO1 group; the expression of Foxp3 mRNA was higher in the two Ps. aer infected groups than that in sterile control group (0.65±0.32, and it was significantly higher in PAO1 group (4.62±1.07 than in ΔlasRΔrhlR group (2.15±1.43, P<0.05. The accumulated optical density value of TGF-β1 was significantly higher in the two Ps. aer infected groups than in sterile control group (3721.66±1412.95, and significantly higher in PAO1 group (65 090.56±33

  19. Expression of luxS gene involved in quorum sensing in Lactobacillus acidophilus NCFM after passage through an in vitro digestion model

    DEFF Research Database (Denmark)

    Moslehi Jenabian, Saloomeh; Jespersen, Lene

    Within recent years, there has been an increasing interest in discovering the beneficial effects of probiotics and the mechanisms by which probiotics interact with the host and the gut microbiota. One of the mechanisms that bacteria interact or communicate with each other is quorum sensing.