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Sample records for disrupt quorum sensing

  1. Mechanisms of quorum sensing and strategies for quorum sensing disruption in aquaculture pathogens.

    PubMed

    Zhao, J; Chen, M; Quan, C S; Fan, S D

    2015-09-01

    In many countries, infectious diseases are a considerable threat to aquaculture. The pathogenicity of micro-organisms that infect aquaculture systems is closely related to the release of virulence factors and the formation of biofilms, both of which are regulated by quorum sensing (QS). Thus, QS disruption is a potential strategy for preventing disease in aquaculture systems. QS inhibitors (QSIs) not only inhibit the expression of virulence-associated genes but also attenuate the virulence of aquaculture pathogens. In this review, we discuss QS systems in important aquaculture pathogens and focus on the relationship between QS mechanisms and bacterial virulence in aquaculture. We further elucidate QS disruption strategies for targeting aquaculture pathogens. Four main types of QSIs that target aquaculture pathogens are discussed based on their mechanisms of action.

  2. Transition state analogs of 5'-methylthioadenosine nucleosidase disrupt quorum sensing.

    SciTech Connect

    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.

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

    PubMed

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

    2015-01-01

    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. PMID:26647822

  4. Specific quorum sensing-disrupting activity (AQSI) of thiophenones and their therapeutic potential

    PubMed Central

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

    2015-01-01

    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. PMID:26647822

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

    PubMed

    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.

  6. A Quorum Sensing-Disrupting Brominated Thiophenone with a Promising Therapeutic Potential to Treat Luminescent Vibriosis

    PubMed Central

    Defoirdt, Tom; Benneche, Tore; Brackman, Gilles; Coenye, Tom; Sorgeloos, Patrick; Scheie, Anne Aamdal

    2012-01-01

    Vibrio harveyi is amongst the most important bacterial pathogens in aquaculture. Novel methods to control this pathogen are needed since many strains have acquired resistance to antibiotics. We previously showed that quorum sensing-disrupting furanones are able to protect brine shrimp larvae against vibriosis. However, a major problem of these compounds is that they are toxic toward higher organisms and therefore, they are not safe to be used in aquaculture. The synthesis of brominated thiophenones, sulphur analogues of the quorum sensing-disrupting furanones, has recently been reported. In the present study, we report that these compounds block quorum sensing in V. harveyi at concentrations in the low micromolar range. Bioluminescence experiments with V. harveyi quorum sensing mutants and a fluorescence anisotropy assay indicated that the compounds disrupt quorum sensing in this bacterium by decreasing the ability of the quorum sensing master regulator LuxR to bind to its target promoter DNA. In vivo challenge tests with gnotobiotic brine shrimp larvae showed that thiophenone compound TF310, (Z)-4-((5-(bromomethylene)-2-oxo-2,5-dihydrothiophen-3-yl)methoxy)-4-oxobutanoic acid, completely protected the larvae from V. harveyi BB120 when dosed to the culture water at 2.5 µM or more, whereas severe toxicity was only observed at 250 µM. This makes TF310 showing the highest therapeutic index of all quorum sensing-disrupting compounds tested thus far in our brine shrimp model system. PMID:22848604

  7. Quorum Sensing and Phytochemicals

    PubMed Central

    Nazzaro, Filomena; Fratianni, Florinda; Coppola, Raffaele

    2013-01-01

    Most infectious diseases are caused by bacteria, which proliferate within quorum sensing (QS)-mediated biofilms. Efforts to block QS in bacteria and disrupt biofilms have enabled the identification of bioactive molecules that are also produced by plants. This mini review primarily focuses on natural QS inhibitors, which display potential for treating bacterial infections and also enhance the safety of food supply. PMID:23774835

  8. Identification of Quorum-Sensing Inhibitors Disrupting Signaling between Rgg and Short Hydrophobic Peptides in Streptococci

    PubMed Central

    Aggarwal, Chaitanya; Jimenez, Juan Cristobal; Lee, Hyun; Chlipala, George E.; Ratia, Kiira

    2015-01-01

    ABSTRACT Bacteria coordinate a variety of social behaviors, important for both environmental and pathogenic bacteria, through a process of intercellular chemical signaling known as quorum sensing (QS). As microbial resistance to antibiotics grows more common, a critical need has emerged to develop novel anti-infective therapies, such as an ability to attenuate bacterial pathogens by means of QS interference. Rgg quorum-sensing pathways, widespread in the phylum Firmicutes, employ cytoplasmic pheromone receptors (Rgg transcription factors) that directly bind and elicit gene expression responses to imported peptide signals. In the human-restricted pathogen Streptococcus pyogenes, the Rgg2/Rgg3 regulatory circuit controls biofilm development in response to the short hydrophobic peptides SHP2 and SHP3. Using Rgg-SHP as a model receptor-ligand target, we sought to identify chemical compounds that could specifically inhibit Rgg quorum-sensing circuits. Individual compounds from a diverse library of known drugs and drug-like molecules were screened for their ability to disrupt complexes of Rgg and FITC (fluorescein isothiocyanate)-conjugated SHP using a fluorescence polarization (FP) assay. The best hits were found to bind Rgg3 in vitro with submicromolar affinities, to specifically abolish transcription of Rgg2/3-controlled genes, and to prevent biofilm development in S. pyogenes without affecting bacterial growth. Furthermore, the top hit, cyclosporine A, as well as its nonimmunosuppressive analog, valspodar, inhibited Rgg-SHP pathways in multiple species of Streptococcus. The Rgg-FITC-peptide-based screen provides a platform to identify inhibitors specific for each Rgg type. Discovery of Rgg inhibitors constitutes a step toward the goal of manipulating bacterial behavior for purposes of improving health. PMID:25968646

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

    PubMed

    Helman, Yael; Chernin, Leonid

    2015-04-01

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

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

    PubMed

    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. Quorum sensing in Serratia.

    PubMed

    Van Houdt, Rob; Givskov, Michael; Michiels, Chris W

    2007-07-01

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

  12. Tea polyphenols as an antivirulence compound Disrupt Quorum-Sensing Regulated Pathogenicity of Pseudomonas aeruginosa.

    PubMed

    Yin, Hongping; Yin, Honging; Deng, Yifeng; Wang, Huafu; Liu, Wugao; Zhuang, Xiyi; Chu, Weihua

    2015-11-09

    Green tea, a water extract of non-fermented leaves of Camellia sinensis L., is one of the nonalcoholic beverages in China. It is becoming increasingly popular worldwide, because of its refreshing, mild stimulant and medicinal properties. Here we examined the quorum sensing inhibitory potentials of tea polyphenols (TP) as antivirulence compounds both in vitro and in vivo. Biosensor assay data suggested minimum inhibitory concentrations (MICs) of TP against selected pathogens were 6.25 ~ 12.5 mg/mL. At sub-MIC, TP can specifically inhibit the production of violacein in Chromobacterium violaceum 12472 with almost 98% reduction at 3.125 mg/mL without affecting its growth rate. Moreover, TP exhibited inhibitory effects on virulence phenotypes regulated by QS in Pseudomonas aeruginosa. The total proteolytic activity, elastase, swarming motility and biofilm formation were reduced in a concentration-dependent manner. In vivo, TP treatment resulted in the reduction of P. aeruginosa pathogenicity in Caenorhabditis elegans. When its concentration was 3.125 mg/mL, the survival rate reached 63.3%. In the excision wound infection model, the wound contraction percentage in treatment groups was relatively increased and the colony-forming units (CFU) in the wound area were significantly decreased. These results suggested that TP could be developed as a novel non-antibiotic QS inhibitor without killing the bacteria but as an antivirulence compound to control bacterial infection.

  13. Identification of Anti-virulence Compounds That Disrupt Quorum-Sensing Regulated Acute and Persistent Pathogenicity

    PubMed Central

    Bandyopadhaya, Arunava; Lesic, Biljana; He, Jianxin; Kitao, Tomoe; Righi, Valeria; Milot, Sylvain; Tzika, Aria; Rahme, Laurence

    2014-01-01

    Etiological agents of acute, persistent, or relapsing clinical infections are often refractory to antibiotics due to multidrug resistance and/or antibiotic tolerance. Pseudomonas aeruginosa is an opportunistic Gram-negative bacterial pathogen that causes recalcitrant and severe acute chronic and persistent human infections. Here, we target the MvfR-regulated P. aeruginosa quorum sensing (QS) virulence pathway to isolate robust molecules that specifically inhibit infection without affecting bacterial growth or viability to mitigate selective resistance. Using a whole-cell high-throughput screen (HTS) and structure-activity relationship (SAR) analysis, we identify compounds that block the synthesis of both pro-persistence and pro-acute MvfR-dependent signaling molecules. These compounds, which share a benzamide-benzimidazole backbone and are unrelated to previous MvfR-regulon inhibitors, bind the global virulence QS transcriptional regulator, MvfR (PqsR); inhibit the MvfR regulon in multi-drug resistant isolates; are active against P. aeruginosa acute and persistent murine infections; and do not perturb bacterial growth. In addition, they are the first compounds identified to reduce the formation of antibiotic-tolerant persister cells. As such, these molecules provide for the development of next-generation clinical therapeutics to more effectively treat refractory and deleterious bacterial-human infections. PMID:25144274

  14. Identification of anti-virulence compounds that disrupt quorum-sensing regulated acute and persistent pathogenicity.

    PubMed

    Starkey, Melissa; Lepine, Francois; Maura, Damien; Bandyopadhaya, Arunava; Lesic, Biljana; He, Jianxin; Kitao, Tomoe; Righi, Valeria; Milot, Sylvain; Tzika, Aria; Rahme, Laurence

    2014-08-01

    Etiological agents of acute, persistent, or relapsing clinical infections are often refractory to antibiotics due to multidrug resistance and/or antibiotic tolerance. Pseudomonas aeruginosa is an opportunistic Gram-negative bacterial pathogen that causes recalcitrant and severe acute chronic and persistent human infections. Here, we target the MvfR-regulated P. aeruginosa quorum sensing (QS) virulence pathway to isolate robust molecules that specifically inhibit infection without affecting bacterial growth or viability to mitigate selective resistance. Using a whole-cell high-throughput screen (HTS) and structure-activity relationship (SAR) analysis, we identify compounds that block the synthesis of both pro-persistence and pro-acute MvfR-dependent signaling molecules. These compounds, which share a benzamide-benzimidazole backbone and are unrelated to previous MvfR-regulon inhibitors, bind the global virulence QS transcriptional regulator, MvfR (PqsR); inhibit the MvfR regulon in multi-drug resistant isolates; are active against P. aeruginosa acute and persistent murine infections; and do not perturb bacterial growth. In addition, they are the first compounds identified to reduce the formation of antibiotic-tolerant persister cells. As such, these molecules provide for the development of next-generation clinical therapeutics to more effectively treat refractory and deleterious bacterial-human infections.

  15. Chemical Composition and Disruption of Quorum Sensing Signaling in Geographically Diverse United States Propolis

    PubMed Central

    Savka, Michael A.; Dailey, Lucas; Popova, Milena; Mihaylova, Ralitsa; Merritt, Benjamin; Masek, Marissa; Le, Phuong; Nor, Sharifah Radziah Mat; Ahmad, Muhammad; Hudson, André O.; Bankova, Vassya

    2015-01-01

    Propolis or bee glue has been used for centuries for various purposes and is especially important in human health due to many of its biological and pharmacological properties. In this work we showed quorum sensing inhibitory (QSI) activity of ten geographically distinct propolis samples from the United States using the acyl-homoserine lactone- (AHL-) dependent Chromobacterium violaceum strain CV026. Based on GC-MS chemical profiling the propolis samples can be classified into several groups that are as follows: (1) rich in cinnamic acid derivatives, (2) rich in flavonoids, and (3) rich in triterpenes. An in-depth analysis of the propolis from North Carolina led to the isolation and identification of a triterpenic acid that was recently isolated from Hondurian propolis (Central America) and ethyl ether of p-coumaric alcohol not previously identified in bee propolis. QSI activity was also observed in the second group US propolis samples which contained the flavonoid pinocembrin in addition to other flavonoid compounds. The discovery of compounds that are involved in QSI activity has the potential to facilitate studies that may lead to the development of antivirulence therapies that can be complementary and/or alternative treatments against antibiotic resistant bacterial pathogens and/or emerging pathogens that have yet to be identified. PMID:25960752

  16. Tea polyphenols as an antivirulence compound Disrupt Quorum-Sensing Regulated Pathogenicity of Pseudomonas aeruginosa

    PubMed Central

    Yin, Honging; Deng, Yifeng; Wang, Huafu; Liu, Wugao; Zhuang, Xiyi; Chu, Weihua

    2015-01-01

    Green tea, a water extract of non-fermented leaves of Camellia sinensis L., is one of the nonalcoholic beverages in China. It is becoming increasingly popular worldwide, because of its refreshing, mild stimulant and medicinal properties. Here we examined the quorum sensing inhibitory potentials of tea polyphenols (TP) as antivirulence compounds both in vitro and in vivo. Biosensor assay data suggested minimum inhibitory concentrations (MICs) of TP against selected pathogens were 6.25 ~ 12.5 mg/mL. At sub-MIC, TP can specifically inhibit the production of violacein in Chromobacterium violaceum 12472 with almost 98% reduction at 3.125 mg/mL without affecting its growth rate. Moreover, TP exhibited inhibitory effects on virulence phenotypes regulated by QS in Pseudomonas aeruginosa. The total proteolytic activity, elastase, swarming motility and biofilm formation were reduced in a concentration-dependent manner. In vivo, TP treatment resulted in the reduction of P. aeruginosa pathogenicity in Caenorhabditis elegans. When its concentration was 3.125 mg/mL, the survival rate reached 63.3%. In the excision wound infection model, the wound contraction percentage in treatment groups was relatively increased and the colony-forming units (CFU) in the wound area were significantly decreased. These results suggested that TP could be developed as a novel non-antibiotic QS inhibitor without killing the bacteria but as an antivirulence compound to control bacterial infection. PMID:26548447

  17. Tea polyphenols as an antivirulence compound Disrupt Quorum-Sensing Regulated Pathogenicity of Pseudomonas aeruginosa.

    PubMed

    Yin, Hongping; Yin, Honging; Deng, Yifeng; Wang, Huafu; Liu, Wugao; Zhuang, Xiyi; Chu, Weihua

    2015-01-01

    Green tea, a water extract of non-fermented leaves of Camellia sinensis L., is one of the nonalcoholic beverages in China. It is becoming increasingly popular worldwide, because of its refreshing, mild stimulant and medicinal properties. Here we examined the quorum sensing inhibitory potentials of tea polyphenols (TP) as antivirulence compounds both in vitro and in vivo. Biosensor assay data suggested minimum inhibitory concentrations (MICs) of TP against selected pathogens were 6.25 ~ 12.5 mg/mL. At sub-MIC, TP can specifically inhibit the production of violacein in Chromobacterium violaceum 12472 with almost 98% reduction at 3.125 mg/mL without affecting its growth rate. Moreover, TP exhibited inhibitory effects on virulence phenotypes regulated by QS in Pseudomonas aeruginosa. The total proteolytic activity, elastase, swarming motility and biofilm formation were reduced in a concentration-dependent manner. In vivo, TP treatment resulted in the reduction of P. aeruginosa pathogenicity in Caenorhabditis elegans. When its concentration was 3.125 mg/mL, the survival rate reached 63.3%. In the excision wound infection model, the wound contraction percentage in treatment groups was relatively increased and the colony-forming units (CFU) in the wound area were significantly decreased. These results suggested that TP could be developed as a novel non-antibiotic QS inhibitor without killing the bacteria but as an antivirulence compound to control bacterial infection. PMID:26548447

  18. Quorum Sensing of Periodontal Pathogens.

    PubMed

    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. PMID:27688408

  19. Quorum Sensing of Periodontal Pathogens.

    PubMed

    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.

  20. Quorum Sensing of Periodontal Pathogens

    PubMed Central

    Plančak, Darije; Musić, Larisa

    2015-01-01

    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.

  1. Quorum Sensing of Periodontal Pathogens

    PubMed Central

    Plančak, Darije; Musić, Larisa

    2015-01-01

    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. PMID:27688408

  2. Small Molecule Disruption of Quorum Sensing Cross-Regulation in Pseudomonas aeruginosa Causes Major and Unexpected Alterations to Virulence Phenotypes

    PubMed Central

    Welsh, Michael A.; Eibergen, Nora R.; Moore, Joseph D.; Blackwell, Helen E.

    2015-01-01

    The opportunistic pathogen Pseudomonas aeruginosa uses three interwoven quorum-sensing (QS) circuits—Las, Rhl, and Pqs—to regulate the global expression of myriad virulence-associated genes. Interception of these signaling networks with small molecules represents an emerging strategy for the development of anti-infective agents against this bacterium. In the current study, we applied a chemical approach to investigate how the Las-Rhl-Pqs QS hierarchy coordinates key virulence phenotypes in wild-type P. aeruginosa. We screened a focused library of synthetic, non-native N-acyl l-homoserine lactones and identified compounds that can drastically alter production of two important virulence factors: pyocyanin and rhamnolipid. We demonstrate that these molecules act by targeting RhlR in P. aeruginosa, a QS receptor that has seen far less scrutiny to date relative to other circuitry. Unexpectedly, modulation of RhlR activity by a single compound induces inverse regulation of pyocyanin and rhamnolipid, a result that was not predicted using genetic approaches to interrogate QS in P. aeruginosa. Further, we show that certain RhlR agonists strongly repress Pqs signaling, revealing disruption of Rhl-Pqs cross-regulation as a novel mechanism for QS inhibition. These compounds significantly expand the known repertoire of chemical probes available to study RhlR in P. aeruginosa. Moreover, our results suggest that designing chemical agents to disrupt Rhl-Pqs crosstalk could be an effective antivirulence strategy to fight this common pathogen. PMID:25574853

  3. Quorum sensing inhibition, relevance to periodontics.

    PubMed

    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.

  4. Messing with Bacterial Quorum Sensing

    PubMed Central

    González, Juan E.; Keshavan, Neela D.

    2006-01-01

    Quorum sensing is widely recognized as an efficient mechanism to regulate expression of specific genes responsible for communal behavior in bacteria. Several bacterial phenotypes essential for the successful establishment of symbiotic, pathogenic, or commensal relationships with eukaryotic hosts, including motility, exopolysaccharide production, biofilm formation, and toxin production, are often regulated by quorum sensing. Interestingly, eukaryotes produce quorum-sensing-interfering (QSI) compounds that have a positive or negative influence on the bacterial signaling network. This eukaryotic interference could result in further fine-tuning of bacterial quorum sensing. Furthermore, recent work involving the synthesis of structural homologs to the various quorum-sensing signal molecules has resulted in the development of additional QSI compounds that could be used to control pathogenic bacteria. The creation of transgenic plants that express bacterial quorum-sensing genes is yet another strategy to interfere with bacterial behavior. Further investigation on the manipulation of quorum-sensing systems could provide us with powerful tools against harmful bacteria. PMID:17158701

  5. Quorum Sensing Inhibition, Relevance to Periodontics

    PubMed Central

    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. PMID:25709373

  6. Optimal census by quorum sensing

    NASA Astrophysics Data System (ADS)

    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.

  7. Bioinspired, releasable quorum sensing modulators.

    PubMed

    Gomes, José; Grunau, Alexander; Lawrence, Adrien K; Eberl, Leo; Gademann, Karl

    2013-01-01

    We demonstrate the synthesis and immobilization of natural product hybrids featuring an acyl-homoserine lactone and a nitrodopamine onto biocompatible TiO(2) surfaces through an operationally simple dip-and-rinse procedure. The resulting immobilized hybrids were shown to be powerful quorum sensing (QS) activators in Pseudomonas strains acting by slow release from the surface. PMID:23169441

  8. Exploiting Quorum Sensing To Confuse Bacterial Pathogens

    PubMed Central

    LaSarre, Breah

    2013-01-01

    SUMMARY Cell-cell communication, or quorum sensing, is a widespread phenomenon in bacteria that is used to coordinate gene expression among local populations. Its use by bacterial pathogens to regulate genes that promote invasion, defense, and spread has been particularly well documented. With the ongoing emergence of antibiotic-resistant pathogens, there is a current need for development of alternative therapeutic strategies. An antivirulence approach by which quorum sensing is impeded has caught on as a viable means to manipulate bacterial processes, especially pathogenic traits that are harmful to human and animal health and agricultural productivity. The identification and development of chemical compounds and enzymes that facilitate quorum-sensing inhibition (QSI) by targeting signaling molecules, signal biogenesis, or signal detection are reviewed here. Overall, the evidence suggests that QSI therapy may be efficacious against some, but not necessarily all, bacterial pathogens, and several failures and ongoing concerns that may steer future studies in productive directions are discussed. Nevertheless, various QSI successes have rightfully perpetuated excitement surrounding new potential therapies, and this review highlights promising QSI leads in disrupting pathogenesis in both plants and animals. PMID:23471618

  9. Lyngbyoic acid, a “tagged” fatty acid from a marine cyanobacterium, disrupts quorum sensing in Pseudomonas aeruginosa†

    PubMed Central

    Kwan, Jason Christopher; Meickle, Theresa; Ladwa, Dheran; Teplitski, Max; Paul, Valerie; Luesch, Hendrik

    2013-01-01

    Quorum sensing (QS) is a mechanism of bacterial gene regulation in response to increases in population density. Perhaps most studied are QS pathways mediated by acylhomoserine lactones (AHLs) in Gram-negative bacteria. Production of small molecule QS signals, their accumulation within a diffusion-limited environment and their binding to a LuxR-type receptor trigger QS-controlled gene regulatory cascades. In Pseudomonas aeruginosa, for example, binding of AHLs to their cognate receptors (LasR, RhlR) controls production of virulence factors, pigments, antibiotics and other behaviors important for its interactions with eukaryotic hosts and other bacteria. We have previously shown that marine cyanobacteria produce QS-inhibitory molecules, including 8-epi-malyngamide C (1), malyngamide C (2) and malyngolide (3). Here we isolated a new small cyclopropane-containing fatty acid, lyngbyoic acid (4), as a major metabolite of the marine cyanobacterium, Lyngbya cf. majuscula, collected at various sites in Florida. We screened 4 against four reporters based on different AHL receptors (LuxR, AhyR, TraR and LasR) and found that 4 most strongly affected LasR. We also show that 4 reduces pyocyanin and elastase (LasB) both on the protein and transcript level in wild-type P. aeruginosa, and that 4 directly inhibits LasB enzymatic activity. Conversely, dodecanoic acid (9) increased pyocyanin and LasB, demonstrating that the fused cyclopropane “tag” is functionally relevant and potentially confers resistance to β-oxidation. Global transcriptional effects of 4 in some ways replicate the gene expression changes of P. aeruginosa during chronic lung infections of cystic fibrosis patients, with reduced lasR signaling, increased biofilm and expression of the virulence locus HSI-I. Compound 4 may therefore prove to be a useful tool in the study of P. aeruginosa adaption during such chronic infections. PMID:21258753

  10. Silencing Quorum Sensing through Extracts of Melicope lunu-ankenda

    PubMed Central

    Tan, Li Ying; Yin, Wai-Fong; Chan, Kok-Gan

    2012-01-01

    Quorum sensing regulates bacterial virulence determinants, therefore making it an interesting target to attenuate pathogens. In this work, we screened edible, endemic plants in Malaysia for anti-quorum sensing properties. Extracts from Melicope lunu-ankenda (Gaertn.) T. G. Hartley, a Malay garden salad, inhibited response of Chromobacterium violaceum CV026 to N-hexanoylhomoserine lactone, thus interfering with violacein production; reduced bioluminescence expression of E. coli [pSB401], disrupted pyocyanin synthesis, swarming motility and expression of lecA::lux of Pseudomonas aeruginosa PAO1. Although the chemical nature of the anti-QS compounds from M. lunu-ankenda is currently unknown, this study proves that endemic Malaysian plants could serve as leads in the search for anti-quorum sensing compounds. PMID:22666033

  11. Interfering with Bacterial Quorum Sensing

    PubMed Central

    Reuter, Kerstin; Steinbach, Anke; Helms, Volkhard

    2016-01-01

    Quorum sensing (QS) describes the exchange of chemical signals in bacterial populations to adjust the bacterial phenotypes according to the density of bacterial cells. This serves to express phenotypes that are advantageous for the group and ensure bacterial survival. To do so, bacterial cells synthesize autoinducer (AI) molecules, release them to the environment, and take them up. Thereby, the AI concentration reflects the cell density. When the AI concentration exceeds a critical threshold in the cells, the AI may activate the expression of virulence-associated genes or of luminescent proteins. It has been argued that targeting the QS system puts less selective pressure on these pathogens and should avoid the development of resistant bacteria. Therefore, the molecular components of QS systems have been suggested as promising targets for developing new anti-infective compounds. Here, we review the QS systems of selected gram-negative and gram-positive bacteria, namely, Vibrio fischeri, Pseudomonas aeruginosa, and Staphylococcus aureus, and discuss various antivirulence strategies based on blocking different components of the QS machinery. PMID:26819549

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

    PubMed Central

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

    2016-01-01

    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. DOI: http://dx.doi.org/10.7554/eLife.14712.001 PMID:27183270

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

    PubMed

    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.

  14. Quorum Sensing in Nitrogen-Fixing Rhizobia

    PubMed Central

    González, Juan E.; Marketon, Melanie M.

    2003-01-01

    Members of the rhizobia are distinguished for their ability to establish a nitrogen-fixing symbiosis with leguminous plants. While many details of this relationship remain a mystery, much effort has gone into elucidating the mechanisms governing bacterium-host recognition and the events leading to symbiosis. Several signal molecules, including plant-produced flavonoids and bacterially produced nodulation factors and exopolysaccharides, are known to function in the molecular conversation between the host and the symbiont. Work by several laboratories has shown that an additional mode of regulation, quorum sensing, intercedes in the signal exchange process and perhaps plays a major role in preparing and coordinating the nitrogen-fixing rhizobia during the establishment of the symbiosis. Rhizobium leguminosarum, for example, carries a multitiered quorum-sensing system that represents one of the most complex regulatory networks identified for this form of gene regulation. This review focuses on the recent stream of information regarding quorum sensing in the nitrogen-fixing rhizobia. Seminal work on the quorum-sensing systems of R. leguminosarum bv. viciae, R. etli, Rhizobium sp. strain NGR234, Sinorhizobium meliloti, and Bradyrhizobium japonicum is presented and discussed. The latest work shows that quorum sensing can be linked to various symbiotic phenomena including nodulation efficiency, symbiosome development, exopolysaccharide production, and nitrogen fixation, all of which are important for the establishment of a successful symbiosis. Many questions remain to be answered, but the knowledge obtained so far provides a firm foundation for future studies on the role of quorum-sensing mediated gene regulation in host-bacterium interactions. PMID:14665677

  15. The apparent quorum-sensing inhibitory activity of pyrogallol is a side effect of peroxide production.

    PubMed

    Defoirdt, Tom; Pande, Gde Sasmita Julyantoro; Baruah, Kartik; Bossier, Peter

    2013-06-01

    There currently is more and more interest in the use of natural products, such as tea polyphenols, as therapeutic agents. The polyphenol compound pyrogallol has been reported before to inhibit quorum-sensing-regulated bioluminescence in Vibrio harveyi. Here, we report that the addition of 10 mg · liter(-1) pyrogallol protects both brine shrimp (Artemia franciscana) and giant river prawn (Macrobrachium rosenbergii) larvae from pathogenic Vibrio harveyi, whereas the compound showed relatively low toxicity (therapeutic index of 10). We further demonstrate that the apparent quorum-sensing-disrupting activity is a side effect of the peroxide-producing activity of this compound rather than true quorum-sensing inhibition. Our results emphasize that verification of minor toxic effects by using sensitive methods and the use of appropriate controls are essential when characterizing compounds as being able to disrupt quorum sensing. PMID:23545532

  16. A Strategy for Antagonizing Quorum Sensing

    SciTech Connect

    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.

  17. Insights into the role of quorum sensing in food spoilage.

    PubMed

    Ammor, Mohammed Salim; Michaelidis, Christos; Nychas, George-John E

    2008-07-01

    Food spoilage is a consequence of the degrading enzymatic activity of some food-associated bacteria. Several proteolytic, lipolytic, chitinolytic, and pectinolytic activities associated with the deterioration of goods are regulated by quorum sensing, suggesting a potential role of such cell-to-cell communication in food spoilage. Here we review quorum sensing signaling molecules and methods of their detection and quantification, and we provide insights into the role of quorum sensing in food spoilage and address potential quorum sensing inhibitors that might be used as biopreservatives.

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

    PubMed

    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.

  19. Global convergence of quorum-sensing networks

    NASA Astrophysics Data System (ADS)

    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.

  20. Custom-Made Quorum Sensing for a Eukaryote.

    PubMed

    May, Robin C

    2016-06-01

    Quorum-sensing systems, common in prokaryotes, enable bacteria to coordinately regulate behavior with population density. Reporting recently in Cell Host & Microbe, Homer et al. (2016) characterize an elegant eukaryotic quorum-sensing pathway in the human pathogenic fungus Cryptococcus neoformans. PMID:27270036

  1. Ambroxol interferes with Pseudomonas aeruginosa quorum sensing.

    PubMed

    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. PMID:20580207

  2. Ambroxol interferes with Pseudomonas aeruginosa quorum sensing.

    PubMed

    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.

  3. Inhibition of quorum sensing in a computational biofilm simulation.

    PubMed

    Fozard, J A; Lees, M; King, J R; Logan, B S

    2012-08-01

    Bacteria communicate through small diffusible molecules in a process known as quorum sensing. Quorum-sensing inhibitors are compounds which interfere with this, providing a potential treatment for infections associated with bacterial biofilms. We present an individual-based computational model for a developing biofilm. Cells are aggregated into particles for computational efficiency, but the quorum-sensing mechanism is modelled as a stochastic process on the level of individual cells. Simulations are used to investigate different treatment regimens. The response to the addition of inhibitor is found to depend significantly on the form of the positive feedback in the quorum-sensing model; in cases where the model exhibits bistability, the time at which treatment is initiated proves to be critical for the effective prevention of quorum sensing and hence potentially of virulence. PMID:22374433

  4. Metagenomic approaches to understanding phylogenetic diversity in quorum sensing

    PubMed Central

    Kimura, Nobutada

    2014-01-01

    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. PMID:24429899

  5. Bacterial quorum sensing and metabolic incentives to cooperate.

    PubMed

    Dandekar, Ajai A; Chugani, Sudha; Greenberg, E Peter

    2012-10-12

    The opportunistic pathogen Pseudomonas aeruginosa uses a cell-cell communication system termed "quorum sensing" to control production of public goods, extracellular products that can be used by any community member. Not all individuals respond to quorum-sensing signals and synthesize public goods. Such social cheaters enjoy the benefits of the products secreted by cooperators. There are some P. aeruginosa cellular enzymes controlled by quorum sensing, and we show that quorum sensing-controlled expression of such private goods can put a metabolic constraint on social cheating and prevent a tragedy of the commons. Metabolic constraint of social cheating provides an explanation for private-goods regulation by a cooperative system and has general implications for population biology, infection control, and stabilization of quorum-sensing circuits in synthetic biology. PMID:23066081

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

    PubMed

    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.

  7. [Quorum sensing in bacteria and yeast].

    PubMed

    March Rosselló, Gabriel Alberto; Eiros Bouza, José María

    2013-10-19

    Bacterial sets are complex dynamic systems, which interact with each other and through the interaction, bacteria coexist, collaborate, compete and share information in a coordinated manner. A way of bacterial communication is quorum sensing. Through this mechanism the bacteria can recognize its concentration in a given environment and they can decide the time at which the expression of a particular set of genes should be started for developing a specific and simultaneous response. The result of these interconnections raises properties that cannot be explained from a single isolated bacterial cell.

  8. Engineered biological nanofactories trigger quorum sensing response in targeted bacteria

    NASA Astrophysics Data System (ADS)

    Fernandes, Rohan; Roy, Varnika; Wu, Hsuan-Chen; Bentley, William E.

    2010-03-01

    Biological nanofactories, which are engineered to contain modules that can target, sense and synthesize molecules, can trigger communication between different bacterial populations. These communications influence biofilm formation, virulence, bioluminescence and many other bacterial functions in a process called quorum sensing. Here, we show the assembly of a nanofactory that can trigger a bacterial quorum sensing response in the absence of native quorum molecules. The nanofactory comprises an antibody (for targeting) and a fusion protein that produces quorum molecules when bound to the targeted bacterium. Our nanofactory selectively targets the appropriate bacteria and triggers a quorum sensing response when added to two populations of bacteria. The nanofactories also trigger communication between two bacterial populations that are otherwise non-communicating. We envision the use of these nanofactories in generating new antimicrobial treatments that target the communication networks of bacteria rather than their viability.

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

    PubMed Central

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

    2013-01-01

    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. PMID:24065091

  10. Quorum Sensing Communication Modules for Microbial Consortia.

    PubMed

    Scott, Spencer R; Hasty, Jeff

    2016-09-16

    The power of a single engineered organism is limited by its capacity for genetic modification. To circumvent the constraints of any singular microbe, a new frontier in synthetic biology is emerging: synthetic ecology, or the engineering of microbial consortia. Here we develop communication systems for such consortia in an effort to allow for complex social behavior across different members of a community. We posit that such communities will outpace monocultures in their ability to perform complicated tasks if communication among and between members of the community is well regulated. Quorum sensing was identified as the most promising candidate for precise control of engineered microbial ecosystems, due to its large diversity and established utility in synthetic biology. Through promoter and protein modification, we engineered two quorum sensing systems (rpa and tra) to add to the extensively used lux and las systems. By testing the cross-talk between all systems, we thoroughly characterized many new inducible systems for versatile control of engineered communities. Furthermore, we've identified several system pairs that exhibit useful types of orthogonality. Most notably, the tra and rpa systems were shown to have neither signal crosstalk nor promoter crosstalk for each other, making them completely orthogonal in operation. Overall, by characterizing the interactions between all four systems and their components, these circuits should lend themselves to higher-level genetic circuitry for use in microbial consortia. PMID:27172092

  11. Quorum Sensing Communication Modules for Microbial Consortia.

    PubMed

    Scott, Spencer R; Hasty, Jeff

    2016-09-16

    The power of a single engineered organism is limited by its capacity for genetic modification. To circumvent the constraints of any singular microbe, a new frontier in synthetic biology is emerging: synthetic ecology, or the engineering of microbial consortia. Here we develop communication systems for such consortia in an effort to allow for complex social behavior across different members of a community. We posit that such communities will outpace monocultures in their ability to perform complicated tasks if communication among and between members of the community is well regulated. Quorum sensing was identified as the most promising candidate for precise control of engineered microbial ecosystems, due to its large diversity and established utility in synthetic biology. Through promoter and protein modification, we engineered two quorum sensing systems (rpa and tra) to add to the extensively used lux and las systems. By testing the cross-talk between all systems, we thoroughly characterized many new inducible systems for versatile control of engineered communities. Furthermore, we've identified several system pairs that exhibit useful types of orthogonality. Most notably, the tra and rpa systems were shown to have neither signal crosstalk nor promoter crosstalk for each other, making them completely orthogonal in operation. Overall, by characterizing the interactions between all four systems and their components, these circuits should lend themselves to higher-level genetic circuitry for use in microbial consortia.

  12. Quorum sensing and Bacterial Pathogenicity: From Molecules to Disease

    PubMed Central

    Deep, Antariksh; Chaudhary, Uma; Gupta, Varsha

    2011-01-01

    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 bacteriaa mechanism to minimize host immune responses by delaying theproduction of tissue-damaging virulence factors until sufficientbacteria have amassed and are prepared to overwhelm host defensemechanisms 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. PMID:21701655

  13. Social Evolution Selects for Redundancy in Bacterial Quorum Sensing

    PubMed Central

    Valastyan, Julie; Ke, Xiaobo; Pollak, Shaul; Bareia, Tasneem; Ben-Zion, Ishay; Bassler, Bonnie L.; Eldar, Avigdor

    2016-01-01

    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. PMID:26927849

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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. PMID:26927849

  17. Is quorum sensing a side effect of diffusion sensing?

    PubMed

    Redfield, Rosemary J

    2002-08-01

    Many bacteria appear to communicate by releasing and sensing autoinducer molecules, which are believed to function primarily as sensors of population density. However, this quorum-sensing hypothesis rests on very weak foundations, as neither the need for group action nor the selective conditions required for its evolution have been demonstrated. Here, I argue for a more direct function of autoinducer secretion and response - the ability to determine whether secreted molecules rapidly move away from the cell. This diffusion sensing allows cells to regulate secretion of degradative enzymes and other effectors to minimize losses owing to extracellular diffusion and mixing.

  18. A mobile quorum-sensing system in Serratia marcescens.

    PubMed

    Wei, Jun-Rong; Tsai, Yu-Huan; Horng, Yu-Tze; Soo, Po-Chi; Hsieh, Shang-Chen; Hsueh, Po-Ren; Horng, Jim-Tong; Williams, Paul; Lai, Hsin-Chih

    2006-02-01

    Quorum-sensing systems that have been widely identified in bacteria play important roles in the regulation of bacterial multicellular behavior by which bacteria sense population density to control various biological functions, including virulence. One characteristic of the luxIR quorum-sensing genes is their diverse and discontinuous distribution among proteobacteria. Here we report that the spnIR quorum-sensing system identified in the enterobacterium Serratia marcescens strain SS-1 is carried in a transposon, TnTIR, which has common characteristics of Tn3 family transposons and is mobile between chromosomes and plasmids of different enterobacterial hosts. SpnIR functions in the new host and was shown to negatively regulate the TnTIR transposition frequency. This finding may help reveal the horizontal transfer and evolutionary mechanism of quorum-sensing genes and alter the way that we perceive regulation of bacterial multicellular behavior.

  19. Evolution of resistance to quorum sensing inhibitors

    PubMed Central

    Kalia, Vipin C.; Wood, Thomas K.; Kumar, Prasun

    2013-01-01

    The major cause of mortality and morbidity in human beings is bacterial infection. Bacteria have developed resistance to most of the antibiotics primarily due to large scale and “indiscriminate” usage. The need is to develop novel mechanisms to treat bacterial infections. The expression of pathogenicity during bacterial infections is mediated by a cell density dependent phenomenon known as quorum sensing (QS). A wide array of QS systems (QSS) is operative in expressing the virulent behavior of bacterial pathogens. Each QSS may be mediated largely by a few major signals along with others produced in minuscule quantities. Efforts to target signal molecules and their receptors have proved effective in alleviating the virulent behavior of such pathogenic bacteria. These QS inhibitors (QSIs) have been reported to be effective in influencing the pathogenicity without affecting bacterial growth. However, evidence is accumulating that bacteria may develop resistance to QSIs. The big question is whether QSIs will meet the same fate as antibiotics? PMID:24194099

  20. Pseudomonas aeruginosa Biofilm Formation and Persistence, along with the Production of Quorum Sensing-Dependent Virulence Factors, Are Disrupted by a Triterpenoid Coumarate Ester Isolated from Dalbergia trichocarpa, a Tropical Legume

    PubMed Central

    Pottier, Laurent; Huet, Joelle; Rabemanantsoa, Christian; Kiendrebeogo, Martin; Andriantsimahavandy, Abel; Rasamindrakotroka, Andry; Stévigny, Caroline; Duez, Pierre; El Jaziri, Mondher

    2015-01-01

    Recently, extracts of Dalbergia trichocarpa bark have been shown to disrupt P. aeruginosa PAO1 quorum sensing (QS) mechanisms, which are key regulators of virulence factor expression and implicated in biofilm formation. One of the active compounds has been isolated and identified as oleanolic aldehyde coumarate (OALC), a novel bioactive compound that inhibits the formation of P. aeruginosa PAO1 biofilm and its maintenance as well as the expression of the las and rhl QS systems. Consequently, the production of QS-controlled virulence factors including, rhamnolipids, pyocyanin, elastase and extracellular polysaccharides as well as twitching and swarming motilities is reduced. Native acylhomoserine lactones (AHLs) production is inhibited by OALC but exogenous supply of AHLs does not restore the production of virulence factors by OALC-treated cultures, indicating that OALC exerts its effect beyond AHLs synthesis in the QS pathways. Further experiments provided a significant inhibition of the global virulence factor activator gacA by OALC. OALC disorganizes established biofilm structure and improves the bactericidal activity of tobramycin against biofilm-encapsulated PAO1 cells. Finally, a significant reduction of Caenorhabditis elegans paralysis was recorded when the worms were infected with OALC-pre-treated P. aeruginosa. Taken together, these results show that triterpenoid coumarate esters are suitable chemical backbones to target P. aeruginosa virulence mechanisms. PMID:26186595

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

    PubMed

    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.

  2. Electronic Implementation of a Repressilator with Quorum Sensing Feedback

    PubMed Central

    Hellen, Edward H.; Dana, Syamal K.; Zhurov, Boris; Volkov, Evgeny

    2013-01-01

    We investigate the dynamics of a synthetic genetic repressilator with quorum sensing feedback. In a basic genetic ring oscillator network in which three genes inhibit each other in unidirectional manner, an additional quorum sensing feedback loop stimulates the activity of a chosen gene providing competition between inhibitory and stimulatory activities localized in that gene. Numerical simulations show several interesting dynamics, multi-stability of limit cycle with stable steady-state, multi-stability of different stable steady-states, limit cycle with period-doubling and reverse period-doubling, and infinite period bifurcation transitions for both increasing and decreasing strength of quorum sensing feedback. We design an electronic analog of the repressilator with quorum sensing feedback and reproduce, in experiment, the numerically predicted dynamical features of the system. Noise amplification near infinite period bifurcation is also observed. An important feature of the electronic design is the accessibility and control of the important system parameters. PMID:23658793

  3. [Foreign body infections--biofilms and quorum sensing].

    PubMed

    Høiby, Niels; Johansen, Helle Krogh; Ciofu, Oana; Jensen, Peter Ø; Bjarnsholt, Thomas; Givskov, Michael

    2007-11-26

    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.

  4. A Mathematical Model of Quorum Sensing Induced Biofilm Detachment

    PubMed Central

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

    2015-01-01

    Background 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. Method 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. Results 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. PMID:26197231

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

    PubMed

    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 (p<0.001) indicating anti-virulent property attributing towards attenuation of virulence of P. aeruginosa. Further zingerone not only had marked effect on the production of quorum 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. PMID:25704369

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

    PubMed

    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 (p<0.001) indicating anti-virulent property attributing towards attenuation of virulence of P. aeruginosa. Further zingerone not only had marked effect on the production of quorum 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. Quorum Sensing Peptides Selectively Penetrate the Blood-Brain Barrier.

    PubMed

    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.

  8. Role of quorum sensing in bacterial infections

    PubMed Central

    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

  9. Role of quorum sensing in bacterial infections.

    PubMed

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

    2015-07-16

    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.

  10. Quorum sensing in group A Streptococcus

    PubMed Central

    Jimenez, Juan Cristobal; Federle, Michael J.

    2014-01-01

    Quorum sensing (QS) is a widespread phenomenon in the microbial world that has important implications in the coordination of population-wide responses in several bacterial pathogens. In Group A Streptococcus (GAS), many questions surrounding QS systems remain to be solved pertaining to their function and their contribution to the GAS lifestyle in the host. The QS systems of GAS described to date can be categorized into four groups: regulator gene of glucosyltransferase (Rgg), Sil, lantibiotic systems, and LuxS/AI-2. The Rgg family of proteins, a conserved group of transcription factors that modify their activity in response to signaling peptides, has been shown to regulate genes involved in virulence, biofilm formation and competence. The sil locus, whose expression is regulated by the activity of signaling peptides and a putative two-component system (TCS), has been implicated on regulating genes involved with invasive disease in GAS isolates. Lantibiotic regulatory systems are involved in the production of bacteriocins and their autoregulation, and some of these genes have been shown to target both bacterial organisms as well as processes of survival inside the infected host. Finally AI-2 (dihydroxy pentanedione, DPD), synthesized by the LuxS enzyme in several bacteria including GAS, has been proposed to be a universal bacterial communication molecule. In this review we discuss the mechanisms of these four systems, the putative functions of their targets, and pose critical questions for future studies. PMID:25309879

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

    PubMed Central

    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. PMID:26536593

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

    PubMed

    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.

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

    PubMed

    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.

  14. Computational modeling of the quorum-sensing network in bacteria

    NASA Astrophysics Data System (ADS)

    Fenley, Andrew; Banik, Suman; Kulkarni, Rahul

    2007-03-01

    Certain species of bacteria are able produce and sense the concentration of small molecules called autodinducers in order to coordinate gene regulation in response to population density, a process known as ``quorum-sensing''. The resulting regulation of gene expression involves both transcriptional and post-transcriptional regulators. In particular, the species of bacteria in the Vibrio genus use small RNAs to regulate the master protein controlling the quorum-sensing response (luminescence, biofilm formation, virulence...). We model the network of interactions using a modular approach which provides a quantitative understanding of how signal transduction occurs. The parameters of the input-module are fit to current experimental results allowing for testable predictions to be made for future experiments. The results of our analysis offer a revised perspective on quorum-sensing based regulation.

  15. Quorum sensing in the squid-Vibrio symbiosis.

    PubMed

    Verma, Subhash C; Miyashiro, Tim

    2013-08-07

    Quorum sensing is an intercellular form of communication that bacteria use to coordinate group behaviors such as biofilm formation and the production of antibiotics and virulence factors. The term quorum sensing was originally coined to describe the mechanism underlying the onset of luminescence production in cultures of the marine bacterium Vibrio fischeri. Luminescence and, more generally, quorum sensing are important for V. fischeri to form a mutualistic symbiosis with the Hawaiian bobtail squid, Euprymna scolopes. The symbiosis is established when V. fischeri cells migrate via flagella-based motility from the surrounding seawater into a specialized structure injuvenile squid called the light organ. The cells grow to high cell densities within the light organ where the infection persists over the lifetime of the animal. A hallmark of a successful symbiosis is the luminescence produced by V. fischeri that camouflages the squid at night by eliminating its shadow within the water column. While the regulatory networks governing quorum sensing are critical for properly regulating V. fischeri luminescence within the squid light organ, they also regulate luminescence-independent processes during symbiosis. In this review, we discuss the quorum-sensing network of V. fischeri and highlight its impact at various stages during host colonization.

  16. Integrated analysis of bacterial quorum-sensing networks

    NASA Astrophysics Data System (ADS)

    Kulkarni, Rahul

    2005-11-01

    The regulation of gene expression is fundamental to most processes in cellular biology. At the transcriptional level, regulation occurs by the binding of specific proteins called transcription factors to DNA. Post-transcriptional regulation is often carried out by small RNAs which have become the focus of intense research activity recently. The talk will discuss the physics and biology of these two regulatory mechanisms by focusing on a specific biological system: quorum-sensing networks in bacteria. Quorum sensing is the process by which bacteria communicate to regulate gene expression in response to cell population density. Using an integrated approach which combines computational modeling, bioinformatics and experimental molecular biology, we are studying quorum-sensing pathways in bacteria. This approach led to the discovery of multiple regulatory small RNAs which are an integral part of the quorum-sensing pathway in Vibrio cholerae and Vibrio harveyi. Modeling of regulation of and by small RNAs in quorum sensing reveals the circuit characteristics controlling the transition from the low cell-density response to the high cell-density response.

  17. Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors

    PubMed Central

    Hentzer, Morten; Wu, Hong; Andersen, Jens Bo; Riedel, Kathrin; Rasmussen, Thomas B.; Bagge, Niels; Kumar, Naresh; Schembri, Mark A.; Song, Zhijun; Kristoffersen, Peter; Manefield, Mike; Costerton, John W.; Molin, Søren; Eberl, Leo; Steinberg, Peter; Kjelleberg, Staffan; Høiby, Niels; Givskov, Michael

    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 afforded a novel opportunity to control infectious bacteria without interfering with growth. Compounds that can override communication signals have been found in the marine environment. Using Pseudomonas aeruginosa PAO1 as an example of an opportunistic human pathogen, we show that a synthetic derivate 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. PMID:12881415

  18. Quorum Sensing in the Squid-Vibrio Symbiosis

    PubMed Central

    Verma, Subhash C.; Miyashiro, Tim

    2013-01-01

    Quorum sensing is an intercellular form of communication that bacteria use to coordinate group behaviors such as biofilm formation and the production of antibiotics and virulence factors. The term quorum sensing was originally coined to describe the mechanism underlying the onset of luminescence production in cultures of the marine bacterium Vibrio fischeri. Luminescence and, more generally, quorum sensing are important for V. fischeri to form a mutualistic symbiosis with the Hawaiian bobtail squid, Euprymna scolopes. The symbiosis is established when V. fischeri cells migrate via flagella-based motility from the surrounding seawater into a specialized structure injuvenile squid called the light organ. The cells grow to high cell densities within the light organ where the infection persists over the lifetime of the animal. A hallmark of a successful symbiosis is the luminescence produced by V. fischeri that camouflages the squid at night by eliminating its shadow within the water column. While the regulatory networks governing quorum sensing are critical for properly regulating V. fischeri luminescence within the squid light organ, they also regulate luminescence-independent processes during symbiosis. In this review, we discuss the quorum-sensing network of V. fischeri and highlight its impact at various stages during host colonization. PMID:23965960

  19. Noisy neighbourhoods: quorum sensing in fungal–polymicrobial infections

    PubMed Central

    Dixon, Emily F.

    2015-01-01

    Summary 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. PMID:26243526

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

    PubMed Central

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

    2016-01-01

    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. PMID:27120081

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

    PubMed

    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.

  2. Bacterial quorum sensing and nitrogen cycling in rhizosphere soil

    SciTech Connect

    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.

  3. Links between Anr and Quorum Sensing in Pseudomonas aeruginosa Biofilms

    PubMed Central

    Hammond, John H.; Dolben, Emily F.; Smith, T. Jarrod; Bhuju, Sabin

    2015-01-01

    ABSTRACT In Pseudomonas aeruginosa, the transcription factor Anr controls the cellular response to low oxygen or anoxia. Anr activity is high in oxygen-limited environments, including biofilms and populations associated with chronic infections, and Anr is necessary for persistence in a model of pulmonary infection. In this study, we characterized the Anr regulon in biofilm-grown cells at 1% oxygen in the laboratory strain PAO1 and in a quorum sensing (QS)-deficient clinical isolate, J215. As expected, transcripts related to denitrification, arginine fermentation, high-affinity cytochrome oxidases, and CupA fimbriae were lower in the Δanr derivatives. In addition, we observed that transcripts associated with quorum sensing regulation, iron acquisition and storage, type VI secretion, and the catabolism of aromatic compounds were also differentially expressed in the Δanr strains. Prior reports have shown that quorum sensing-defective mutants have higher levels of denitrification, and we found that multiple Anr-regulated processes, including denitrification, were strongly inversely proportional to quorum sensing in both transcriptional and protein-based assays. We also found that in LasR-defective strains but not their LasR-intact counterparts, Anr regulated the production of the 4-hydroxy-2-alkylquinolines, which play roles in quorum sensing and interspecies interactions. These data show that Anr was required for the expression of important metabolic pathways in low-oxygen biofilms, and they reveal an expanded and compensatory role for Anr in the regulation of virulence-related genes in quorum sensing mutants, such as those commonly isolated from infections. IMPORTANCE Pseudomonas aeruginosa causes acute ocular, soft tissue, and pulmonary infections, as well as chronic infections in the airways of cystic fibrosis patients. P. aeruginosa uses quorum sensing (QS) to regulate virulence, but mutations in the gene encoding the master regulator of QS, lasR, are frequently

  4. Quorum-Sensing Regulation of a Copper Toxicity System in Pseudomonas aeruginosa▿

    PubMed Central

    Thaden, Joshua T.; Lory, Stephen; Gardner, Timothy S.

    2010-01-01

    The LasR/LasI quorum-sensing system in Pseudomonas aeruginosa influences global gene expression and mediates pathogenesis. In this study, we show that the quorum-sensing system activates, via the transcriptional regulator PA4778, a copper resistance system composed of 11 genes. The quorum-sensing global regulator LasR was recently shown to directly activate transcription of PA4778, a cueR homolog and a MerR-type transcriptional regulator. Using molecular genetic methods and bioinformatics, we verify the interaction of LasR with the PA4778 promoter and further demonstrate the LasR binding site. We also identify a putative PA4778 binding motif and show that the protein directly binds to and activates five promoters controlling the expression of 11 genes—PA3519 to -15, PA3520, mexPQ-opmE, PA3574.1, and cueA, a virulence factor in a murine model. Using gene disruptions, we show that PA4778, along with 7 of 11 gene targets of PA4778, increases the sensitivity of P. aeruginosa to elevated copper concentrations. This work identifies a cellular function for PA4778 and four other previously unannotated genes (PA3515, PA3516, PA3517, and PA3518) and suggests a potential role for copper in the quorum response. We propose to name PA4778 cueR. PMID:20233934

  5. Collective sensing and collective responses in quorum-sensing bacteria

    PubMed Central

    Popat, R.; Cornforth, D. M.; McNally, L.; Brown, S. P.

    2015-01-01

    Bacteria often face fluctuating environments, and in response many species have evolved complex decision-making mechanisms to match their behaviour to the prevailing conditions. Some environmental cues provide direct and reliable information (such as nutrient concentrations) and can be responded to individually. Other environmental parameters are harder to infer and require a collective mechanism of sensing. In addition, some environmental challenges are best faced by a group of cells rather than an individual. In this review, we discuss how bacteria sense and overcome environmental challenges as a group using collective mechanisms of sensing, known as ‘quorum sensing’ (QS). QS is characterized by the release and detection of small molecules, potentially allowing individuals to infer environmental parameters such as density and mass transfer. While a great deal of the molecular mechanisms of QS have been described, there is still controversy over its functional role. We discuss what QS senses and how, what it controls and why, and how social dilemmas shape its evolution. Finally, there is a growing focus on the use of QS inhibitors as antibacterial chemotherapy. We discuss the claim that such a strategy could overcome the evolution of resistance. By linking existing theoretical approaches to data, we hope this review will spur greater collaboration between experimental and theoretical researchers. PMID:25505130

  6. [Research advance in the function of quorum sensing in the biological aggregates].

    PubMed

    Dai, Xin; Zhou, Jia-Heng; Zhu, Liang; Xu, Xiang-Yang

    2014-04-01

    Quorum sensing is a microbial phenomenon that microorganisms use signal molecules to perceive environmental conditions and regulate specific gene expressions. As the communication function of quorum sensing is increasingly highlighted in the microbial field, researches on quorum sensing in the formation process of biological aggregates (biofilm and granules) attract wide attentions. The paper reviewed autoinducers (AI) classification and the corresponding regulation methods in quorum sensing, and provided an up-to-date account on research progress of AIs regulating biological aggregates formation and structural stability. New territories and future of quorum sensing were also outlined.

  7. Exploring the chemical space of quorum sensing peptides.

    PubMed

    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.

  8. [Growth and mutation of Escherichia coli with suicide gene circuit based on quorum sensing].

    PubMed

    Gao, Qi; Zheng, Xuesong

    2013-06-01

    Constructing robust gene circuits is a fundamental work for synthetic biology. Bacteria with suicide gene circuit based on quorum-sensing will kill themselves in a controllable pattern upon certain cell density. In the media of different IPTG inducer concentration, we observed the growth and suicidal behavior of the Escherichia coli. Top10F' with such gene circuit, screened the mutants and determined their mutated loci. The results show that, with higher IPTG concentration, the more wild type bacteria were killed; as well the mutants emerged earlier and spread over the population more quickly. The sequence of plasmids in those mutants revealed that a transposon inserted into the luxR gene and therefore disrupted Quorum-Sensing of these individuals. Furthermore, the insertion sequence of the plasmid can solely result in the mutants escaping from suicide.

  9. The art of antibacterial warfare: Deception through interference with quorum sensing-mediated communication.

    PubMed

    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.

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

    PubMed

    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. PMID:27507587

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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.

  13. RETRACTED ARTICLE: Quorum-sensing of bacteria and its application

    NASA Astrophysics Data System (ADS)

    Jiang, Guoliang; Su, Mingxia

    2009-12-01

    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.

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

    PubMed

    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.

  15. Characterization of Quorum Sensing and Quorum Quenching Soil Bacteria Isolated from Malaysian Tropical Montane Forest

    PubMed Central

    Chong, Teik-Min; Koh, Chong-Lek; Sam, Choon-Kook; Choo, Yeun-Mun; Yin, Wai-Fong; Chan, Kok-Gan

    2012-01-01

    We report the production and degradation of quorum sensing N-acyl-homoserine lactones by bacteria isolated from Malaysian montane forest soil. Phylogenetic analysis indicated that these isolates clustered closely to the genera of Arthrobacter, Bacillus and Pseudomonas. Quorum quenching activity was detected in six isolates of these three genera by using a series of bioassays and rapid resolution liquid chromatography analysis. Biosensor screening and high resolution liquid chromatography-mass spectrometry analysis revealed the production of N-dodecanoyl-L-homoserine lactone (C12-HSL) by Pseudomonas frederiksbergensis (isolate BT9). In addition to degradation of a wide range of N-acyl-homoserine lactones, Arthrobacter and Pseudomonas spp. also degraded p-coumaroyl-homoserine lactone. To the best of our knowledge, this is the first documentation of Arthrobacter and Pseudomonas spp. capable of degrading p-coumaroyl-homoserine lactone and the production of C12-HSL by P. frederiksbergensis. PMID:22666062

  16. Global Analysis of the Burkholderia thailandensis Quorum Sensing-Controlled Regulon

    PubMed Central

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

    2014-01-01

    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. PMID:24464461

  17. Improved quorum sensing capacity by culturing Vibrio harveyi in microcapsules.

    PubMed

    Gao, Meng; Song, Huiyi; Liu, Xiudong; Yu, Weiting; Ma, Xiaojun

    2016-04-01

    Microcapsule entrapped low density cells with culture (ELDCwc), different from free cell culture, conferred stronger stress resistance and improved cell viability of microorganisms. In this paper, the quorum sensing (QS) system of Vibrio harveyi was used to investigate changes when cells were cultured in microcapsules. Cells in ELDCwc group grew into cell aggregates, which facilitated cell-cell communication and led to increased bioluminescence intensity. Moreover, the luxS-AI-2 system, a well-studied QS signal pathway, was detected as both luxS gene and the AI-2 signaling molecule, and the results were analyzed with respect to QS capacity of unit cell. The V. harveyi of ELDCwc also showed higher relative gene expression and stronger quorum sensing capacity when compared with free cells. In conclusion, the confined microcapsule space can promote the cell aggregates formation, reduce cell-cell communication distance and increase local concentration of signal molecule, which are beneficial to bacterial QS.

  18. The role of quorum sensing in the in vivo virulence of Pseudomonas aeruginosa.

    PubMed

    Rumbaugh, K P; Griswold, J A; Hamood, A N

    2000-11-01

    Pseudomonas aeruginosa is an opportunistic pathogen that causes a wide variety of infections. The cell-density-dependent signaling mechanisms known as quorum sensing play a role in several of these infections including corneal, lung and burn wound infections. In addition, the quorum-sensing systems contribute to the ability of P. aeruginosa to form biofilms on medically important devices. The quorum-sensing systems accomplish their effect by controlling the production of different virulence factors and by manipulating the host immune response.

  19. [Quorum sensing mechanism as a factor regulating virulence of Gram-negative bacteria].

    PubMed

    Myszka, Kamila; Czaczyk, Katarzyna

    2010-11-25

    The metabolism of a high density population of bacteria is regulated by a quorum sensing mechanism. Cell-to-cell communication of microorganisms regulates the process of production of pathogenicity factors including formation and differentiation of bacterial biofilms. The role of the quorum sensing system in the expression of virulence features is described in this paper. The possibility of application of the quorum sensing mechanism in medicine is also discussed.

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

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  2. Simple models for quorum sensing: Nonlinear dynamical analysis

    NASA Astrophysics Data System (ADS)

    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.

  3. Negative Feedback in the Vibrio harveyi Quorum-Sensing Circuit

    NASA Astrophysics Data System (ADS)

    Teng, Shu-Wen; Schaffer, Jessie; Wingreen, Ned; Bassler, Bonnie; Phuan Ong, Nai

    2010-03-01

    Quorum sensing is the mechanism by which bacteria communicate and synchronize group behaviors. Multiple feedbacks have been identified in the model quorum-sensing bacterium Vibrio harveyi, but it has been unclear how these feedbacks interact in individual cells to control the fidelity of signal transduction. We measured the copy number distribution of the master regulators to quantify the activity of the signaling network. We find that the feedbacks affect the production rate, level, and noise of the core quorum-sensing components. Using fluorescence time-lapse microscopy, we directly observed the master regulator in individual cells, and analyzed the persistence of heterogeneity in terms of the normalized time-delayed direct correlation. Our findings suggest that feedback from small regulatory RNAs regulates a receptor to control the noise level in signal transduction. We further tested this model by re-engineering the gene circuit to specifically diminish this feedback. We conclude that negative feedbacks mediated by sRNAs permit fine-tuning of gene regulation, thereby increasing the fidelity of signal transduction.

  4. Chlamydomonas reinhardtii Secretes Compounds That Mimic Bacterial Signals and Interfere with Quorum Sensing Regulation in Bacteria1

    PubMed Central

    Teplitski, Max; Chen, Hancai; Rajamani, Sathish; Gao, Mengsheng; Merighi, Massimo; Sayre, Richard T.; Robinson, Jayne B.; Rolfe, Barry G.; Bauer, Wolfgang D.

    2004-01-01

    The unicellular soil-freshwater alga Chlamydomonas reinhardtii was found to secrete substances that mimic the activity of the N-acyl-l-homoserine lactone (AHL) signal molecules used by many bacteria for quorum sensing regulation of gene expression. More than a dozen chemically separable but unidentified substances capable of specifically stimulating the LasR or CepR but not the LuxR, AhyR, or CviR AHL bacterial quorum sensing reporter strains were detected in ethyl acetate extracts of C. reinhardtii culture filtrates. Colonies of C. reinhardtii and Chlorella spp. stimulated quorum sensing-dependent luminescence in Vibrio harveyi, indicating that these algae may produce compounds that affect the AI-2 furanosyl borate diester-mediated quorum sensing system of Vibrio spp. Treatment of the soil bacterium Sinorhizobium meliloti with a partially purified LasR mimic from C. reinhardtii affected the accumulation of 16 of the 25 proteins that were altered in response to the bacterium's own AHL signals, providing evidence that the algal mimic affected quorum sensing-regulated functions in this wild-type bacterium. Peptide mass fingerprinting identified 32 proteins affected by the bacterium's AHLs or the purified algal mimic, including GroEL chaperonins, the nitrogen regulatory protein PII, and a GTP-binding protein. The algal mimic was able to cancel the stimulatory effects of bacterial AHLs on the accumulation of seven of these proteins, providing evidence that the secretion of AHL mimics by the alga could be effective in disruption of quorum sensing in naturally encountered bacteria. PMID:14671013

  5. Extensive and specific responses of a eukaryote to bacterial quorum-sensing signals

    PubMed Central

    Mathesius, Ulrike; Mulders, Susan; Gao, Mengsheng; Teplitski, Max; Caetano-Anollés, Gustavo; Rolfe, Barry G.; Bauer, Wolfgang D.

    2003-01-01

    Many bacteria use N-acyl homoserine lactone (AHL) signals to coordinate the behavior of individual cells in a local population. The successful infection of eukaryotic hosts by bacteria seems to depend particularly on such AHL-mediated “quorum-sensing” regulation. We have used proteome analysis to show that a eukaryotic host, the model legume Medicago truncatula, is able to detect nanomolar to micromolar concentrations of bacterial AHLs from both symbiotic (Sinorhizobium meliloti) and pathogenic (Pseudomonas aeruginosa) bacteria, and that it responds in a global manner by significant changes in the accumulation of over 150 proteins, 99 of which have been identified by peptide mass fingerprinting. The accumulation of specific proteins and isoforms depended on AHL structure, concentration, and time of exposure. AHLs were also found to induce tissue-specific activation of β-glucuronidase (GUS) reporter fusions to an auxin-responsive and three chalcone synthase promoters, consistent with AHL-induced changes in the accumulation of auxin-responsive and flavonoid synthesis proteins. In addition, exposure to AHLs was found to induce changes in the secretion of compounds by the plants that mimic quorum-sensing signals and thus have the potential to disrupt quorum sensing in associated bacteria. Our results indicate that eukaryotes have an extensive range of functional responses to AHLs that may play important roles in the beneficial or pathogenic outcomes of eukaryote–prokaryote interactions. PMID:12511600

  6. Natural Guided Genome Engineering Reveals Transcriptional Regulators Controlling Quorum-Sensing Signal Degradation

    PubMed Central

    Mothe, Nicolas; Velours, Christophe; Legrand, Pierre; Moréra, Solange; Faure, Denis

    2015-01-01

    Quorum-quenching (QQ) are natural or engineered processes disrupting the quorum-sensing (QS) signalling which controls virulence and persistence (e.g. biofilm) in numerous bacteria. QQ involves different enzymes including lactonases, amidases, oxidases and reductases which degrade the QS molecules such as N-acylhomoserine lactones (NAHL). Rhodococcus erythropolis known to efficiently degrade NAHL is proposed as a biocontrol agent and a reservoir of QQ-enzymes for biotechnology. In R. erythropolis, regulation of QQ-enzymes remains unclear. In this work, we performed genome engineering on R. erythropolis, which is recalcitrant to reverse genetics, in order to investigate regulation of QQ-enzymes at a molecular and structural level with the aim to improve the QQ activity. Deep-sequencing of the R. erythropolis enhanced variants allowed identification of a punctual mutation in a key-transcriptional factor QsdR (Quorum sensing degradation Regulation) which regulates the sole QQ-lactonase QsdA identified so far. Using biophysical and structural studies on QsdR, we demonstrate that QQ activity can be improved by modifying the regulation of QQ-enzymes degrading QS signal. This modification requiring the change of only one amino-acid in a transcriptional factor leads to an enhanced R. erythropolis in which the QS-signal degradation pathway is strongly activated. PMID:26554837

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

    PubMed

    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. 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.

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

    NASA Astrophysics Data System (ADS)

    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.

  9. Can the Natural Diversity of Quorum-Sensing Advance Synthetic Biology?

    PubMed Central

    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. PMID:25806368

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

    PubMed

    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.

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

    PubMed

    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. PMID:27465850

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

    PubMed Central

    2011-01-01

    Background 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. Model 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. Results 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. Conclusions 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. PMID:21477365

  13. Biofilm formation and sloughing in Serratia marcescens are controlled by quorum sensing and nutrient cues.

    PubMed

    Rice, S A; Koh, K S; Queck, S Y; Labbate, M; Lam, K W; Kjelleberg, S

    2005-05-01

    We describe here a role for quorum sensing in the detachment, or sloughing, of Serratia marcescens filamentous biofilms, and we show that nutrient conditions affect the biofilm morphotype. Under reduced carbon or nitrogen conditions, S. marcescens formed a classical biofilm consisting of microcolonies. The filamentous biofilm could be converted to a microcolony-type biofilm by switching the medium after establishment of the biofilm. Similarly, when initially grown as a microcolony biofilm, S. marcescens could be converted back to a filamentous biofilm by increasing the nutrient composition. Under high-nutrient conditions, an N-acyl homoserine lactone quorum-sensing mutant formed biofilms that were indistinguishable from the wild-type biofilms. Similarly, other quorum-sensing-dependent behaviors, such as swarming motility, could be rendered quorum sensing independent by manipulating the growth medium. Quorum sensing was also found to be involved in the sloughing of the filamentous biofilm. The biofilm formed by the bacterium consistently sloughed from the substratum after approximately 75 to 80 h of development. The quorum-sensing mutant, when supplemented with exogenous signal, formed a wild-type filamentous biofilm and sloughed at the same time as the wild type, and this was independent of surfactant production. When we removed the signal from the quorum-sensing mutant prior to the time of sloughing, the biofilm did not undergo significant detachment. Together, the data suggest that biofilm formation by S. marcescens is a dynamic process that is controlled by both nutrient cues and the quorum-sensing system.

  14. Bacterial Quorum Sensing: Its Role in Virulence and Possibilities for Its Control

    PubMed Central

    Rutherford, Steven T.; Bassler, Bonnie L.

    2012-01-01

    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. PMID:23125205

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

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  17. Quorum-sensing-directed protein expression in Serratia proteamaculans B5a.

    PubMed

    Christensen, Allan B; Riedel, Kathrin; Eberl, Leo; Flodgaard, Lars R; Molin, Søren; Gram, Lone; Givskov, Michael

    2003-02-01

    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 quorum sensor was identified in the N-(3-oxo-hexanoyl)-L-homoserine lactone (3-oxo-C6-HSL)-producing Serratia proteamaculans strain B5a. The 3-oxo-C6-HSL synthase SprI showed 79 % similarity with EsaI from Pantoea stewartii and the putative regulatory protein SprR was 86 % similar to the SpnR of Serratia marcescens. Proteome analysis suggested that the presence of at least 39 intracellular proteins was affected by the 3-oxo-C6-HSL-based quorum sensing system. The lipB-encoded secretion system was identified as one target gene of the quorum sensing system. LipB was required for the production of extracellular lipolytic and proteolytic activities, thus rendering the production of food-deterioration-relevant exoenzymes indirectly under the control of quorum sensing. Strain B5a caused quorum-sensing-controlled spoilage of milk. Furthermore, chitinolytic activity was controlled by quorum sensing. This control appeared to be direct and not mediated via LipB. The data presented here demonstrate that quorum-sensing-controlled exoenzymic activities affect food quality.

  18. Targeting Staphylococcus aureus Quorum Sensing with Nonpeptidic Small Molecule Inhibitors

    PubMed Central

    2014-01-01

    A series of 3-oxo-C12-HSL, tetramic acid, and tetronic acid analogues were synthesized to gain insights into the structural requirements for quorum sensing inhibition in Staphylococcus aureus. Compounds active against agr were noncompetitive inhibitors of the autoinducing peptide (AIP) activated AgrC receptor, by altering the activation efficacy of the cognate AIP-1. They appeared to act as negative allosteric modulators and are exemplified by 3-tetradecanoyltetronic acid 17, which reduced nasal cell colonization and arthritis in a murine infection model. PMID:24592914

  19. Structure and Inhibition of Quorum Sensing Target from Streptococcus pneumoniae

    SciTech Connect

    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 MTAN with MT

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

    PubMed

    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.

  1. Quorum sensing positively regulates flagellar motility in pathogenic Vibrio harveyi.

    PubMed

    Yang, Qian; Defoirdt, Tom

    2015-04-01

    Vibrios belonging to the Harveyi clade are among the major pathogens of aquatic organisms. Quorum sensing (QS) is essential for virulence of V. harveyi towards different hosts. However, most virulence factors reported to be controlled by QS to date are negatively regulated by QS, therefore suggesting that their impact on virulence is limited. In this study, we report that QS positively regulates flagellar motility. We found that autoinducer synthase mutants showed significantly lower swimming motility than the wild type, and the swimming motility could be restored by adding synthetic signal molecules. Further, motility of a luxO mutant with inactive QS (LuxO D47E) was significantly lower than that of the wild type and of a luxO mutant with constitutively maximal QS activity (LuxO D47A). Furthermore, we found that the expression of flagellar genes (both early, middle and late genes) was significantly lower in the luxO mutant with inactive QS when compared with wild type and the luxO mutant with maximal QS activity. Motility assays and gene expression also revealed the involvement of the quorum-sensing master regulator LuxR in the QS regulation of motility. Finally, the motility inhibitor phenamil significantly decreased the virulence of V. harveyi towards gnotobiotic brine shrimp larvae. PMID:24528485

  2. Functional Amyloids Keep Quorum-sensing Molecules in Check*

    PubMed Central

    Seviour, Thomas; Hansen, Susan Hove; Yang, Liang; Yau, Yin Hoe; Wang, Victor Bochuan; Stenvang, Marcel R.; Christiansen, Gunna; Marsili, Enrico; Givskov, Michael; Chen, Yicai; Otzen, Daniel E.; Nielsen, Per Halkjær; Geifman-Shochat, Susana; Kjelleberg, Staffan; Dueholm, Morten S.

    2015-01-01

    The mechanism by which extracellular metabolites, including redox mediators and quorum-sensing signaling molecules, traffic through the extracellular matrix of biofilms is poorly explored. We hypothesize that functional amyloids, abundant in natural biofilms and possessing hydrophobic domains, retain these metabolites. Using surface plasmon resonance, we demonstrate that the quorum-sensing (QS) molecules, 2-heptyl-3-hydroxy-4(1H)-quinolone and N-(3-oxododecanoyl)-l-homoserine lactone, and the redox mediator pyocyanin bind with transient affinity to functional amyloids from Pseudomonas (Fap). Their high hydrophobicity predisposes them to signal-amyloid interactions, but specific interactions also play a role. Transient interactions allow for rapid association and dissociation kinetics, which make the QS molecules bioavailable and at the same time secure within the extracellular matrix as a consequence of serial bindings. Retention of the QS molecules was confirmed using Pseudomonas aeruginosa PAO1-based 2-heptyl-3-hydroxy-4(1H)-quinolone and N-(3-oxododecanoyl)-l-homoserine lactone reporter assays, showing that Fap fibrils pretreated with the QS molecules activate the reporters even after sequential washes. Pyocyanin retention was validated by electrochemical analysis of pyocyanin-pretreated Fap fibrils subjected to the same washing process. Results suggest that QS molecule-amyloid interactions are probably important in the turbulent environments commonly encountered in natural habitats. PMID:25586180

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

    PubMed

    Sanchez-Contreras, Maria; Bauer, Wolfgang D; Gao, Mengsheng; Robinson, Jayne B; Allan Downie, J

    2007-07-29

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

  4. Computer-Aided Identification of Recognized Drugs as Pseudomonas aeruginosa Quorum-Sensing Inhibitors▿ †

    PubMed Central

    Yang, Liang; Rybtke, Morten Theil; Jakobsen, Tim Holm; Hentzer, Morten; Bjarnsholt, Thomas; Givskov, Michael; Tolker-Nielsen, Tim

    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 LasR, 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 phenotypes in a dose-dependent manner. These results suggest that the identified compounds have the potential to be used as antipathogenic drugs. Furthermore, the results indicate that structure-based virtual screening is an efficient tool in the search for novel compounds to combat bacterial infections. PMID:19364871

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

    PubMed

    Yang, Liang; Rybtke, Morten Theil; Jakobsen, Tim Holm; Hentzer, Morten; Bjarnsholt, Thomas; Givskov, Michael; Tolker-Nielsen, Tim

    2009-06-01

    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 LasR, 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 phenotypes in a dose-dependent manner. These results suggest that the identified compounds have the potential to be used as antipathogenic drugs. Furthermore, the results indicate that structure-based virtual screening is an efficient tool in the search for novel compounds to combat bacterial infections. PMID:19364871

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

    PubMed

    Rasch, Maria; Kastbjerg, Vicky Gaedt; Bruhn, Jesper Bartholin; Dalsgaard, Inger; Givskov, Michael; Gram, Lone

    2007-12-13

    Many pathogens control production of virulence factors by self-produced signals in a process called quorum sensing (QS). We demonstrate that acyl homoserine lactone (AHL) signals, which enable bacteria to express certain phenotypes in relation to cell density, are produced by a wide spectrum 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. 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. The most efficient compound N-(heptylsulfanylacetyl)-L-homoserine lactone (HepS-AHL), reduced protease production by a factor of 10. Five extracellular proteases were detected on gelatin-containing sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) gels and 3 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.

  7. Effects of AiiA-mediated quorum quenching in Sinorhizobium meliloti on quorum-sensing signals, proteome patterns, and symbiotic interactions.

    PubMed

    Gao, Mengsheng; Chen, Hancai; Eberhard, Anatol; Gronquist, Matthew R; Robinson, Jayne B; Connolly, Mary; Teplitski, Max; Rolfe, Barry G; Bauer, Wolfgang D

    2007-07-01

    Many behaviors in bacteria, including behaviors important to pathogenic and symbiotic interactions with eukaryotic hosts, are regulated by a mechanism called quorum sensing (QS). A "quorum-quenching" approach was used here to identify QS-regulated behaviors in the N-fixing bacterial symbiont Sinorhizobium meliloti. The AiiA lactonase from Bacillus produced in S. meliloti was shown to enzymatically inactivate S. meliloti's N-acyl homoserine lactone (AHL) QS signals, thereby disrupting normal QS regulation. Sixty proteins were differentially accumulated in the AiiA-producing strain versus the control in early log or early stationary phase cultures. Fifty-two of these QS-regulated proteins, with putative functions that include cell division, protein processing and translation, metabolite transport, oxidative stress, and amino acid metabolism, were identified by peptide mass fingerprinting. Transcription of representative genes was reduced significantly in the AiiA-producing strain, although the effects of AiiA on protein accumulation did not always correspond to effects on transcription. The QS signal-deficient strain was reduced significantly in nodule initiation during the first 12 h after inoculation onto Medicago truncatula host plants. The AiiA lactonase also was found to substantially inactivate two of the AHL mimic compounds secreted by M. truncatula. This suggests some structural similarity between bacterial AHLs and these mimic compounds. It also indicates that quorum quenching could be useful in identifying Sinorhizobium genes that are affected by such host QS mimics in planta.

  8. A Host-Produced Autoinducer-2 Mimic Activates Bacterial Quorum Sensing.

    PubMed

    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.

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

    PubMed

    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. PMID:27510864

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

    PubMed

    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.

  11. Malabaricone C from Myristica cinnamomea exhibits anti-quorum sensing activity.

    PubMed

    Chong, Yee Meng; Yin, Wai Fong; Ho, Chia Yong; Mustafa, Mohamad Rais; Hadi, A Hamid A; Awang, Khalijah; Narrima, Putri; Koh, Chong-Lek; Appleton, David R; Chan, Kok-Gan

    2011-10-28

    A methanol-soluble extract of the bark of Myristica cinnamomea was found to exhibit anti-quorum sensing activity, and subsequent bioassay-guided isolation led to the identification of the active compound malabaricone C (1). Compound 1 inhibited violacein production by Chromobacterium violaceum CV026 when grown in the presence of a cognate signaling molecule, N-3-oxohexanoyl-homoserine lactone. Furthermore, 1 inhibited the quorum sensing-regulated pyocyanin production and biofilm formation in Pseudomonas aeruginosa PAO1. These results suggest that the anti-quorum sensing activity of 1 and related molecules should be investigated further.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed Central

    Zan, Jindong; Liu, Yue; Fuqua, Clay; Hill, Russell T.

    2014-01-01

    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. PMID:24402124

  15. The use of quorum sensing to improve vaccine immune response.

    PubMed

    Sturbelle, R T; Conceição, R C S; Da Rosa, M C; Roos, T B; Dummer, L; Leite, F P L

    2013-12-17

    Enterotoxigenic Escherichia coli (ETEC) infection is an important cause of diarrhea in both newborn and post-weaning pigs, it is also responsible for economic losses on farms worldwide. Vaccines that use ETEC virulence factors have been well documented, and several vaccines containing inactivated bacteria with protective antigens, or purified (isolated) antigens are available on the market. Vaccination of pregnant sows is widely seen as an effective strategy for the control of the disease. Yet these vaccines very often do not lead to efficient protection. In this study, we produced an ETEC bacterin with the use of quorum sensing (QS), and observed a significant expression of F4 adhesin, and heat-labile toxin (LT) in the cultures when compared to the controls. Mice, and pigs vaccinated with the QS bacterin demonstrated higher antibody titers against these antigens when compared with commercial and control bacterin. Our results suggest that the system might bring promising improvements in ETEC bacterin efficacy. PMID:24188753

  16. Quorum-sensing regulation in staphylococci—an overview

    PubMed Central

    Le, Katherine Y.; Otto, Michael

    2015-01-01

    Staphylococci are frequent human commensals and some species can cause disease. Staphylococcus aureus in particular is a dangerous human pathogen. In staphylococci, the ability to sense the bacterial cell density, or quorum, and to respond with genetic adaptations is due to one main system, which is called accessory gene regulator (Agr). The extracellular signal of Agr is a post-translationally modified peptide containing a thiolactone structure. Under conditions of high cell density, Agr is responsible for the increased expression of many toxins and degradative exoenzymes, and decreased expression of several colonization factors. This regulation is important for the timing of virulence factor expression during infection and the development of acute disease, while low activity of Agr is associated with chronic staphylococcal infections, such as those involving biofilm formation. Accordingly, drugs inhibiting Agr are being evaluated for their capacity to control acute forms of S. aureus infection. PMID:26579084

  17. Quorum sensing inhibitors of Staphylococcus aureus from Italian medicinal plants.

    PubMed

    Quave, Cassandra L; Plano, Lisa R W; Bennett, Bradley C

    2011-01-01

    Morbidity and mortality estimates due to methicillin-resistant Staphylococcus aureus (MRSA) infections continue to rise. Therapeutic options are limited by antibiotic resistance. Anti-pathogenic compounds, which inhibit quorum sensing (QS) pathways, may be a useful alternative to antibiotics. Staphylococcal QS is encoded by the AGR locus and is responsible for the production of δ-hemolysin. Quantification of δ-hemolysin found in culture supernatants permits the analysis of AGR activity at the translational rather than transcriptional level. We employed reversed phase high performance chromatographic (RP-HPLC) techniques to investigate the anti-QS activity of 168 extracts from 104 Italian plants through quantification of δ-hemolysin. Extracts from three medicinal plants (Ballota nigra, Castanea sativa, and Sambucus ebulus) exhibited a dose-dependent response in the production of δ-hemolysin, indicating anti-QS activity in a pathogenic MRSA isolate.

  18. Quorum sensing activity of Hafnia alvei isolated from packed food.

    PubMed

    Tan, Jia-Yi; Yin, Wai-Fong; Chan, Kok-Gan

    2014-01-01

    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.

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

    PubMed Central

    Tan, Jia-Yi; Yin, Wai-Fong; Chan, Kok-Gan

    2014-01-01

    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. PMID:24736131

  20. Quorum Sensing Inhibitors for Staphylococcus aureus from Italian Medicinal Plants

    PubMed Central

    Quave, Cassandra L.; Plano, Lisa R.W.; Bennett, Bradley C.

    2010-01-01

    Morbidity and mortality estimates due to methicillin-resistant Staphylococcus aureus (MRSA) infections continue to rise. Therapeutic options are limited by antibiotic resistance. Anti-pathogenic compounds, which inhibit quorum sensing (QS) pathways, may be a useful alternative to antibiotics. Staphylococcal QS is encoded by the agr locus and is responsible for the production of δ-hemolysin. Quantification of δ-hemolysin found in culture supernatants permits the analysis of agr activity at the translational, rather than transcriptional, level. We employed RP-HPLC techniques to investigate the anti-QS activity of 168 extracts from 104 Italian plants through quantification of δ-hemolysin. Extracts from three medicinal plants (Ballota nigra, Castanea sativa, and Sambucus ebulus) exhibited a dose-dependent response in the production of δ-hemolysin, indicating strong anti-QS activity in a pathogenic MRSA isolate. PMID:20645243

  1. Modeling a synthetic multicellular clock: Repressilators coupled by quorum sensing

    NASA Astrophysics Data System (ADS)

    Garcia-Ojalvo, Jordi; Elowitz, Michael B.; Strogatz, Steven H.

    2004-07-01

    Diverse biochemical rhythms are generated by thousands of cellular oscillators that somehow manage to operate synchronously. In fields ranging from circadian biology to endocrinology, it remains an exciting challenge to understand how collective rhythms emerge in multicellular structures. Using mathematical and computational modeling, we study the effect of coupling through intercell signaling in a population of Escherichia coli cells expressing a synthetic biological clock. Our results predict that a diverse and noisy community of such genetic oscillators interacting through a quorum-sensing mechanism should self-synchronize in a robust way, leading to a substantially improved global rhythmicity in the system. As such, the particular system of coupled genetic oscillators considered here might be a good candidate to provide the first quantitative example of a synchronization transition in a population of biological oscillators.

  2. Quorum sensing activity of Hafnia alvei isolated from packed food.

    PubMed

    Tan, Jia-Yi; Yin, Wai-Fong; Chan, Kok-Gan

    2014-01-01

    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. PMID:24736131

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

    NASA Astrophysics Data System (ADS)

    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. Studying bacterial quorum-sensing at the single cell level

    NASA Astrophysics Data System (ADS)

    Delfino Perez, Pablo; Pelakh, Leslie; Young, Jonathan; Johnson, Elaine; Hagen, Stephen

    2010-03-01

    Like many bacterial species, Vibrio fischeri can detect its own population density through a quorum sensing (QS) mechanism. The bacterium releases a signal molecule (AI, autoinducer), which accumulates at high population density and triggers a genetic switch. In V.fischeri this leads to bioluminescence. Little is known about how stochastic gene expression affects QS at the level of single cells. We are imaging the luminescence of individual V.fischeri cells in a flow chamber and directly measuring the intercell variability in AI activation of the QS circuit. Our single-cell luminescence experiments allow us to track cells over time and characterize variations in their response to AI levels. We find heterogeneous response to the external signal: at a given AI concentration some cells may be strongly luminescent while others are virtually dark. The analysis of noise in the individual cell response can eventually lead to a better understanding of how cells use QS to gather information about their environment.

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

    PubMed

    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. PMID:27483473

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

    PubMed Central

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

    2016-01-01

    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. PMID:27483473

  7. More than a signal: non-signaling properties of quorum sensing molecules.

    PubMed

    Schertzer, Jeffrey W; Boulette, Megan L; Whiteley, Marvin

    2009-05-01

    Quorum sensing in bacteria serves as an example of the adaptation of single-celled organisms to engage in cooperative group behaviors. This phenomenon is much more widespread than originally thought, with many different species 'speaking' through various secreted small molecules. Despite some variation in signaling molecules, the principles of quorum sensing are conserved across a wide range of organisms. Small molecules, secreted into the environment, are detected by neighbors who respond by altering gene expression and, as a consequence, behavior. However, it is not known whether these systems evolved specifically for this purpose, or even if their role is exclusive to information trafficking. Rather, clues exist that many quorum sensing molecules function as more than just signals. Here, we discuss non-signaling roles for quorum sensing molecules in such important processes as nutrient scavenging, ultrastructure modification and competition.

  8. Analysis of Quorum-Sensing Pantoea stewartii Strain M073A through Whole-Genome Sequencing.

    PubMed

    Izzati Mohamad, Nur; Tan, Wen-Si; Chang, Chien-Yi; Keng Tee, Kok; Yin, Wai-Fong; Chan, Kok-Gan

    2015-01-01

    Pantoea stewartii strain M073a is a Gram-negative bacterium isolated from a tropical waterfall. This strain exhibits quorum-sensing activity. Here, the assembly and annotation of its genome are presented. PMID:25700398

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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

    2015-04-01

    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.

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

    PubMed Central

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

    2013-01-01

    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. PMID:23669710

  12. The plant pathogen Pantoea ananatis produces N-acylhomoserine lactone and causes center rot disease of onion by quorum sensing.

    PubMed

    Morohoshi, Tomohiro; Nakamura, Yuta; Yamazaki, Go; Ishida, Akio; Kato, Norihiro; Ikeda, Tsukasa

    2007-11-01

    A number of gram-negative bacteria have a quorum-sensing system and produce N-acyl-l-homoserine lactone (AHL) that they use them as a quorum-sensing signal molecule. Pantoea ananatis is reported as a common colonist of wheat heads at ripening and causes center rot of onion. In this study, we demonstrated that P. ananatis SK-1 produced two AHLs, N-hexanoyl-l-homoserine lactone (C6-HSL) and N-(3-oxohexanoyl)-l-homoserine lactone (3-oxo-C6-HSL). We cloned the AHL-synthase gene (eanI) and AHL-receptor gene (eanR) and revealed that the deduced amino acid sequence of EanI/EanR showed high identity to those of EsaI/EsaR from P. stewartii. EanR repressed the ean box sequence and the addition of AHLs resulted in derepression of ean box. Inactivation of the chromosomal eanI gene in SK-1 caused disruption of exopolysaccharide (EPS) biosynthesis, biofilm formation, and infection of onion leaves, which were recovered by adding exogenous 3-oxo-C6-HSL. These results demonstrated that the quorum-sensing system involved the biosynthesis of EPS, biofilm formation, and infection of onion leaves in P. ananatis SK-1.

  13. The natural antimicrobial carvacrol inhibits quorum sensing in Chromobacterium violaceum and reduces bacterial biofilm formation at sub-lethal concentrations.

    PubMed

    Burt, Sara A; Ojo-Fakunle, Victoria T A; Woertman, Jenifer; Veldhuizen, Edwin J A

    2014-01-01

    The formation of biofilm by bacteria confers resistance to biocides and presents problems in medical and veterinary clinical settings. Here we report the effect of carvacrol, one of the major antimicrobial components of oregano oil, on the formation of biofilms and its activity on existing biofilms. Assays were carried out in polystyrene microplates to observe (a) the effect of 0-0.8 mM carvacrol on the formation of biofilms by selected bacterial pathogens over 24 h and (b) the effect of 0-8 mM carvacrol on the stability of pre-formed biofilms. Carvacrol was able to inhibit the formation of biofilms of Chromobacterium violaceum ATCC 12472, Salmonella enterica subsp. Typhimurium DT104, and Staphylococcus aureus 0074, while it showed no effect on formation of Pseudomonas aeruginosa (field isolate) biofilms. This inhibitory effect of carvacrol was observed at sub-lethal concentrations (<0.5 mM) where no effect was seen on total bacterial numbers, indicating that carvacrol's bactericidal effect was not causing the observed inhibition of biofilm formation. In contrast, carvacrol had (up to 8 mM) very little or no activity against existing biofilms of the bacteria described, showing that formation of the biofilm also confers protection against this compound. Since quorum sensing is an essential part of biofilm formation, the effect of carvacrol on quorum sensing of C. violaceum was also studied. Sub-MIC concentrations of carvacrol reduced expression of cviI (a gene coding for the N-acyl-L-homoserine lactone synthase), production of violacein (pigmentation) and chitinase activity (both regulated by quorum sensing) at concentrations coinciding with carvacrol's inhibiting effect on biofilm formation. These results indicate that carvacrol's activity in inhibition of biofilm formation may be related to the disruption of quorum sensing.

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

    PubMed Central

    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. PMID:26904007

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

    PubMed

    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.

  16. Resilience of bacterial quorum sensing against fluid flow.

    PubMed

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

    2016-01-01

    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. PMID:27650454

  17. Mathematical Modelling of Bacterial Quorum Sensing: A Review.

    PubMed

    Pérez-Velázquez, Judith; Gölgeli, Meltem; García-Contreras, Rodolfo

    2016-08-01

    Bacterial quorum sensing (QS) refers to the process of cell-to-cell bacterial communication enabled through the production and sensing of the local concentration of small molecules called autoinducers to regulate the production of gene products (e.g. enzymes or virulence factors). Through autoinducers, bacteria interact with individuals of the same species, other bacterial species, and with their host. Among QS-regulated processes mediated through autoinducers are aggregation, biofilm formation, bioluminescence, and sporulation. Autoinducers are therefore "master" regulators of bacterial lifestyles. For over 10 years, mathematical modelling of QS has sought, in parallel to experimental discoveries, to elucidate the mechanisms regulating this process. In this review, we present the progress in mathematical modelling of QS, highlighting the various theoretical approaches that have been used and discussing some of the insights that have emerged. Modelling of QS has benefited almost from the onset of the involvement of experimentalists, with many of the papers which we review, published in non-mathematical journals. This review therefore attempts to give a broad overview of the topic to the mathematical biology community, as well as the current modelling efforts and future challenges. PMID:27561265

  18. Resilience of bacterial quorum sensing against fluid flow

    NASA Astrophysics Data System (ADS)

    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.

  19. A crucial role for spatial distribution in bacterial quorum sensing

    PubMed Central

    Gao, Meng; Zheng, Huizhen; Ren, Ying; Lou, Ruyun; Wu, Fan; Yu, Weiting; Liu, Xiudong; Ma, Xiaojun

    2016-01-01

    Quorum sensing (QS) is a process that enables bacteria to communicate using secreted signaling molecules, and then makes a population of bacteria to regulate gene expression collectively and control behavior on a community-wide scale. Theoretical studies of efficiency sensing have suggested that both mass-transfer performance in the local environment and the spatial distribution of cells are key factors affecting QS. Here, an experimental model based on hydrogel microcapsules with a three-dimensional structure was established to investigate the influence of the spatial distribution of cells on bacterial QS. Vibrio harveyi cells formed different spatial distributions in the microcapsules, i.e., they formed cell aggregates with different structures and sizes. The cell aggregates displayed stronger QS than did unaggregated cells even when equal numbers of cells were present. Large aggregates (LA) of cells, with a size of approximately 25 μm, restricted many more autoinducers (AIs) than did small aggregates (SA), with a size of approximately 10 μm, thus demonstrating that aggregate size significantly affects QS. These findings provide a powerful demonstration of the fact that the spatial distribution of cells plays a crucial role in bacterial QS. PMID:27698391

  20. Resilience of bacterial quorum sensing against fluid flow

    PubMed Central

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

    2016-01-01

    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. PMID:27650454

  1. Impacts of quorum sensing on microbial metabolism and human health.

    PubMed

    Yong, Yang-Chun; Zhong, Jian-Jiang

    2013-01-01

    Bacteria were considered to be lonely 'mutes' for hundreds of years. However, recently it was found that bacteria usually coordinate their behaviors at the population level by producing (speaking), sensing (listening), and responding to small signal molecules. This so-called quorum sensing (QS) regulation enables bacteria to live in a 'society' with cell-cell communication and controls many important bacterial behaviors. In this chapter, QS systems and their signal molecules for Gram-negative and Gram-positive bacteria are introduced. Most interestingly, QS regulates the important bacterial behaviors such as metabolism and pathogenesis. QS-regulated microbial metabolism includes antibiotic synthesis, pollutant biodegradation, and bioenergy production, which are very relevant to human health. QS is also well-known for its involvement in bacterial pathogenesis, such as iin nfections by Pseudomonas aeruginosa and Staphylococcus aureus. Novel disease diagnosis strategies and antimicrobial agents have also been developed based on QS regulation on bacterial infections. In addition, to meet the requirements for the detection/quantification of QS signaling molecules for research and application, different biosensors have been constructed, which will also be reviewed here. QS regulation is essential to bacterial survival and important to human health. A better understanding of QS could lead better control/manipulation of bacteria, thus making them more helpful to people.

  2. Cooperation, quorum sensing, and evolution of virulence in Staphylococcus aureus.

    PubMed

    Pollitt, Eric J G; West, Stuart A; Crusz, Shanika A; Burton-Chellew, Maxwell N; Diggle, Stephen P

    2014-03-01

    The virulence and fitness in vivo of the major human pathogen Staphylococcus aureus are associated with a cell-to-cell signaling mechanism known as quorum sensing (QS). QS coordinates the production of virulence factors via the production and sensing of autoinducing peptide (AIP) signal molecules by the agr locus. Here we show, in a wax moth larva virulence model, that (i) QS in S. aureus is a cooperative social trait that provides a benefit to the local population of cells, (ii) agr mutants, which do not produce or respond to QS signal, are able to exploit the benefits provided by the QS of others ("cheat"), allowing them to increase in frequency when in mixed populations with cooperators, (iii) these social interactions between cells determine virulence, with the host mortality rate being negatively correlated to the percentage of agr mutants ("cheats") in a population, and (iv) a higher within-host relatedness (lower strain diversity) selects for QS and hence higher virulence. Our results provide an explanation for why agr mutants show reduced virulence in animal models but can be isolated from infections of humans. More generally, by providing the first evidence that QS is a cooperative social behavior in a Gram-positive bacterium, our results suggest convergent, and potentially widespread, evolution for signaling to coordinate cooperation in bacteria. PMID:24343650

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

    PubMed Central

    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

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

    PubMed

    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

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

    PubMed

    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

  6. Quorum sensing enhancement of the stress response promotes resistance to quorum quenching and prevents social cheating.

    PubMed

    García-Contreras, Rodolfo; Nuñez-López, Leslie; Jasso-Chávez, Ricardo; Kwan, Brian W; Belmont, Javier A; Rangel-Vega, Adrián; Maeda, Toshinari; Wood, Thomas K

    2015-01-01

    Quorum sensing (QS) coordinates the expression of virulence factors and allows bacteria to counteract the immune response, partly by increasing their tolerance to the oxidative stress generated by immune cells. Despite the recognized role of QS in enhancing the oxidative stress response, the consequences of this relationship for the bacterial ecology remain unexplored. Here we demonstrate that QS increases resistance also to osmotic, thermal and heavy metal stress. Furthermore a QS-deficient lasR rhlR mutant is unable to exert a robust response against H2O2 as it has less induction of catalase and NADPH-producing dehydrogenases. Phenotypic microarrays revealed that the mutant is very sensitive to several toxic compounds. As the anti-oxidative enzymes are private goods not shared by the population, only the individuals that produce them benefit from their action. Based on this premise, we show that in mixed populations of wild-type and the mexR mutant (resistant to the QS inhibitor furanone C-30), treatment with C-30 and H2O2 increases the proportion of mexR mutants; hence, oxidative stress selects resistance to QS compounds. In addition, oxidative stress alone strongly selects for strains with active QS systems that are able to exert a robust anti oxidative response and thereby decreases the proportion of QS cheaters in cultures that are otherwise prone to invasion by cheats. As in natural environments stress is omnipresent, it is likely that this QS enhancement of stress tolerance allows cells to counteract QS inhibition and invasions by social cheaters, therefore having a broad impact in bacterial ecology.

  7. Identification of quorum sensing-controlled genes in Burkholderia ambifaria

    PubMed Central

    Chapalain, Annelise; Vial, Ludovic; Laprade, Natacha; Dekimpe, Valérie; Perreault, Jonathan; Déziel, Eric

    2013-01-01

    The Burkholderia cepacia complex (Bcc) comprises strains with a virulence potential toward immunocompromised patients as well as plant growth–promoting rhizobacteria (PGPR). Owing to the link between quorum sensing (QS) and virulence, most studies among Bcc species have been directed toward QS of pathogenic bacteria. We have investigated the QS of B. ambifaria, a PGPR only infrequently recovered from patients. The cepI gene, responsible for the synthesis of the main signaling molecule N-octanoylhomoserine lactone (C8-HSL), was inactivated. Phenotypes of the B. ambifaria cepI mutant we observed, such as increased production of siderophores and decreased proteolytic and antifungal activities, are in agreement with those of other Bcc cepI mutants. The cepI mutant was then used as background strain for a whole-genome transposon-insertion mutagenesis strategy, allowing the identification of 20 QS-controlled genes, corresponding to 17 loci. The main functions identified are linked to antifungal and antimicrobial properties, as we have identified QS-controlled genes implicated in the production of pyrrolnitrin, burkholdines (occidiofungin-like molecules), and enacyloxins. This study provides insights in the QS-regulated functions of a PGPR, which could lead to beneficial potential biotechnological applications. PMID:23382083

  8. Quorum sensing and social networking in the microbial world

    PubMed Central

    Atkinson, Steve; Williams, Paul

    2009-01-01

    For many years, bacterial cells were considered primarily as selfish individuals, but, in recent years, it has become evident that, far from operating in isolation, they coordinate collective behaviour in response to environmental challenges using sophisticated intercellular communication networks. Cell-to-cell communication between bacteria is mediated by small diffusible signal molecules that trigger changes in gene expression in response to fluctuations in population density. This process, generally referred to as quorum sensing (QS), controls diverse phenotypes in numerous Gram-positive and Gram-negative bacteria. Recent advances have revealed that bacteria are not limited to communication within their own species but are capable of ‘listening in’ and ‘broadcasting to’ unrelated species to intercept messages and coerce cohabitants into behavioural modifications, either for the good of the population or for the benefit of one species over another. It is also evident that QS is not limited to the bacterial kingdom. The study of two-way intercellular signalling networks between bacteria and both uni- and multicellular eukaryotes as well as between eukaryotes is just beginning to unveil a rich diversity of communication pathways. PMID:19674996

  9. Specificity and complexity in bacterial quorum-sensing systems

    PubMed Central

    Hawver, Lisa A.; Jung, Sarah A.; Ng, Wai-Leung

    2016-01-01

    Quorum sensing (QS) is a microbial cell-to-cell communication process that relies on the production and detection of chemical signals called autoinducers (AIs) to monitor cell density and species complexity in the population. QS allows bacteria to behave as a cohesive group and coordinate collective behaviors. While most QS receptors display high specificity to their AI ligands, others are quite promiscuous in signal detection. How do specific QS receptors respond to their cognate signals with high fidelity? Why do some receptors maintain low signal recognition specificity? In addition, many QS systems are composed of multiple intersecting signaling pathways: what are the benefits of preserving such a complex signaling network when a simple linear ‘one-to-one’ regulatory pathway seems sufficient to monitor cell density? Here, we will discuss different molecular mechanisms employed by various QS systems that ensure productive and specific QS responses. Moreover, the network architectures of some well-characterized QS circuits will be reviewed to understand how the wiring of different regulatory components achieves different biological goals. PMID:27354348

  10. Quorum-sensing and cheating in bacterial biofilms

    PubMed Central

    Popat, Roman; Crusz, Shanika A.; Messina, Marco; Williams, Paul; West, Stuart A.; Diggle, Stephen P.

    2012-01-01

    The idea from human societies that self-interest can lead to a breakdown of cooperation at the group level is sometimes termed the public goods dilemma. We tested this idea in the opportunistic bacterial pathogen, Pseudomonas aeruginosa, by examining the influence of putative cheats that do not cooperate via cell-to-cell signalling (quorum-sensing, QS). We found that: (i) QS cheating occurs in biofilm populations owing to exploitation of QS-regulated public goods; (ii) the thickness and density of biofilms was reduced by the presence of non-cooperative cheats; (iii) population growth was reduced by the presence of cheats, and this reduction was greater in biofilms than in planktonic populations; (iv) the susceptibility of biofilms to antibiotics was increased by the presence of cheats; and (v) coercing cooperator cells to increase their level of cooperation decreases the extent to which the presence of cheats reduces population productivity. Our results provide clear support that conflict over public goods reduces population fitness in bacterial biofilms, and that this effect is greater than in planktonic populations. Finally, we discuss the clinical implications that arise from altering the susceptibility to antibiotics. PMID:23034707

  11. Antibodies to Streptococcus pneumoniae Capsular Polysaccharide Enhance Pneumococcal Quorum Sensing

    PubMed Central

    Yano, Masahide; Gohil, Shruti; Coleman, J. Robert; Manix, Catherine; Pirofski, Liise-anne

    2011-01-01

    ABSTRACT The use of pneumococcal capsular polysaccharide (PPS)-based vaccines has resulted in a substantial reduction in invasive pneumococcal disease. However, much remains to be learned about vaccine-mediated immunity, as seven-valent PPS-protein conjugate vaccine use in children has been associated with nonvaccine serotype replacement and 23-valent vaccine use in adults has not prevented pneumococcal pneumonia. In this report, we demonstrate that certain PPS-specific monoclonal antibodies (MAbs) enhance the transformation frequency of two different Streptococcus pneumoniae serotypes. This phenomenon was mediated by PPS-specific MAbs that agglutinate but do not promote opsonic effector cell killing of the homologous serotype in vitro. Compared to the autoinducer, competence-stimulating peptide (CSP) alone, transcriptional profiling of pneumococcal gene expression after incubation with CSP and one such MAb to the PPS of serotype 3 revealed changes in the expression of competence (com)-related and bacteriocin-like peptide (blp) genes involved in pneumococcal quorum sensing. This MAb was also found to induce a nearly 2-fold increase in CSP2-mediated bacterial killing or fratricide. These observations reveal a novel, direct effect of PPS-binding MAbs on pneumococcal biology that has important implications for antibody immunity to pneumococcus in the pneumococcal vaccine era. Taken together, our data suggest heretofore unsuspected mechanisms by which PPS-specific antibodies could affect genetic exchange and bacterial viability in the absence of host cells. PMID:21917597

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

    PubMed

    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.

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

    PubMed Central

    Lang, Julien; Faure, Denis

    2014-01-01

    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 20 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. PMID:24550924

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

    PubMed

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

    2016-01-01

    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. PMID:27571752

  15. Quorum Sensing in Some Representative Species of Halomonadaceae

    PubMed Central

    Tahrioui, Ali; Schwab, Melanie; Quesada, Emilia; Llamas, Inmaculada

    2013-01-01

    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. PMID:25371343

  16. Quorum sensing inhibitors as anti-biofilm agents.

    PubMed

    Brackman, Gilles; Coenye, Tom

    2015-01-01

    Biofilms are microbial sessile communities characterized by cells that are attached to a substratum or interface or to each other, are embedded in a self-produced matrix of extracellular polymeric substances and exhibit an altered phenotype compared to planktonic cells. Biofilms are estimated to be associated with 80% of microbial infections and it is currently common knowledge that growth of micro-organisms in biofilms can enhance their resistance to antimicrobial agents. As a consequence antimicrobial therapy often fails to eradicate biofilms from the site of infection. For this reason, innovative anti-biofilm agents with novel targets and modes of action are needed. One alternative approach is targeting the bacterial communication system (quorum sensing, QS). QS is a process by which bacteria produce and detect signal molecules and thereby coordinate their behavior in a cell-density dependent manner. Three main QS systems can be distinguished: the acylhomoserine lactone (AHL) QS system in Gram-negative bacteria, the autoinducing peptide (AIP) QS system in Gram-positive bacteria and the autoinducer-2 (AI-2) QS system in both Gram-negative and -positive bacteria. Although much remains to be learned about the involvement of QS in biofilm formation, maintenance, and dispersal, QS inhibitors (QSI) have been proposed as promising antibiofilm agents. In this article we will give an overview of QS inhibitors which have been shown to play a role in biofilm formation and/or maturation. PMID:25189863

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

    PubMed

    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.

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

    PubMed

    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.

  19. Local and Global Consequences of Flow on Bacterial Quorum Sensing

    PubMed Central

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

    2016-01-01

    Bacteria use a chemical communication process called quorum sensing (QS) to control collective behaviours, such as pathogenesis and biofilm formation1,2. 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 QS3. Although flow is ubiquitous to nearly all living systems4, 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 have showed that sufficiently strong flow represses QS5–7. 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. PMID:27571752

  20. Quorum-sensing Salmonella selectively trigger protein expression within tumors

    PubMed Central

    Swofford, Charles A.; Van Dessel, Nele; Forbes, Neil S.

    2015-01-01

    Salmonella that secrete anticancer proteins have the potential to eliminate tumors, but nonspecific expression causes damage to healthy tissue. We hypothesize that Salmonella, integrated with a density-dependent switch, would only express proteins in tightly packed colonies within tumors. To test this hypothesis, we cloned the lux quorum-sensing (QS) system and a GFP reporter into nonpathogenic Salmonella. Fluorescence and bacterial density were measured in culture and in a tumor-on-a-chip device to determine the critical density necessary to initiate expression. QS Salmonella were injected into 4T1 tumor-bearing mice to quantify GFP expression in vivo using immunofluorescence. At densities below 0.6 × 1010 cfu/g in tumors, less than 3% of QS Salmonella expressed GFP. Above densities of 4.2 × 1010 cfu/g, QS Salmonella had similar expression levels to constitutive controls. GFP expression by QS colonies was dependent upon the distance to neighboring bacteria. No colonies expressed GFP when the average distance to neighbors was greater than 155 µm. Calculations of autoinducer concentrations showed that expression was sigmoidally dependent on density and inversely dependent on average radial distance. Based on bacterial counts from excised tissue, the liver density (0.0079 × 1010 cfu/g) was less than the critical density (0.11 × 1010 cfu/g) necessary to initiate expression. QS Salmonella are a promising tool for cancer treatment that will target drugs to tumors while preventing damage to healthy tissue. PMID:25737556

  1. The fitness burden imposed by synthesising quorum sensing signals

    PubMed Central

    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.

    2016-01-01

    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. PMID:27616328

  2. Mycofabricated biosilver nanoparticles interrupt Pseudomonas aeruginosa quorum sensing systems.

    PubMed

    Singh, Braj R; Singh, Brahma N; Singh, Akanksha; Khan, Wasi; Naqvi, Alim H; Singh, Harikesh B

    2015-01-01

    Quorum sensing (QS) is a chemical communication process that Pseudomonas aeruginosa uses to regulate virulence and biofilm formation. Disabling of QS is an emerging approach for combating its pathogenicity. Silver nanoparticles (AgNPs) have been widely applied as antimicrobial agents against human pathogenic bacteria and fungi, but not for the attenuation of bacterial QS. Here we mycofabricated AgNPs (mfAgNPs) using metabolites of soil fungus Rhizopus arrhizus BRS-07 and tested their effect on QS-regulated virulence and biofilm formation of P. aeruginosa. Transcriptional studies demonstrated that mfAgNPs reduced the levels of LasIR-RhlIR. Treatment of mfAgNPs inhibited biofilm formation, production of several virulence factors (e.g. LasA protease, LasB elastrase, pyocyanin, pyoverdin, pyochelin, rhamnolipid, and alginate) and reduced AHLs production. Further genes quantification analyses revealed that mfAgNPs significantly down-regulated QS-regulated genes, specifically those encoded to the secretion of virulence factors. The results clearly indicated the anti-virulence property of mfAgNPs by inhibiting P. aeruginosa QS signaling. PMID:26347993

  3. Mycofabricated biosilver nanoparticles interrupt Pseudomonas aeruginosa quorum sensing systems

    PubMed Central

    Singh, Braj R.; Singh, Brahma N.; Singh, Akanksha; Khan, Wasi; Naqvi, Alim H.; Singh, Harikesh B.

    2015-01-01

    Quorum sensing (QS) is a chemical communication process that Pseudomonas aeruginosa uses to regulate virulence and biofilm formation. Disabling of QS is an emerging approach for combating its pathogenicity. Silver nanoparticles (AgNPs) have been widely applied as antimicrobial agents against human pathogenic bacteria and fungi, but not for the attenuation of bacterial QS. Here we mycofabricated AgNPs (mfAgNPs) using metabolites of soil fungus Rhizopus arrhizus BRS-07 and tested their effect on QS-regulated virulence and biofilm formation of P. aeruginosa. Transcriptional studies demonstrated that mfAgNPs reduced the levels of LasIR-RhlIR. Treatment of mfAgNPs inhibited biofilm formation, production of several virulence factors (e.g. LasA protease, LasB elastrase, pyocyanin, pyoverdin, pyochelin, rhamnolipid, and alginate) and reduced AHLs production. Further genes quantification analyses revealed that mfAgNPs significantly down-regulated QS-regulated genes, specifically those encoded to the secretion of virulence factors. The results clearly indicated the anti-virulence property of mfAgNPs by inhibiting P. aeruginosa QS signaling. PMID:26347993

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

    PubMed

    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

    2016-01-01

    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. PMID:27616328

  5. Quorum-sensing and cheating in bacterial biofilms.

    PubMed

    Popat, Roman; Crusz, Shanika A; Messina, Marco; Williams, Paul; West, Stuart A; Diggle, Stephen P

    2012-12-01

    The idea from human societies that self-interest can lead to a breakdown of cooperation at the group level is sometimes termed the public goods dilemma. We tested this idea in the opportunistic bacterial pathogen, Pseudomonas aeruginosa, by examining the influence of putative cheats that do not cooperate via cell-to-cell signalling (quorum-sensing, QS). We found that: (i) QS cheating occurs in biofilm populations owing to exploitation of QS-regulated public goods; (ii) the thickness and density of biofilms was reduced by the presence of non-cooperative cheats; (iii) population growth was reduced by the presence of cheats, and this reduction was greater in biofilms than in planktonic populations; (iv) the susceptibility of biofilms to antibiotics was increased by the presence of cheats; and (v) coercing cooperator cells to increase their level of cooperation decreases the extent to which the presence of cheats reduces population productivity. Our results provide clear support that conflict over public goods reduces population fitness in bacterial biofilms, and that this effect is greater than in planktonic populations. Finally, we discuss the clinical implications that arise from altering the susceptibility to antibiotics.

  6. Social conflict drives the evolutionary divergence of quorum sensing.

    PubMed

    Eldar, Avigdor

    2011-08-16

    In microbial "quorum sensing" (QS) communication systems, microbes produce and respond to a signaling molecule, enabling a cooperative response at high cell densities. Many species of bacteria show fast, intraspecific, evolutionary divergence of their QS pathway specificity--signaling molecules activate cognate receptors in the same strain but fail to activate, and sometimes inhibit, those of other strains. Despite many molecular studies, it has remained unclear how a signaling molecule and receptor can coevolve, what maintains diversity, and what drives the evolution of cross-inhibition. Here I use mathematical analysis to show that when QS controls the production of extracellular enzymes--"public goods"--diversification can readily evolve. Coevolution is positively selected by cycles of alternating "cheating" receptor mutations and "cheating immunity" signaling mutations. The maintenance of diversity and the evolution of cross-inhibition between strains are facilitated by facultative cheating between the competing strains. My results suggest a role for complex social strategies in the long-term evolution of QS systems. More generally, my model of QS divergence suggests a form of kin recognition where different kin types coexist in unstructured populations.

  7. Quorum-sensing inhibitors as anti-pathogenic drugs.

    PubMed

    Rasmussen, Thomas B; Givskov, Michael

    2006-04-01

    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 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 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.

  8. Draft Genome Sequence of Aeromonas caviae Strain L12, a Quorum-Sensing Strain Isolated from a Freshwater Lake in Malaysia.

    PubMed

    Chan, Kok-Gan; Chin, Pui-San; Tee, Kok Keng; Chang, Chien-Yi; Yin, Wai-Fong; Sheng, Kit-Yeng

    2015-03-05

    Here, we present the draft genome sequence of Aeromonas caviae strain L12, which shows quorum-sensing activity. The availability of this genome sequence is important to the research of the quorum-sensing regulatory system in this isolate.

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

    NASA Technical Reports Server (NTRS)

    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.

  10. Anti-Quorum Sensing Activity of the Traditional Chinese Herb, Phyllanthus amarus

    PubMed Central

    Priya, Kumutha; Yin, Wai-Fong; Chan, Kok-Gan

    2013-01-01

    The discovery of quorum sensing in Proteobacteria and its function in regulating virulence determinants makes it an attractive alternative towards attenuation of bacterial pathogens. In this study, crude extracts of Phyllanthus amarus Schumach. & Thonn, a traditional Chinese herb, were screened for their anti-quorum sensing properties through a series of bioassays. Only the methanolic extract of P. amarus exhibited anti-quorum sensing activity, whereby it interrupted the ability of Chromobacterium violaceum CVO26 to response towards exogenously supplied N-hexanoylhomoserine lactone and the extract reduced bioluminescence in E. coli [pSB401] and E. coli [pSB1075]. In addition to this, methanolic extract of P. amarus significantly inhibited selected quorum sensing-regulated virulence determinants of Pseudomonas aeruginosa PA01. Increasing concentrations of the methanolic extracts of P. amarus reduced swarming motility, pyocyanin production and P. aeruginosa PA01 lecA∷lux expression. Our data suggest that P. amarus could be useful for attenuating pathogens and hence, more local traditional herbs should be screened for its anti-quorum sensing properties as their active compounds may serve as promising anti-pathogenic drugs. PMID:24169540

  11. Inhibition of bacterial quorum sensing and biofilm formation by extracts of neotropical rainforest plants.

    PubMed

    Ta, Chieu Anh; Freundorfer, Marie; Mah, Thien-Fah; Otárola-Rojas, Marco; Garcia, Mario; Sanchez-Vindas, Pablo; Poveda, Luis; Maschek, J Alan; Baker, Bill J; Adonizio, Allison L; Downum, Kelsey; Durst, Tony; Arnason, John T

    2014-03-01

    Bacterial biofilms are responsible for many persistent infections by many clinically relevant pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa. Biofilms are much more resistant to conventional antibiotics than their planktonic counterparts. Quorum sensing, an intercellular communication system, controls pathogenesis and biofilm formation in most bacterial species. Quorum sensing provides an important pharmacological target since its inhibition does not provide a selective pressure for resistance. In this study, we investigated the quorum sensing and biofilm inhibitory activities of 126 plant extracts from 71 species collected from neotropical rainforests in Costa Rica. Quorum sensing and biofilm interference were assessed using a modified disc diffusion bioassay with Chromobacterium violaceum ATCC 12,472 and a spectrophotometric bioassay with Pseudomonas aeruginosa PA14, respectively. Species with significant anti-quorum sensing and/or anti-biofilm activities belonged to the Meliaceae, Melastomataceae, Lepidobotryaceae, Sapindaceae, and Simaroubaceae families. IC50 values ranged from 45 to 266 µg/mL. Extracts of these active species could lead to future development of botanical treatments for biofilm-associated infections. PMID:24488718

  12. Quorum sensing: How bacteria can coordinate activity and synchronize their response to external signals?

    PubMed Central

    Li, Zhi; Nair, Satish K

    2012-01-01

    Quorum sensing is used by a large variety of bacteria to regulate gene expression in a cell-density-dependent manner. Bacteria can synchronize population behavior using small molecules called autoinducers that are produced by cognate synthases and recognized by specific receptors. Quorum sensing plays critical roles in regulating diverse cellular functions in bacteria, including bioluminescence, virulence gene expression, biofilm formation, and antibiotic resistance. The best-studied autoinducers are acyl homoserine lactone (AHL) molecules, which are the primary quorum sensing signals used by Gram-negative bacteria. In this review we focus on the AHL-dependent quorum sensing system and highlight recent progress on structural and mechanistic studies of AHL synthases and the corresponding receptors. Crystal structures of LuxI-type AHL synthases provide insights into acyl-substrate specificity, but the current knowledge is still greatly limited. Structural studies of AHL receptors have facilitated a more thorough understanding of signal perception and established the molecular framework for the development of quorum sensing inhibitors. PMID:22825856

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

    PubMed

    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.

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

    PubMed

    Hentzer, Morten; Riedel, Kathrin; Rasmussen, Thomas B; Heydorn, Arne; Andersen, Jens Bo; Parsek, Matthew R; Rice, Scott A; Eberl, Leo; Molin, Søren; Høiby, Niels; Kjelleberg, Staffan; Givskov, Michael

    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). 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 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 of important virulence factors, indicating a general effect on target genes of the las quorum sensing circuit. The furanone was applied to P. aeruginosa biofilms established in biofilm flow chambers. The Gfp-based analysis reveals that the compound penetrates microcolonies and blocks cell signalling and quorum sensing in most biofilm cells. The compound did not affect initial attachment to the abiotic substratum. It does, however, affect the architecture of the biofilm and enhances the process of bacterial detachment, leading to a loss of bacterial biomass from the substratum.

  15. Food as a Source for Quorum Sensing Inhibitors: Iberin from Horseradish Revealed as a Quorum Sensing Inhibitor of Pseudomonas aeruginosa

    PubMed Central

    Jakobsen, Tim Holm; Bragason, Steinn Kristinn; Phipps, Richard Kerry; Christensen, Louise Dahl; van Gennip, Maria; Alhede, Morten; Skindersoe, Mette; Larsen, Thomas Ostenfeld; Høiby, Niels; Bjarnsholt, Thomas

    2012-01-01

    Foods with health-promoting effects beyond nutritional values have been gaining increasing research focus in recent years, although not much has been published on this subject in relation to bacterial infections. With respect to treatment, a novel antimicrobial strategy, which is expected to transcend problems with selective pressures for antibiotic resistance, is to interrupt bacterial communication, also known as quorum sensing (QS), by means of signal antagonists, the so-called QS inhibitors (QSIs). Furthermore, QSI agents offer a potential solution to the deficiencies associated with use of traditional antibiotics to treat infections caused by bacterial biofilms and multidrug-resistant bacteria. Several QSIs of natural origin have been identified, and in this study, several common food products and plants were extracted and screened for QSI activity in an attempt to isolate and characterize previously unknown QSI compounds active against the common opportunistic pathogen Pseudomonas aeruginosa. Several extracts displayed activity, but horseradish exhibited the highest activity. Chromatographic separation led to the isolation of a potent QSI compound that was identified by liquid chromatography-diode array detector-mass spectrometry (LC-DAD-MS) and nuclear magnetic resonance (NMR) spectroscopy as iberin—an isothiocyanate produced by many members of the Brassicaceae family. Real-time PCR (RT-PCR) and DNA microarray studies showed that iberin specifically blocks expression of QS-regulated genes in P. aeruginosa. PMID:22286987

  16. Molecular Basis for the Recognition of Structurally Distinct Autoinducer Mimics by the Pseudomonas aeruginosa LasR Quorum-Sensing Signaling Receptor

    SciTech Connect

    Zou, Yaozhong; Nair, Satish K.

    2010-01-12

    The human pathogen Pseudomonas aeruginosa coordinates the expression of virulence factors using quorum sensing, a signaling cascade triggered by the activation of signal receptors by small-molecule autoinducers. These homoserine lactone autoinducers stabilize their cognate receptors and activate their functions as transcription factors. Because quorum sensing regulates the progression of infection and host immune resistance, significant efforts have been devoted toward the identification of small molecules that disrupt this process. Screening efforts have identified a class of triphenyl compounds that are structurally distinct from the homoserine lactone autoinducer, yet interact specifically and potently with LasR receptor to modulate quorum sensing (Muh et al., 2006a). Here we present the high-resolution crystal structures of the ligand binding domain of LasR in complex with the autoinducer N-3-oxo-dodecanoyl homoserine lactone (1.4 {angstrom} resolution), and with the triphenyl mimics TP-1, TP-3, and TP-4 (to between 1.8 {angstrom} and 2.3 {angstrom} resolution). These crystal structures provide a molecular rationale for understanding how chemically distinct compounds can be accommodated by a highly selective receptor, and provide the framework for the development of novel quorum-sensing regulators, utilizing the triphenyl scaffold.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  18. Negative regulation of quorum-sensing systems in Pseudomonas aeruginosa by ATP-dependent Lon protease.

    PubMed

    Takaya, Akiko; Tabuchi, Fumiaki; Tsuchiya, Hiroko; Isogai, Emiko; Yamamoto, Tomoko

    2008-06-01

    Lon protease, a member of the ATP-dependent protease family, regulates numerous cellular systems by degrading specific substrates. Here, we demonstrate that Lon is involved in the regulation of quorum-sensing (QS) signaling systems in Pseudomonas aeruginosa, an opportunistic human pathogen. The organism has two acyl-homoserine lactone (HSL)-mediated QS systems, LasR/LasI and RhlR/RhlI. Many reports have demonstrated that these two systems are regulated and interconnected by global regulators. We found that lon-disrupted cells overproduce pyocyanin, the biosynthesis of which depends on the RhlR/RhlI system, and show increased levels of a transcriptional regulator, RhlR. The QS systems are organized hierarchically: the RhlR/RhlI system is subordinate to LasR/LasI. To elucidate the mechanism by which Lon negatively regulates RhlR/RhlI, we examined the effect of lon disruption on the LasR/LasI system. We found that Lon represses the expression of LasR/LasI by degrading LasI, an HSL synthase, leading to negative regulation of the RhlR/RhlI system. RhlR/RhlI was also shown to be regulated by Lon independently of LasR/LasI via regulation of RhlI, an HSL synthase. In view of these findings, it is suggested that Lon protease is a powerful negative regulator of both HSL-mediated QS systems in P. aeruginosa.

  19. A metabolic regulator modulates virulence and quorum sensing signal production in Pectobacterium atrosepticum.

    PubMed

    Cubitt, Marion F; Hedley, Peter E; Williamson, Neil R; Morris, Jenny A; Campbell, Emma; Toth, Ian K; Salmond, George P C

    2013-03-01

    Plant cell wall-degrading enzymes (PCWDE) are key virulence determinants in the pathogenesis of the potato pathogen Pectobacterium atrosepticum. In this study, we report the impact on virulence of a transposon insertion mutation in the metJ gene that codes for the repressor of the methionine biosynthesis regulon. In a mutant strain defective for the small regulatory RNA rsmB, PCWDE are not produced and virulence in potato tubers is almost totally abolished. However, when the metJ gene is disrupted in this background, the rsmB(-) phenotype is suppressed and virulence and PCWDE production are restored. Additionally, when metJ is disrupted, production of the quorum-sensing signal, N-(3-oxohexanoyl)-homoserine lactone, is increased. The metJ mutant strains showed pleiotropic transcriptional impacts affecting approximately a quarter of the genome. Genes involved in methionine biosynthesis were most highly upregulated but many virulence-associated transcripts were also upregulated. This is the first report of the impact of the MetJ repressor on virulence in bacteria.

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

    PubMed

    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.

  1. Quorum Sensing Controls Swarming Motility of Burkholderia glumae through Regulation of Rhamnolipids.

    PubMed

    Nickzad, Arvin; Lépine, François; Déziel, Eric

    2015-01-01

    Burkholderia glumae is a plant pathogenic bacterium that uses an acyl-homoserine lactone-mediated quorum sensing system to regulate protein secretion, oxalate production and major virulence determinants such as toxoflavin and flagella. B. glumae also releases surface-active rhamnolipids. In Pseudomonas aeruginosa and Burkholderia thailandensis, rhamnolipids, along with flagella, are required for the social behavior called swarming motility. In the present study, we demonstrate that quorum sensing positively regulates the production of rhamnolipids in B. glumae and that rhamnolipids are necessary for swarming motility also in this species. We show that a rhlA- mutant, which is unable to produce rhamnolipids, loses its ability to swarm, and that this can be complemented by providing exogenous rhamnolipids. Impaired rhamnolipid production in a quorum sensing-deficient B. glumae mutant is the main factor responsible for its defective swarming motility behaviour. PMID:26047513

  2. The effect of the chemical, biological, and physical environment on quorum sensing in structured microbial communities

    PubMed Central

    Horswill, Alexander R.; Stoodley, Paul; Stewart, Philip S.

    2006-01-01

    As researchers attempt to study quorum sensing in relevant clinical or environmental settings, it is apparent that many factors have the potential to affect signaling. These factors span a range of physical, chemical, and biological variables that can impact signal production, stability and distribution. Optimizing experimental systems to natural or clinical environments may be crucial for defining when and where quorum sensing occurs. These points are illustrated in our case study of S. aureus signaling in biofilms, where signal stability may be affected by the host environment. The basic signaling schemes have been worked out at the molecular level for a few of the major quorum-sensing systems. As these studies continue to refine our understanding of these mechanisms, an emerging challenge is to identify if and when the local environment can affect signaling. PMID:17047948

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

    NASA Astrophysics Data System (ADS)

    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.

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

    NASA Astrophysics Data System (ADS)

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

    PubMed Central

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

    2016-01-01

    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. PMID:26787913

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

    PubMed

    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.

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

    PubMed

    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. PMID:26787913

  8. Colostrum hexasaccharide, a novel Staphylococcus aureus quorum-sensing inhibitor.

    PubMed

    Srivastava, A; Singh, B N; Deepak, D; Rawat, A K S; Singh, B R

    2015-04-01

    The discovery of quorum-sensing (QS) systems regulating antibiotic resistance and virulence factors (VFs) has afforded a novel opportunity to prevent bacterial pathogenicity. Dietary molecules have been demonstrated to attenuate QS circuits of bacteria. But, to our knowledge, no study exploring the potential of colostrum hexasaccharide (CHS) in regulating QS systems has been published. In this study, we analyzed CHS for inhibiting QS signaling in Staphylococcus aureus. We isolated and characterized CHS from mare colostrum by high-performance thin-layer chromatography (HPTLC), reverse-phase high-performance liquid chromatography evaporative light-scattering detection (RP-HPLC-ELSD), (1)H and (13)C nuclear magnetic resonance (NMR), and electrospray ionization mass spectrometry (ESI-MS). Antibiofilm activity of CHS against S. aureus and its possible interference with bacterial QS systems were determined. The inhibition and eradication potentials of the biofilms were studied by microscopic analyses and quantified by 96-well-microtiter-plate assays. Also, the ability of CHS to interfere in bacterial QS by degrading acyl-homoserine lactones (AHLs), one of the most studied signal molecules for Gram-negative bacteria, was evaluated. The results revealed that CHS exhibited promising inhibitory activities against QS-regulated secretion of VFs, including spreading ability, hemolysis, protease, and lipase activities, when applied at a rate of 5 mg/ml. The results of biofilm experiments indicated that CHS is a strong inhibitor of biofilm formation and also has the ability to eradicate it. The potential of CHS to interfere with bacterial QS systems was also examined by degradation of AHLs. Furthermore, it was documented that CHS decreased antibiotic resistance in S. aureus. The results thus give a lead that mare colostrum can be a promising source for isolating a next-generation antibacterial. PMID:25645850

  9. Anti-quorum sensing potential of Adenanthera pavonina

    PubMed Central

    Vasavi, Halkare Suryanarayana; Arun, Ananthapadmanabha Bhagwath; Rekha, Punchappady-Devasya

    2015-01-01

    Background: Quorum sensing (QS) in Pseudomonas aeruginosa plays a key role in virulence factor production, biofilm formation and antimicrobial resistance. Because of emerging antimicrobial resistance in P. aeruginosa, there is a need to find an alternate nonantibiotic agent for the control of infections caused by this organism. Objective: To evaluate anti-QS activity of Adenanthera pavonina L., a medicinal plant used in traditional medicine. Materials and Methods: Preliminary screening for anti-QS activity of ethanol extract of A. pavonina was carried out using Chromobacterium violaceum CV026 biosensor strain and inhibition of QS-regulated violacein production was quantified using C. violaceum ATCC12472. Bioassay guided fractionation of ethanol extract resulted in ethyl acetate fraction (AEF) with strong anti-QS activity and AEF was evaluated for inhibition of QS-regulated pyocyanin production, proteolytic, elastolytic activity, swarming motility and biofilm formation in P. aeruginosa PAO1. Results: AEF, at 0.5 mg/ml, inhibited pyocyanin production completely and at 1 mg/ml of AEF, complete inhibition of proteolytic and elastolytic activities were observed. However, viability of P. aeruginosa PAO1 was not affected at the tested concentrations of AEF as observed by cell count. Swarming motility was inhibited at the concentration of 0.1 mg/ml of AEF. Thin layer chromatography and biosensor overlay of AEF showed violacein inhibition zone at Rf value 0.63. Conclusion: From the results of this study, it can be concluded that A. pavonina extracts can be used as effective anti-QS agents. PMID:25598643

  10. Quorum Sensing in the Context of Food Microbiology

    PubMed Central

    Skandamis, Panagiotis N.

    2012-01-01

    Food spoilage may be defined as a process that renders a product undesirable or unacceptable for consumption and is the outcome of the biochemical activity of a microbial community that eventually dominates according to the prevailing ecological determinants. Although limited information are reported, this activity has been attributed to quorum sensing (QS). Consequently, the potential role of cell-to-cell communication in food spoilage and food safety should be more extensively elucidated. Such information would be helpful in designing approaches for manipulating these communication systems, thereby reducing or preventing, for instance, spoilage reactions or even controlling the expression of virulence factors. Due to the many reports in the literature on the fundamental features of QS, e.g., chemistry and definitions of QS compounds, in this minireview, we only allude to the types and chemistry of QS signaling molecules per se and to the (bioassay-based) methods of their detection and quantification, avoiding extensive documentation. Conversely, we attempt to provide insights into (i) the role of QS in food spoilage, (ii) the factors that may quench the activity of QS in foods and review the potential QS inhibitors that might “mislead” the bacterial coordination of spoilage activities and thus may be used as biopreservatives, and (iii) the future experimental approaches that need to be undertaken in order to explore the “gray” or “black” areas of QS, increase our understanding of how QS affects microbial behavior in foods, and assist in finding answers as to how we can exploit QS for the benefit of food preservation and food safety. PMID:22706047

  11. Colostrum Hexasaccharide, a Novel Staphylococcus aureus Quorum-Sensing Inhibitor

    PubMed Central

    Srivastava, A.; Deepak, D.; Singh, B. R.

    2015-01-01

    The discovery of quorum-sensing (QS) systems regulating antibiotic resistance and virulence factors (VFs) has afforded a novel opportunity to prevent bacterial pathogenicity. Dietary molecules have been demonstrated to attenuate QS circuits of bacteria. But, to our knowledge, no study exploring the potential of colostrum hexasaccharide (CHS) in regulating QS systems has been published. In this study, we analyzed CHS for inhibiting QS signaling in Staphylococcus aureus. We isolated and characterized CHS from mare colostrum by high-performance thin-layer chromatography (HPTLC), reverse-phase high-performance liquid chromatography evaporative light-scattering detection (RP-HPLC-ELSD), 1H and 13C nuclear magnetic resonance (NMR), and electrospray ionization mass spectrometry (ESI-MS). Antibiofilm activity of CHS against S. aureus and its possible interference with bacterial QS systems were determined. The inhibition and eradication potentials of the biofilms were studied by microscopic analyses and quantified by 96-well-microtiter-plate assays. Also, the ability of CHS to interfere in bacterial QS by degrading acyl-homoserine lactones (AHLs), one of the most studied signal molecules for Gram-negative bacteria, was evaluated. The results revealed that CHS exhibited promising inhibitory activities against QS-regulated secretion of VFs, including spreading ability, hemolysis, protease, and lipase activities, when applied at a rate of 5 mg/ml. The results of biofilm experiments indicated that CHS is a strong inhibitor of biofilm formation and also has the ability to eradicate it. The potential of CHS to interfere with bacterial QS systems was also examined by degradation of AHLs. Furthermore, it was documented that CHS decreased antibiotic resistance in S. aureus. The results thus give a lead that mare colostrum can be a promising source for isolating a next-generation antibacterial. PMID:25645850

  12. Quorum-sensing Salmonella selectively trigger protein expression within tumors.

    PubMed

    Swofford, Charles A; Van Dessel, Nele; Forbes, Neil S

    2015-03-17

    Salmonella that secrete anticancer proteins have the potential to eliminate tumors, but nonspecific expression causes damage to healthy tissue. We hypothesize that Salmonella, integrated with a density-dependent switch, would only express proteins in tightly packed colonies within tumors. To test this hypothesis, we cloned the lux quorum-sensing (QS) system and a GFP reporter into nonpathogenic Salmonella. Fluorescence and bacterial density were measured in culture and in a tumor-on-a-chip device to determine the critical density necessary to initiate expression. QS Salmonella were injected into 4T1 tumor-bearing mice to quantify GFP expression in vivo using immunofluorescence. At densities below 0.6 × 10(10) cfu/g in tumors, less than 3% of QS Salmonella expressed GFP. Above densities of 4.2 × 10(10) cfu/g, QS Salmonella had similar expression levels to constitutive controls. GFP expression by QS colonies was dependent upon the distance to neighboring bacteria. No colonies expressed GFP when the average distance to neighbors was greater than 155 µm. Calculations of autoinducer concentrations showed that expression was sigmoidally dependent on density and inversely dependent on average radial distance. Based on bacterial counts from excised tissue, the liver density (0.0079 × 10(10) cfu/g) was less than the critical density (0.11 × 10(10) cfu/g) necessary to initiate expression. QS Salmonella are a promising tool for cancer treatment that will target drugs to tumors while preventing damage to healthy tissue.

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

    PubMed Central

    Paul, Diby

    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. PMID:25147787

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

    PubMed

    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.

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

    PubMed

    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

  16. On the Influence of Quorum Sensing in the Competition Between Bacteria and Immune System of Invertebrates

    NASA Astrophysics Data System (ADS)

    Fergola, Paolo; Zhang, Juan; Cerasuolo, Marianna; Ma, Zhien

    2008-07-01

    The competition between bacteria and innate immune system of invertebrate animals is described by means of ODEs. Two different systems are considered corresponding to the absence or the presence of Quorum Sensing (Q.S.) mechanism. Qualitative properties of the solutions of both systems as well as the stability of their meaningful equilibria are analyzed. By constructing suitable Lyapunov functions, global asymptotic stability results have been proved when the quorum sensing is absent. In order to better illustrate the dynamics of competition, some numerical simulations, obtained by means of MATHEMATICA (Wolfram Research, 1989) are presented.

  17. Inhibition of quorum sensing in Serratia marcescens H30 by molecular regulation.

    PubMed

    Zhu, H; Shen, Y L; Wei, D Z; Zhu, J W

    2008-06-01

    Quorum sensing in Serratia marcescens, which uses two types of signaling molecules-N-acyl homoserine lactones and furanosyl borate diester-play important regulatory roles in the synthesis of 2,3-butanediol and prodigiosin. In the hope of understanding the effect of quorum sensing on physiologic metabolism, we established two molecular strategies, one to express acyl-homoserine lactone hydrolase to inactivate AI-1 signaling molecule using an expression vector with lactose as the inducer and the other to mutate luxS gene with a suicide plasmid pUTKm2 to inhibit the synthesis of AI-2 signaling molecule.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

    Hentzer, Morten; Givskov, Michael

    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 systems), which orchestrate important temporal events during the infection process, has afforded a novel opportunity to ameliorate bacterial infection by means other than growth inhibition. Compounds able to override bacterial signaling are present in nature. Herein we discuss the known signaling 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. PMID:14597754

  1. Choosing an Appropriate Infection Model to Study Quorum Sensing Inhibition in Pseudomonas Infections

    PubMed Central

    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 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. PMID:24065108

  2. Artificially Constructed Quorum-Sensing Circuits Are Used for Subtle Control of Bacterial Population Density

    PubMed Central

    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. PMID:25119347

  3. Quorum sensing and a global regulator TsrA control expression of type VI secretion and virulence in Vibrio cholerae.

    PubMed

    Zheng, Jun; Shin, Ok S; Cameron, D Ewen; Mekalanos, John J

    2010-12-01

    Vibrio cholerae is a human pathogen that causes the life-threatening diarrheal disease cholera. A type VI secretion system (T6SS) was recently shown to be required for full virulence in the O37 serogroup strain V52, which causes only sporadic human disease, but T6SS is not expressed in seventh pandemic O1 El Tor strains under standard laboratory conditions. In this study, we show that in the O1 El Tor strain C6706, T6SS is repressed by both quorum sensing and the uncharacterized protein VC0070 (TsrA). Disruption of TsrA and the quorum sensing regulator LuxO induces expression and secretion of the T6SS substrate Hcp, and this is dependent on the downstream regulator HapR, which directly binds to the promoter region of the T6SS genes hcp1 and hcp2 to induce expression. The activated T6SS in C6706 is functional and can translocate the effector protein VgrG-1 into macrophage cells, and T6SS activation leads to fecal diarrhea and intestinal inflammation in infant rabbits. Using an infant mouse infection model, we show that deletion of tsrA results in a 9.3-fold increase in intestinal colonization compared with wild type. TsrA functions as a global regulator to activate expression of hemagglutinin protease and repress cholera toxin and toxin coregulated pilus. Our findings provide significant insight into the molecular mechanism of T6SS and ToxT regulon gene regulation by quorum sensing and TsrA.

  4. Rosmarinic acid is a homoserine lactone mimic produced by plants that activates a bacterial quorum-sensing regulator.

    PubMed

    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.

  5. Whole-Genome Analysis of Quorum-Sensing Burkholderia sp. Strain A9

    PubMed Central

    Chen, Jian Woon; Tee, Kok Keng; Chang, Chien-Yi; Yin, Wai-Fong; Chan, Xin-Yue

    2015-01-01

    Burkholderia spp. rely on N-acyl homoserine lactone as quorum-sensing signal molecules which coordinate their phenotype at the population level. In this work, we present the whole genome of Burkholderia sp. strain A9, which enables the discovery of its N-acyl homoserine lactone synthase gene. PMID:25745000

  6. Inhibition of Quorum Sensing in Pseudomonas aeruginosa by N-Acyl Cyclopentylamides▿

    PubMed Central

    Ishida, Takenori; Ikeda, Tsukasa; Takiguchi, Noboru; Kuroda, Akio; Ohtake, Hisao; Kato, Junichi

    2007-01-01

    N-Octanoyl cyclopentylamide (C8-CPA) was found to moderately inhibit quorum sensing in Pseudomonas aeruginosa PAO1. To obtain more powerful inhibitors, a series of structural analogs of C8-CPA were synthesized and examined for their ability to inhibit quorum sensing in P. aeruginosa PAO1. The lasB-lacZ and rhlA-lacZ reporter assays revealed that the chain length and the ring structure were critical for C8-CPA analogs to inhibit quorum sensing. N-Decanoyl cyclopentylamide (C10-CPA) was found to be the strongest inhibitor, and its concentrations required for half-maximal inhibition for lasB-lacZ and rhlA-lacZ expression were 80 and 90 μM, respectively. C10-CPA also inhibited production of virulence factors, including elastase, pyocyanin, and rhamnolipid, and biofilm formation without affecting growth of P. aeruginosa PAO1. C10-CPA inhibited induction of both lasI-lacZ by N-(3-oxododecanoyl)-l-homoserine lactone (PAI1) and rhlA-lacZ by N-butanoyl-l-homoserine lactone (PAI2) in the lasI rhlI mutant of P. aeruginosa PAO1, indicating that C10-CPA interferes with the las and rhl quorum-sensing systems via inhibiting interaction between their response regulators (LasR and RhlR) and autoinducers. PMID:17369333

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

    PubMed

    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.

  8. A Mathematical model to investigate quorum sensing regulation and its heterogenecity in pseudomonas syringae on leaves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  9. Going beyond the Control of Quorum-Sensing to Combat Biofilm Infections

    PubMed Central

    Abraham, Wolf-Rainer

    2016-01-01

    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. PMID:27025518

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

    PubMed

    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. PMID:27020680

  11. A new class of bacterial quorum sensing antagonists: glycomonoterpenols synthesized using linalool and alpha terpineol.

    PubMed

    Mukherji, Ruchira; Prabhune, Asmita

    2015-06-01

    With increasing burden of antibiotic resistant microorganism search for newer drug targets and potent drug molecules is a never ending scenario. Quorum sensing (QS), the phenomenon of bacterial cross-talk, is one such target that has captured the attention of many and has been touted as the future of new age antimicrobials. Quorum sensing has the potential to regulate a plethora of bacterial virulence phenotypes and search of molecules with powerful quorum sensing inhibitory (QSI) capacity are underway. Monoterpene alcohols like linalool and alpha terpineol have been shown to possess antimicrobial and anti-biofilm activity. However in this article we attempt to bring forth a new class of compounds, glycomonoterpenols, derived from monoterpenoids alcohols. These glycomonoterpenols have been synthesized using Candida bombicola ATCC 22214 by feeding the cells with linalool and alpha terpineol respectively as substrates in 10% glucose, production medium. The advantage of these molecules over their parent compound is their additional surfactant like property, increased solubility and enhanced QSI potential. A variety of gram-negative bacteria capable of elaborating quorum sensing mediated phenotypes have been selected and both these glycoterpenoid derivatives have been shown to possess strong anti-QS activity. PMID:25931373

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

    PubMed

    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

  13. A qrr noncoding RNA deploys four different regulatory mechanisms to optimize quorum-sensing dynamics.

    PubMed

    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.

  14. A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation.

    PubMed

    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.

  15. A new class of bacterial quorum sensing antagonists: glycomonoterpenols synthesized using linalool and alpha terpineol.

    PubMed

    Mukherji, Ruchira; Prabhune, Asmita

    2015-06-01

    With increasing burden of antibiotic resistant microorganism search for newer drug targets and potent drug molecules is a never ending scenario. Quorum sensing (QS), the phenomenon of bacterial cross-talk, is one such target that has captured the attention of many and has been touted as the future of new age antimicrobials. Quorum sensing has the potential to regulate a plethora of bacterial virulence phenotypes and search of molecules with powerful quorum sensing inhibitory (QSI) capacity are underway. Monoterpene alcohols like linalool and alpha terpineol have been shown to possess antimicrobial and anti-biofilm activity. However in this article we attempt to bring forth a new class of compounds, glycomonoterpenols, derived from monoterpenoids alcohols. These glycomonoterpenols have been synthesized using Candida bombicola ATCC 22214 by feeding the cells with linalool and alpha terpineol respectively as substrates in 10% glucose, production medium. The advantage of these molecules over their parent compound is their additional surfactant like property, increased solubility and enhanced QSI potential. A variety of gram-negative bacteria capable of elaborating quorum sensing mediated phenotypes have been selected and both these glycoterpenoid derivatives have been shown to possess strong anti-QS activity.

  16. Whole-Genome Sequencing Analysis of Quorum-Sensing Aeromonas hydrophila Strain M023 from Freshwater.

    PubMed

    Tan, Wen-Si; Yin, Wai-Fong; Chang, Chien-Yi; Chan, Kok-Gan

    2015-01-01

    Aeromonas hydrophila is a well-known waterborne pathogen that recently was found to infect humans. Here, we report the draft genome of a freshwater isolate from a Malaysian waterfall, A. hydrophila strain M023, which portrays N-acylhomoserine lactone-dependent quorum sensing. PMID:25700404

  17. Going beyond the Control of Quorum-Sensing to Combat Biofilm Infections.

    PubMed

    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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  19. A structural perspective on the mechanisms of quorum sensing activation in bacteria.

    PubMed

    Lixa, Carolina; Mujo, Amanda; Anobom, Cristiane D; Pinheiro, Anderson S

    2015-01-01

    Bacteria are able to synchronize the population behavior in order to regulate gene expression through a cell-to-cell communication mechanism called quorum sensing. This phenomenon involves the production, detection and the response to extracellular signaling molecules named autoinducers, which directly or indirectly regulate gene expression in a cell density-dependent manner. Quorum sensing may control a wide range of biological processes in bacteria, such as bioluminescence, virulence factor production, biofilm formation and antibiotic resistance. The autoinducers are recognized by specific receptors that can either be membrane-bound histidine kinase receptors, which work by activating cognate cytoplasmic response regulators, or cytoplasmic receptors acting as transcription factors. In this review, we focused on the cytosolic quorum sensing regulators whose three-dimensional structures helped elucidate their mechanisms of action. Structural studies of quorum sensing receptors may enable the rational design of inhibitor molecules. Ultimately, this approach may represent an effective alternative to treat infections where classical antimicrobial therapy fails to overcome the microorganism virulence.

  20. Pseudomonas aeruginosa quorum sensing molecules correlate with clinical status in cystic fibrosis.

    PubMed

    Barr, Helen L; Halliday, Nigel; Cámara, Miguel; Barrett, David A; Williams, Paul; Forrester, Douglas L; Simms, Rebecca; Smyth, Alan R; Honeybourne, David; Whitehouse, Joanna L; Nash, Edward F; Dewar, Jane; Clayton, Andrew; Knox, Alan J; Fogarty, Andrew W

    2015-10-01

    Pseudomonas aeruginosa produces quorum sensing signal molecules that are potential biomarkers for infection.A prospective study of 60 cystic fibrosis patients with chronic P. aeruginosa, who required intravenous antibiotics for pulmonary exacerbations, was undertaken. Clinical measurements and biological samples were obtained at the start and end of the treatment period. Additional data were available for 29 of these patients when they were clinically stable.Cross-sectionally, quorum sensing signal molecules were detectable in the sputum, plasma and urine of 86%, 75% and 83% patients, respectively. They were positively correlated between the three biofluids. Positive correlations were observed for most quorum sensing signal molecules in sputum, plasma and urine, with quantitative measures of pulmonary P. aeruginosa load at the start of a pulmonary exacerbation. Plasma concentrations of 2-nonyl-4-hydroxy-quinoline (NHQ) were significantly higher at the start of a pulmonary exacerbation compared to clinical stability (p<0.01). Following the administration of systemic antibiotics, plasma 2-heptyl-4-hydroxyquinoline (p=0.02) and NHQ concentrations (p<0.01) decreased significantly.In conclusion, quorum sensing signal molecules are detectable in cystic fibrosis patients with pulmonary P. aeruginosa infection and are positively correlated with quantitative measures of P. aeruginosa. NHQ correlates with clinical status and has potential as a novel biomarker for P. aeruginosa infection.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed Central

    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

  4. Effects of natural and chemically synthesized furanones on quorum sensing in Chromobacterium violaceum

    PubMed Central

    Martinelli, Daniel; Grossmann, Gilles; Séquin, Urs; Brandl, Helmut; Bachofen, Reinhard

    2004-01-01

    Background Cell to cell signaling systems in Gram-negative bacteria rely on small diffusible molecules such as the N-acylhomoserine lactones (AHL). These compounds are involved in the production of antibiotics, exoenzymes, virulence factors and biofilm formation. They belong to the class of furanone derivatives which are frequently found in nature as pheromones, flavor compounds or secondary metabolites. To obtain more information on the relation between molecular structure and quorum sensing, we tested a variety of natural and chemically synthesized furanones for their ability to interfere with the quorum sensing mechanism using a quantitative bioassay with Chromobacterium violaceum CV026 for antagonistic and agonistic action. We were looking at the following questions: 1. Do these compounds affect growth? 2) Do these compounds activate the quorum sensing system of C. violaceum CV026? 3) Do these compounds inhibit violacein formation induced by the addition of the natural inducer N-hexanoylhomoserine lactone (HHL)? 4) Do these compounds enhance violacein formation in presence of HHL? Results The naturally produced N-acylhomoserine lactones showed a strong non-linear concentration dependent influence on violacein production in C. violaceum with a maximum at 3.7*10-8 M with HHL. Apart from the N-acylhomoserine lactones only one furanone (emoxyfurane) was found to simulate N-acylhomoserine lactone activity and induce violacein formation. The most effective substances acting negatively both on growth and quorum sensing were analogs and intermediates in synthesis of the butenolides from Streptomyces antibioticus. Conclusion As the regulation of many bacterial processes is governed by quorum sensing systems, the finding of natural and synthetic furanones acting as agonists or antagonists suggests an interesting tool to control and handle detrimental AHL induced effects. Some effects are due to general toxicity; others are explained by a competitive interaction for Lux

  5. Induction of a quorum sensing pathway by environmental signals enhances group A streptococcal resistance to lysozyme

    PubMed Central

    Chang, Jennifer C.; Jimenez, Juan Cristobal; Federle, Michael J.

    2015-01-01

    Summary The human-restricted pathogen Streptococcus pyogenes (Group A Streptococcus, GAS) is responsible for wide-ranging pathologies at numerous sites in the body, but has the proclivity to proliferate in individuals asymptomatically. The ability to survive in diverse tissues is undoubtedly benefited by sensory pathways that recognize environmental cues corresponding to stress and nutrient availability and thereby trigger adaptive responses. We investigated the impact that environmental signals contribute to cell-to-cell chemical communication (quorum sensing, QS) by monitoring activity of the Rgg2/Rgg3 and SHP-pheromone system in GAS. We identified metal limitation and the alternate carbon source mannose as two environmental indicators likely to be encountered by GAS in the host that significantly induced the Rgg-SHP system. Disruption of the metal regulator MtsR partially accounted for the response to metal depletion, whereas ptsABCD was primarily responsible for QS induction due to mannose, but each sensory system induced Rgg-SHP signaling apparently by different mechanisms. Significantly, we found that induction of QS, regardless of the GAS serotype tested, led to enhanced resistance to the antimicrobial agent lysozyme. These results indicate the benefits for GAS to integrate environmental signals with intercellular communication pathways in protection from host defenses. PMID:26062094

  6. Structure, Regulation, and Inhibition of the Quorum-Sensing Signal Integrator LuxO

    PubMed Central

    Hurley, Amanda; Li, Zhijie; Ventocilla, Christian; Jeffrey, Philip D.; Semmelhack, Martin F.; Fairman, Robert; Bassler, Bonnie L.; Hughson, Frederick M.

    2016-01-01

    In a process called quorum sensing, bacteria communicate with chemical signal molecules called autoinducers to control collective behaviors. In pathogenic vibrios, including Vibrio cholerae, the accumulation of autoinducers triggers repression of genes responsible for virulence factor production and biofilm formation. The vibrio autoinducer molecules bind to transmembrane receptors of the two-component histidine sensor kinase family. Autoinducer binding inactivates the receptors’ kinase activities, leading to dephosphorylation and inhibition of the downstream response regulator LuxO. Here, we report the X-ray structure of LuxO in its unphosphorylated, autoinhibited state. Our structure reveals that LuxO, a bacterial enhancer-binding protein of the AAA+ ATPase superfamily, is inhibited by an unprecedented mechanism in which a linker that connects the catalytic and regulatory receiver domains occupies the ATPase active site. The conformational change that accompanies receiver domain phosphorylation likely disrupts this interaction, providing a mechanistic rationale for LuxO activation. We also determined the crystal structure of the LuxO catalytic domain bound to a broad-spectrum inhibitor. The inhibitor binds in the ATPase active site and recapitulates elements of the natural regulatory mechanism. Remarkably, a single inhibitor molecule may be capable of inhibiting an entire LuxO oligomer. PMID:27219477

  7. Structure, Regulation, and Inhibition of the Quorum-Sensing Signal Integrator LuxO.

    PubMed

    Boyaci, Hande; Shah, Tayyab; Hurley, Amanda; Kokona, Bashkim; Li, Zhijie; Ventocilla, Christian; Jeffrey, Philip D; Semmelhack, Martin F; Fairman, Robert; Bassler, Bonnie L; Hughson, Frederick M

    2016-05-01

    In a process called quorum sensing, bacteria communicate with chemical signal molecules called autoinducers to control collective behaviors. In pathogenic vibrios, including Vibrio cholerae, the accumulation of autoinducers triggers repression of genes responsible for virulence factor production and biofilm formation. The vibrio autoinducer molecules bind to transmembrane receptors of the two-component histidine sensor kinase family. Autoinducer binding inactivates the receptors' kinase activities, leading to dephosphorylation and inhibition of the downstream response regulator LuxO. Here, we report the X-ray structure of LuxO in its unphosphorylated, autoinhibited state. Our structure reveals that LuxO, a bacterial enhancer-binding protein of the AAA+ ATPase superfamily, is inhibited by an unprecedented mechanism in which a linker that connects the catalytic and regulatory receiver domains occupies the ATPase active site. The conformational change that accompanies receiver domain phosphorylation likely disrupts this interaction, providing a mechanistic rationale for LuxO activation. We also determined the crystal structure of the LuxO catalytic domain bound to a broad-spectrum inhibitor. The inhibitor binds in the ATPase active site and recapitulates elements of the natural regulatory mechanism. Remarkably, a single inhibitor molecule may be capable of inhibiting an entire LuxO oligomer.

  8. Extracts of Cordia gilletii de wild (Boraginaceae) quench the quorum sensing of Pseudomonas aeruginosa PAO1

    PubMed Central

    Okusa, Philippe N.; Rasamiravaka, Tsiry; Vandeputte, Olivier; Stévigny, Caroline; Jaziri, Mondher El; Duez, Pierre

    2014-01-01

    Aim: The fight against infectious diseases and antimicrobial resistances needs the exploration of new active compounds with new proprieties like disrupting quorum sensing (QS) mechanisms, which is a cell-to-cell communication that regulates bacterial virulence factors. In this work, leaves and root barks extracts of a Congolese medicinal plant, Cordia gilletii, were investigated for their effect on the production of Pseudomonas aeruginosa major virulence factors regulated by QS. Materials and Methods: The effect of C. gilletii extracts on virulence factors of P. aeruginosa PAO1 was studied by the evaluation of the production of pyocyanine, elastase and biofilm; and by the measurement of the expression of QS-related genes. Results: The dichloromethane extract from root barks was found to quench the production of pyocyanin, a QS-dependent virulence factor in P. aeruginosa PAO1. Moreover, this extract specifically inhibits the expression of several QS-regulated genes (i.e. lasB, rhlA, lasI, lasR, rhlI, and rhlR) and reduces biofilm formation by PAO1. Conclusion: This study contributes to explain the efficacy of C. gilletii in the traditional treatment of infectious diseases caused by P. aeruginosa. PMID:26401363

  9. Inhibition of quorum sensing in gram-negative bacteria by alkylamine-modified cyclodextrins.

    PubMed

    Morohoshi, Tomohiro; Tokita, Kazuho; Ito, Satoshi; Saito, Yuki; Maeda, Saki; Kato, Norihiro; Ikeda, Tsukasa

    2013-08-01

    N-Acylhomoserine lactones (AHLs) are used as quorum-sensing (QS) signals by gram-negative bacteria. We have reported that the cyclic oligosaccharides known as cyclodextrins (CDs) form inclusion complexes with AHLs and disrupt QS signaling. In this study, a series of CD derivatives were designed and synthesized to improve the QS inhibitory activity over that of native CDs. The production of the red pigment prodigiosin by Serratia marcescens AS-1, which is regulated by AHL-mediated QS, was drastically decreased by adding 10 mg/ml 6-alkylacylamino-β-CD with an alkyl chain ranging from C7 to C12. An improvement in the QS inhibitory activity was also observed for 6-alkylamino-α- or γ-CDs and 2-alkylamino-CDs. Furthermore, 6,6'-dioctylamino-β-CD, which contains two octylamino groups, exhibited greater inhibitory activity than 6-monooctylamino-β-CD. The synthesized CD derivatives also had strong inhibitory effects on QS by other gram-negative bacteria, including Chromobacterium violaceum and Pseudomonas aeruginosa. The synthetic alkylamine-modified CD derivatives had higher equilibrium binding constants for binding with AHL than the native CDs did, consistent with the improved QS inhibition. ¹H NMR measurements suggested that the alkyl side chains of 6-alkylacylamino-β-CDs with alkyl chains up to 6 carbon atoms long could form self-inclusion complexes with the CD unit.

  10. Andrographolide interferes quorum sensing to reduce cell damage caused by avian pathogenic Escherichia coli.

    PubMed

    Guo, Xun; Zhang, Li-Yan; Wu, Shuai-Cheng; Xia, Fang; Fu, Yun-Xing; Wu, Yong-Li; Leng, Chun-Qing; Yi, Peng-Fei; Shen, Hai-Qing; Wei, Xu-Bin; Fu, Ben-Dong

    2014-12-01

    Avian pathogenic Escherichia coli (APEC) induce septicemia in chickens by invading type II pneumocytes to breach the blood-air barrier. The virulence of APEC can be regulated by quorum sensing (QS). Andrographolide is a QS inhibitor of Pseudomonas aeruginosa (P. aeruginosa). Therefore, we investigate whether andrographolide inhibits the injury of chicken type II pneumocytes by avian pathogenic E. coli O78 (APEC-O78) by disrupting the bacterial QS system. The results showed that sub-MIC of andrographolide significantly reduced the release of lactate dehydrogenase (LDH), F-actin cytoskeleton polymerization, and the degree of the adherence to chicken type II pneumocytes induced by APEC-O78. Further, we found that andrographolide significantly decreased the autoinducer-2 (AI-2) activity and the expression of virulence factors of APEC-O78. These results suggest that andrographolide reduce the pathogenicity of APEC-O78 in chicken type II pneumocytes by interfering QS and decreasing virulence. These results provide new evidence for colibacillosis prevention methods in chickens.

  11. Inhibition of Bacterial Quorum Sensing by Extracts from Aquatic Fungi: First Report from Marine Endophytes

    PubMed Central

    Martín-Rodríguez, Alberto J.; Reyes, Fernando; Martín, Jesús; Pérez-Yépez, Juan; León-Barrios, Milagros; Couttolenc, Alan; Espinoza, César; Trigos, Ángel; Martín, Víctor S.; Norte, Manuel; Fernández, José J.

    2014-01-01

    In our search for quorum-sensing (QS) disrupting molecules, 75 fungal isolates were recovered from reef organisms (endophytes), saline lakes and mangrove rhizosphere. Their QS inhibitory activity was evaluated in Chromobacterium violaceum CVO26. Four strains of endophytic fungi stood out for their potent activity at concentrations from 500 to 50 μg mL−1. The molecular characterization, based on the internal transcribed spacer (ITS) region sequences (ITS1, 5.8S and ITS2) between the rRNA of 18S and 28S, identified these strains as belonging to four genera: Sarocladium (LAEE06), Fusarium (LAEE13), Epicoccum (LAEE14), and Khuskia (LAEE21). Interestingly, three came from coral species and two of them came from the same organism, the coral Diploria strigosa. Metabolic profiles obtained by Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS) suggest that a combination of fungal secondary metabolites and fatty acids could be the responsible for the observed activities. The LC-HRMS analysis also revealed the presence of potentially new secondary metabolites. This is, to the best of our knowledge, the first report of QS inhibition by marine endophytic fungi. PMID:25415350

  12. Inhibition of bacterial quorum sensing by extracts from aquatic fungi: first report from marine endophytes.

    PubMed

    Martín-Rodríguez, Alberto J; Reyes, Fernando; Martín, Jesús; Pérez-Yépez, Juan; León-Barrios, Milagros; Couttolenc, Alan; Espinoza, César; Trigos, Angel; Martín, Víctor S; Norte, Manuel; Fernández, José J

    2014-11-19

    In our search for quorum-sensing (QS) disrupting molecules, 75 fungal isolates were recovered from reef organisms (endophytes), saline lakes and mangrove rhizosphere. Their QS inhibitory activity was evaluated in Chromobacterium violaceum CVO26. Four strains of endophytic fungi stood out for their potent activity at concentrations from 500 to 50 μg mL-1. The molecular characterization, based on the internal transcribed spacer (ITS) region sequences (ITS1, 5.8S and ITS2) between the rRNA of 18S and 28S, identified these strains as belonging to four genera: Sarocladium (LAEE06), Fusarium (LAEE13), Epicoccum (LAEE14), and Khuskia (LAEE21). Interestingly, three came from coral species and two of them came from the same organism, the coral Diploria strigosa. Metabolic profiles obtained by Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS) suggest that a combination of fungal secondary metabolites and fatty acids could be the responsible for the observed activities. The LC-HRMS analysis also revealed the presence of potentially new secondary metabolites. This is, to the best of our knowledge, the first report of QS inhibition by marine endophytic fungi.

  13. Microbiome shifts and the inhibition of quorum sensing by Black Band Disease cyanobacteria.

    PubMed

    Meyer, Julie L; Gunasekera, Sarath P; Scott, Raymond M; Paul, Valerie J; Teplitski, Max

    2016-05-01

    Disruption of the microbiome often correlates with the appearance of disease symptoms in metaorganisms such as corals. In Black Band Disease (BBD), a polymicrobial disease consortium dominated by the filamentous cyanobacterium Roseofilum reptotaenium displaces members of the epibiotic microbiome. We examined both normal surface microbiomes and BBD consortia on Caribbean corals and found that the microbiomes of healthy corals were dominated by Gammaproteobacteria, in particular Halomonas spp., and were remarkably stable across spatial and temporal scales. In contrast, the microbial community structure in black band consortia was more variable and more diverse. Nevertheless, deep sequencing revealed that members of the disease consortium were present in every sampled surface microbiome of Montastraea, Orbicella and Pseudodiploria corals, regardless of the health status. Within the BBD consortium, we identified lyngbic acid, a cyanobacterial secondary metabolite. It strongly inhibited quorum sensing (QS) in the Vibrio harveyi QS reporters. The effects of lyngbic acid on the QS reporters depended on the presence of the CAI-1 receptor CqsS. Lyngbic acid inhibited luminescence in native coral Vibrio spp. that also possess the CAI-1-mediated QS. The effects of this naturally occurring QS inhibitor on bacterial regulatory networks potentially contribute to the structuring of the interactions within BBD consortia. PMID:26495995

  14. Quorum Quenching of Nitrobacter winogradskyi Suggests that Quorum Sensing Regulates Fluxes of Nitrogen Oxide(s) during Nitrification

    PubMed Central

    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. PMID:27795404

  15. Quorum Sensing Determines the Choice of Antiphage Defense Strategy in Vibrio anguillarum

    PubMed Central

    Tan, Demeng; Svenningsen, Sine Lo

    2015-01-01

    ABSTRACT Selection for phage resistance is a key driver of bacterial diversity and evolution, and phage-host interactions may therefore have strong influence on the genetic and functional dynamics of bacterial communities. In this study, we found that an important, but so far largely overlooked, determinant 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 mutant strains are accurately reflected in the behavior of wild-type V. anguillarum, which (i) displays increased OmpK expression in aggregated cells compared to free-living variants in the same culture, (ii) displays a clear inverse correlation between ompK mRNA levels and the concentration of N-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 antiphage defense strategies. Further, the prevalence of nonmutational defense mechanisms in strain PF430-3 suggests highly flexible adaptations to KVP40 phage infection pressure, possibly allowing the long-term coexistence of phage and host. PMID:26081633

  16. How ants use quorum sensing to estimate the average quality of a fluctuating resource

    PubMed Central

    Franks, Nigel R.; Stuttard, Jonathan P.; Doran, Carolina; Esposito, Julian C.; Master, Maximillian C.; Sendova-Franks, Ana B.; Masuda, Naoki; Britton, Nicholas F.

    2015-01-01

    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. PMID:26153535

  17. How ants use quorum sensing to estimate the average quality of a fluctuating resource.

    PubMed

    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. Coexistence of quorum-quenching and quorum-sensing in tropical marine Pseudomonas aeruginosa strain MW3A.

    PubMed

    Wong, Cheng-Siang; Yin, Wai-Fong; Choo, Yeun-Mun; Sam, Choon-Kook; Koh, Chong-Lek; Chan, Kok-Gan

    2012-02-01

    A chemically defined medium called KGm medium was used to isolate from a sample of sea water a bacterial strain, MW3A, capable of using N-3-oxohexanoyl-L: -homoserine lactone as the sole carbon source. MW3A was clustered closely to Pseudomonas aeruginosa by 16S ribosomal DNA sequence analysis. It degraded both N-acylhomoserine lactones (AHLs) with a 3-oxo group substitution and, less preferably, AHLs with unsubstituted groups at C3 position in the acyl side chain, as determined by Rapid Resolution Liquid Chromatography. Its quiP and pvdQ homologue gene sequences showed high similarities to those of known acylases. Spent supernatant of MW3A harvested at 8-h post inoculation was shown to contain long-chain AHLs when assayed with the biosensor Escherichia coli [pSB1075], and specifically N-dodecanoyl-L: -homoserine lactone and N-3-oxotetradecanoyl-L: -homoserine lactone by high resolution mass spectrometry. Hence, we report here a novel marine P. aeruginosa strain MW3A possessing both quorum-quenching and quorum-sensing properties.

  19. An age-dependent model to analyse the evolutionary stability of bacterial quorum sensing.

    PubMed

    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. PMID:26796220

  20. Ligand-Induced Asymmetry in Histidine Sensor Kinase Complex Regulates Quorum Sensing

    SciTech Connect

    Neiditch,M.; Federle, M.; Pompeani, A.; Kelly, R.; Swem, D.; Jeffrey, P.; Bassler, B.; Hughson, F.

    2006-01-01

    Bacteria sense their environment using receptors of the histidine sensor kinase family, but how kinase activity is regulated by ligand binding is not well understood. Autoinducer-2 (AI-2), a secreted signaling molecule originally identified in studies of the marine bacterium Vibrio harveyi, regulates quorum-sensing responses and allows communication between different bacterial species. AI-2 signal transduction in V. harveyi requires the integral membrane receptor LuxPQ, comprised of periplasmic binding protein (LuxP) and histidine sensor kinase (LuxQ) subunits. Combined X-ray crystallographic and functional studies show that AI-2 binding causes a major conformational change within LuxP, which in turn stabilizes a quaternary arrangement in which two LuxPQ monomers are asymmetrically associated. We propose that formation of this asymmetric quaternary structure is responsible for repressing the kinase activity of both LuxQ subunits and triggering the transition of V. harveyi into quorum-sensing mode.

  1. An age-dependent model to analyse the evolutionary stability of bacterial quorum sensing.

    PubMed

    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.

  2. A nitric oxide-responsive quorum sensing circuit in Vibrio harveyi regulates flagella production and biofilm formation.

    PubMed

    Henares, Bernadette M; Xu, Yueming; Boon, Elizabeth M

    2013-01-01

    Cell signaling plays an important role in the survival of bacterial colonies. They use small molecules to coordinate gene expression in a cell density dependent manner. This process, known as quorum sensing, helps bacteria regulate diverse functions such as bioluminescence, biofilm formation and virulence. In Vibrio harveyi, a bioluminescent marine bacterium, four parallel quorum-sensing systems have been identified to regulate light production. We have previously reported that nitric oxide (NO), through the H-NOX/HqsK quorum sensing pathway contributes to light production in V. harveyi through the LuxU/LuxO/LuxR quorum sensing pathway. In this study, we show that nitric oxide (NO) also regulates flagellar production and enhances biofilm formation. Our data suggest that V. harveyi is capable of switching between lifestyles to be able to adapt to changes in the environment.

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

    PubMed

    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.

  4. Secondary metabolites produced by marine streptomyces as antibiofilm and quorum-sensing inhibitor of uropathogen Proteus mirabilis.

    PubMed

    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

  5. Secondary metabolites produced by marine streptomyces as antibiofilm and quorum-sensing inhibitor of uropathogen Proteus mirabilis.

    PubMed

    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

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

    PubMed

    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.

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

    PubMed

    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.

  8. [Networks involving quorum sensing, cyclic-di-GMP and nitric oxide on biofilm production in bacteria].

    PubMed

    Ramírez-Mata, Alberto; Fernández-Domínguez, Ileana J; Nuñez-Reza, Karen J; Xiqui-Vázquez, María L; Baca, Beatriz E

    2014-01-01

    Bacterial biofilms are ubiquitous in nature, and their flexibility is derived in part from a complex extracellular matrix that can be made-to-order to cope with environmental demand. Although common developmental stages leading to biofilm formation have been described, an in-depth knowledge of genetic and signaling is required to understand biofilm formation. Bacteria detect changes in population density by quorum sensing and particular environmental conditions, using signals such as cyclic di-GMP or nitric oxide. The significance of understanding these signaling pathways lies in that they control a broad variety of functions such as biofilm formation, and motility, providing benefits to bacteria as regards host colonization, defense against competitors, and adaptation to changing environments. Due to the importance of these features, we here review the signaling network and regulatory connections among quorum sensing, c-di-GMP and nitric oxide involving biofilm formation.

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

    PubMed Central

    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

  10. Transsexuality in the rhizosphere: quorum sensing reversibly converts Agrobacterium tumefaciens from phenotypically female to male.

    PubMed

    Cho, Hongbaek; Pinto, Uelinton M; Winans, Stephen C

    2009-05-01

    Conjugative plasmids generally encode proteins that block the conjugative entry of identical or similar plasmids into the host cell, a phenomenon known as entry exclusion. Here, we demonstrate that two Ti plasmids of Agrobacterium tumefaciens encode robust entry exclusion functions. Two proteins, TrbJ and TrbK, can each mediate entry exclusion and act synergistically. The trbJ and trbK genes are included within the trb operon, which is tightly regulated by the quorum-sensing regulator TraR and the cognate acylhomoserine lactone. In the absence of quorum-sensing signals, these proteins are not significantly expressed, and cells lacking TrbJ and TrbK are efficient Ti plasmid recipients. In the presence of these signals, these strains block the entry of Ti plasmids and instead become efficient conjugal donors.

  11. Transsexuality in the Rhizosphere: Quorum Sensing Reversibly Converts Agrobacterium tumefaciens from Phenotypically Female to Male▿

    PubMed Central

    Cho, Hongbaek; Pinto, Uelinton M.; Winans, Stephen C.

    2009-01-01

    Conjugative plasmids generally encode proteins that block the conjugative entry of identical or similar plasmids into the host cell, a phenomenon known as entry exclusion. Here, we demonstrate that two Ti plasmids of Agrobacterium tumefaciens encode robust entry exclusion functions. Two proteins, TrbJ and TrbK, can each mediate entry exclusion and act synergistically. The trbJ and trbK genes are included within the trb operon, which is tightly regulated by the quorum-sensing regulator TraR and the cognate acylhomoserine lactone. In the absence of quorum-sensing signals, these proteins are not significantly expressed, and cells lacking TrbJ and TrbK are efficient Ti plasmid recipients. In the presence of these signals, these strains block the entry of Ti plasmids and instead become efficient conjugal donors. PMID:19304847

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

    PubMed

    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.

  13. Inhibiting N-acyl-homoserine lactone synthesis and quenching Pseudomonas quinolone quorum sensing to attenuate virulence

    PubMed Central

    Chan, Kok-Gan; Liu, Yi-Chia; Chang, Chien-Yi

    2015-01-01

    Bacteria sense their own population size, tune the expression of responding genes, and behave accordingly to environmental stimuli by secreting signaling molecules. This phenomenon is termed as quorum sensing (QS). By exogenously manipulating the signal transduction bacterial population behaviors could be controlled, which may be done through quorum quenching (QQ). QS related regulatory networks have been proven their involvement in regulating many virulence determinants in pathogenic bacteria in the course of infections. Interfering with QS signaling system could be a novel strategy against bacterial infections and therefore requires more understanding of their fundamental mechanisms. Here we review the development of studies specifically on the inhibition of production of N-acyl-homoserine lactone (AHL), a common proteobacterial QS signal. The opportunistic pathogen, Pseudomonas aeruginosa, equips the alkylquinolone (AQ)-mediated QS which also plays crucial roles in its pathogenicity. The studies in QQ targeting on AQ are also discussed. PMID:26539190

  14. Classifying the Topology of AHL-Driven Quorum Sensing Circuits in Proteobacterial Genomes

    PubMed Central

    Gelencsér, Zsolt; Choudhary, Kumari Sonal; Coutinho, Bruna Goncalves; Hudaiberdiev, Sanjarbek; Galbáts, Borisz; Venturi, Vittorio; Pongor, Sándor

    2012-01-01

    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/. PMID:22778593

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

    PubMed

    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.

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

    PubMed

    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. PMID:26669119

  17. Polyphosphate kinase is essential for biofilm development, quorum sensing, and virulence of Pseudomonas aeruginosa.

    PubMed

    Rashid, M H; Rumbaugh, K; Passador, L; Davies, D G; Hamood, A N; Iglewski, B H; Kornberg, A

    2000-08-15

    The human opportunistic pathogen Pseudomonas aeruginosa causes a variety of infections in immunocompromised hosts and in individuals with cystic fibrosis. A knockout mutation in the polyphosphate kinase (ppk) gene, encoding PPK responsible for the synthesis of inorganic polyphosphate from ATP, renders P. aeruginosa cells unable to form a thick and differentiated biofilm. The mutant is aberrant in quorum sensing and responses in that production of the quorum-sensing controlled virulence factors elastase and rhamnolipid are severely reduced. In a burned-mouse pathogenesis model, the virulence of the mutant is greatly reduced with severe defects in the colonization of mouse tissues. The conservation of PPK among many bacterial pathogens and its absence in eukaryotes suggest that PPK might be an attractive target for antimicrobial drugs.

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

    PubMed

    Hansen, Mette R; Jakobsen, Tim H; Bang, Claus G; Cohrt, Anders Emil; Hansen, Casper L; Clausen, Janie W; Le Quement, Sebastian T; Tolker-Nielsen, Tim; Givskov, Michael; Nielsen, Thomas E

    2015-04-01

    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 pathogenesis and antibiotic tolerance of a bacterial biofilm. To identify the structural elements important for antagonistic or agonistic activity against the Pseudomonas aeruginosa LasR protein, we report the synthesis and screening of new triazole-containing mimics of natural N-acyl homoserine lactones. A series of azide- and alkyne-containing homoserine lactone building blocks was used to prepare an expanded set of 123 homoserine lactone analogues through a combination of solution- and solid-phase synthesis methods. The resulting compounds were subjected to cell-based quorum sensing screening assays, thereby revealing several bioactive compounds, including 13 compounds with antagonistic activity and 9 compounds with agonistic activity.

  19. Effects of PNPG on cell growth cycle, motility machinery and quorum sensing in Serratia marcescens.

    PubMed

    Wei, Jun-Rong; Horng, Yu-Tze; Lai, Hsin-Chih; Luh, Kwen-Tay; Ho, Shen-Wu

    2004-02-01

    p-Nitrophenylglycerol (PNPG) effectively inhibits swarming of the enterobacterium Proteus mirabilis. The underlying mechanism of inhibition is unclear. We have now found that both PNPG also inhibits motility and swarming in another enterobacterium, Serratia marcescens. While the peak promoter activities of the flagellar master operon (flhDCSm), the flagellin structural gene (hagSm) and the nuclease gene (nucASm) in S. marcescens increased with increasing PNPG concentration, the expression of these genes was delayed in accordance with the reduced growth rate. As the quorum-sensing system is involved in the regulation of swarming in S. marcescens, we also examined the effect of PNPG on the production of quorum-sensing signal molecules and found that their expression was delayed with a reduced level. PNPG, therefore, had a pleiotropic effect on all aspects of S. marcescens physiology relating to swarming. The underlying molecular mechanism remains to be elucidated.

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

    PubMed

    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. PMID:27237773

  1. A Burkholderia cenocepacia orphan LuxR homolog is involved in quorum-sensing regulation.

    PubMed

    Malott, Rebecca J; O'Grady, Eoin P; Toller, Jessica; Inhülsen, Silja; Eberl, Leo; Sokol, Pamela A

    2009-04-01

    Burkholderia cenocepacia utilizes quorum sensing to control gene expression, including the expression of genes involved in virulence. In addition to CepR and CciR, a third LuxR homolog, CepR2, was found to regulate gene expression and virulence factor production. All B. cenocepacia strains examined contained this orphan LuxR homolog, which was not associated with an adjacent N-acyl-homoserine lactone synthase gene. Expression of cepR2 was negatively autoregulated and was negatively regulated by CciR in strain K56-2. Microarray analysis and quantitative reverse transcription-PCR determined that CepR2 did not influence expression of cepIR or cciIR. However, in strain K56-2, CepR2 negatively regulated expression of several known quorum-sensing-controlled genes, including genes encoding zinc metalloproteases. CepR2 exerted positive and negative regulation on genes on three chromosomes, including strong negative regulation of a gene cluster located adjacent to cepR2. In strain H111, which lacks the CciIR quorum-sensing system, CepR2 positively regulated pyochelin production by controlling transcription of one of the operons required for the biosynthesis of the siderophore in an N-acyl-homoserine lactone-independent manner. CepR2 activation of a luxI promoter was demonstrated in a heterologous Escherichia coli host, providing further evidence that CepR2 can function in the absence of signaling molecules. This study demonstrates that the orphan LuxR homolog CepR2 contributes to the quorum-sensing regulatory network in two distinct strains of B. cenocepacia. PMID:19201791

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

    PubMed

    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.

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

    PubMed

    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.

  4. Development of a mimotope vaccine targeting the Staphylococcus aureus quorum sensing pathway.

    PubMed

    O'Rourke, John P; Daly, Seth M; Triplett, Kathleen D; Peabody, David; Chackerian, Bryce; Hall, Pamela R

    2014-01-01

    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. PMID:25379726

  5. Quorum sensing activity of Aeromonas caviae strain YL12, a bacterium isolated from compost.

    PubMed

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

    2014-04-22

    Quorum sensing is a well-studied cell-to-cell communication method that involves a cell-density dependent regulation of genes expression mediated by signalling molecules. In this study, a bacterium isolated from a plant material compost pile was found to possess quorum sensing activity based on bioassay screening. Isolate YL12 was identified using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry and molecular typing using rpoD gene which identified the isolate as Aeromonas caviae. High resolution tandem mass spectrometry was subsequently employed to identify the N-acyl homoserine lactone profile of Aeromonas caviae YL12 and confirmed that this isolate produced two short chain N-acyl homoserine lactones, namely C4-HSL and C6, and the production was observed to be cell density-dependent. Using the thin layer chromatography (TLC) bioassay, both AHLs were found to activate C. violaceum CV026, whereas only C6-HSL was revealed to induce bioluminescence expression of E. coli [pSB401]. The data presented in this study will be the leading steps in understanding the role of quorum sensing in Aeromonas caviae strain YL12.

  6. From deep-sea volcanoes to human pathogens: a conserved quorum-sensing signal in Epsilonproteobacteria.

    PubMed

    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. The Role of the CAI-1 Fatty Acid Tail in the Vibrio cholerae Quorum Sensing Response

    PubMed Central

    Perez, Lark J.; Ng, Wai-Leung; Marano, Paul; Brook, Karolina; Bassler, Bonnie L.; Semmelhack, Martin F.

    2013-01-01

    Quorum sensing is a mechanism of chemical communication among bacteria that enables collective behaviors. In V. cholerae, the etiological agent of the disease cholera, quorum sensing controls group behaviors including virulence factor production and biofilm formation. The major V. cholerae quorum-sensing system consists of the extracellular signal molecule called CAI-1 and its cognate membrane bound receptor called CqsS. Here, the ligand binding activity of CqsS is probed with structural analogs of the natural signal. Enabled by our discovery of a structurally simplified analog of CAI-1, we prepared and analyzed a focused library. The molecules were designed to probe the effects of conformational and structural changes along the length of the fatty acid tail of CAI-1. Our results, combined with pharmacophore modeling, suggest a molecular basis for signal molecule recognition and receptor fidelity with respect to the fatty acid tail portion of CAI-1. These efforts provide novel probes to enhance discovery of anti-virulence agents for the treatment of V. cholerae. PMID:23092313

  8. From deep-sea volcanoes to human pathogens: a conserved quorum-sensing signal in Epsilonproteobacteria.

    PubMed

    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. PMID:25397946

  9. Rule–based regulatory and metabolic model for Quorum sensing in P. aeruginosa

    PubMed Central

    2013-01-01

    Background 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. Results 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. Conclusions 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. PMID:23965312

  10. Imidazolines as non-classical bioisosteres of N-acyl homoserine lactones and quorum sensing inhibitors.

    PubMed

    Reyes-Arellano, Alicia; Bucio-Cano, Alejandro; Montenegro-Sustaita, Mabel; Curiel-Quesada, Everardo; Salgado-Zamora, Héctor

    2012-01-01

    A series of selected 2-substituted imidazolines were synthesized in moderate to excellent yields by a modification of protocols reported in the literature. They were evaluated as potential non-classical bioisosteres of AHL with the aim of counteracting bacterial pathogenicity. Imidazolines 18a, 18e and 18f at various concentrations reduced the violacein production by Chromobacterium violaceum, suggesting an anti-quorum sensing profile against Gram-negative bacteria. Imidazoline 18b did not affect the production of violacein, but had a bacteriostatic effect at 100 μM and a bactericidal effect at 1 mM. Imidazoline 18a bearing a hexyl phenoxy moiety was the most active compound of the series, rendering a 72% inhibitory effect of quorum sensing at 100 μM. Imidazoline 18f bearing a phenyl nonamide substituent presented an inhibitory effect on quorum sensing at a very low concentration (1 nM), with a reduction percentage of 28%. This compound showed an irregular performance, decreasing inhibition at concentrations higher than 10 μM, until reaching 100 μM, at which concentration it increased the inhibitory effect with a 49% reduction percentage. When evaluated on Serratia marcescens, compound 18f inhibited the production of prodigiosin by 40% at 100 μM.

  11. Measurement of the Copy Number of the Master Quorum-Sensing Regulator of a Bacterial Cell

    NASA Astrophysics Data System (ADS)

    Teng, Shu-Wen; Wang, Yufang; Tu, Kimberly C.; Long, Tao; Mehta, Pankaj; Wingreen, Ned S.; Bassler, Bonnie L.; Ong, N. P.

    2010-05-01

    Quorum sensing is the mechanism by which bacteria communicate and synchronize group behaviors. Quantitative information on parameters such as the copy number of particular quorum-sensing proteins should contribute strongly to understanding how the quorum-sensing network functions. Here we show that the copy number of the master regulator protein LuxR in Vibrio harveyi, can be determined in vivo by exploiting small-number fluctuations of the protein distribution when cells undergo division. When a cell divides, both its volume and LuxR protein copy number N are partitioned with slight asymmetries. We have measured the distribution functions describing the partitioning of the protein fluorescence and the cell volume. The fluorescence distribution is found to narrow systematically as the LuxR population increases while the volume partitioning is unchanged. Analyzing these changes statistically, we have determined that N = 80-135 dimers at low cell density and 575 dimers at high cell density. In addition, we have measured the static distribution of LuxR over a large (3,000) clonal population. Combining the static and time-lapse experiments, we determine the magnitude of the Fano factor of the distribution. This technique has broad applicability as a general, in vivo technique for measuring protein copy number and burst size.

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

    PubMed

    Arevalo-Ferro, Catalina; Hentzer, Morten; Reil, Gerold; Görg, Angelika; Kjelleberg, Staffan; Givskov, Michael; Riedel, Kathrin; Eberl, Leo

    2003-12-01

    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 on N-acyl-homoserine lactone (AHL) signal molecules, to control the expression of virulence factors and biofilm development. In this study, we compared the protein patterns of the intracellular, extracellular and surface protein fractions of the PAO1 parent strain with those of an isogenic lasI rhlI double mutant by means of two-dimensional gel electrophoresis (2-DE). This analysis showed that the intensities of 23.7% of all detected protein spots differed more than 2.5-fold between the two strains. We only considered those protein spots truly QS regulated that were changed in the mutant in the absence of signal molecules but were rescued to the wild-type situation when the medium was supplemented with AHLs. These protein spots were characterized by MALDI-TOF peptide mapping. Twenty-seven proteins were identified that were previously reported to be AHL controlled, among them several well-characterized virulence factors. For one of the identified proteins, the serine protease PrpL, a biochemical assay was established to verify that expression of this factor is indeed QS regulated. Furthermore, it is shown that the quorum-sensing blocker C-30 specifically interferes with the expression of 67% of the AHL-controlled protein spots of the surface fraction, confirming the high specificity of the compound. Importantly, 20 novel QS-regulated proteins were identified, many of which are involved in iron utilization, suggesting a link between quorum sensing and the iron regulatory system. Two of these proteins, PhuR and HasAp, are components of the two distinct haem-uptake systems present in P. aeruginosa. In agreement with the finding that both proteins are positively regulated by the

  13. Lead Precipitation by Vibrio harveyi: Evidence for Novel Quorum-Sensing Interactions

    PubMed Central

    Mire, Chad E.; Tourjee, Jeanette A.; O'Brien, William F.; Ramanujachary, Kandalam V.; Hecht, Gregory B.

    2004-01-01

    Three pleiotropic, quorum sensing-defective Vibrio harveyi mutants were observed to precipitate soluble Pb2+ as an insoluble compound. The compound was purified and subjected to X-ray diffraction and elemental analyses. These assays identified the precipitated compound as Pb9(PO4)6, an unusual and complex lead phosphate salt that is produced synthetically at temperatures of ca. 200°C. Regulation of the precipitation phenotype was also examined. Introduction of a luxO::kan allele into one of the mutants abolished lead precipitation, indicating that the well-characterized autoinducer 1 (AI1)-AI2 quorum-sensing system can block lead precipitation in dense cell populations. Interestingly, the V. harveyi D1 mutant, a strain defective for secretion of both AI1 and AI2, was shown to be an effective trans inhibitor of lead precipitation. This suggests that a previously undescribed V. harveyi autoinducer, referred to as AI3, can also negatively regulate lead precipitation. Experiments with heterologous bacterial populations demonstrated that many different species are capable of trans regulating the V. harveyi lead precipitation phenotype. Moreover, one of the V. harveyi mutants in this study exhibited little or no response to intercellular signals from other V. harveyi inocula but was quite responsive to some of the heterologous bacteria. Based on these observations, we propose that V. harveyi carries at least one quorum sensor that is specifically dedicated to receiving cross-species communication. PMID:14766565

  14. Bioactive proteins from Solanaceae as quorum sensing inhibitors against virulence in Pseudomonas aeruginosa.

    PubMed

    Singh, Gurpreet; Tamboli, Ekant; Acharya, Aurovind; Kumarasamy, Chellan; Mala, Kanchana; Raman, Pachaiappan

    2015-06-01

    Cell-to-cell communication or quorum sensing (QS) is a generic event in bacteria that is used to coordinate gene expression among local populations. The phenomenon of QS depends on the fact that presence of sufficient bacteria ascertains a threshold level of autoinducer concentration that allows bacteria to sense a critical cell mass and to activate or repress target genes. Thus, QS has been an attractive target for the development of anti-infective strategies that are not based on the use of antibiotics. Several anti-QS approaches have been demonstrated including natural products from plant-based secondary metabolites. However, the role of plant bioactive proteins as an anti-QS peptide is yet to be deciphered. Against a backdrop of ever-increasing antibiotic resistant pathogens, there is a strong need for development of alternative therapeutic strategies. Thus, our hypothesis is that bioactive proteins from the plant family Solanaceae are quorum quenching molecules that can be exploited to develop a therapeutic strategy against virulence. We presume that bioactive proteins will inactivate or inhibit or degrade QS signals from bacteria to prevent cell-to-cell communication and thus inhibit development of virulence in Pseudomonas aeruginosa. Further, the use of proteins as quorum quenchers will delay the bacteria to develop resistance against these quenching molecules.

  15. Modulation of Host Biology by Pseudomonas aeruginosa Quorum Sensing Signal Molecules: Messengers or Traitors

    PubMed Central

    Liu, Yi-Chia; Chan, Kok-Gan; Chang, Chien-Yi

    2015-01-01

    Bacterial cells sense their population density and respond accordingly by producing various signal molecules to the surrounding environments thereby trigger a plethora of gene expression. This regulatory pathway is termed quorum sensing (QS). Plenty of bacterial virulence factors are controlled by QS or QS-mediated regulatory systems and QS signal molecules (QSSMs) play crucial roles in bacterial signaling transduction. Moreover, bacterial QSSMs were shown to interfere with host cell signaling and modulate host immune responses. QSSMs not only regulate the expression of bacterial virulence factors but themselves act in the modulation of host biology that can be potential therapeutic targets. PMID:26617576

  16. The role of quorum sensing in Escherichia coli (ETEC) virulence factors.

    PubMed

    Sturbelle, Régis Tuchtenhagen; de Avila, Luciana Farias da Costa; Roos, Talita Bandeira; Borchardt, Jéssica Lopes; da Conceição, Rita de Cássia dos Santos; Dellagostin, Odir Antonio; Leite, Fábio Pereira Leivas

    2015-11-18

    Quorum sensing (QS) is a signaling system among bacteria mediated by auto-inducer substances (AI). Whenever the concentration of these molecules reaches a threshold corresponding to a high cell density or quorum, the whole population starts a coordinated expression of specific genes. Studies have shown that epinephrine is also responsible for activating specific bacterial genes. This work aimed to investigate the role of conditioned medium (containing AI), epinephrine and their association on growth, motility, F4 fimbriae and heat-labile toxin (LT) expression on enterotoxigenic Escherichia coli (ETEC, E68). A significant increase in motility, F4 and LT expression, was observed in the ETEC culture supplemented with conditioned medium and epinephrine. These findings suggest that ETEC uses some components of conditioned medium (e.g., AI molecules), host molecules (epinephrine), and their association to modulate the expression of important virulence genes. PMID:26386492

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

    NASA Astrophysics Data System (ADS)

    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.

  18. Selective Chemical Inhibition of agr Quorum Sensing in Staphylococcus aureus Promotes Host Defense with Minimal Impact on Resistance

    PubMed Central

    Sully, Erin K.; Malachowa, Natalia; Elmore, Bradley O.; Alexander, Susan M.; Femling, Jon K.; Gray, Brian M.; DeLeo, Frank R.; Otto, Michael; Cheung, Ambrose L.; Edwards, Bruce S.; Sklar, Larry A.; Horswill, Alexander R.; Hall, Pamela R.; Gresham, Hattie D.

    2014-01-01

    Bacterial signaling systems are prime drug targets for combating the global health threat of antibiotic resistant bacterial infections including those caused by Staphylococcus aureus. S. aureus is the primary cause of acute bacterial skin and soft tissue infections (SSTIs) and the quorum sensing operon agr is causally associated with these. Whether efficacious chemical inhibitors of agr signaling can be developed that promote host defense against SSTIs while sparing the normal microbiota of the skin is unknown. In a high throughput screen, we identified a small molecule inhibitor (SMI), savirin (S. aureus virulence inhibitor) that disrupted agr-mediated quorum sensing in this pathogen but not in the important skin commensal Staphylococcus epidermidis. Mechanistic studies employing electrophoretic mobility shift assays and a novel AgrA activation reporter strain revealed the transcriptional regulator AgrA as the target of inhibition within the pathogen, preventing virulence gene upregulation. Consistent with its minimal impact on exponential phase growth, including skin microbiota members, savirin did not provoke stress responses or membrane dysfunction induced by conventional antibiotics as determined by transcriptional profiling and membrane potential and integrity studies. Importantly, savirin was efficacious in two murine skin infection models, abating tissue injury and selectively promoting clearance of agr+ but not Δagr bacteria when administered at the time of infection or delayed until maximal abscess development. The mechanism of enhanced host defense involved in part enhanced intracellular killing of agr+ but not Δagr in macrophages and by low pH. Notably, resistance or tolerance to savirin inhibition of agr was not observed after multiple passages either in vivo or in vitro where under the same conditions resistance to growth inhibition was induced after passage with conventional antibiotics. Therefore, chemical inhibitors can selectively target AgrA in

  19. Selective chemical inhibition of agr quorum sensing in Staphylococcus aureus promotes host defense with minimal impact on resistance.

    PubMed

    Sully, Erin K; Malachowa, Natalia; Elmore, Bradley O; Alexander, Susan M; Femling, Jon K; Gray, Brian M; DeLeo, Frank R; Otto, Michael; Cheung, Ambrose L; Edwards, Bruce S; Sklar, Larry A; Horswill, Alexander R; Hall, Pamela R; Gresham, Hattie D

    2014-06-01

    Bacterial signaling systems are prime drug targets for combating the global health threat of antibiotic resistant bacterial infections including those caused by Staphylococcus aureus. S. aureus is the primary cause of acute bacterial skin and soft tissue infections (SSTIs) and the quorum sensing operon agr is causally associated with these. Whether efficacious chemical inhibitors of agr signaling can be developed that promote host defense against SSTIs while sparing the normal microbiota of the skin is unknown. In a high throughput screen, we identified a small molecule inhibitor (SMI), savirin (S. aureus virulence inhibitor) that disrupted agr-mediated quorum sensing in this pathogen but not in the important skin commensal Staphylococcus epidermidis. Mechanistic studies employing electrophoretic mobility shift assays and a novel AgrA activation reporter strain revealed the transcriptional regulator AgrA as the target of inhibition within the pathogen, preventing virulence gene upregulation. Consistent with its minimal impact on exponential phase growth, including skin microbiota members, savirin did not provoke stress responses or membrane dysfunction induced by conventional antibiotics as determined by transcriptional profiling and membrane potential and integrity studies. Importantly, savirin was efficacious in two murine skin infection models, abating tissue injury and selectively promoting clearance of agr+ but not Δagr bacteria when administered at the time of infection or delayed until maximal abscess development. The mechanism of enhanced host defense involved in part enhanced intracellular killing of agr+ but not Δagr in macrophages and by low pH. Notably, resistance or tolerance to savirin inhibition of agr was not observed after multiple passages either in vivo or in vitro where under the same conditions resistance to growth inhibition was induced after passage with conventional antibiotics. Therefore, chemical inhibitors can selectively target AgrA in

  20. Sodium houttuyfonate affects production of N-acyl homoserine lactone and quorum sensing-regulated genes expression in Pseudomonas aeruginosa

    PubMed Central

    Wu, Daqiang; Huang, Weifeng; Duan, Qiangjun; Li, Fang; Cheng, Huijuan

    2014-01-01

    Quorum sensing (QS) is a means of cell-to-cell communication that uses diffusible signaling molecules that are sensed by the population to determine population density, thus allowing co-ordinate gene regulation in response to population density. In Pseudomonas aeruginosa, production of the QS signaling molecule, N-acyl homoserine lactone (AHL), co-ordinates expression of key factors of pathogenesis, including biofilm formation and toxin secretion. It is predicted that the inhibition of AHL sensing would provide an effective clinical treatment to reduce the expression of virulence factors and increase the effectiveness of antimicrobial agents. We previously demonstrated that sodium houttuyfonate (SH), commonly used in traditional Chinese medicine to treat infectious diseases, can effectively inhibit QS-regulated processes, including biofilm formation. Here, using a model system, we demonstrate that SH causes the dose-dependent inhibition of AHL production, through down-regulation of the AHL biosynthesis gene, lasI. Addition of SH also resulted in down-regulation of expression of the AHL sensor and transcriptional regulator, LasR, and inhibited the production of the QS-regulated virulence factors, pyocyanin and LasA. These results suggest that the antimicrobial activity of SH may be due to its ability to disrupt QS in P. aeruginosa. PMID:25505457

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

    PubMed

    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. PMID:26636765

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

    PubMed Central

    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. PMID:26636765

  3. Functional determinants of the quorum-sensing non-coding RNAs and their roles in target regulation.

    PubMed

    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.

  4. Inhibition of quorum sensing in Serratia marcescens AS-1 by synthetic analogs of N-acylhomoserine lactone.

    PubMed

    Morohoshi, Tomohiro; Shiono, Toshitaka; Takidouchi, Kiyomi; Kato, Masashi; Kato, Norihiro; Kato, Junichi; Ikeda, Tsukasa

    2007-10-01

    Quorum sensing is a regulatory system for controlling gene expression in response to increasing cell density. N-Acylhomoserine lactone (AHL) is produced by gram-negative bacteria, which use it as a quorum-sensing signal molecule. Serratia marcescens is a gram-negative opportunistic pathogen which is responsible for an increasing number of serious nosocomial infections. S. marcescens AS-1 produces N-hexanoyl homoserine lactone (C(6)-HSL) and N-(3-oxohexanoyl) homoserine lactone and regulates prodigiosin production, swarming motility, and biofilm formation by AHL-mediated quorum sensing. We synthesized a series of N-acyl cyclopentylamides with acyl chain lengths ranging from 4 to 12 and estimated their inhibitory effects on prodigiosin production in AS-1. One of these molecules, N-nonanoyl-cyclopentylamide (C(9)-CPA), had a strong inhibitory effect on prodigiosin production. C(9)-CPA also inhibited the swarming motility and biofilm formation of AS-1. A competition assay revealed that C(9)-CPA was able to inhibit quorum sensing at four times the concentration of exogenous C(6)-HSL and was more effective than the previously reported halogenated furanone. Our results demonstrated that C(9)-CPA was an effective quorum-sensing inhibitor for S. marcescens AS-1.

  5. RpoN Regulates Virulence Factors of Pseudomonas aeruginosa via Modulating the PqsR Quorum Sensing Regulator.

    PubMed

    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.

  6. Prevention of bacterial quorum sensing in aquifer materials and effect on bioclogging

    NASA Astrophysics Data System (ADS)

    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.

  7. Draft Genome Sequence of Aeromonas caviae Strain L12, a Quorum-Sensing Strain Isolated from a Freshwater Lake in Malaysia

    PubMed Central

    Chin, Pui-San; Tee, Kok Keng; Chang, Chien-Yi; Yin, Wai-Fong; Sheng, Kit-Yeng

    2015-01-01

    Here, we present the draft genome sequence of Aeromonas caviae strain L12, which shows quorum-sensing activity. The availability of this genome sequence is important to the research of the quorum-sensing regulatory system in this isolate. PMID:25745006

  8. N-acyl-L-homoserine lactone quorum sensing controls butanediol fermentation in Serratia plymuthica RVH1 and Serratia marcescens MG1.

    PubMed

    Van Houdt, Rob; Moons, Pieter; Hueso Buj, Maria; Michiels, Chris W

    2006-06-01

    Butanediol fermentation in two Serratia species is shown to be affected by N-acyl-L-homoserine lactone-dependent quorum sensing. Knockout of quorum-sensing signal production caused a shift towards enhanced acid production, resulting in early growth arrest, which was reversible by the addition of synthetic signal molecules.

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

    PubMed

    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. PMID:24055027

  10. Quorum Sensing Signal Synthesis May Represent a Selective Advantage Independent of Its Role in Regulation of Bioluminescence in Vibrio fischeri

    PubMed Central

    Chong, Grace; Kimyon, Önder; Manefield, Mike

    2013-01-01

    The evolution of biological signalling systems and apparently altruistic or cooperative traits in diverse organisms has required selection against the subversive tendencies of self-interested biological entities. The bacterial signalling and response system known as quorum sensing or Acylated Homoserine Lactone (AHL) mediated gene expression is thought to have evolved through kin selection. In this in vitro study on the model quorum sensing bioluminescent marine symbiont Vibrio fischeri, competition and long-term sub culturing experiments suggest that selection for AHL synthesis (encoded by the AHL synthase gene luxI) is independent of the quorum sensing regulated phenotype (bioluminescence encoded by luxCDABE). Whilst results support the hypothesis that signal response (AHL binding and transcriptional activation encoded by the luxR gene) is maintained through indirect fitness benefits (kin selection), signal synthesis is maintained in the V. fischeri genome over evolutionary time through direct fitness benefits at the individual level from an unknown function. PMID:23825662

  11. Inhibition of Candida albicans Biofilm Formation by Farnesol, a Quorum-Sensing Molecule

    PubMed Central

    Ramage, Gordon; Saville, Stephen P.; Wickes, Brian L.; López-Ribot, José L.

    2002-01-01

    Farnesol is a quorum-sensing molecule that inhibits filamentation in Candida albicans. Both filamentation and quorum sensing are deemed to be important factors in C. albicans biofilm development. Here we examined the effect of farnesol on C. albicans biofilm formation. C. albicans adherent cell populations (after 0, 1, 2, and 4 h of adherence) and preformed biofilms (24 h) were treated with various concentrations of farnesol (0, 3, 30, and 300 μM) and incubated at 37°C for 24 h. The extent and characteristics of biofilm formation were then assessed microscopically and with a semiquantitative colorimetric technique based on the use of 2,3-bis(2-methoxy-4-nitro-5-sulfo-phenyl)-2H-tetrazolium-5-carboxanilide. The results indicated that the effect of farnesol was dependent on the concentration of this compound and the initial adherence time, and preincubation with 300 μM farnesol completely inhibited biofilm formation. Supernatant media recovered from mature biofilms inhibited the ability of planktonic C. albicans to form filaments, indicating that a morphogenetic autoregulatory compound is produced in situ in biofilms. Northern blot analysis of RNA extracted from cells in biofilms indicated that the levels of expression of HWP1, encoding a hypha-specific wall protein, were decreased in farnesol-treated biofilms compared to the levels in controls. Our results indicate that farnesol acts as a naturally occurring quorum-sensing molecule which inhibits biofilm formation, and we discuss its potential for further development and use as a novel therapeutic agent. PMID:12406738

  12. Roles of Pseudomonas aeruginosa las and rhl Quorum-Sensing Systems in Control of Twitching Motility

    PubMed Central

    Glessner, Alex; Smith, Roger S.; Iglewski, Barbara H.; Robinson, Jayne B.

    1999-01-01

    Pseudomonas aeruginosa is a ubiquitous environmental bacterium and an important human pathogen. The production of several virulence factors by P. aeruginosa is controlled through two quorum-sensing systems, las and rhl. We have obtained evidence that both the las and rhl quorum-sensing systems are also required for type 4 pilus-dependent twitching motility and infection by the pilus-specific phage D3112cts. Mutants which lack the ability to synthesize PAI-1, PAI-2, or both autoinducers were significantly or greatly impaired in twitching motility and in susceptibility to D3112cts. Twitching motility and phage susceptibility in the autoinducer-deficient mutants were partially restored by exposure to exogenous PAI-1 and PAI-2. Both twitching motility and infection by pilus-specific phage are believed to be dependent on the extension and retraction of polar type 4 pili. Western blot analysis of whole-cell lysates and enzyme-linked immunosorbent assays of intact cells were used to measure the amounts of pilin on the cell surfaces of las and rhl mutants relative to that of the wild type. It appears that PAI-2 plays a crucial role in twitching motility and phage infection by affecting the export and assembly of surface type 4 pili. The ability of P. aeruginosa cells to adhere to human bronchial epithelial cells was also found to be dependent on the rhl quorum-sensing system. Microscopic analysis of twitching motility indicated that mutants which were unable to synthesize PAI-1 were defective in the maintenance of cellular monolayers and migrating packs of cells. Thus, PAI-1 appears to have an essential role in maintaining cell-cell spacing and associations required for effective twitching motility. PMID:10049396

  13. Nonenzymatic turnover of an Erwinia carotovora quorum-sensing signaling molecule.

    PubMed

    Byers, Joseph T; Lucas, Claire; Salmond, George P C; Welch, Martin

    2002-02-01

    The production of virulence factors and carbapenem antibiotic in the phytopathogen Erwinia carotovora is under the control of quorum sensing. The quorum-sensing signaling molecule, N-(3-oxohexanoyl)-L-homoserine lactone (OHHL), accumulates in log-phase culture supernatants of E. carotovora but diminishes in concentration during the stationary phase. In this study, we show that the diminution in OHHL was not due to sequestration of the ligand by the cells, although some partitioning did occur. Rather, it was caused by degradation of the molecule. The rate of stationary-phase degradation of OHHL was as rapid as the rate of log-phase accumulation of the ligand, but it was nonenzymatic and led to a decrease in the expression of selected genes known to be under the control of quorum sensing. The degradation of OHHL was dependent on the pH of the supernatant, which increased as the growth curve progressed in cultures grown in Luria-Bertani medium from pH 7 to approximately 8.5. OHHL became unstable over a narrow pH range (pH 7 to 8). Instability was increased at high temperatures even at neutral pH but could be prevented at the growth temperature (30 degrees C) by buffering the samples at pH 6.8. These results may provide a rationale for the observation that an early response of plants which are under attack by Erwinia is to activate a proton pump which alkalizes the site of infection to a pH of >8.2.

  14. Airway Epithelial Cell Integrity Protects from Cytotoxicity of Pseudomonas aeruginosa Quorum-Sensing Signals.

    PubMed

    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.

  15. Attenuation of adhesion, quorum sensing and biofilm mediated virulence of carbapenem resistant Escherichia coli by selected natural plant products.

    PubMed

    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.

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

    PubMed

    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.

  17. Discovery of potent inhibitors of pseudomonal quorum sensing via pharmacophore modeling and in silico screening.

    PubMed

    Taha, Mutasem O; Al-Bakri, Amal G; Zalloum, Waleed A

    2006-11-15

    HipHop-Refine was employed to derive a binding hypothesis for pseudomonal quorum sensing (QS) antagonists. The model was employed as 3D search query to screen the National Cancer Institute (NCI) database. One of the hits illustrated nanomolar QS inhibitory activity. The fact that this compound contained tetravalent lead (Pb) prompted us to evaluate the activities of phenyl mercuric nitrate and thimerosal, both fit the binding pharmacophore. The two mercurials illustrated nanomolar to low micromolar IC50 inhibitory values against pseudomonal QS. The three compounds represent a new class of QS inhibitors. PMID:16945524

  18. Social interactions in the Burkholderia cepacia complex: biofilms and quorum sensing.

    PubMed

    Coenye, Tom

    2010-07-01

    Burkholderia cepacia complex bacteria are opportunistic pathogens that cause respiratory tract infections in susceptible patients, mainly people with cystic fibrosis. There is convincing evidence that B. cepacia complex bacteria can form biofilms, not only on abiotic surfaces (e.g., glass and plastics), but also on biotic surfaces such as epithelial cells, leading to the suggestion that biofilm formation plays a key role in persistent infection of cystic fibrosis lungs. This article presents an overview of the molecular mechanisms involved in B. cepacia complex biofilm formation, the increased resistance of sessile B. cepacia complex cells and the role of quorum sensing in B. cepacia complex biofilm formation.

  19. N-Sulfonyl homoserine lactones as antagonists of bacterial quorum sensing.

    PubMed

    Castang, Sandra; Chantegrel, Bernard; Deshayes, Christian; Dolmazon, René; Gouet, Patrice; Haser, Richard; Reverchon, Sylvie; Nasser, William; Hugouvieux-Cotte-Pattat, Nicole; Doutheau, Alain

    2004-10-18

    A series of 11 new analogues of N-acylhomoserine lactones in which the carboxamide bond was replaced by a sulfonamide one, has been synthesised. These compounds were evaluated for their ability to competitively inhibit the action of 3-oxohexanoyl-L-homoserine lactone, the natural ligand of the quorum sensing transcriptional regulator LuxR, which in turn activates expression of bioluminescence in the model bacterium Vibrio fischeri. Several compounds were found to display antagonist activity. Molecular modeling suggests that the latter prevent a cascade of structural rearrangements necessary for the formation of the active LuxR dimer.

  20. Suppression of biofilm related, device-associated infections by staphylococcal quorum sensing inhibitors.

    PubMed

    Kiran, M D; Giacometti, A; Cirioni, O; Balaban, N

    2008-09-01

    Staphylococcal spp. are notorious for causing biofilm-related device-associated infections, leading to tens of thousands of deaths per year. In this paper, we review quorum sensing inhibitors as potential therapeutics for even the most persistent infections. The animal models reviewed are subcutaneous graft, central venous catheter (CVC), ureteral stent and wound models, and a wound case study. The therapeutic approaches reviewed are the use of RNAIII inhibiting peptide (RIP) and its non-peptide analog. These have been shown to prevent or treat infections caused by any staphylococcal strain tested, including antibiotic-resistant strains like CA-MRSA USA300.

  1. Discovery of potent inhibitors of pseudomonal quorum sensing via pharmacophore modeling and in silico screening.

    PubMed

    Taha, Mutasem O; Al-Bakri, Amal G; Zalloum, Waleed A

    2006-11-15

    HipHop-Refine was employed to derive a binding hypothesis for pseudomonal quorum sensing (QS) antagonists. The model was employed as 3D search query to screen the National Cancer Institute (NCI) database. One of the hits illustrated nanomolar QS inhibitory activity. The fact that this compound contained tetravalent lead (Pb) prompted us to evaluate the activities of phenyl mercuric nitrate and thimerosal, both fit the binding pharmacophore. The two mercurials illustrated nanomolar to low micromolar IC50 inhibitory values against pseudomonal QS. The three compounds represent a new class of QS inhibitors.

  2. Inhibition of quorum sensing in Pseudomonas aeruginosa by two herbal essential oils from Apiaceae family.

    PubMed

    Sepahi, Ehsan; Tarighi, Saeed; Ahmadi, Farajollah Shahriari; Bagheri, Abdolreza

    2015-02-01

    Ferula (Ferula asafoetida L.) and Dorema (Dorema aucheri Bioss.) both from Apiaceae family were tested for their anti-quorum sensing (QS) activity against Pseudomonas aeruginosa. Both essential oils exhibited anti-QS activity at 25 μg/ml of concenteration. At this concenteration Ferula fully abolished and Dorema reduced the violacein production by C. violaceum. Pyocyanin, pyoverdine, elastase and biofilm production were decreased in Ferula oil treatments. Dorema oil reduced pyoverdine and elastase production, while pyocyanin and biofilm production were not affacted. Expresion analysis of QS-dependent genes confirmed our phenotypic data. Our data introduced native Dorema and Ferula plants as novel QS and virulence inhibitors. PMID:25564444

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

    NASA Astrophysics Data System (ADS)

    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.

  4. Collective Behavior of Quorum-Sensing Run-and-Tumble Particles under Confinement

    NASA Astrophysics Data System (ADS)

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  6. DqsIR quorum sensing-mediated gene regulation of the extremophilic bacterium Deinococcus radiodurans in response to oxidative stress.

    PubMed

    Lin, Lin; Dai, Shang; Tian, Bing; Li, Tao; Yu, Jiangliu; Liu, Chengzhi; Wang, Liangyan; Xu, Hong; Zhao, Ye; Hua, Yuejin

    2016-05-01

    Here, we show that AHLs can be employed by Deinococcus radiodurans, which belongs to the unique phylum Deinococcus-Thermus and is known for its cellular resistance to environmental stresses. An AHL-mediated quorum-sensing system (DqsI/DqsR) was identified in D. radiodurans. We found that under non-stress conditions, the AHL level was "shielded" by quorum quenching enzymes, whereas AHLs accumulated when D. radiodurans was exposed to oxidative stress. Upon exposure to H2 O2 , AHL synthetic enzymes (DqsI) were immediately induced, while the expression of quorum-quenching enzymes began to increase approximately 30 min after exposure to H2 O2 , as shown by time-course analyses of gene expression. Both dqsI mutant (DMDqsI) and dqsR mutant (MDqsR) were more sensitive to oxidative stress compared with the wild-type strain. Exogenous AHLs (5 μM) could completely restore the survival fraction of DMDqsI under oxidative stress. RNA-seq analysis showed that a number of genes involved in stress-response, cellular cleansing, and DNA repair had altered transcriptional levels in MDqsR. The DqsR, acting as a regulator of quorum sensing, controls gene expression along with AHLs. Hence, the DqsIR-mediated quorum sensing that mediates gene regulation is an adaptive strategy for D. radiodurans in response to oxidative stresses and is conserved in the extremophilic Deinococcus bacteria.

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

    PubMed

    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. Inhaled Lactonase Reduces Pseudomonas aeruginosa Quorum Sensing and Mortality in Rat Pneumonia

    PubMed Central

    Lafleur, John; Lepidi, Hubert; Papazian, Laurent; Rolain, Jean-Marc; Raoult, Didier; Elias, Mikael; Silby, Mark W.; Bzdrenga, Janek; Bregeon, Fabienne; Chabriere, Eric

    2014-01-01

    Rationale The effectiveness of antibiotic molecules in treating Pseudomonas aeruginosa pneumonia is reduced as a result of the dissemination of bacterial resistance. The existence of bacterial communication systems, such as quorum sensing, has provided new opportunities of treatment. Lactonases efficiently quench acyl-homoserine lactone-based bacterial quorum sensing, implicating these enzymes as potential new anti-Pseudomonas drugs that might be evaluated in pneumonia. Objectives The aim of the present study was to evaluate the ability of a lactonase called SsoPox-I to reduce the mortality of a rat P. aeruginosa pneumonia. Methods To assess SsoPox-I-mediated quorum quenching, we first measured the activity of the virulence gene lasB, the synthesis of pyocianin, the proteolytic activity of a bacterial suspension and the formation of biofilm of a PAO1 strain grown in the presence of lactonase. In an acute lethal model of P. aeruginosa pneumonia in rats, we evaluated the effects of an early or deferred intra-tracheal treatment with SsoPox-I on the mortality, lung bacterial count and lung damage. Measurements and Primary Results SsoPox-I decreased PAO1 lasB virulence gene activity, pyocianin synthesis, proteolytic activity and biofilm formation. The early use of SsoPox-I reduced the mortality of rats with acute pneumonia from 75% to 20%. Histological lung damage was significantly reduced but the lung bacterial count was not modified by the treatment. A delayed treatment was associated with a non-significant reduction of mortality. Conclusion These results demonstrate the protective effects of lactonase SsoPox-I in P. aeruginosa pneumonia and open the way for a future therapeutic use. PMID:25350373

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

    PubMed

    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.

  10. A Quorum-Sensing Factor in Vegetative Dictyostelium Discoideum Cells Revealed by Quantitative Migration Analysis

    PubMed Central

    Golé, Laurent; Rivière, Charlotte; Hayakawa, Yoshinori; Rieu, Jean-Paul

    2011-01-01

    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 (), 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. PMID:22073217

  11. Evidence for quorum sensing and differential metabolite production by a marine bacterium in response to DMSP.

    PubMed

    Johnson, Winifred M; Kido Soule, Melissa C; Kujawinski, Elizabeth B

    2016-09-01

    Microbes, the foundation of the marine foodweb, do not function in isolation, but rather rely on molecular level interactions among species to thrive. Although certain types of interactions between autotrophic and heterotrophic microorganisms have been well documented, the role of specific organic molecules in regulating inter-species relationships and supporting growth are only beginning to be understood. Here, we examine one such interaction by characterizing the metabolic response of a heterotrophic marine bacterium, Ruegeria pomeroyi DSS-3, to growth on dimethylsulfoniopropionate (DMSP), an abundant organosulfur metabolite produced by phytoplankton. When cultivated on DMSP, R. pomeroyi synthesized a quorum-sensing molecule, N-(3-oxotetradecanoyl)-l-homoserine lactone, at significantly higher levels than during growth on propionate. Concomitant with the production of a quorum-sensing molecule, we observed differential production of intra- and extracellular metabolites including glutamine, vitamin B2 and biosynthetic intermediates of cyclic amino acids. Our metabolomics data indicate that R. pomeroyi changes regulation of its biochemical pathways in a manner that is adaptive for a cooperative lifestyle in the presence of DMSP, in anticipation of phytoplankton-derived nutrients and higher microbial density. This behavior is likely to occur on sinking marine particles, indicating that this response may impact the fate of organic matter. PMID:26882264

  12. Sustained Release of a Novel Anti-Quorum-Sensing Agent against Oral Fungal Biofilms

    PubMed Central

    Feldman, Mark; Shenderovich, Julia; Al-Quntar, Abed Al Aziz; Friedman, Michael

    2015-01-01

    Thiazolidinedione-8 (S-8) has recently been identified as a potential anti-quorum-sensing/antibiofilm agent against bacteria and fungi. Based on these results, we investigated the possibility of incorporating S-8 in a sustained-release membrane (SRM) to increase its pharmaceutical potential against Candida albicans biofilm. We demonstrated that SRM containing S-8 inhibits fungal biofilm formation in a time-dependent manner for 72 h, due to prolonged release of S-8. Moreover, the SRM effectively delivered the agent in its active form to locations outside the membrane reservoir. In addition, eradication of mature biofilm by the SRM containing S-8 was also significant. Of note, S-8-containing SRM affected the characteristics of mature C. albicans biofilm, such as thickness, exopolysaccharide (EPS) production, and morphogenesis of fungal cells. The concept of using an antibiofilm agent with no antifungal activity incorporated into a sustained-release delivery system is new in medicine and dentistry. This concept of an SRM containing a quorum-sensing quencher with an antibiofilm effect could pave the way for combating oral fungal infectious diseases. PMID:25645835

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

    PubMed

    Ta, Chieu Anh Kim; Arnason, John Thor

    2015-01-01

    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. PMID:26712734

  14. Anti-quorum sensing activity of essential oils from Colombian plants.

    PubMed

    Jaramillo-Colorado, Beatriz; Olivero-Verbel, Jesus; Stashenko, Elena E; Wagner-Döbler, Irene; Kunze, Brigitte

    2012-01-01

    Essential oils from Colombian plants were characterised by GC-MS, and assayed for anti-quorum sensing activity in bacteria sensor strains. Two major chemotypes were found for Lippia alba, the limonene-carvone and the citral (geranial-neral). For other species, the main components included α-pinene (Ocotea sp.), β-pinene (Swinglea glutinosa), cineol (Elettaria cardamomun), α-zingiberene (Zingiber officinale) and pulegone (Minthostachys mollis). Several essential oils presented promising inhibitory properties for the short chain AHL quorum sensing (QS) system, in Escherichia coli containing the biosensor plasmid pJBA132, in particular Lippia alba. Moderate activity as anti-QS using the same plasmid, were also found for selected constituents of essential oils studied here, such as citral, carvone and α-pinene, although solely at the highest tested concentration (250 µg mL(-1)). Only citral presented some activity for the long chain AHL QS system, in Pseudomonas putida containing the plasmid pRK-C12. In short, essential oils from Colombian flora have promising properties as QS modulators. PMID:21936639

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

    PubMed

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

    2016-01-01

    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. PMID:27463706

  16. Quorum sensing and biofilm formation investigated using laser-trapped bacterial arrays

    NASA Astrophysics Data System (ADS)

    Gordon, Vernita; Butler, John; Smalyukh, Ivan; Parsek, Matthew; Wong, Gerard

    2008-03-01

    Studies of individual, free-swimming (planktonic) bacteria have yielded much information about their genetic and phenotypic characteristics and about ``quorum sensing,'' the autoinducing process by which bacteria detect high concentrations of other bacteria. However, in most environments the majority of bacteria are not in the planktonic form but are rather in biofilms, which are highly-structured, dynamic communities of multiple bacteria that adhere to a surface and to each other using an extracellular polysaccharide matrix. Bacteria in biofilms are phenotypically very different from their genetically-identical planktonic counterparts. Among other characteristics, they are much more antibiotic-resistant and virulent. Such biofilms form persistent infections on medical implants and in the lungs of cystic fibrosis patients, where Pseudomonas aeruginosa biofilms are the leading cause of lung damage and, ultimately, death. To understand the importance of different extracellular materials, motility mechanisms, and quorum sensing for biofilm formation and stability, we use single-gene knockout mutants and an infrared laser trap to create a bacterial aggregate that serves as a model biofilm and allows us to measure the importance of these factors as a function of trapping time, surface, and nutritional environment.

  17. Is Quorum Sensing Interference a Viable Alternative to Treat Pseudomonas aeruginosa Infections?

    PubMed Central

    García-Contreras, Rodolfo

    2016-01-01

    Quorum sensing (QS) coordinates the expression of multiple virulence factors in Pseudomonas aeruginosa; hence its inhibition has been postulated as a new alternative to treat its infections. In particular, QS interference approaches claim that they attenuate bacterial virulence without directly decreasing bacterial growth and suggest that in vivo the immune system would control the infections. Moreover, since in vitro experiments performed in rich medium demonstrate that interfering with QS decreases the production of virulence factors without affecting bacterial growth it was assumed than in vivo therapies will minimize the selection of resistant strains. Therefore, the underlying assumptions toward an effective implementation of a successful Quorum sensing interference (QSI) therapy for treating P. aeruginosa infections are that (i) QS only exerts important effects in the regulation of virulence genes but it does not affect metabolic processes linked to growth, (ii) the expression of virulence factors is only positively regulated by QS, (iii) inhibition of virulence factors in vivo do not affect bacterial growth, (iv) the immune system of the infected patients will be able to get rid of the infections, and (v) the therapy will be effective in the strains that are actively producing the infections. Nevertheless, for QSI in P. aeruginosa, substantial experimental evidence against the validity of most of these assumptions has accumulated during the past years, suggesting that a far better understanding of its virulence and its behavior during infections is needed in order to design truly solid QSI therapeutic alternatives to combat this remarkable pathogen. PMID:27683577

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

    PubMed Central

    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. PMID:25477905

  19. Determinants governing ligand specificity of the Vibrio harveyi LuxN quorum-sensing receptor.

    PubMed

    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. Hydnophytum formicarum Jack ethanol extract modulates quorum sensing-controlled pathogenicity in Pseudomonas aeruginosa.

    PubMed

    Hertiani, Triana; Pratiwi, Sylvia Utami Tunjung

    2015-09-01

    The discovery of new mechanism to control microbial pathogenicity by quorum sensing modulation has generated the search for quorum sensing inhibitor from natural resources. The objective of this research was to evaluate the ability of Hydnophytum formicarum Jack (Rubiaceae) ethanol extract to antagonize cell-to cell communication. Pulverized H. formicarum tuber was macerated in ethyl alcohol 96% and evaporated to yield ethanol extract. A dillution technique using Luria-Bertani (LB) medium was used to observe the capability of the extract to reduce the violacein production in Chromobacterium violaceum. Samples in two-fold dilution were prepared to obtain 2 - 0.0625 mg/mL concentration. The effects on swimming, swarming and twitching motility as well as the formation of biofilm towards Pseudomonas aeruginosa PAO1 were recorded over control. All experiments were done in triplicate. The architecture of Ps. aeruginosa biofilm treated with samples was examined by CLSM (Confocal Laser Scanning Microscopy) . Our results suggested that the ethanol extract of H. formicarum caused violacein production inhibition. Furthermore, inhibition of Ps. aeruginosa motility and biofilm formation were recorded to be significant over control in a concentration dependent manner. H. formicarum serves as a potential source for new QS-based antibacterial drugs towards Ps. aeruginosa. PMID:26408889

  1. Silencing quorum sensing and ICE mobility through antiactivation and ribosomal frameshifting

    PubMed Central

    Ramsay, Joshua P; Ronson, Clive W

    2015-01-01

    Mobile genetic elements run an evolutionary gauntlet to maintain their mobility in the face of selection against their selfish dissemination but, paradoxically, they can accelerate the adaptability of bacteria through the gene-transfer events that they facilitate. These temporally conflicting evolutionary forces have shaped exquisite regulation systems that silence mobility and maximize the competitive fitness of the host bacterium, but maintain the ability of the element to deliver itself to a new host should the opportunity arise. Here we review the excision regulation system of the Mesorhizobium loti symbiosis island ICEMlSymR7A, a 502-kb integrative and conjugative element (ICE) capable of converting non-symbiotic mesorhizobia into plant symbionts. ICEMlSymR7A excision is activated by quorum sensing, however, both quorum sensing and excision are strongly repressed in the vast majority of cells by dual-target antiactivation and programmed ribosomal-frameshifting mechanisms. We examine these recently discovered regulatory features under the light of natural selection and discuss common themes that can be drawn from recent developments in ICE biology. PMID:26942047

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

    PubMed

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

    2014-01-01

    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.

  3. Evidence for quorum sensing and differential metabolite production by a marine bacterium in response to DMSP

    PubMed Central

    Johnson, Winifred M; Kido Soule, Melissa C; Kujawinski, Elizabeth B

    2016-01-01

    Microbes, the foundation of the marine foodweb, do not function in isolation, but rather rely on molecular level interactions among species to thrive. Although certain types of interactions between autotrophic and heterotrophic microorganisms have been well documented, the role of specific organic molecules in regulating inter-species relationships and supporting growth are only beginning to be understood. Here, we examine one such interaction by characterizing the metabolic response of a heterotrophic marine bacterium, Ruegeria pomeroyi DSS-3, to growth on dimethylsulfoniopropionate (DMSP), an abundant organosulfur metabolite produced by phytoplankton. When cultivated on DMSP, R. pomeroyi synthesized a quorum-sensing molecule, N-(3-oxotetradecanoyl)-l-homoserine lactone, at significantly higher levels than during growth on propionate. Concomitant with the production of a quorum-sensing molecule, we observed differential production of intra- and extracellular metabolites including glutamine, vitamin B2 and biosynthetic intermediates of cyclic amino acids. Our metabolomics data indicate that R. pomeroyi changes regulation of its biochemical pathways in a manner that is adaptive for a cooperative lifestyle in the presence of DMSP, in anticipation of phytoplankton-derived nutrients and higher microbial density. This behavior is likely to occur on sinking marine particles, indicating that this response may impact the fate of organic matter. PMID:26882264

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

    PubMed

    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.

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

    PubMed Central

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

    2014-01-01

    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. PMID:24625739

  6. Towards Predictive Modeling of Information Processing in Microbial Ecosystems With Quorum-Sensing Interactions

    NASA Astrophysics Data System (ADS)

    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-

  7. Quantum gate circuit model of signal integration in bacterial quorum sensing.

    PubMed

    Karafyllidis, Ioannis G

    2012-01-01

    Bacteria evolved cell to cell communication processes to gain information about their environment and regulate gene expression. Quorum sensing is such a process in which signaling molecules, called autoinducers, are produced, secreted and detected. In several cases bacteria use more than one autoinducers and integrate the information conveyed by them. It has not yet been explained adequately why bacteria evolved such signal integration circuits and what can learn about their environments using more than one autoinducers since all signaling pathways merge in one. Here quantum information theory, which includes classical information theory as a special case, is used to construct a quantum gate circuit that reproduces recent experimental results. Although the conditions in which biosystems exist do not allow for the appearance of quantum mechanical phenomena, the powerful computation tools of quantum information processing can be carefully used to cope with signal and information processing by these complex systems. A simulation algorithm based on this model has been developed and numerical experiments that analyze the dynamical operation of the quorum sensing circuit were performed for various cases of autoinducer variations, which revealed that these variations contain significant information about the environment in which bacteria exist.

  8. Study of Signal Detection, Integration, and Propagation in Quorum Sensing at the Single Cell Level

    NASA Astrophysics Data System (ADS)

    Long, Tao; Bassler, Bonnie; Wingreen, Ned

    2007-03-01

    Bacteria respond to their environment and to each other and accordingly adjust their gene-expression levels. Accurate signal detection, appropriate signal integration, and faithful signal propagation are essential for a cell to make correct adjustments in response to various extracellular cues. To better understand this information processing by living cells, we studied a model system -- the quorum-sensing circuit in Vibrio harveyi. Quorum sensing is a process in which bacteria communicate with each other by diffusible chemical molecules, termed ``autoinducers'', to commit to coordinated developmental decisions. Three types of autoinducers are detected coincidently by three parallel receptors. The signals are then integrated into the same signaling pathway and propagated by phosphorylation or dephosphorylation of the pathway components. To quantitatively measure the intracellular response, we applied a fluorescent protein reporter, whose production is regulated by a phosphorylated protein in the pathway. By single-cell microscopy, we can explore features of this information-processing circuit such as coincidence detection, signal integration, noise reduction or filtering, and especially the fidelity in signal processing achieved in the presence of inevitable fluctuations.

  9. Is Quorum Sensing Interference a Viable Alternative to Treat Pseudomonas aeruginosa Infections?

    PubMed

    García-Contreras, Rodolfo

    2016-01-01

    Quorum sensing (QS) coordinates the expression of multiple virulence factors in Pseudomonas aeruginosa; hence its inhibition has been postulated as a new alternative to treat its infections. In particular, QS interference approaches claim that they attenuate bacterial virulence without directly decreasing bacterial growth and suggest that in vivo the immune system would control the infections. Moreover, since in vitro experiments performed in rich medium demonstrate that interfering with QS decreases the production of virulence factors without affecting bacterial growth it was assumed than in vivo therapies will minimize the selection of resistant strains. Therefore, the underlying assumptions toward an effective implementation of a successful Quorum sensing interference (QSI) therapy for treating P. aeruginosa infections are that (i) QS only exerts important effects in the regulation of virulence genes but it does not affect metabolic processes linked to growth, (ii) the expression of virulence factors is only positively regulated by QS, (iii) inhibition of virulence factors in vivo do not affect bacterial growth, (iv) the immune system of the infected patients will be able to get rid of the infections, and (v) the therapy will be effective in the strains that are actively producing the infections. Nevertheless, for QSI in P. aeruginosa, substantial experimental evidence against the validity of most of these assumptions has accumulated during the past years, suggesting that a far better understanding of its virulence and its behavior during infections is needed in order to design truly solid QSI therapeutic alternatives to combat this remarkable pathogen.

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

    PubMed

    Ta, Chieu Anh Kim; Arnason, John Thor

    2015-12-26

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  12. Effect of the quorum-sensing luxS gene on biofilm formation by Enterococcus faecalis.

    PubMed

    He, Zhiyan; Liang, Jingping; Zhou, Wei; Xie, Qian; Tang, Zisheng; Ma, Rui; Huang, Zhengwei

    2016-06-01

    Enterococcus faecalis is the species of bacterium most frequently isolated from the root canals of teeth that exhibit chronic apical periodontitis refractory to endodontic treatment. In this study, we evaluated the effect of the S-ribosylhomocysteine lyase (luxS) quorum-sensing gene on E. faecalis biofilm formation by constructing a knockout mutant. The biofilms formed by both E. faecalis and its luxS mutant strain were evaluated using the MTT method. Important parameters that influence biofilm formation, including cell-surface hydrophobicity and the nutrient content of the growth medium, were also studied. Biofilm structures were observed using confocal laser scanning microscopy (CLSM), and expression of biofilm-related genes was investigated using RT-PCR. The results showed that the luxS gene can affect biofilm formation, whereas it does not affect the bacterial growth rate. Deletion of the luxS gene also increased cell-surface hydrophobicity. Biofilm formation was accelerated by the addition of increasing concentrations of glucose. The CLSM images revealed that the luxS mutant strain tends to aggregate into distinct clusters and relatively dense structures, whereas the wild-type strain appears confluent and more evenly distributed. All genes examined were up-regulated in the biofilms formed by the luxS mutant strain. The quorum-sensing luxS gene can affect E. faecalis biofilm formation.

  13. ``Quorum sensing'' generated multistability and chaos in a synthetic genetic oscillator

    NASA Astrophysics Data System (ADS)

    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.

  14. Regulation of Yersina pestis Virulence by AI-2 Mediated Quorum Sensing

    SciTech Connect

    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

  15. The function of SpnR and the inhibitory effects by halogenated furanone on quorum sensing in Serratia marcescens AS-1.

    PubMed

    Tao, Yinlu; Morohoshi, Tomohiro; Kato, Norihiro; Ikeda, Tsukasa; Zhuang, Huisheng

    2008-03-01

    By secretion and detection of a series of signaling molecules, bacteria are able to coordinate gene expression as a community, to regulate a variety of important phenotypes, from virulence factor production to biofilm formation to symbiosis related behaviours such as bioluminescence. This widespread signaling mechanism is called quorum sensing. There are several quorum sensing systems described in Serratia. Serratia marcescens AS-1, isolated from soil, had the LuxI/LuxR homologues called SpnI/SpnR. S. marcescens AS-1 produced two kinds of N-acyl-L-homoserine lactones, N-hexanoyl-L-homoserine lactone and N-(3-oxohexanoyl)-L-homoserine lactone as signal molecules, which involved in quorum sensing to control the gene expression in response to increased cell density. By gene replacement method, the spnR mutant was constructed, named S. marcescens AS-1R. SpnR acted as a negative regulator for the production of prodigiosin, swarming motility and biofilm formation, which were regulated by quorum sensing. Halogenated furanone, known as a natural inhibitor of quorum sensing, could effectively inhibit the quorum sensing of S. marcescens AS-1 but without interrupting AHL-SpnR interaction. All results will be helpful to understand the mechanisms of halogenated furanone inhibition on quorum sensing and the potential application of halogenated furanone in effectively preventing infection disease caused by Serratia strains.

  16. Integration of Metabolic and Quorum Sensing Signals Governing the Decision to Cooperate in a Bacterial Social Trait.

    PubMed

    Boyle, Kerry E; Monaco, Hilary; van Ditmarsch, Dave; Deforet, Maxime; Xavier, Joao B

    2015-05-01

    Many unicellular organisms live in multicellular communities that rely on cooperation between cells. However, cooperative traits are vulnerable to exploitation by non-cooperators (cheaters). We expand our understanding of the molecular mechanisms that allow multicellular systems to remain robust in the face of cheating by dissecting the dynamic regulation of cooperative rhamnolipids required for swarming in Pseudomonas aeruginosa. We combine mathematical modeling and experiments to quantitatively characterize the integration of metabolic and population density signals (quorum sensing) governing expression of the rhamnolipid synthesis operon rhlAB. The combined computational/experimental analysis reveals that when nutrients are abundant, rhlAB promoter activity increases gradually in a density dependent way. When growth slows down due to nutrient limitation, rhlAB promoter activity can stop abruptly, decrease gradually or even increase depending on whether the growth-limiting nutrient is the carbon source, nitrogen source or iron. Starvation by specific nutrients drives growth on intracellular nutrient pools as well as the qualitative rhlAB promoter response, which itself is modulated by quorum sensing. Our quantitative analysis suggests a supply-driven activation that integrates metabolic prudence with quorum sensing in a non-digital manner and allows P. aeruginosa cells to invest in cooperation only when the population size is large enough (quorum sensing) and individual cells have enough metabolic resources to do so (metabolic prudence). Thus, the quantitative description of rhlAB regulatory dynamics brings a greater understating to the regulation required to make swarming cooperation stable. PMID:26102206

  17. Integration of Metabolic and Quorum Sensing Signals Governing the Decision to Cooperate in a Bacterial Social Trait

    PubMed Central

    Boyle, Kerry E.; Monaco, Hilary; van Ditmarsch, Dave; Deforet, Maxime; Xavier, Joao B.

    2015-01-01

    Many unicellular organisms live in multicellular communities that rely on cooperation between cells. However, cooperative traits are vulnerable to exploitation by non-cooperators (cheaters). We expand our understanding of the molecular mechanisms that allow multicellular systems to remain robust in the face of cheating by dissecting the dynamic regulation of cooperative rhamnolipids required for swarming in Pseudomonas aeruginosa. We combine mathematical modeling and experiments to quantitatively characterize the integration of metabolic and population density signals (quorum sensing) governing expression of the rhamnolipid synthesis operon rhlAB. The combined computational/experimental analysis reveals that when nutrients are abundant, rhlAB promoter activity increases gradually in a density dependent way. When growth slows down due to nutrient limitation, rhlAB promoter activity can stop abruptly, decrease gradually or even increase depending on whether the growth-limiting nutrient is the carbon source, nitrogen source or iron. Starvation by specific nutrients drives growth on intracellular nutrient pools as well as the qualitative rhlAB promoter response, which itself is modulated by quorum sensing. Our quantitative analysis suggests a supply-driven activation that integrates metabolic prudence with quorum sensing in a non-digital manner and allows P. aeruginosa cells to invest in cooperation only when the population size is large enough (quorum sensing) and individual cells have enough metabolic resources to do so (metabolic prudence). Thus, the quantitative description of rhlAB regulatory dynamics brings a greater understating to the regulation required to make swarming cooperation stable. PMID:26102206

  18. Effect of a BlpC-based quorum-sensing induction peptide on bacteriocin production in Streptococcus thermophiles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacteriocin synthesis in Streptococcus thermophilus is controlled by a complex blp locus. High levels of bacteriocin are produced only if the quorum-sensing regulatory mechanism is activated by the 30mer induction peptide (QSIP) which is embedded in the BlpC protein product of the blpC component. T...

  19. Pandoraea sp. Strain E26: Discovery of Its Quorum-Sensing Properties via Whole-Genome Sequence Analysis.

    PubMed

    Chan, Kok-Gan; Yin, Wai-Fong; Tee, Kok Keng; Chang, Chien-Yi; Priya, Kumutha

    2015-01-01

    We report the draft genome sequence of Pandoraea sp. strain E26 isolated from a former landfill site, sequenced by the Illumina MiSeq platform. This genome sequence will be useful to further understand the quorum-sensing system of this isolate. PMID:26021935

  20. Draft Genome Sequence of Pseudoalteromonas tetraodonis Strain MQS005, a Bacterium with Potential Quorum-Sensing Regulation.

    PubMed

    Pan, Yonglong; Wang, Yanbo; Yan, Xiaoqing; Mazumder, Asit; Liang, Yan

    2016-01-01

    We present here the draft genome sequence of Pseudoalteromonas tetraodonis strain MQS005, a bacterium possessing potential quorum-sensing regulatory activity. This strain was isolated from water from the South China Sea, People's Republic of China. The assembly consists of 4,252,538 bp and contains 144 contigs, with a G+C content of 41.85%. PMID:27491986

  1. Programming the quorum sensing-based AND gate in Shewanella oneidensis for logic gated-microbial fuel cells.

    PubMed

    Hu, Yidan; Yang, Yun; Katz, Evgeny; Song, Hao

    2015-03-11

    An AND logic gate based on a synthetic quorum-sensing (QS) module was constructed in a Shewanella oneidensis MR-1 mtrA knockout mutant. The presence of two input signals activated the expression of a periplasmic decaheme cytochrome MtrA to regenerate the extracellular electron transfer conduit, enabling the construction of AND-gated microbial fuel cells.

  2. Genomic Insights of Pectobacterium carotovorum Strain M022 Quorum-Sensing Activity through Whole-Genome Sequencing.

    PubMed

    Chan, Kok-Gan; Tan, Wen-Si

    2015-01-01

    Pectobacterium carotovorum is known to cause serious damage to various major crops worldwide. Here, we report the draft genome of Pectobacterium carotovorum strain M022, a freshwater isolate from a Malaysian waterfall, which has been reported as a plant pathogen and is able to communicate with N-acylhomoserine lactone-mediated quorum sensing. PMID:25676763

  3. Insights into the Quorum-Sensing Activity in Aeromonas hydrophila Strain M013 as Revealed by Whole-Genome Sequencing.

    PubMed

    Tan, Wen-Si; Yin, Wai-Fong; Chan, Kok-Gan

    2015-01-01

    Aeromonas hydrophila species can be found in warm climates and can survive in different environments. They possess the ability to communicate within their populations, which is known as quorum sensing. In this work, we present the draft genome sequence of A. hydrophila M013, a bacterium isolated from a Malaysian tropical rainforest waterfall. PMID:25555739

  4. Integration host factor and LuxR synergistically bind DNA to coactivate quorum-sensing genes in Vibrio harveyi.

    PubMed

    Chaparian, Ryan R; Olney, Stephen G; Hustmyer, Christine M; Rowe-Magnus, Dean A; van Kessel, Julia C

    2016-09-01

    The cell-cell signaling process called quorum sensing allows bacteria to control behaviors in response to changes in population density. In Vibrio harveyi, the master quorum-sensing transcription factor LuxR is a member of the TetR family of transcription factors that both activates and represses genes to coordinate group behaviors, including bioluminescence. Here, we show that integration host factor (IHF) is a key coactivator of the luxCDABE bioluminescence genes that is required together with LuxR for precise timing and expression levels of bioluminescence during quorum sensing. IHF binds to multiple sites in the luxCDABE promoter and bends the DNA in vitro. IHF and LuxR synergistically bind luxCDABE promoter DNA at overlapping, essential binding sites that are required for maximal gene expression in vivo. RNA-seq analysis demonstrated that IHF regulates 300 genes in V. harveyi, and among these are a core set of 19 genes that are also directly bound and regulated by LuxR. We validated these global analyses by demonstrating that both IHF and LuxR are required for transcriptional activation of the osmotic stress response genes betIBA-proXWV. These data suggest that IHF plays an integral role in one mechanism of transcriptional activation by the LuxR-type family of quorum-sensing regulators in vibrios.

  5. Draft Genome Sequence of Pseudoalteromonas tetraodonis Strain MQS005, a Bacterium with Potential Quorum-Sensing Regulation.

    PubMed

    Pan, Yonglong; Wang, Yanbo; Yan, Xiaoqing; Mazumder, Asit; Liang, Yan

    2016-01-01

    We present here the draft genome sequence of Pseudoalteromonas tetraodonis strain MQS005, a bacterium possessing potential quorum-sensing regulatory activity. This strain was isolated from water from the South China Sea, People's Republic of China. The assembly consists of 4,252,538 bp and contains 144 contigs, with a G+C content of 41.85%.

  6. The involvement of bacterial quorum sensing in the spoilage of refrigerated Litopenaeus vannamei.

    PubMed

    Zhu, Suqin; Wu, Haohao; Zeng, Mingyong; Liu, Zunying; Wang, Ying

    2015-01-01

    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

  7. The involvement of bacterial quorum sensing in the spoilage of refrigerated Litopenaeus vannamei.

    PubMed

    Zhu, Suqin; Wu, Haohao; Zeng, Mingyong; Liu, Zunying; Wang, Ying

    2015-01-01

    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

  8. Molecular Insights into the Impact of Oxidative Stress on the Quorum-Sensing Regulator Protein LasR.

    PubMed

    Kafle, Prapti; Amoh, Amanda N; Reaves, Jocelyn M; Suneby, Emma G; Tutunjian, Kathryn A; Tyson, Reed L; Schneider, Tanya L

    2016-05-27

    The LasR regulator protein functions at the top of the Pseudomonas aeruginosa quorum-sensing hierarchy and is implicated in promoting bacterial virulence. Of note is recent evidence that this transcription factor may also respond to oxidative stress. Here, all cysteines in LasR were inspected to deduce their redox sensitivity and to probe the connection between stress response and LasR activity using purified LasR and individual LasR domains. Cys(79) in the ligand binding domain of LasR appears to be important for ligand recognition and folding of this domain to potentiate DNA binding but does not seem to be sensitive to oxidative stress when bound to its native ligand. Two cysteines in the DNA binding domain of LasR do form a disulfide bond when treated with hydrogen peroxide, and formation of this Cys(201)-Cys(203) disulfide bond appears to disrupt the DNA binding activity of the transcription factor. Mutagenesis of either of these cysteines leads to expression of a protein that no longer binds DNA. A cell-based reporter assay linking LasR function with β-galactosidase activity gave results consistent with those obtained with purified LasR. This work provides a possible mechanism for oxidative stress response by LasR and indicates that multiple cysteines within the protein may prove to be useful targets for disabling its activity. PMID:27053110

  9. The quorum sensing molecule N-acyl homoserine lactone produced by Acinetobacter baumannii displays antibacterial and anticancer properties.

    PubMed

    John, James; Saranathan, Rajagopalan; Adigopula, Lakshmi Narayana; Thamodharan, Vasanth; Singh, Satya Prakash; Lakshmi, T Pragna; CharanTej, Mallu Abhiram; Rao, R Srinivasa; Krishna, R; Rao, H Surya Prakash; Prashanth, K

    2016-10-01

    Secretory N-acyl homoserine lactones (AHLs) mediate quorum sensing (QS) in bacteria. AHLs are shown to be inhibitory for an unrelated group of bacteria and might mimic host signalling elements, thereby subverting the regulatory events in host cells. This study investigated the AHL produced by Acinetobacter baumannii and analysed its effect on other bacterial species and mammalian cells. Chemically characterized AHL had an m/z value of 325 with a molecular formula C18H31NO4 and showed its inhibitory potential against Staphylococcus aureus. Molecular docking studies identified D-alanine-D-alanine synthetase A, a cell wall synthesizing enzyme of S. aureus having a strong binding affinity towards AHL. Electron microscopy showed the disruption and sloughing off of the S. aureus cell wall when treated with AHL. In vitro experiments revealed that this bacteriostatic AHL showed time-dependent activity and induced apoptosis in cancer cell lines. This compound could be a potential structural backbone for constructing new AHL analogues against S. aureus. The findings emphasize the need to re-evaluate all previously characterized AHLs for any additional new biological functions other than QS. PMID:27643959

  10. Mobilization of horizontally acquired island 2 is induced in planta in the phytopathogen Pectobacterium atrosepticum SCRI1043 and involves the putative relaxase ECA0613 and quorum sensing.

    PubMed

    Vanga, Bhanupratap R; Ramakrishnan, Pavithra; Butler, Ruth C; Toth, Ian K; Ronson, Clive W; Jacobs, Jeanne M E; Pitman, Andrew R

    2015-11-01

    Integrative and conjugative elements (ICEs) contribute to the rapid evolution of bacterial pathogens via horizontal gene transfer of virulence determinants. ICEs have common mechanisms for transmission, yet the cues triggering this process under natural environmental or physiological conditions are largely unknown. In this study, mobilization of the putative ICE horizontally acquired island 2 (HAI2), present in the chromosome of the phytopathogen Pectobacterium atrosepticum SCRI1043, was examined during infection of the host plant potato. Under these conditions, mobilization of HAI2 increased markedly compared with in vitro cultures. In planta-induced mobilization of HAI2 was regulated by quorum sensing and involved the putative ICE-encoded relaxase ECA0613. Disruption of ECA0613 also reduced transcription of genes involved in production of coronafacic acid (Cfa), the major virulence factor harboured on HAI2, whereas their expression was unaffected in the quorum-sensing (expI) mutant. Thus, suppression of cfa gene expression was not regulated by the mobilization of the ICE per se, but was due directly to inactivation of the relaxase. The identification of genetic factors associated solely with in planta mobilization of an ICE demonstrates that this process is highly adapted to the natural environment of the bacterial host and can influence the expression of virulence determinants.

  11. Exposure to Static Magnetic Field Stimulates Quorum Sensing Circuit in Luminescent Vibrio Strains of the Harveyi Clade

    PubMed Central

    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. PMID:24960170

  12. Identification of Five Structurally Unrelated Quorum-Sensing Inhibitors of Pseudomonas aeruginosa from a Natural-Derivative Database

    PubMed Central

    Tan, Sean Yang-Yi; Chua, Song-Lin; Chen, Yicai; Rice, Scott A.; Kjelleberg, Staffan; Nielsen, Thomas E.; Givskov, Michael

    2013-01-01

    Bacteria communicate by means of small signal molecules in a process termed quorum sensing (QS). QS enables bacteria to organize their activities at the population level, including the coordinated secretion of virulence factors. Certain small-molecule compounds, known as quorum-sensing inhibitors (QSIs), have been shown to effectively block QS and subsequently attenuate the virulence of Pseudomonas aeruginosa, as well as increasing its susceptibility to both antibiotics and the immune system. In this study, a structure-based virtual screening (SB-VS) approach was used for the discovery of novel QSI candidates. Three-dimensional structures of 3,040 natural compounds and their derivatives were obtained, after which molecular docking was performed using the QS receptor LasR as a target. Based on docking scores and molecular masses, 22 compounds were purchased to determine their efficacies as quorum-sensing inhibitors. Using a live reporter assay for quorum sensing, 5 compounds were found to be able to inhibit QS-regulated gene expression in P. aeruginosa in a dose-dependent manner. The most promising compound, G1, was evaluated by isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic analysis, and it was found to significantly affect the abundance of 46 proteins (19 were upregulated; 27 were downregulated) in P. aeruginosa PAO1. It specifically reduced the expression of several quorum-sensing-regulated virulence factors, such as protease IV, chitinase, and pyoverdine synthetases. G1 was also able to reduce extracellular DNA release and inhibited the secretion of the virulence factor, elastase, whose expression is regulated by LasR. These results demonstrate the utility of SB-VS for the discovery of target-specific QSIs. PMID:24002091

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

    PubMed

    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. PMID:24974195

  14. Novel Reporter for Identification of Interference with Acyl Homoserine Lactone and Autoinducer-2 Quorum Sensing

    PubMed Central

    Weiland-Bräuer, Nancy; Pinnow, Nicole

    2014-01-01

    Two reporter strains were established to identify novel biomolecules interfering with bacterial communication (quorum sensing [QS]). The basic design of these Escherichia coli-based systems comprises a gene encoding a lethal protein fused to promoters induced in the presence of QS signal molecules. Consequently, these E. coli strains are unable to grow in the presence of the respective QS signal molecules unless a nontoxic QS-interfering compound is present. The first reporter strain designed to detect autoinducer-2 (AI-2)-interfering activities (AI2-QQ.1) contained the E. coli ccdB lethal gene under the control of the E. coli lsrA promoter. The second reporter strain (AI1-QQ.1) contained the Vibrio fischeri luxI promoter fused to the ccdB gene to detect interference with acyl-homoserine lactones. Bacteria isolated from the surfaces of several marine eukarya were screened for quorum-quenching (QQ) activities using the established reporter systems AI1-QQ.1 and AI2-QQ.1. Out of 34 isolates, two interfered with acylated homoserine lactone (AHL) signaling, five interfered with AI-2 QS signaling, and 10 were demonstrated to interfere with both signal molecules. Open reading frames (ORFs) conferring QQ activity were identified for three selected isolates (Photobacterium sp., Pseudoalteromonas sp., and Vibrio parahaemolyticus). Evaluation of the respective heterologously expressed and purified QQ proteins confirmed their ability to interfere with the AHL and AI-2 signaling processes. PMID:25527543

  15. Organ-level quorum sensing directs regeneration in hair stem cell populations

    PubMed Central

    Chen, Chih-Chiang; Wang, Lei; Plikus, Maksim V.; Jiang, Ting Xin; Murray, Philip J.; Ramos, Raul; Guerrero-Juarez, Christian F.; Hughes, Michael W; Lee, Oscar K.; Shi, Songtao; Widelitz, Randall B.; Lander, Arthur D.; Chuong, Cheng Ming

    2015-01-01

    SUMMARY Coordinated organ behavior is crucial for an effective response to environmental stimuli. By studying regeneration of hair follicles in response to patterned hair removal, we demonstrate that organ-level quorum sensing allows coordinated responses to skin injury. Removing hair at different densities leads to a regeneration of up to 5 times more neighboring, unplucked resting hairs, indicating activation of a collective decision-making process. Through data modeling, the range of the quorum signal was estimated to be on the order of 1 mm, greater than expected for a diffusible molecular cue. Molecular and genetic analysis uncovered a two-step mechanism, where release of CCL2 from injured hairs leads to recruitment of TNF-α secreting macrophages, which accumulate and signal to both plucked and unplucked follicles. By coupling immune response with regeneration, this mechanism allows skin to respond predictively to distress, disregarding mild injury, while meeting stronger injury with full-scale cooperative activation of stem cells. PMID:25860610

  16. Programmed Lab Experiments for Biochemical Investigation of Quorum-Sensing Signal Molecules in Rhizospheric Soil Bacteria.

    PubMed

    Nievas, Fiorela L; Bogino, Pablo C; Giordano, Walter

    2016-05-01

    Biochemistry courses in the Department of Molecular Biology at the National University of Río Cuarto, Argentina, are designed for undergraduate students in biology, microbiology, chemistry, agronomy, and veterinary medicine. Microbiology students typically have previous coursework in general, analytical, and organic chemistry. Programmed sequences of lab experiments allow these students to investigate biochemical problems whose solution is feasible within the context of their knowledge and experience. We previously designed and reported a programmed lab experiment that familiarizes microbiology students with techniques for detection and characterization of quorum-sensing (QS) and quorum-quenching (QQ) signal molecules. Here, we describe a sequence of experiments designed to expand the understanding and capabilities of biochemistry students using techniques for extraction and identification of QS and QQ signal molecules from peanut rhizospheric soil bacteria, including culturing and manipulation of bacteria under sterile conditions. The program provides students with an opportunity to perform useful assays, draw conclusions from their results, and discuss possible extensions of the study. © 2016 by The International Union of Biochemistry and Molecular Biology, 44:256-262, 2016.

  17. Evolution of Microbial Quorum Sensing to Human Global Quorum Sensing: An Insight into How Gap Junctional Intercellular Communication Might Be Linked to the Global Metabolic Disease Crisis.

    PubMed

    Trosko, James E

    2016-06-15

    The first anaerobic organism extracted energy for survival and reproduction from its source of nutrients, with the genetic means to ensure protection of its individual genome but also its species survival. While it had a means to communicate with its community via simple secreted molecules ("quorum sensing"), the eventual shift to an aerobic environment led to multi-cellular metazoan organisms, with evolutionary-selected genes to form extracellular matrices, stem cells, stem cell niches, and a family of gap junction or "connexin" genes. These germinal and somatic stem cells responded to extracellular signals that triggered intra-cellular signaling to regulate specific genes out of the total genome. These extra-cellular induced intra-cellular signals also modulated gap junctional intercellular communication (GJIC) in order to regulate the new cellular functions of symmetrical and asymmetrical cell division, cell differentiation, modes of cell death, and senescence. Within the hierarchical and cybernetic concepts, differentiated by neurons organized in the brain of the Homo sapiens, the conscious mind led to language, abstract ideas, technology, myth-making, scientific reasoning, and moral decision-making, i.e., the creation of culture. Over thousands of years, this has created the current collision between biological and cultural evolution, leading to the global "metabolic disease" crisis.

  18. Evolution of Microbial Quorum Sensing to Human Global Quorum Sensing: An Insight into How Gap Junctional Intercellular Communication Might Be Linked to the Global Metabolic Disease Crisis.

    PubMed

    Trosko, James E

    2016-01-01

    The first anaerobic organism extracted energy for survival and reproduction from its source of nutrients, with the genetic means to ensure protection of its individual genome but also its species survival. While it had a means to communicate with its community via simple secreted molecules ("quorum sensing"), the eventual shift to an aerobic environment led to multi-cellular metazoan organisms, with evolutionary-selected genes to form extracellular matrices, stem cells, stem cell niches, and a family of gap junction or "connexin" genes. These germinal and somatic stem cells responded to extracellular signals that triggered intra-cellular signaling to regulate specific genes out of the total genome. These extra-cellular induced intra-cellular signals also modulated gap junctional intercellular communication (GJIC) in order to regulate the new cellular functions of symmetrical and asymmetrical cell division, cell differentiation, modes of cell death, and senescence. Within the hierarchical and cybernetic concepts, differentiated by neurons organized in the brain of the Homo sapiens, the conscious mind led to language, abstract ideas, technology, myth-making, scientific reasoning, and moral decision-making, i.e., the creation of culture. Over thousands of years, this has created the current collision between biological and cultural evolution, leading to the global "metabolic disease" crisis. PMID:27314399

  19. Conformational change-induced repeat domain expansion regulates Rap phosphatase quorum-sensing signal receptors.

    PubMed

    Parashar, Vijay; Jeffrey, Philip D; Neiditch, Matthew B

    2013-01-01

    The large family of Gram-positive quorum-sensing receptors known as the RNPP proteins consists of receptors homologous to the Rap, NprR, PlcR, and PrgX proteins that are regulated by imported oligopeptide autoinducers. Rap proteins are phosphatases and transcriptional anti-activators, and NprR, PlcR, and PrgX proteins are DNA binding transcription factors. Despite their obvious importance, the mechanistic basis of oligopeptide receptor regulation is largely unknown. Here, we report the X-ray crystal structure of the Bacillus subtilis quorum-sensing receptor RapJ in complex with the centrally important oligopeptide autoinducer competence and sporulation factor (CSF, also termed PhrC), a member of the Phr family of quorum-sensing signals. Furthermore, we present the crystal structure of RapI. Comparison of the RapJ-PhrC, RapI, RapH-Spo0F, and RapF-ComA(C) crystal structures reveals the mechanistic basis of Phr activity. More specifically, when complexed with target proteins, Rap proteins consist of a C-terminal tetratricopeptide repeat (TPR) domain connected by a flexible helix-containing linker to an N-terminal 3-helix bundle. In the absence of a target protein or regulatory peptide, the Rap protein 3-helix bundle adopts different conformations. However, in the peptide-bound conformation, the Rap protein N-terminal 3-helix bundle and linker undergo a radical conformational change, form TPR-like folds, and merge with the existing C-terminal TPR domain. To our knowledge, this is the first example of conformational change-induced repeat domain expansion. Furthermore, upon Phr binding, the entire Rap protein is compressed along the TPR superhelical axis, generating new intramolecular contacts that lock the Rap protein in an inactive state. The fact that Rap proteins are conformationally flexible is surprising considering that it is accepted dogma that TPR proteins do not undergo large conformational changes. Repeat proteins are widely used as scaffolds for the

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

    PubMed

    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.

  1. Antimicrobial and quorum sensing inhibitory activities of the pericarp of Garcinia mangostana.

    PubMed

    Asfour, Hani Z

    2016-07-01

    A prenylated xanthone, α-mangostin was separated from the alcoholic extract of Garcinia mangostana pericarp. Its structure was established by different spectroscopic analysis. The total methanolic extract (TME) and different fractions of G. mangostana pericarp as well as α-mangostin were assessed for their antimicrobial and quorum sensing inhibitory effects (QSI). The TME, CHCl3 fraction, and α-mangostin exhibited strong activity against all tested strains. While, EtOAc, n-BuOH, and aqueous fractions showed moderate activity against some of the tested organisms. In addition TME, CHCl3, EtOAc, and α-mangostin showed promising QSI, while n-BuOH and aqueous fractions showed moderate activity. Minimal inhibitory concentration (MIC) for TME, CHCl3 fractions, and α-mangostin was also assessed. PMID:27592485

  2. What role does the quorum-sensing accessory gene regulator system play during Staphylococcus aureus bacteremia?

    PubMed

    Painter, Kimberley L; Krishna, Aishwarya; Wigneshweraraj, Sivaramesh; Edwards, Andrew M

    2014-12-01

    Staphylococcus aureus is a major cause of bacteremia, which frequently results in serious secondary infections such as infective endocarditis, osteomyelitis, and septic arthritis. The ability of S. aureus to cause such a wide range of infections has been ascribed to its huge armoury of different virulence factors, many of which are under the control of the quorum-sensing accessory gene regulator (Agr) system. However, a significant fraction of S. aureus bacteremia cases are caused by agr-defective isolates, calling into question the role of Agr in invasive staphylococcal infections. This review draws on recent work to define the role of Agr during bacteremia and explain why the loss of this major virulence regulator is sometimes a price worth paying for S. aureus.

  3. [The ability of the natural ketones to interact with bacterial quorum sensing systems].

    PubMed

    Pliuta, V A; Popova, F F; Koksharova, O A; Kuznetsov, A E; khmel', I A

    2014-01-01

    The effect of the natural ketones emitted by bacteria (2-nonanone, 2-heptanone, 2-undecanone) on the functioning of the Quorum Sensing (QS) systems was studied. In this work, three lux-reporter strains containing the components of the LasI/LasR, RhlI/RhlR, LuxI LuxR QS systems were used as biosensors for the N-acyl-homoserine lactones. It was shown that at concentrations of ketones that exhibited little or no bactericidal action the ketones could modulate the QS-response by suppressing the expression of the lux-operon reporter to a greater extent than the cell viability of these strains. PMID:25845135

  4. Synthesis and biological evaluation of novel N-α-haloacylated homoserine lactones as quorum sensing modulators

    PubMed Central

    Syrpas, Michail; Ruysbergh, Ewout; Stevens, Christian V; De Kimpe, Norbert

    2014-01-01

    Summary Novel N-α-haloacylated homoserine lactones, in which a halogen atom was introduced at the α-position of the carbonyl function of the N-acyl chain, have been studied as quorum sensing (QS) modulators and compared with a library of natural N-acylated homoserine lactones (AHLs). The series of novel analogues consists of α-chloro, α-bromo and α-iodo AHL analogues. Furthermore, the biological QS activity of the synthetic AHL analogues compared to the natural AHLs was evaluated. Halogenated analogues demonstrated a reduced activity in the Escherichia coli JB523 bioassay, with the α-iodo lactones being the less active ones and the α-chloro AHLs the most potent QS agonists. Most of the α-haloacylated analogues did not exhibit a significant reduction when tested in the QS inhibition test. Therefore, these novel analogues could be utilized as chemical probes for QS structure–activity studies. PMID:25383125

  5. Bacterial behaviors associated with the quorum-sensing peptide pheromone ('alarmone') in streptococci.

    PubMed

    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. PMID:23642115

  6. Synthesis and quorum sensing inhibitory activity of key phenolic compounds of ginger and their derivatives.

    PubMed

    Kumar, N Vijendra; Murthy, Pushpa S; Manjunatha, J R; Bettadaiah, B K

    2014-09-15

    Phenolic components of ginger (Zingiber officinale Roscoe) viz. [6]-gingerol, [6]-shogaol and zingerone exhibited quorum sensing inhibitory activity (QSI) against Chromobacterium violaceum and Pseudomonas aeruginosa. The inhibitory activity of all the compounds was studied by zone inhibition, pyocyanin, and violacein assay. All the compounds displayed good inhibition at 500ppm. [6]-Azashogaol, a new derivative of [6]-shogaol has been synthesized by Beckmann rearrangement of its oxime in the presence of ZnCl2. The structure elucidation of this new derivative was carried out by 1D ((1)H NMR and (13)C NMR) and 2D-NMR (COSY, HSQC and NOESY) spectral studies. This compound showed good QSI activity against P. aeruginosa. An isoxazoline derivative of [6]-gingerol was prepared and it exhibited good QSI activity. Present study illustrated that, the phenolic compounds of ginger and their derivatives form a class of compounds with promising QSI activity. PMID:24767081

  7. Pseudomonas cremoricolorata Strain ND07 Produces N-acyl Homoserine Lactones as Quorum Sensing Molecules

    PubMed Central

    Yunos, Nina Yusrina Muhamad; Tan, Wen-Si; Koh, Chong-Lek; Sam, Choon-Kook; Mohamad, Nur Izzati; Tan, Pui-Wan; Adrian, Tan-Guan-Sheng; Yin, Wai-Fong; Chan, Kok-Gan

    2014-01-01

    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. PMID:24984061

  8. Piper nigrum, Piper betle and Gnetum gnemon- Natural Food Sources with Anti-Quorum Sensing Properties

    PubMed Central

    Tan, Li Ying; Yin, Wai-Fong; Chan, Kok-Gan

    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 have anti-QS ability. Interestingly, the hexane, chloroform and methanol extracts from P. betle showed the most potent anti-QS activity as judged by the bioassays. Since there is a variety of plants that serve as food sources in Malaysia that have yet to be tested for anti-QS activity, future work should focus on identification of these plants and isolation of the anti-QS compounds. PMID:23519352

  9. Tandem Mass Spectrometry Detection of Quorum Sensing Activity in Multidrug Resistant Clinical Isolate Acinetobacter baumannii

    PubMed Central

    Chan, Kok-Gan; Cheng, Huey Jia; Chen, Jian Woon; Yin, Wai-Fong; Ngeow, Yun Fong

    2014-01-01

    Many Proteobacteria communicate via production followed by response of quorum sensing molecules, namely, N-acyl homoserine lactones (AHLs). These molecules consist of a lactone moiety with N-acyl side chain with various chain lengths and degrees of saturation at C-3 position. AHL-dependent QS is often associated with regulation of diverse bacterial phenotypes including the expression of virulence factors. With the use of biosensor and high resolution liquid chromatography tandem mass spectrometry, the AHL production of clinical isolate A. baumannii 4KT was studied. Production of short chain AHL, namely, N-hexanoyl-homoserine lactone (C6-HSL) and N-octanoyl-homoserine lactone (C8-HSL), was detected. PMID:25101326

  10. Biofouling control by quorum sensing inhibition and its dependence on membrane surface.

    PubMed

    Kim, Mijin; Lee, Sangyoup; Park, Hee-Deung; Choi, Suing-Il; Hong, Seungkwan

    2012-01-01

    Biofouling control by quorum sensing (QS) inhibition and the influence of membrane surface characteristics on biofilm formation and QS inhibition were investigated. Pseudomonas putida isolated from the bio-fouled reverse osmosis (RO) membranes in a real plant was used. Acylase was chosen as a model QS inhibitor. Bacteria on the membrane coupons were quantified with the heterotrophic plate count method. Cell distribution was imaged by a confocal laser scanning microscope. Results showed that biofilm formation on the membrane was reduced by acylase as it inhibits the activity of N-acylhomoserine lactone (AHL) which is a signal molecule of QS. It was also shown that membrane surface characteristics were influential factors affecting bacterial adhesion, biofilm formation, and QS inhibition.

  11. Autonomous induction of recombinant proteins by minimally rewiring native quorum sensing regulon of E. coli.

    PubMed

    Tsao, Chen-Yu; Hooshangi, Sara; Wu, Hsuan-Chen; Valdes, James J; Bentley, William E

    2010-05-01

    Quorum sensing (QS) enables an individual bacterium's metabolic state to be communicated to and ultimately control the phenotype of an emerging population. Harnessing the hierarchical nature of this signal transduction process may enable the exploitation of individual cell characteristics to direct or "program" entire populations of cells. We re-engineered the native QS regulon so that individual cell signals (autoinducers) are used to guide high level expression of recombinant proteins in E. coli populations. Specifically, the autoinducer-2 (AI-2) QS signal initiates and guides the overexpression of green fluorescent protein (GFP), chloramphenicol acetyl transferase (CAT) and beta-galactosidase (LacZ). The new process requires no supervision or input (e.g., sampling for optical density measurement, inducer addition, or medium exchange) and represents a low-cost, high-yield platform for recombinant protein production. Moreover, rewiring a native signal transduction circuit exemplifies an emerging class of metabolic engineering approaches that target regulatory functions. PMID:20060924

  12. Dynamics and Mechanism of A Quorum Sensing Network Regulated by Small RNAs in Vibrio Harveyi

    NASA Astrophysics Data System (ADS)

    Shen, Jian-Wei

    2011-03-01

    Bacterial quorum sensing (QS) has attracted much interests and it is an important process of cell communication. Recently, Bassler et al. studied the phenomena of QS regulated by small RNAs and the experimental data showed that small RNAs played important role in the QS of Vibrio harveyi and it can permit the fine-tuning of gene regulation and maintenance of homeostasis. According to Michaelis—Menten kinetics and mass action law in this paper, we construct a mathematical model to investigate the mechanism induced QS by coexist of small RNA and signal molecular (AI) and show that there are periodic oscillation when the time delay and Hill coefficient exceed a critical value and the periodic oscillation produces the change of concentration and induces QS. These results are fit to the experimental results. In the meanwhile, we also get some theoretical value of Hopf Bifurcation on time deday. In addition, we also find this network is robust against noise.

  13. Synthetic quorum-sensing circuit to control consortial biofilm formation and dispersal in a microfluidic device

    PubMed Central

    Hong, Seok Hoon; Hegde, Manjunath; Kim, Jeongyun; Wang, Xiaoxue; Jayaraman, Arul; Wood, Thomas K.

    2012-01-01

    To utilize biofilms for chemical transformations in biorefineries they need to be controlled and replaced. Previously, we engineered the global regulator Hha and cyclic diguanylate-binding BdcA to create proteins that enable biofilm dispersal. Here we report a biofilm circuit that utilizes these two dispersal proteins along with a population-driven quorum-sensing switch. With this synthetic circuit, in a novel microfluidic device, we form an initial colonizer biofilm, introduce a second cell type (dispersers) into this existing biofilm, form a robust dual-species biofilm and displace the initial colonizer cells in the biofilm with an extracellular signal from the disperser cells. We also remove the disperser biofilm with a chemically induced switch, and the consortial population could tune. Therefore, for the first time, cells have been engineered that are able to displace an existing biofilm and then be removed on command allowing one to control consortial biofilm formation for various applications. PMID:22215088

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

    PubMed

    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

  15. Vibrio campbellii hmgA-mediated pyomelanization impairs quorum sensing, virulence, and cellular fitness

    PubMed Central

    Wang, Zheng; Lin, Baochuan; Mostaghim, Anahita; Rubin, Robert A.; Glaser, Evan R.; Mittraparp-arthorn, Pimonsri; Thompson, Janelle R.; Vuddhakul, Varaporn; Vora, Gary J.

    2013-01-01

    Melanization due to the inactivation of the homogentisate-1,2-dioxygenase gene (hmgA) has been demonstrated to increase stress resistance, persistence, and virulence in some bacterial species but such pigmented mutants have not been observed in pathogenic members of the Vibrio Harveyi clade. In this study, we used Vibrio campbellii ATCC BAA-1116 as model organism to understand how melanization affected cellular phenotype, metabolism, and virulence. An in-frame deletion of the hmgA gene resulted in the overproduction of a pigment in cell culture supernatants and cellular membranes that was identified as pyomelanin. Unlike previous demonstrations in Vibrio cholerae, Burkholderia cepacia, and Pseudomonas aeruginosa, the pigmented V. campbellii mutant did not show increased UV resistance and was found to be ~2.7 times less virulent than the wild type strain in Penaeus monodon shrimp virulence assays. However, the extracted pyomelanin pigment did confer a higher resistance to oxidative stress when incubated with wild type cells. Microarray-based transcriptomic analyses revealed that the hmgA gene deletion and subsequent pyomelanin production negatively effected the expression of 129 genes primarily involved in energy production, amino acid, and lipid metabolism, and protein translation and turnover. This transcriptional response was mediated in part by an impairment of the quorum sensing regulon as transcripts of the quorum sensing high cell density master regulator LuxR and other operonic members of this regulon were significantly less abundant in the hmgA mutant. Taken together, the results suggest that the pyomelanization of V. campbellii sufficiently impairs the metabolic activities of this organism and renders it less fit and virulent than its isogenic wild type strain. PMID:24376440

  16. Baicalein Inhibits Staphylococcus aureus Biofilm Formation and the Quorum Sensing System In Vitro

    PubMed Central

    Wang, Ke; Hou, Changchun; Cai, Shuangqi; Huang, Yingying; Du, Zhongye; Huang, Hong; Kong, Jinliang; Chen, Yiqiang

    2016-01-01

    Biofilm formed by Staphylococcus aureus significantly enhances antibiotic resistance by inhibiting the penetration of antibiotics, resulting in an increasingly serious situation. This study aimed to assess whether baicalein can prevent Staphylococcus aureus biofilm formation and whether it may have synergistic bactericidal effects with antibiotics in vitro. To do this, we used a clinically isolated strain of Staphylococcus aureus 17546 (t037) for biofilm formation. Virulence factors were detected following treatment with baicalein, and the molecular mechanism of its antibiofilm activity was studied. Plate counting, crystal violet staining, and fluorescence microscopy revealed that 32 μg/mL and 64 μg/mL baicalein clearly inhibited 3- and 7-day biofilm formation in vitro. Moreover, colony forming unit count, confocal laser scanning microscopy, and scanning electron microscopy showed that vancomycin (VCM) and baicalein generally enhanced destruction of biofilms, while VCM alone did not. Western blotting and real-time quantitative polymerase chain reaction analyses (RTQ-PCR) confirmed that baicalein treatment reduced staphylococcal enterotoxin A (SEA) and α-hemolysin (hla) levels. Most strikingly, real-time qualitative polymerase chain reaction data demonstrated that 32 μg/mL and 64 μg/mL baicalein downregulated the quorum-sensing system regulators agrA, RNAIII, and sarA, and gene expression of ica, but 16 μg/mL baicalein had no effect. In summary, baicalein inhibited Staphylococcus aureus biofilm formation, destroyed biofilms, increased the permeability of vancomycin, reduced the production of staphylococcal enterotoxin A and α-hemolysin, and inhibited the quorum sensing system. These results support baicalein as a novel drug candidate and an effective treatment strategy for Staphylococcus aureus biofilm-associated infections. PMID:27128436

  17. Production of tyrosol by Candida albicans biofilms and its role in quorum sensing and biofilm development.

    PubMed

    Alem, Mohammed A S; Oteef, Mohammed D Y; Flowers, T Hugh; Douglas, L Julia

    2006-10-01

    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 extracellular tyrosol during growth at 37 degrees C. There was a correlation between tyrosol production and biomass for both cell types. However, biofilm cells secreted at least 50% more tyrosol than did planktonic cells when tyrosol production was related to cell dry weight. The addition of exogenous farnesol to a wild-type strain inhibited biofilm formation by up to 33% after 48 h. Exogenous tyrosol appeared to have no effect, but scanning electron microscopy revealed that tyrosol stimulated hypha production during the early stages (1 to 6 h) of biofilm development. Experiments involving the simultaneous addition of tyrosol and farnesol at different concentrations suggested that the action of farnesol was dominant, and 48-h biofilms formed in the presence of both compounds consisted almost entirely of yeast cells. When biofilm supernatants were tested for their abilities to inhibit or enhance germ tube formation by planktonic cells, the results indicated that tyrosol activity exceeds that of farnesol after 14 h, but not after 24 h, and that farnesol activity increases significantly during the later stages (48 to 72 h) of biofilm development. Overall, our results support the conclusion that tyrosol acts as a quorum-sensing molecule for biofilms as well as for planktonic cells and that its action is most significant during the early and intermediate stages of biofilm formation. PMID:16980403

  18. Baicalein Inhibits Staphylococcus aureus Biofilm Formation and the Quorum Sensing System In Vitro.

    PubMed

    Chen, Yan; Liu, Tangjuan; Wang, Ke; Hou, Changchun; Cai, Shuangqi; Huang, Yingying; Du, Zhongye; Huang, Hong; Kong, Jinliang; Chen, Yiqiang

    2016-01-01

    Biofilm formed by Staphylococcus aureus significantly enhances antibiotic resistance by inhibiting the penetration of antibiotics, resulting in an increasingly serious situation. This study aimed to assess whether baicalein can prevent Staphylococcus aureus biofilm formation and whether it may have synergistic bactericidal effects with antibiotics in vitro. To do this, we used a clinically isolated strain of Staphylococcus aureus 17546 (t037) for biofilm formation. Virulence factors were detected following treatment with baicalein, and the molecular mechanism of its antibiofilm activity was studied. Plate counting, crystal violet staining, and fluorescence microscopy revealed that 32 μg/mL and 64 μg/mL baicalein clearly inhibited 3- and 7-day biofilm formation in vitro. Moreover, colony forming unit count, confocal laser scanning microscopy, and scanning electron microscopy showed that vancomycin (VCM) and baicalein generally enhanced destruction of biofilms, while VCM alone did not. Western blotting and real-time quantitative polymerase chain reaction analyses (RTQ-PCR) confirmed that baicalein treatment reduced staphylococcal enterotoxin A (SEA) and α-hemolysin (hla) levels. Most strikingly, real-time qualitative polymerase chain reaction data demonstrated that 32 μg/mL and 64 μg/mL baicalein downregulated the quorum-sensing system regulators agrA, RNAIII, and sarA, and gene expression of ica, but 16 μg/mL baicalein had no effect. In summary, baicalein inhibited Staphylococcus aureus biofilm formation, destroyed biofilms, increased the permeability of vancomycin, reduced the production of staphylococcal enterotoxin A and α-hemolysin, and inhibited the quorum sensing system. These results support baicalein as a novel drug candidate and an effective treatment strategy for Staphylococcus aureus biofilm-associated infections.

  19. Baicalein Inhibits Staphylococcus aureus Biofilm Formation and the Quorum Sensing System In Vitro.

    PubMed

    Chen, Yan; Liu, Tangjuan; Wang, Ke; Hou, Changchun; Cai, Shuangqi; Huang, Yingying; Du, Zhongye; Huang, Hong; Kong, Jinliang; Chen, Yiqiang

    2016-01-01

    Biofilm formed by Staphylococcus aureus significantly enhances antibiotic resistance by inhibiting the penetration of antibiotics, resulting in an increasingly serious situation. This study aimed to assess whether baicalein can prevent Staphylococcus aureus biofilm formation and whether it may have synergistic bactericidal effects with antibiotics in vitro. To do this, we used a clinically isolated strain of Staphylococcus aureus 17546 (t037) for biofilm formation. Virulence factors were detected following treatment with baicalein, and the molecular mechanism of its antibiofilm activity was studied. Plate counting, crystal violet staining, and fluorescence microscopy revealed that 32 μg/mL and 64 μg/mL baicalein clearly inhibited 3- and 7-day biofilm formation in vitro. Moreover, colony forming unit count, confocal laser scanning microscopy, and scanning electron microscopy showed that vancomycin (VCM) and baicalein generally enhanced destruction of biofilms, while VCM alone did not. Western blotting and real-time quantitative polymerase chain reaction analyses (RTQ-PCR) confirmed that baicalein treatment reduced staphylococcal enterotoxin A (SEA) and α-hemolysin (hla) levels. Most strikingly, real-time qualitative polymerase chain reaction data demonstrated that 32 μg/mL and 64 μg/mL baicalein downregulated the quorum-sensing system regulators agrA, RNAIII, and sarA, and gene expression of ica, but 16 μg/mL baicalein had no effect. In summary, baicalein inhibited Staphylococcus aureus biofilm formation, destroyed biofilms, increased the permeability of vancomycin, reduced the production of staphylococcal enterotoxin A and α-hemolysin, and inhibited the quorum sensing system. These results support baicalein as a novel drug candidate and an effective treatment strategy for Staphylococcus aureus biofilm-associated infections. PMID:27128436

  20. Quorum sensing signal molecules (acylated homoserine lactones) in gram-negative fish pathogenic bacteria.

    PubMed

    Bruhn, Jesper B; Dalsgaard, Inger; Nielsen, Kristian F; Buchholtz, Christiane; Larsen, Jens L; Gram, Lone

    2005-06-14

    The aim of the present study was to investigate the production of quorum sensing signals (specifically acylated homoserine lactones, AHLs) among a selection of strains of Gram-negative fish bacterial pathogens. These signals are involved in the regulation of virulence factors in some human and plant-pathogenic bacteria. A total of 59 strains, representing 9 different fish pathogenic species, were tested against 2 AHL monitor bacteria (Agrobacterium tumefaciens NT1 [pZLR4] and Chromobacterium violaceum CV026) in a well diffusion assay and by thin-layer chromatography (TLC). Representative samples were further characterized by high performance liquid chromatography-high resolution mass spectrometry (HPLC-HR-MS). AHLs were produced by all strains of Aeromonas salmonicida, Aeromonas hydrophila, Yersinia ruckeri, Vibrio salmonicida, and Vibrio vulnificus. Some strains of atypical Aeromonas salmonicida and Vibrio splendidus were also positive. Aeromonas species produced N-butanoyl homoserine lactone (BHL) and N-hexanoyl homoserine lactone (HHL) and 1 additional product, whereas N-3-oxo-hexanoyl homoserine lactone (OHHL) and HHL were detected in Vibrio salmonicida. N-3-oxo-octanoyl homoserine lactone (OOHL) and N-3-octanoyl homoserine lactone (OHL) were detected in Y. ruckeri. AHLs were not detected from strains of Photobacterium damselae, Flavobacterium psychrophilum or Moritella viscosa. AHLs were extracted from fish infected with Y. ruckeri but not from fish infected with A. salmonicida. In conclusion, the production of quorum sensing signals, AHLs, is common among the strains that we examined. If the AHL molecules regulate the expression of the virulence phenotype in these bacteria, as shown to occur in some bacterial pathogens, novel disease control measures may be developed by blocking AHL-mediated communication and suppressing virulence.

  1. Involvement of bacterial quorum-sensing signals in spoilage of bean sprouts.

    PubMed

    Rasch, Maria; Andersen, Jens Bo; Nielsen, Kristian Fog; Flodgaard, Lars Ravn; Christensen, Henrik; Givskov, Michael; Gram, Lone

    2005-06-01

    Bacterial communication signals, acylated homoserine lactones (AHLs), were extracted from samples of commercial bean sprouts undergoing soft-rot spoilage. Bean sprouts produced in the laboratory did not undergo soft-rot spoilage and did not contain AHLs or AHL-producing bacteria, although the bacterial population reached levels similar to those in the commercial sprouts, 10(8) to 10(9) CFU/g. AHL-producing bacteria (Enterobacteriaceae and pseudomonads) were isolated from commercial sprouts, and strains that were both proteolytic and pectinolytic were capable of causing soft-rot spoilage in bean sprouts. Thin-layer chromatography and liquid chromatography-high-resolution mass spectrometry revealed the presence of N-3-oxo-hexanoyl-l-homoserine lactone in spoiled bean sprouts and in extracts from pure cultures of bacteria. During normal spoilage, the pH of the sprouts increased due to proteolytic activity, and the higher pH probably facilitated the activity of pectate lyase. The AHL synthetase gene (I gene) from a spoilage Pectobacterium was cloned, sequenced, and inactivated in the parent strain. The predicted amino acid sequence showed 97% homology to HslI and CarI in Erwinia carotovora. Spoilage of laboratory bean sprouts inoculated with the AHL-negative mutant was delayed compared to sprouts inoculated with the wild type, and the AHL-negative mutant did not cause the pH to rise. Compared to the wild-type strain, the AHL-negative mutant had significantly reduced protease and pectinase activities and was negative in an iron chelation (siderophore) assay. This is the first study demonstrating AHL regulation of iron chelation in Enterobacteriaceae. The present study clearly demonstrates that the bacterial spoilage of some food products is influenced by quorum-sensing-regulated phenotypes, and understanding these processes may be useful in the development of novel food preservation additives that specifically block the quorum-sensing systems.

  2. SepM, a Streptococcal Protease Involved in Quorum Sensing, Displays Strict Substrate Specificity

    PubMed Central

    Biswas, Saswati; Cao, Luyang; Kim, Albert

    2015-01-01

    ABSTRACT Streptococcus mutans, a causative agent of dental caries, relies on multiple quorum-sensing (QS) pathways that coordinate the expression of factors needed for colonization in the oral cavity. S. mutans uses small peptides as QS signaling molecules that typically are secreted into the outside milieu. Competence-stimulating peptide (CSP) is one such QS signaling molecule that functions through the ComDE two-component signal transduction pathway. CSP is secreted through NlmTE, a dedicated ABC transporter that cleaves off the N-terminal leader peptide to generate a mature peptide that is 21 residues long (CSP-21). We recently identified a surface-localized protease, SepM, which further cleaves the CSP-21 peptide at the C-terminal end and removes the last 3 residues to generate CSP-18. CSP-18 is the active QS molecule that interacts with the ComD sensor kinase to activate the QS pathway. In this study, we show that SepM specifically cleaves CSP-21 between the Ala18 and Leu19 residues. We also show that SepM recognizes only Ala at position 18 and Leu at position 19, although some CSP-18 variants with a substitution at position 18 can function equally as well as the QS peptide. Furthermore, we demonstrate that SepM homologs from other streptococci are capable of processing CSP-21 to generate functional CSP-18. IMPORTANCE SepM is a membrane-associated streptococcal protease that processes competence-stimulating peptide (CSP) to generate an active quorum-sensing molecule in S. mutans. SepM belongs to the S16 family of serine proteases, and in this study, we found that SepM behaves as an endopeptidase. SepM displays strict substrate specificity and cleaves the peptide bond between the Ala and Leu residues. This is the first report of an endopeptidase that specifically cleaves these two residues. PMID:26553848

  3. Inhibition of quorum sensing-controlled virulence factor production in Pseudomonas aeruginosa PAO1 by Ayurveda spice clove (Syzygium aromaticum) bud extract.

    PubMed

    Krishnan, Thiba; Yin, Wai-Fong; Chan, Kok-Gan

    2012-01-01

    Quorum sensing controls the virulence determinants in most proteobacteria. In this work, the hexane, chloroform and methanol extracts of an Ayurveda spice, namely clove (Syzygium aromaticum), shown anti-quorum sensing activity. Hexane and methanol extracts of clove inhibited the response of C. violaceum CV026 to exogenously supplied N-hexanoylhomoserine lactone, in turn preventing violacein production. Chloroform and methanol extracts of clove significantly reduced bioluminescence production by E. coli [pSB1075] grown in the presence of N-(3-oxododecanoyl)-L-homoserine lactone. We demonstrated that clove extract inhibited quorum sensing-regulated phenotypes in Pseudomonas aeruginosa PA01, including expression of lecA::lux (by hexane extract), swarming (maximum inhibition by methanol extract), pyocyanin (maximum inhibition by hexane extract). This study shows that the presence of natural compounds that exhibit anti-quorum sensing activity in the clove extracts may be useful as the lead of anti-infective drugs.

  4. Inhibition of quorum sensing-controlled virulence factor production in Pseudomonas aeruginosa PAO1 by Ayurveda spice clove (Syzygium aromaticum) bud extract.

    PubMed

    Krishnan, Thiba; Yin, Wai-Fong; Chan, Kok-Gan

    2012-01-01

    Quorum sensing controls the virulence determinants in most proteobacteria. In this work, the hexane, chloroform and methanol extracts of an Ayurveda spice, namely clove (Syzygium aromaticum), shown anti-quorum sensing activity. Hexane and methanol extracts of clove inhibited the response of C. violaceum CV026 to exogenously supplied N-hexanoylhomoserine lactone, in turn preventing violacein production. Chloroform and methanol extracts of clove significantly reduced bioluminescence production by E. coli [pSB1075] grown in the presence of N-(3-oxododecanoyl)-L-homoserine lactone. We demonstrated that clove extract inhibited quorum sensing-regulated phenotypes in Pseudomonas aeruginosa PA01, including expression of lecA::lux (by hexane extract), swarming (maximum inhibition by methanol extract), pyocyanin (maximum inhibition by hexane extract). This study shows that the presence of natural compounds that exhibit anti-quorum sensing activity in the clove extracts may be useful as the lead of anti-infective drugs. PMID:22666015

  5. Inhibition of Quorum Sensing-Controlled Virulence Factor Production in Pseudomonas aeruginosa PAO1 by Ayurveda Spice Clove (Syzygium Aromaticum) Bud Extract

    PubMed Central

    Krishnan, Thiba; Yin, Wai-Fong; Chan, Kok-Gan

    2012-01-01

    Quorum sensing controls the virulence determinants in most proteobacteria. In this work, the hexane, chloroform and methanol extracts of an Ayurveda spice, namely clove (Syzygium aromaticum), shown anti-quorum sensing activity. Hexane and methanol extracts of clove inhibited the response of C. violaceum CV026 to exogenously supplied N‐hexanoylhomoserine lactone, in turn preventing violacein production. Chloroform and methanol extracts of clove significantly reduced bioluminescence production by E. coli [pSB1075] grown in the presence of N-(3-oxododecanoyl)-l-homoserine lactone. We demonstrated that clove extract inhibited quorum sensing-regulated phenotypes in Pseudomonas aeruginosa PA01, including expression of lecA::lux (by hexane extract), swarming (maximum inhibition by methanol extract), pyocyanin (maximum inhibition by hexane extract). This study shows that the presence of natural compounds that exhibit anti-quorum sensing activity in the clove extracts may be useful as the lead of anti-infective drugs. PMID:22666015

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

    PubMed

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

    2016-01-01

    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. PMID:27626397

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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. PMID:27683573

  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

    PubMed Central

    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 23270T 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. ferrooxidansT, 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. ferrooxidansT 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 23270T 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. PMID:27683573

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

    PubMed Central

    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 23270T 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. ferrooxidansT, 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. ferrooxidansT 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 23270T 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.

  12. Nanoporous Superhydrophobic Coatings that Promote the Extended Release of Water-Labile Quorum Sensing Inhibitors and Enable Long-Term Modulation of Quorum Sensing in Staphylococcus aureus

    PubMed Central

    2015-01-01

    Materials and coatings that inhibit bacterial colonization are of interest in a broad range of biomedical, environmental, and industrial applications. In view of the rapid increase in bacterial resistance to conventional antibiotics, the development of new strategies that target nonessential pathways in bacterial pathogens—and that thereby limit growth and reduce virulence through nonbiocidal means—has attracted considerable attention. Bacterial quorum sensing (QS) represents one such target, and is intimately connected to virulence in many human pathogens. Here, we demonstrate that the properties of nanoporous, polymer-based superhydrophobic coatings can be exploited to host and subsequently sustain the extended release of potent and water-labile peptide-based inhibitors of QS (QSIs) in Staphylococcus aureus. Our results demonstrate that these peptidic QSIs can be released into surrounding media for periods of at least 8 months, and that they strongly inhibit agr-based QS in S. aureus for at least 40 days. These results also suggest that these extremely nonwetting coatings can confer protection against the rapid hydrolysis of these water-labile peptides, thereby extending their useful lifetimes. Finally, we demonstrate that these peptide-loaded superhydrophobic coatings can strongly modulate the QS-controlled formation of biofilm in wild-type S. aureus. These nanoporous superhydrophobic films provide a new, useful, and nonbiocidal approach to the design of coatings that attenuate bacterial virulence. This approach has the potential to be general, and could prove suitable for the encapsulation, protection, and release of other classes of water-sensitive agents. We anticipate that the materials, strategies, and concepts reported here will enable new approaches to the long-term attenuation of QS and associated bacterial phenotypes in a range of basic research and applied contexts. PMID:26501126

  13. Microbial Communication, Cooperation and Cheating: Quorum Sensing Drives the Evolution of Cooperation in Bacteria

    PubMed Central

    Czárán, Tamás; Hoekstra, Rolf F.

    2009-01-01

    An increasing body of empirical evidence suggests that cooperation among clone-mates is common in bacteria. Bacterial cooperation may take the form of the excretion of “public goods”: exoproducts such as virulence factors, exoenzymes or components of the matrix in biofilms, to yield significant benefit for individuals joining in the common effort of producing them. Supposedly in order to spare unnecessary costs when the population is too sparse to supply the sufficient exoproduct level, many bacteria have evolved a simple chemical communication system called quorum sensing (QS), to “measure” the population density of clone-mates in their close neighborhood. Cooperation genes are expressed only above a threshold rate of QS signal molecule re-capture, i.e., above the local quorum of cooperators. The cooperative population is exposed to exploitation by cheaters, i.e., mutants who contribute less or nil to the effort but fully enjoy the benefits of cooperation. The communication system is also vulnerable to a different type of cheaters (“Liars”) who may produce the QS signal but not the exoproduct, thus ruining the reliability of the signal. Since there is no reason to assume that such cheaters cannot evolve and invade the populations of honestly signaling cooperators, the empirical fact of the existence of both bacterial cooperation and the associated QS communication system seems puzzling. Using a stochastic cellular automaton approach and allowing mutations in an initially non-cooperating, non-communicating strain we show that both cooperation and the associated communication system can evolve, spread and remain persistent. The QS genes help cooperative behavior to invade the population, and vice versa; cooperation and communication might have evolved synergistically in bacteria. Moreover, in good agreement with the empirical data recently available, this synergism opens up a remarkably rich repertoire of social interactions in which cheating and

  14. Inhibition of biofilm development of uropathogens by curcumin - an anti-quorum sensing agent from Curcuma longa.

    PubMed

    Packiavathy, Issac Abraham Sybiya Vasantha; Priya, Selvam; Pandian, Shunmugiah Karutha; Ravi, Arumugam Veera

    2014-04-01

    Urinary tract infection is caused primarily by the quorum sensing (QS)-dependent biofilm forming ability of uropathogens. In the present investigation, an anti-quorum sensing (anti-QS) agent curcumin from Curcuma longa (turmeric) was shown to inhibit the biofilm formation of uropathogens, such as Escherichia coli, Pseudomonas aeruginosa PAO1, Proteus mirabilis and Serratia marcescens, possibly by interfering with their QS systems. The antibiofilm potential of curcumin on uropathogens as well as its efficacy in disturbing the mature biofilms was examined under light microscope and confocal laser scanning microscope. The treatment with curcumin was also found to attenuate the QS-dependent factors, such as exopolysaccharide production, alginate production, swimming and swarming motility of uropathogens. Furthermore, it was documented that curcumin enhanced the susceptibility of a marker strain and uropathogens to conventional antibiotics. PMID:24262582

  15. Inhibition of biofilm development of uropathogens by curcumin - an anti-quorum sensing agent from Curcuma longa.

    PubMed

    Packiavathy, Issac Abraham Sybiya Vasantha; Priya, Selvam; Pandian, Shunmugiah Karutha; Ravi, Arumugam Veera

    2014-04-01

    Urinary tract infection is caused primarily by the quorum sensing (QS)-dependent biofilm forming ability of uropathogens. In the present investigation, an anti-quorum sensing (anti-QS) agent curcumin from Curcuma longa (turmeric) was shown to inhibit the biofilm formation of uropathogens, such as Escherichia coli, Pseudomonas aeruginosa PAO1, Proteus mirabilis and Serratia marcescens, possibly by interfering with their QS systems. The antibiofilm potential of curcumin on uropathogens as well as its efficacy in disturbing the mature biofilms was examined under light microscope and confocal laser scanning microscope. The treatment with curcumin was also found to attenuate the QS-dependent factors, such as exopolysaccharide production, alginate production, swimming and swarming motility of uropathogens. Furthermore, it was documented that curcumin enhanced the susceptibility of a marker strain and uropathogens to conventional antibiotics.

  16. A novel quorum sensing system co-regulated by chromosome- and plasmid-encoded genes in Serratia marcescens H30.

    PubMed

    Zhu, Hu; Shen, Ya-Ling; Wei, Dong-Zhi; Zhu, Jia-Wen

    2008-12-01

    The key genes, SpnI and SpnR, involved in AI-1-quorum sensing system of Serratia marcescens strain H30 were cloned and localized using specific primers (5'-CTTGAACTGTTTGACGTCAGC-3' and 5'-AGCGGCCAGGTAATAACTGA-3', 5'-GCCTTCAATGAAAATCAGACC-3' and 5'-TGTCGCTGTGATAAGCTCCA-3') designed according to the nucleic acid sequences published at NCBI (accession no. AB234869). The PCR result demonstrated that the genes SpnI and SpnR were located on the bacterial chromosome and plasmid, respectively. This was also confirmed by Southern blotting using an internal fragment (379 bp) from SpnR gene as a probe. These results imply a new type quorum sensing regulation system that had never been reported previously.

  17. Quorum sensing signals affect spoilage of refrigerated large yellow croaker (Pseudosciaena crocea) by Shewanella baltica.

    PubMed

    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. Quorum sensing signals affect spoilage of refrigerated large yellow croaker (Pseudosciaena crocea) by Shewanella baltica.

    PubMed

    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. PMID

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

    PubMed

    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.

  20. Iron- and Quorum-sensing Signals Converge on Small Quorum-regulatory RNAs for Coordinated Regulation of Virulence Factors in Vibrio vulnificus.

    PubMed

    Wen, Yancheng; Kim, In Hwang; Kim, Kun-Soo

    2016-07-01

    Vibrio vulnificus is a marine bacterium that causes human infections resulting in high mortality. This pathogen harbors five quorum-regulatory RNAs (Qrr1-5) that affect the expression of pathogenicity genes by modulating the expression of the master regulator SmcR. The qrr genes are activated by phosphorylated LuxO to different degrees; qrr2 is strongly activated; qrr3 and qrr5 are moderately activated, and qrr1 and qrr4 are marginally activated and are the only two that do not respond to cell density-dependent regulation. Qrrs function redundantly to inhibit SmcR at low cell density and fully repress when all five are activated. In this study, we found that iron inhibits qrr expression in three distinct ways. First, the iron-ferric uptake regulator (Fur) complex directly binds to qrr promoter regions, inhibiting LuxO activation by competing with LuxO for cis-acting DNA elements. Second, qrr transcription is repressed by iron independently of Fur. Third, LuxO expression is repressed by iron independently of Fur. We also found that, under iron-limiting conditions, the five Qrrs functioned additively, not redundantly, to repress SmcR, suggesting that cells lacking iron enter a high cell density mode earlier and could thereby modulate expression of virulence factors sooner. This study suggests that iron and quorum sensing, along with their cognate regulatory circuits, are linked together in the coordinated expression of virulence factors.

  1. Draft Genome Sequence of Pseudoalteromonas tetraodonis Strain MQS005, a Bacterium with Potential Quorum-Sensing Regulation

    PubMed Central

    Pan, Yonglong; Wang, Yanbo; Yan, Xiaoqing; Mazumder, Asit

    2016-01-01

    We present here the draft genome sequence of Pseudoalteromonas tetraodonis strain MQS005, a bacterium possessing potential quorum-sensing regulatory activity. This strain was isolated from water from the South China Sea, People’s Republic of China. The assembly consists of 4,252,538 bp and contains 144 contigs, with a G+C content of 41.85%. PMID:27491986

  2. The Stringent Response Modulates 4-Hydroxy-2-Alkylquinoline Biosynthesis and Quorum-Sensing Hierarchy in Pseudomonas aeruginosa

    PubMed Central

    Schafhauser, James; Lepine, Francois; McKay, Geoffrey; Ahlgren, Heather G.; Khakimova, Malika

    2014-01-01

    As a ubiquitous environmental organism and an important human pathogen, Pseudomonas aeruginosa readily adapts and responds to a wide range of conditions and habitats. The intricate regulatory networks that link quorum sensing and other global regulators allow P. aeruginosa to coordinate its gene expression and cell signaling in response to different growth conditions and stressors. Upon nutrient transitions and starvation, as well as other environmental stresses, the stringent response is activated, mediated by the signal (p)ppGpp. P. aeruginosa produces a family of molecules called HAQ (4-hydroxy-2-alkylquinolines), some of which exhibit antibacterial and quorum-sensing signaling functions and regulate virulence genes. In this study, we report that (p)ppGpp negatively regulates HAQ biosynthesis: in a (p)ppGpp-null (ΔSR) mutant, HHQ (4-hydroxyl-2-heptylquinoline) and PQS (3,4-dihydroxy-2-heptylquinoline) levels are increased due to upregulated pqsA and pqsR expression and reduced repression by the rhl system. We also found that (p)ppGpp is required for full expression of both rhl and las AHL (acyl-homoserine lactone) quorum-sensing systems, since the ΔSR mutant has reduced rhlI, rhlR, lasI, and lasR expression, butanoyl-homoserine lactone (C4-HSL) and 3-oxo-dodecanoyl-homoserine lactone (3-oxo-C12-HSL) levels, and rhamnolipid and elastase production. Furthermore, (p)ppGpp significantly modulates the AHL and PQS quorum-sensing hierarchy, as the las system no longer has a dominant effect on HAQ biosynthesis when the stringent response is inactivated. PMID:24509318

  3. Lipoxin A4 augments host defense in sepsis and reduces Pseudomonas aeruginosa virulence through quorum sensing inhibition.

    PubMed

    Wu, Benedict; Capilato, Joseph; Pham, Michelle P; Walker, Jean; Spur, Bernd; Rodriguez, Ana; Perez, Lark J; Yin, Kingsley

    2016-06-01

    Bacterial infections can quickly turn into sepsis, with its attendant clinical sequelae of inflammation, tissue injury, and organ failure. Paradoxically, sustained inflammation in sepsis may lead to immune suppression, because of which the host is unable to clear the existing infection. Use of agents that suppress the inflammatory response may accelerate host immune suppression, whereas use of traditional antibiotics does not significantly affect inflammation. In this study, we investigated whether lipoxin A4 (LXA4), a specialized, proresolution lipid mediator, could increase neutrophil phagocytic activity as well as reduce bacterial virulence. Using the mouse cecal ligation and puncture (CLP) model of sepsis, the administration of LXA4 (7 μg/kg i.v.) 1 h after surgery increased neutrophil phagocytic ability and Fcγ receptor I (CD64) expression. Ex vivo studies have confirmed that the direct addition of LXA4 to CLP neutrophils increased phagocytic ability but not CD64 expression. LXA4 did not affect neutrophils taken from control mice in which CD64 expression was minimal. Taken together with in vivo data, these results suggest that LXA4 directly augments CD64-mediated neutrophil phagocytic ability but does not directly increase neutrophil CD64 expression. Bacterial communication and virulence is regulated by quorum sensing inducers. In Pseudomonas aeruginosa, virulence is induced with release of various virulence factors, by N-3-oxododecanolyl homoserine lactone binding to the quorum sensing receptor, LasR. We show that LXA4 is an inhibitor of LasR in P. aeruginosa and that it decreases the release of pyocyanin exotoxin. These results suggest that LXA4 has the novel dual properties of increasing host defense and decreasing pathogen virulence by inhibiting quorum sensing.-Wu, B., Capilato, J., Pham, M. P., Walker, J., Spur, B., Rodriguez, A., Perez, L. J., Yin, K. Lipoxin A4 augments host defense in sepsis and reduces Pseudomonas aeruginosa virulence through

  4. The Crystal Structure of Burkholderia cenocepacia DfsA Provides Insights into Substrate Recognition and Quorum Sensing Fatty Acid Biosynthesis.

    PubMed

    Spadaro, Francesca; Scoffone, Viola C; Chiarelli, Laurent R; Fumagalli, Marco; Buroni, Silvia; Riccardi, Giovanna; Forneris, Federico

    2016-06-14

    Burkholderia cenocepacia is a major concern among respiratory tract infections in cystic fibrosis patients. This pathogen is particularly difficult to treat because of its high level of resistance to the clinically relevant antimicrobial agents. In B. cenocepacia, the quorum sensing cell-cell communication system is involved in different processes that are important for bacterial virulence, such as biofilm formation and protease and siderophore production. Targeting the enzymes involved in this process represents a promising therapeutic approach. With the aim of finding effective quorum sensing inhibitors, we have determined the three-dimensional structure of B. cenocepacia diffusible factor synthase A, DfsA. This bifunctional crotonase (dehydratase/thioesterase) produces the characteristic quorum sensing molecule of B. cenocepacia, cis-2-dodecenoic acid or BDSF, starting from 3-hydroxydodecanoyl-acyl carrier protein. Unexpectedly, the crystal structure revealed the presence of a lipid molecule in the catalytic site of the enzyme, which was identified as dodecanoic acid. Our biochemical characterization shows that DfsA is able to use dodecanoyl-acyl carrier protein as a substrate, demonstrating that dodecanoic acid, the product of this reaction, is released very slowly from the DfsA active site, therefore acting as a DfsA inhibitor. This molecule shows an unprecedented conformational arrangement inside the DfsA active site. In contrast with previous hypotheses, our data illustrate how DfsA and closely related homologous enzymes can recognize long hydrophobic substrates without large conformational changes or assistance by additional regulator molecules. The elucidation of the substrate binding mode in DfsA provides the starting point for structure-based drug discovery studies targeting B. cenocepacia quorum sensing-assisted virulence.

  5. The Crystal Structure of Burkholderia cenocepacia DfsA Provides Insights into Substrate Recognition and Quorum Sensing Fatty Acid Biosynthesis.

    PubMed

    Spadaro, Francesca; Scoffone, Viola C; Chiarelli, Laurent R; Fumagalli, Marco; Buroni, Silvia; Riccardi, Giovanna; Forneris, Federico

    2016-06-14

    Burkholderia cenocepacia is a major concern among respiratory tract infections in cystic fibrosis patients. This pathogen is particularly difficult to treat because of its high level of resistance to the clinically relevant antimicrobial agents. In B. cenocepacia, the quorum sensing cell-cell communication system is involved in different processes that are important for bacterial virulence, such as biofilm formation and protease and siderophore production. Targeting the enzymes involved in this process represents a promising therapeutic approach. With the aim of finding effective quorum sensing inhibitors, we have determined the three-dimensional structure of B. cenocepacia diffusible factor synthase A, DfsA. This bifunctional crotonase (dehydratase/thioesterase) produces the characteristic quorum sensing molecule of B. cenocepacia, cis-2-dodecenoic acid or BDSF, starting from 3-hydroxydodecanoyl-acyl carrier protein. Unexpectedly, the crystal structure revealed the presence of a lipid molecule in the catalytic site of the enzyme, which was identified as dodecanoic acid. Our biochemical characterization shows that DfsA is able to use dodecanoyl-acyl carrier protein as a substrate, demonstrating that dodecanoic acid, the product of this reaction, is released very slowly from the DfsA active site, therefore acting as a DfsA inhibitor. This molecule shows an unprecedented conformational arrangement inside the DfsA active site. In contrast with previous hypotheses, our data illustrate how DfsA and closely related homologous enzymes can recognize long hydrophobic substrates without large conformational changes or assistance by additional regulator molecules. The elucidation of the substrate binding mode in DfsA provides the starting point for structure-based drug discovery studies targeting B. cenocepacia quorum sensing-assisted virulence. PMID:27198181

  6. Synthetic Quorum Sensing and Cell-Cell Communication in Gram-Positive Bacillus megaterium.

    PubMed

    Marchand, Nicholas; Collins, Cynthia H

    2016-07-15

    The components of natural quorum-sensing (QS) systems can be used to engineer synthetic communication systems that regulate gene expression in response to chemical signals. We have used the machinery from the peptide-based agr QS system from Staphylococcus aureus to engineer a synthetic QS system in Bacillus megaterium to enable autoinduction of a target gene at high cell densities. Growth and gene expression from these synthetic QS cells were characterized in both complex and minimal media. We also split the signal production and sensing components between two strains of B. megaterium to produce sender and receiver cells and characterized the resulting communication in liquid media and on semisolid agar. The system described in this work represents the first synthetic QS and cell-cell communication system that has been engineered to function in a Gram-positive host, and it has the potential to enable the generation of dynamic gene regulatory networks in B. megaterium and other Gram-positive organisms. PMID:26203497

  7. Quorum sensing protects bacterial co-operation from exploitation by cheats

    PubMed Central

    Allen, Richard C; McNally, Luke; Popat, Roman; Brown, Sam P

    2016-01-01

    Quorum sensing (QS) is a cell–cell communication system found in many bacterial species, commonly controlling secreted co-operative traits, including extracellular digestive enzymes. We show that the canonical QS regulatory architecture allows bacteria to sense the genotypic composition of high-density populations, and limit co-operative investments to social environments enriched for co-operators. Using high-density populations of the opportunistic pathogen Pseudomonas aeruginosa we map per-capita signal and co-operative enzyme investment in the wild type as a function of the frequency of non-responder cheats. We demonstrate mathematically and experimentally that the observed response rule of ‘co-operate when surrounded by co-operators' allows bacteria to match their investment in co-operation to the composition of the group, therefore allowing the maintenance of co-operation at lower levels of population structuring (that is, lower relatedness). Similar behavioural responses have been described in vertebrates under the banner of ‘generalised reciprocity'. Our results suggest that mechanisms of reciprocity are not confined to taxa with advanced cognition, and can be implemented at the cellular level via positive feedback circuits. PMID:26744811

  8. The LuxS Based Quorum Sensing Governs Lactose Induced Biofilm Formation by Bacillus subtilis

    PubMed Central

    Duanis-Assaf, Danielle; Steinberg, Doron; Chai, Yunrong; Shemesh, Moshe

    2016-01-01

    Bacillus species present a major concern in the dairy industry as they can form biofilms in pipelines and on surfaces of equipment and machinery used in the entire line of production. These biofilms represent a continuous hygienic problem and can lead to serious economic losses due to food spoilage and equipment impairment. Biofilm formation by Bacillus subtilis is apparently dependent on LuxS quorum sensing (QS) by Autoinducer-2 (AI-2). However, the link between sensing environmental cues and AI-2 induced biofilm formation remains largely unknown. The aim of this study is to investigate the role of lactose, the primary sugar in milk, on biofilm formation by B. subtilis and its possible link to QS processes. Our phenotypic analysis shows that lactose induces formation of biofilm bundles as well as formation of colony type biofilm. Furthermore, using reporter strain assays, we observed an increase in AI-2 production by B. subtilis in response to lactose in a dose dependent manner. Moreover, we found that expression of eps and tapA operons, responsible for extracellular matrix synthesis in B. subtilis, were notably up-regulated in response to lactose. Importantly, we also observed that LuxS is essential for B. subtilis biofilm formation in the presence of lactose. Overall, our results suggest that lactose may induce biofilm formation by B. subtilis through the LuxS pathway. PMID:26779171

  9. Methyl 3-Hydroxymyristate, a Diffusible Signal Mediating phc Quorum Sensing in Ralstonia solanacearum.

    PubMed

    Kai, Kenji; Ohnishi, Hideyuki; Shimatani, Mika; Ishikawa, Shiho; Mori, Yuka; Kiba, Akinori; Ohnishi, Kouhei; Tabuchi, Mitsuaki; Hikichi, Yasufumi

    2015-11-01

    Ralstonia solanacearum, a plant pathogenic bacterium causing "bacterial wilt" on crops, uses a quorum sensing (QS) system consisting of phc regulatory elements to control its virulence. Methyl 3-hydroxypalmitate (3-OH PAME) was previously identified as the QS signal in strain AW1. However, 3-OH PAME has not been reportedly detected from any other strains, and this suggests that they produce another unknown QS signal. Here we identify (R)-methyl 3-hydroxymyristate [(R)-3-OH MAME] as a new QS signal that regulates the production of virulence factors and secondary metabolites. (R)-3-OH MAME was synthesized by the methyltransferase PhcB and sensed by the histidine kinase PhcS. The phylogenetic trees of these proteins from R. solanacearum strains were divided into two groups, according to their QS signal types--(R)-3-OH MAME or (R)-3-OH PAME. These results demonstrate that (R)-3-OH MAME is another crucial QS signal and highlight the unique evolution of QS systems in R. solanacearum.

  10. Mechanistic analysis of a synthetic inhibitor of the Pseudomonas aeruginosa LasI quorum-sensing signal synthase

    PubMed Central

    Lidor, O.; Al-Quntar, A.; Pesci, E. C.; Steinberg, D.

    2015-01-01

    Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen responsible for many human infections. LasI is an acyl-homoserine lactone synthase that produces a quorum-sensing (QS) signal that positively regulates numerous P. aeruginosa virulence determinants. The inhibition of the LasI protein is therefore an attractive drug target. In this study, a novel in silico to in vitro complementation was applied to screen thiazolidinedione-type compounds for their ability to inhibit biofilm formation at concentrations not affecting bacterial growth. The compound (z)-5-octylidenethiazolidine-2, 4-dione (TZD-C8) was a strong inhibitor of biofilm formation and chosen for further study. Structural exploration of in silico docking predicted that the compound had high affinity for the LasI activity pocket. The TZD-C8 compound was also predicted to create hydrogen bonds with residues Arg30 and Ile107. Site-directed mutagenesis (SDM) of these two sites demonstrated that TZD-C8 inhibition was abolished in the lasI double mutant PAO-R30D, I107S. In addition, in vitro swarming motility and quorum sensing signal production were affected by TZD-C 8, confirming this compound alters the cell to cell signalling circuitry. Overall, this novel inhibitor of P. aeruginosa quorum sensing shows great promise and validates our mechanistic approach to discovering inhibitors of LuxI-type acyl-homoserine lactone synthases. PMID:26593271

  11. Quorum sensing signalling and biofilm formation of brewery-derived bacteria, and inhibition of signalling by natural compounds.

    PubMed

    Priha, O; Virkajärvi, V; Juvonen, R; Puupponen-Pimiä, R; Nohynek, L; Alakurtti, S; Pirttimaa, M; Storgårds, E

    2014-11-01

    Bacteria use quorum sensing signalling in various functions, e.g. while forming biofilms, and inhibition of this signalling could be one way to control biofilm formation. The aim of this study was to evaluate the production of signalling molecules and its correlation with the biofilm formation capability of bacteria isolated from brewery filling process. A further aim was to study berry extracts and wood-derived terpenes for their possible quorum sensing inhibitory effects. Out of the twenty bacteria studied, five produced short-chain and five long-chain AHL (acyl homoserine lactone) signalling molecules when tested with the Chromobacterium violaceum CV026 reporter bacterium. Production of AI-2 (autoinducer-2) signalling molecules was detected from nine strains with the Vibrio harveyi BB170 bioassay. Over half of the strains produced biofilm in the microtitre plate assay, but the production of AHL and AI-2 signalling molecules and biofilm formation capability did not directly correlate with each other. Out of the 13 berry extracts and wood-derived terpenes screened, four compounds decreased AHL signalling without effect on growth. These were betulin, raspberry extract and two cloudberry extracts. The effect of these compounds on biofilm formation of the selected six bacterial strains varied. The phenolic extract of freeze-dried cloudberry fruit caused a statistically significant reduction of biofilm formation of Obesumbacterium proteus strain. Further experiments should aim at identifying the active compounds and revealing whether quorum sensing inhibition causes structural changes in the biofilms formed. PMID:24944110

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

    PubMed

    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.

  13. Characterization of phenotype variations of luminescent and non-luminescent variants of Vibrio harveyi wild type and quorum sensing mutants.

    PubMed

    Hong, N T X; Baruah, K; Vanrompay, D; Bossier, P

    2016-03-01

    Vibrio harveyi, a luminescent Gram-negative motile marine bacterium, is an important pathogen responsible for causing severe diseases in shrimp, finfish and molluscs leading to severe economic losses. Non-luminescent V. harveyi obtained by culturing luminescent strains under static and dark condition were reported to alter the levels of virulence factors and metalloprotease gene and luxR expression when compared to their luminescent variants. Presently, we conducted an in vitro study aiming at the characterization of virulence-related phenotypic traits of the wild-type V. harveyi BB120 strain and its isogenic quorum sensing mutants before and after switching to the non-luminescent status. We measured the production of caseinase, haemolysin and elastase and examined swimming motility and biofilm formation. Our results showed that switching from the bioluminescent to the non-luminescent state changed the phenotypic physiology or behaviour of V. harveyi resulting in alterations in caseinase and haemolytic activities, swimming motility and biofilm formation. The switching capacity was to a large extent independent from the quorum sensing status, in that quorum sensing mutants were equally capable of making the phenotypic switch.

  14. Surface polysaccharides and quorum sensing are involved in the attachment and survival of Xanthomonas albilineans on sugarcane leaves.

    PubMed

    Mensi, Imene; Daugrois, Jean-Heinrich; Pieretti, Isabelle; Gargani, Daniel; Fleites, Laura A; Noell, Julie; Bonnot, Francois; Gabriel, Dean W; Rott, Philippe

    2016-02-01

    Xanthomonas albilineans, the causal agent of sugarcane leaf scald, is a bacterial plant pathogen that is mainly spread by infected cuttings and contaminated harvesting tools. However, some strains of this pathogen are known to be spread by aerial means and are able to colonize the phyllosphere of sugarcane before entering the host plant and causing disease. The objective of this study was to identify the molecular factors involved in the survival or growth of X. albilineans on sugarcane leaves. We developed a bioassay to test for the attachment of X. albilineans on sugarcane leaves using tissue-cultured plantlets grown in vitro. Six mutants of strain XaFL07-1 affected in surface polysaccharide production completely lost their capacity to survive on the sugarcane leaf surface. These mutants produced more biofilm in vitro and accumulated more cellular poly-β-hydroxybutyrate than the wild-type strain. A mutant affected in the production of small molecules (including potential biosurfactants) synthesized by non-ribosomal peptide synthetases (NRPSs) attached to the sugarcane leaves as well as the wild-type strain. Surprisingly, the attachment of bacteria on sugarcane leaves varied among mutants of the rpf gene cluster involved in bacterial quorum sensing. Therefore, quorum sensing may affect polysaccharide production, or both polysaccharides and quorum sensing may be involved in the survival or growth of X. albilineans on sugarcane leaves.

  15. Intracellular Ca(2+) mobilization and kinase activity during acylated homoserine lactone-dependent quorum sensing in Serratia liquefaciens.

    PubMed

    Werthén, M; Lundgren, T

    2001-03-01

    Quorum sensing in Gram-negative bacteria involves acylated homoserine lactones (AHLs) and a transcription factor, activated by the AHLs. In this study, a possible involvement of intracellular Ca(2+) as second messenger and/or protein kinase activity during signal transduction is analyzed. When N-hexanoyl-l-homoserine lactone was added to a suspension of Fura-2-loaded Serratia liquefaciens, there was a decline in [Ca(2+)](i), measured as a decrease in the Fura-2 fluorescence ratio. As controls, the addition of the signal molecule N-3-oxohexanoyl-l-homoserine lactone, which is not produced by S. liquefaciens, did not induce changes in [Ca(2+)](i). Using a protein kinase activity assay on AHL-stimulated cells, an increase in kinase activity after N-butanoyl-l-homoserine lactone stimulation of S. liquefaciens cells was detected, whereas the kinase activity induced by N-3-oxohexanoyl-l-homoserine lactone was not statistically significant. The conclusion from this study is that changes in [Ca(2+)](i) are involved in quorum sensing signal transduction in the Gram-negative bacteria S. liquefaciens. We also conclude that kinase activity is induced in S. liquefaciens upon AHL stimulation. We suggest that the transient intracellular [Ca(2+)] changes and kinase activity, activated by the AHL signal, are critical for the quorum-sensing signal transduction.

  16. Degradation of Bacterial Quorum Sensing Signaling Molecules by the Microscopic Yeast Trichosporon loubieri Isolated from Tropical Wetland Waters

    PubMed Central

    Wong, Cheng-Siang; Koh, Chong-Lek; Sam, Choon-Kook; Chen, Jian Woon; Chong, Yee Meng; Yin, Wai-Fong; Chan, Kok-Gan

    2013-01-01

    Proteobacteria produce N-acylhomoserine lactones as signaling molecules, which will bind to their cognate receptor and activate quorum sensing-mediated phenotypes in a population-dependent manner. Although quorum sensing signaling molecules can be degraded by bacteria or fungi, there is no reported work on the degradation of such molecules by basidiomycetous yeast. By using a minimal growth medium containing N-3-oxohexanoylhomoserine lactone as the sole source of carbon, a wetland water sample from Malaysia was enriched for microbial strains that can degrade N-acylhomoserine lactones, and consequently, a basidiomycetous yeast strain WW1C was isolated. Morphological phenotype and molecular analyses confirmed that WW1C was a strain of Trichosporon loubieri. We showed that WW1C degraded AHLs with N-acyl side chains ranging from 4 to 10 carbons in length, with or without oxo group substitutions at the C3 position. Re-lactonisation bioassays revealed that WW1C degraded AHLs via a lactonase activity. To the best of our knowledge, this is the first report of degradation of N-acyl-homoserine lactones and utilization of N-3-oxohexanoylhomoserine as carbon and nitrogen source for growth by basidiomycetous yeast from tropical wetland water; and the degradation of bacterial quorum sensing molecules by an eukaryotic yeast. PMID:24072030

  17. Influence of the AgrC-AgrA complex on the response time of Staphylococcus aureus quorum sensing.

    PubMed

    Srivastava, Sandeep K; Rajasree, Kalagiri; Fasim, Aneesa; Arakere, Gayathri; Gopal, Balasubramanian

    2014-08-01

    The Staphylococcus aureus agr quorum-sensing system plays a major role in the transition from the persistent to the virulent phenotype. S. aureus agr type I to IV strains are characterized by mutations in the sensor domain of the histidine kinase AgrC and differences in the sequences of the secreted autoinducing peptides (AIP). Here we demonstrate that interactions between the cytosolic domain of AgrC (AgrCCyto) and the response regulator domain of AgrA (AgrARR) dictate the spontaneity of the cellular response to AIP stimuli. The crystal structure of AgrCCyto provided a basis for a mechanistic model of AgrC-AgrA interactions. This model enabled an analysis of the biochemical and biophysical parameters of AgrC-AgrA interactions in the context of the conformational features of the AgrC-AgrA complex. This analysis revealed distinct sequence and conformational features that determine the affinity, specificity, and kinetics of the phosphotransfer reaction. This step, which governs the response time for transcriptional reengineering triggered by an AIP stimulus, is independent of the agr type and similar for agonist and antagonist stimuli. These experimental data could serve as a basis on which to validate simulations of the quorum-sensing response and for strategies that employ the agr quorum-sensing system to combat biofilm formation in S. aureus infections. PMID:24858185

  18. The dependence of quorum sensing in Serratia marcescens JG on the transcription of luxS gene.

    PubMed

    Sun, Shu-Jing; Liu, Yu-Chen; Sun, Jiao; Zhu, Hu

    2015-06-01

    Bacteria communicate with one another using chemical signal molecules. This phenomenon termed quorum sensing enables the bacteria to monitor the environment for other bacteria and to alter behavior on a population-wide scale in response to cell density. Serratia marcescens JG, a quorum sensing bacterium, can secrete a furanosyl borate diester autoinducer (AI-2) in the exponential phase of growth. In this study, to further investigate the regulation of AI-2 production in S. marcescens JG, the pfs and luxS promoter fusions to an operon luxCDABE reporter were constructed in a low-copy-number vector pBR322K, which allows an examination of transcription of the genes in the pathway for signal synthesis. The results show that the luxS expression is constitutive, and the transcription of luxS is tightly correlated with AI-2 production in S. marcescens JG because the peaks of AI-2 production and transcriptional level of luxS appear at the same time point. The close relation of the profiles of luxS transcription and AI-2 production was also confirmed with real-time PCR technology. These results support the hypothesis that the quorum sensing in S. marcescens JG is luxS dependent.

  19. Influence of the AgrC-AgrA Complex on the Response Time of Staphylococcus aureus Quorum Sensing

    PubMed Central

    Srivastava, Sandeep K.; Rajasree, Kalagiri; Fasim, Aneesa; Arakere, Gayathri

    2014-01-01

    The Staphylococcus aureus agr quorum-sensing system plays a major role in the transition from the persistent to the virulent phenotype. S. aureus agr type I to IV strains are characterized by mutations in the sensor domain of the histidine kinase AgrC and differences in the sequences of the secreted autoinducing peptides (AIP). Here we demonstrate that interactions between the cytosolic domain of AgrC (AgrCCyto) and the response regulator domain of AgrA (AgrARR) dictate the spontaneity of the cellular response to AIP stimuli. The crystal structure of AgrCCyto provided a basis for a mechanistic model of AgrC-AgrA interactions. This model enabled an analysis of the biochemical and biophysical parameters of AgrC-AgrA interactions in the context of the conformational features of the AgrC-AgrA complex. This analysis revealed distinct sequence and conformational features that determine the affinity, specificity, and kinetics of the phosphotransfer reaction. This step, which governs the response time for transcriptional reengineering triggered by an AIP stimulus, is independent of the agr type and similar for agonist and antagonist stimuli. These experimental data could serve as a basis on which to validate simulations of the quorum-sensing response and for strategies that employ the agr quorum-sensing system to combat biofilm formation in S. aureus infections. PMID:24858185

  20. Inhibition of quorum sensing-mediated biofilm formation in Pseudomonas aeruginosa by a locally isolated Bacillus cereus.

    PubMed

    Wahman, Shaimaa; Emara, Mohamed; Shawky, Riham M; El-Domany, Ramadan A; Aboulwafa, Mohammad Mabrouk

    2015-12-01

    Quorum sensing has been shown to play a crucial role in Pseudomonas aeruginosa pathogenesis where it activates expression of myriad genes that regulate the production of important virulence factors such as biofilm formation. Antagonism of quorum sensing is an excellent target for antimicrobial therapy and represents a novel approach to combat drug resistance. In this study, Chromobacterium violaceum biosensor strain was employed as a fast, sensitive, reliable, and easy to use tool for rapid screening of soil samples for Quorum Sensing Inhibitors (QSI) and the optimal conditions for maximal QSI production were scrutinized. Screening of 127 soil isolates showed that 43 isolates were able to breakdown the HHL signal. Out of the 43 isolates, 38 isolates were able to inhibit the violet color of the biosensor and to form easily detectable zones of color inhibition around their growth. A confirmatory bioassay was carried out after concentrating the putative positive cell-free lysates. Three different isolates that belonged to Bacillus cereus group were shown to have QSI activities and their QSI activities were optimized by changing their culture conditions. Further experiments revealed that the cell-free lysates of these isolates were able to inhibit biofilm formation by P. aeruginosa clinical isolates.

  1. Beneficial effects of bacteria-plant communication based on quorum sensing molecules of the N-acyl homoserine lactone group.

    PubMed

    Schikora, Adam; Schenk, Sebastian T; Hartmann, Anton

    2016-04-01

    Bacterial quorum sensing (QS) mechanisms play a crucial role in the proper performance and ecological fitness of bacterial populations. Many key physiological processes are regulated in a QS-dependent manner by auto-inducers, like the N-acyl homoserine lactones (AHLs) in numerous Gram-negative bacteria. In addition, also the interaction between bacteria and eukaryotic hosts can be regulated by AHLs. Those mechanisms gained much attention, because of the positive effects of different AHL molecules on plants. This positive impact ranges from growth promotion to induced resistance and is quite contrasting to the rather negative effects observed in the interactions between bacterial AHL molecules and animals. Only very recently, we began to understand the molecular mechanisms underpinning plant responses to AHL molecules. In this review, we gathered the latest information in this research field. The first part gives an overview of the bacterial aspects of quorum sensing. Later we focus on the impact of AHLs on plant growth and AHL-priming, as one of the most understood phenomena in respect to the inter-kingdom interactions based on AHL-quorum sensing molecules. Finally, we discuss the potential benefits of the understanding of bacteria-plant interaction for the future agricultural applications.

  2. Quorum Sensing Is Accompanied by Global Metabolic Changes in the Opportunistic Human Pathogen Pseudomonas aeruginosa

    PubMed Central

    Davenport, Peter W.; Griffin, Julian L.

    2015-01-01

    ABSTRACT Pseudomonas aeruginosa uses N-acyl-homoserine lactone (AHL)-dependent quorum sensing (QS) systems to control the expression of secreted effectors. These effectors can be crucial to the ecological fitness of the bacterium, playing roles in nutrient acquisition, microbial competition, and virulence. In this study, we investigated the metabolic consequences of AHL-dependent QS by monitoring the metabolic profile(s) of a lasI rhlI double mutant (unable to make QS signaling molecules) and its wild-type progenitor as they progressed through the growth curve. Analysis of culture supernatants by 1H-nuclear magnetic resonance (1H-NMR) spectroscopy revealed that at the point where AHL concentrations peaked in the wild type, the metabolic footprints (i.e., extracellular metabolites) of the wild-type and lasI rhlI mutant diverged. Subsequent gas chromatography-mass spectrometry (GC-MS)-based analysis of the intracellular metabolome revealed QS-dependent perturbations in around one-third of all identified metabolites, including altered concentrations of tricarboxylic acid (TCA) cycle intermediates, amino acids, and fatty acids. Further targeted fatty acid methyl ester (FAME) GC-MS-based profiling of the cellular total fatty acid pools revealed that QS leads to changes associated with decreased membrane fluidity and higher chemical stability. However, not all of the changes we observed were necessarily a direct consequence of QS; liquid chromatography (LC)-MS analyses revealed that polyamine levels were elevated in the lasI rhlI mutant, perhaps a response to the absence of QS-dependent adaptations. Our data suggest that QS leads to a global readjustment in central metabolism and provide new insight into the metabolic changes associated with QS during stationary-phase adaptation. IMPORTANCE Quorum sensing (QS) is a transcriptional regulatory mechanism that allows bacteria to coordinate their gene expression profile with the population cell density. The opportunistic

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

    PubMed Central

    Rajamani, Sathish; Bauer, Wolfgang D.; Robinson, Jayne B.; Farrow, John M.; Pesci, Everett C.; Teplitski, Max; Gao, Mengsheng; Sayre, Richard T.; Phillips, Donald A.

    2013-01-01

    Many bacteria use quorum sensing (QS) as an intercellular signaling mechanism to regulate gene expression in local populations. Plant and algal hosts, in turn, secrete compounds that mimic bacterial QS signals, allowing these hosts to manipulate QS-regulated gene expression in bacteria. Lumichrome, a derivative of the vitamin riboflavin, was purified and chemically identified from culture filtrates of the alga Chlamydomonas as a QS signal-mimic compound capable of stimulating the Pseudomonas aeruginosa LasR QS receptor. LasR normally recognizes the N-acyl homoserine lactone (AHL) signal, N-3-oxo-dodecanoyl homoserine lactone (3-oxo-C12-HSL). Authentic lumichrome and riboflavin stimulated the LasR receptor in bioassays, and lumichrome activated LasR in gel shift experiments. Amino acid substitutions in LasR residues required for AHL binding altered responses to both AHLs and lumichrome/riboflavin. These results and docking studies indicate that the AHL binding pocket of LasR recognizes both AHLs and the structurally dissimilar lumichrome/riboflavin. Bacteria, plants and algae commonly secrete riboflavin and/or lumichrome, raising the possibility that these compounds could serve as either QS signals or as interkingdom signal-mimics capable of manipulating QS in bacteria with a LasR-like receptor. PMID:18700823

  4. Ajoene, a Sulfur-Rich Molecule from Garlic, Inhibits Genes Controlled by Quorum Sensing

    PubMed Central

    Jakobsen, Tim Holm; van Gennip, Maria; Phipps, Richard Kerry; Shanmugham, Meenakshi Sundaram; Christensen, Louise Dahl; Alhede, Morten; Skindersoe, Mette Eline; Rasmussen, Thomas Bovbjerg; Friedrich, Karlheinz; Uthe, Friedrich; Jensen, Peter Østrup; Moser, Claus; Nielsen, Kristian Fog; Eberl, Leo; Larsen, Thomas Ostenfeld; Tanner, David; Høiby, Niels; Bjarnsholt, Thomas

    2012-01-01

    In relation to emerging multiresistant bacteria, development of antimicrobials and new treatment strategies of infections should be expected to become a high-priority research area. Quorum sensing (QS), a communication system used by pathogenic bacteria like Pseudomonas aeruginosa to synchronize the expression of specific genes involved in pathogenicity, is a possible drug target. Previous in vitro and in vivo studies revealed a significant inhibition of P. aeruginosa QS by crude garlic extract. By bioassay-guided fractionation of garlic extracts, we determined the primary QS inhibitor present in garlic to be ajoene, a sulfur-containing compound with potential as an antipathogenic drug. By comprehensive in vitro and in vivo studies, the effect of synthetic ajoene toward P. aeruginosa was elucidated. DNA microarray studies of ajoene-treated P. aeruginosa cultures revealed a concentration-dependent attenuation of a few but central QS-controlled virulence factors, including rhamnolipid. Furthermore, ajoene treatment of in vitro biofilms demonstrated a clear synergistic, antimicrobial effect with tobramycin on biofilm killing and a cease in lytic necrosis of polymorphonuclear leukocytes. Furthermore, in a mouse model of pulmonary infection, a significant clearing of infecting P. aeruginosa was detected in ajoene-treated mice compared to a nontreated control group. This study adds to the list of examples demonstrating the potential of QS-interfering compounds in the treatment of bacterial infections. PMID:22314537

  5. Inhibition of quorum sensing regulated biofilm formation in Serratia marcescens causing nosocomial infections.

    PubMed

    Bakkiyaraj, Dhamodharan; Sivasankar, Chandran; Pandian, Shunmugiah Karutha

    2012-05-01

    Serratia marcescens is an opportunistic pathogen causing severe urinary tract infections in hospitalized individuals. Infections of S. marcescens are of great concern because of its increasing resistance towards conventional antibiotics. Quorum sensing (QS)-a cell to cell communication-system of S. marcescens acts as a global regulator of almost all the virulence factors and majorly its biofilm formation. Since, the QS system of S. marcescens directly accords to its pathogenesis, targeting QS system will provide an improved strategy to combat drug resistant pathogens. In the present study, QS system of S. marcescens has been used as target and its inhibition has been studied upon exposure to bioactives from coral associated bacteria (CAB). This study also emphasises the potential of CAB in producing bioactive agents with anti-QS and antibiofilm properties. Two CAB isolates CAB 23 and 41 have shown to inhibit biofilm formation and the production of QS dependent virulence factors like prodigiosin, protease, lipase and swarming motility. The study, on the whole explicates the potential of QS system as a target to treat drug resistant bacterial infections. PMID:22487181

  6. A quorum sensing small volatile molecule promotes antibiotic tolerance in bacteria.

    PubMed

    Que, Yok-Ai; Hazan, Ronen; Strobel, Benjamin; Maura, Damien; He, Jianxin; Kesarwani, Meenu; Panopoulos, Panagiotis; Tsurumi, Amy; Giddey, Marlyse; Wilhelmy, Julie; Mindrinos, Michael N; Rahme, Laurence G

    2013-01-01

    Bacteria can be refractory to antibiotics due to a sub-population of dormant cells, called persisters that are highly tolerant to antibiotic exposure. The low frequency and transience of the antibiotic tolerant "persister" trait has complicated elucidation of the mechanism that controls antibiotic tolerance. In this study, we show that 2' Amino-acetophenone (2-AA), a poorly studied but diagnostically important small, volatile molecule produced by the recalcitrant gram-negative human pathogen Pseudomonas aeruginosa, promotes antibiotic tolerance in response to quorum-sensing (QS) signaling. Our results show that 2-AA mediated persister cell accumulation occurs via alteration of the expression of genes involved in the translational capacity of the cell, including almost all ribosomal protein genes and other translation-related factors. That 2-AA promotes persisters formation also in other emerging multi-drug resistant pathogens, including the non 2-AA producer Acinetobacter baumannii implies that 2-AA may play an important role in the ability of gram-negative bacteria to tolerate antibiotic treatments in polymicrobial infections. Given that the synthesis, excretion and uptake of QS small molecules is a common hallmark of prokaryotes, together with the fact that the translational machinery is highly conserved, we posit that modulation of the translational capacity of the cell via QS molecules, may be a general, widely distributed mechanism that promotes antibiotic tolerance among prokaryotes.

  7. A Quorum Sensing Small Volatile Molecule Promotes Antibiotic Tolerance in Bacteria

    PubMed Central

    Strobel, Benjamin; Maura, Damien; He, Jianxin; Kesarwani, Meenu; Panopoulos, Panagiotis; Tsurumi, Amy; Giddey, Marlyse; Wilhelmy, Julie; Mindrinos, Michael N.; Rahme, Laurence G.

    2013-01-01

    Bacteria can be refractory to antibiotics due to a sub-population of dormant cells, called persisters that are highly tolerant to antibiotic exposure. The low frequency and transience of the antibiotic tolerant “persister” trait has complicated elucidation of the mechanism that controls antibiotic tolerance. In this study, we show that 2’ Amino-acetophenone (2-AA), a poorly studied but diagnostically important small, volatile molecule produced by the recalcitrant gram-negative human pathogen Pseudomonas aeruginosa, promotes antibiotic tolerance in response to quorum-sensing (QS) signaling. Our results show that 2-AA mediated persister cell accumulation occurs via alteration of the expression of genes involved in the translational capacity of the cell, including almost all ribosomal protein genes and other translation-related factors. That 2-AA promotes persisters formation also in other emerging multi-drug resistant pathogens, including the non 2-AA producer Acinetobacter baumannii implies that 2-AA may play an important role in the ability of gram-negative bacteria to tolerate antibiotic treatments in polymicrobial infections. Given that the synthesis, excretion and uptake of QS small molecules is a common hallmark of prokaryotes, together with the fact that the translational machinery is highly conserved, we posit that modulation of the translational capacity of the cell via QS molecules, may be a general, widely distributed mechanism that promotes antibiotic tolerance among prokaryotes. PMID:24367477

  8. Synthetic Quorum Sensing and Induced Aggregation in Model Microcapsule Colonies with Repressilator Feedback

    NASA Astrophysics Data System (ADS)

    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.

  9. Detection of Quorum Sensing Molecules and Biofilm Formation in Ralstonia solanacearum.

    PubMed

    Kumar, J Shiva; Umesha, S; Prasad, K Shiva; Niranjana, P

    2016-03-01

    Many bacteria use small diffusible signaling molecules to communicate each other termed as quorum sensing (QS). Most Gram-negative bacteria use acyl homoserine lactone (AHL) as QS signal molecules. Using these signaling molecules, bacteria are able to express specific genes in response to population density. This work aimed to detect the production of QS signal molecules and biofilm formation in Ralstonia solanacearum isolated from various diseased tomato plants with symptoms of bacterial wilt. A total of 30 R. solanacearum strains were investigated for the production of QS signal molecules using Chromobacterium violaceum CV026 and Agrobacterium tumefaciens NT1 (pZLR4) biosensor systems. All 30 bacterial isolates from various bacterial wilt-affected tomato plants produced AHL molecules that induced the biosensor. The microtiter plate assay demonstrated that of the 30 bacterial isolates, 60 % formed biofilm, among which four isolates exhibited a higher degree of biofilm formation. The biofilm-inducing factor was purified from these four culture supernatants. The structure of the responsible molecule was solved using nuclear magnetic resonance and mass spectroscopy and was determined to be 2-hydroxy-4-((methylamino)(phenyl)methyl) cyclopentanone (HMCP), which was confirmed by chemical synthesis and NMR. The Confocal laser scanning microscopic analysis showed well-developed biofilm architecture of bacteria when treated with HMCP. The knowledge we obtained from this study will be useful for further researcher on the role of HMCP molecule in biofilm formation. PMID:26620535

  10. Non-thermal Plasma Exposure Rapidly Attenuates Bacterial AHL-Dependent Quorum Sensing and Virulence

    PubMed Central

    Flynn, Padrig B.; Busetti, Alessandro; Wielogorska, Ewa; Chevallier, Olivier P.; Elliott, Christopher T.; Laverty, Garry; Gorman, Sean P.; Graham, William G.; Gilmore, Brendan F.

    2016-01-01

    The antimicrobial activity of atmospheric pressure non-thermal plasma has been exhaustively characterised, however elucidation of the interactions between biomolecules produced and utilised by bacteria and short plasma exposures are required for optimisation and clinical translation of cold plasma technology. This study characterizes the effects of non-thermal plasma exposure on acyl homoserine lactone (AHL)-dependent quorum sensing (QS). Plasma exposure of AHLs reduced the ability of such molecules to elicit a QS response in bacterial reporter strains in a dose-dependent manner. Short exposures (30–60 s) produce of a series of secondary compounds capable of eliciting a QS response, followed by the complete loss of AHL-dependent signalling following longer exposures. UPLC-MS analysis confirmed the time-dependent degradation of AHL molecules and their conversion into a series of by-products. FT-IR analysis of plasma-exposed AHLs highlighted the appearance of an OH group. In vivo assessment of the exposure of AHLs to plasma was examined using a standard in vivo model. Lettuce leaves injected with the rhlI/lasI mutant PAO-MW1 alongside plasma treated N-butyryl-homoserine lactone and n-(3-oxo-dodecanoyl)-homoserine lactone, exhibited marked attenuation of virulence. This study highlights the capacity of atmospheric pressure non-thermal plasma to modify and degrade AHL autoinducers thereby attenuating QS-dependent virulence in P. aeruginosa. PMID:27242335

  11. Quorum sensing-mediated regulation of staphylococcal virulence and antibiotic resistance.

    PubMed

    Singh, Rachna; Ray, Pallab

    2014-01-01

    Accessory gene regulator (agr)-mediated quorum sensing plays a central role in staphylococcal pathogenesis. It primarily upregulates secreted virulence factors and downregulates cell surface proteins, thereby governing invasiveness of staphylococci and cell dispersal from biofilms. Except for α- and β-PSMs, which are directly controlled by AgrA, the effector functions of agr are primarily mediated by RNAIII, a regulatory RNA encoded by this operon. agr phenotype and expression considerably influence the chronicity of an infection. It has also been linked with altered susceptibility of Staphylococcus aureus against antibiotics. Four classes of S. aureus and Staphylococcus epidermidis AIPs exist based on sequence variation, and lead to inter-strain and species cross-inhibition. Certain agr classes have been associated with specific clonal complexes, disease syndromes and intermediate-susceptibility to glycopeptides. It is also being investigated as a prophylactic and therapeutic target. This article describes the presently available literature regarding the role of agr in S. aureus and S. epidermidis infections.

  12. Comprehensive analysis reveals how single nucleotides contribute to noncoding RNA function in bacterial quorum sensing.

    PubMed

    Rutherford, Steven T; Valastyan, Julie S; Taillefumier, Thibaud; Wingreen, Ned S; Bassler, Bonnie L

    2015-11-01

    Five homologous noncoding small RNAs (sRNAs), called the Qrr1-5 sRNAs, function in the Vibrio harveyi quorum-sensing cascade to drive its operation. Qrr1-5 use four different regulatory mechanisms to control the expression of ∼ 20 mRNA targets. Little is known about the roles individual nucleotides play in mRNA target selection, in determining regulatory mechanism, or in defining Qrr potency and dynamics of target regulation. To identify the nucleotides vital for Qrr function, we developed a method we call RSort-Seq that combines saturating mutagenesis, fluorescence-activated cell sorting, high-throughput sequencing, and mutual information theory to explore the role that every nucleotide in Qrr4 plays in regulation of two mRNA targets, luxR and luxO. Companion biochemical assays allowed us to assign specific regulatory functions/underlying molecular mechanisms to each important base. This strategy yielded a regional map of nucleotides in Qrr4 vital for stability, Hfq interaction, stem-loop formation, and base pairing to both luxR and luxO, to luxR only, and to luxO only. In terms of nucleotides critical for sRNA function, the RSort-Seq analysis provided strikingly different results from those predicted by commonly used regulatory RNA-folding algorithms. This approach is applicable to any RNA-RNA interaction, including sRNAs in other bacteria and regulatory RNAs in higher organisms.

  13. Quorum sensing inhibitory activities of surface immobilized antibacterial dihydropyrrolones via click chemistry.

    PubMed

    Ho, Kitty K K; Chen, Renxun; Willcox, Mark D P; Rice, Scott A; Cole, Nerida; Iskander, George; Kumar, Naresh

    2014-02-01

    Device-related infection remains a major barrier to the use of biomaterial implants as life-saving devices. This study aims to examine the effectiveness and mechanism of action of surface attached dihydropyrrolones (DHPs), a quorum sensing (QS) inhibitor, against bacterial colonization. DHPs were covalently attached on glass surfaces via copper-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) click reaction. The covalent attachment of DHP surfaces was confirmed by X-ray photoelectron spectroscopy (XPS) and contact angle measurements, and the antimicrobial efficacy of the DHP coatings was assessed by confocal laser scanning microscopy (CLSM) and image analysis. The results demonstrated that covalently bound DHP compounds are effective in reducing the adhesion by up to 97% (p < 0.05) for both Pseudomonas aeruginosa and Staphylococcus aureus. Furthermore, using the green fluorescent protein (Gfp)-based reporter technology, it is demonstrated that surface attached DHPs were able to repress the expression of a lasB-gfp reporter fusion of P. aeruginosa by 72% (p < 0.001) without affecting cell viability. This demonstrates the ability of the covalently bound QS inhibitor to inhibit QS and suggests the existence of a membrane-based pathway(s) for QS inhibition. Hence, strategies based on incorporation of QS inhibitors such as DHPs represent a potential approach for prevention of device-related infections.

  14. Physiological framework for the regulation of quorum sensing-dependent public goods in Pseudomonas aeruginosa.

    PubMed

    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.

  15. Non-thermal Plasma Exposure Rapidly Attenuates Bacterial AHL-Dependent Quorum Sensing and Virulence.

    PubMed

    Flynn, Padrig B; Busetti, Alessandro; Wielogorska, Ewa; Chevallier, Olivier P; Elliott, Christopher T; Laverty, Garry; Gorman, Sean P; Graham, William G; Gilmore, Brendan F

    2016-05-31

    The antimicrobial activity of atmospheric pressure non-thermal plasma has been exhaustively characterised, however elucidation of the interactions between biomolecules produced and utilised by bacteria and short plasma exposures are required for optimisation and clinical translation of cold plasma technology. This study characterizes the effects of non-thermal plasma exposure on acyl homoserine lactone (AHL)-dependent quorum sensing (QS). Plasma exposure of AHLs reduced the ability of such molecules to elicit a QS response in bacterial reporter strains in a dose-dependent manner. Short exposures (30-60 s) produce of a series of secondary compounds capable of eliciting a QS response, followed by the complete loss of AHL-dependent signalling following longer exposures. UPLC-MS analysis confirmed the time-dependent degradation of AHL molecules and their conversion into a series of by-products. FT-IR analysis of plasma-exposed AHLs highlighted the appearance of an OH group. In vivo assessment of the exposure of AHLs to plasma was examined using a standard in vivo model. Lettuce leaves injected with the rhlI/lasI mutant PAO-MW1 alongside plasma treated N-butyryl-homoserine lactone and n-(3-oxo-dodecanoyl)-homoserine lactone, exhibited marked attenuation of virulence. This study highlights the capacity of atmospheric pressure non-thermal plasma to modify and degrade AHL autoinducers thereby attenuating QS-dependent virulence in P. aeruginosa.

  16. Methylobacterium-plant interaction genes regulated by plant exudate and quorum sensing molecules.

    PubMed

    Dourado, Manuella Nóbrega; Bogas, Andrea Cristina; Pomini, Armando M; Andreote, Fernando Dini; Quecine, Maria Carolina; Marsaioli, Anita J; Araújo, Welington Luiz

    2013-12-01

    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.

  17. Methylobacterium-plant interaction genes regulated by plant exudate and quorum sensing molecules

    PubMed Central

    Dourado, Manuella Nóbrega; Bogas, Andrea Cristina; Pomini, Armando M.; Andreote, Fernando Dini; Quecine, Maria Carolina; Marsaioli, Anita J.; Araújo, Welington Luiz

    2013-01-01

    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. PMID:24688531

  18. Bacillus marcorestinctum sp. nov., a Novel Soil Acylhomoserine Lactone Quorum-Sensing Signal Quenching Bacterium

    PubMed Central

    Han, Yan; Chen, Fang; Li, Nuo; Zhu, Bo; Li, Xianzhen

    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 relatives based on the 16S rRNA gene sequence are Bacillus anthracis, Bacillus thuringiensis, and Brevibacillus brevis (syn. Bacillus brevis) with the similarity of 96.5%. The DNA–DNA hybridization data indicates a low level of genomic relatedness with the relative type strains of Bacillus thuringiensis (6.1%), Bacillus anthracis (10.5%) and Brevibacillus brevis (8.7%). On the basis of the phenotypic and phylogenetic data together with the genomic distinctiveness, the LQQ strain represents a novel species of the genus Bacillus, for which the name Bacillus marcorestinctum sp. nov. is proposed. The type strain is LQQT. PMID:20386651

  19. Cranberry-derived proanthocyanidins impair virulence and inhibit quorum sensing of Pseudomonas aeruginosa

    PubMed Central

    Maisuria, Vimal B.; Los Santos, Yossef Lopez-de; Tufenkji, Nathalie; Déziel, Eric

    2016-01-01

    Bacteria have evolved multiple strategies for causing infections that include producing virulence factors, undertaking motility, developing biofilms, and invading host cells. N-acylhomoserine lactone (AHL)-mediated quorum sensing (QS) tightly regulates the expression of multiple virulence factors in the opportunistic pathogenic bacterium Pseudomonas aeruginosa. Thus, inhibiting QS could lead to health benefits. In this study, we demonstrate an anti-virulence activity of a cranberry extract rich in proanthocyanidins (cerPAC) against P. aeruginosa in the model host Drosophila melanogaster and show this is mediated by QS interference. cerPAC reduced the production of QS-regulated virulence determinants and protected D. melanogaster from fatal infection by P. aeruginosa PA14. Quantification of AHL production using liquid chromatography-mass spectrometry confirmed that cerPAC effectively reduced the level of AHLs produced by the bacteria. Furthermore, monitoring QS signaling gene expression revealed that AHL synthases LasI/RhlI and QS transcriptional regulators LasR/RhlR genes were inhibited and antagonized, respectively, by cerPAC. Molecular docking studies suggest that cranberry-derived proanthocyanidin binds to QS transcriptional regulators, mainly interacting with their ligand binding sites. These findings provide insights into the underlying mechanisms of action of a cerPAC to restrict the virulence of P. aeruginosa and can have implications in the development of alternative approaches to control infections. PMID:27503003

  20. Chemical probes of quorum sensing: from compound development to biological discovery.

    PubMed

    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. PMID:27268906

  1. Quorum-sensing-regulated virulence factors in Pseudomonas aeruginosa are toxic to Lucilia sericata maggots

    PubMed Central

    Andersen, A. S.; Joergensen, B.; Bjarnsholt, T.; Johansen, H.; Karlsmark, T.; Givskov, M.; Krogfelt, K. A.

    2010-01-01

    Maggot debridement therapy (MDT) is widely used for debridement of chronic infected wounds; however, for wounds harbouring specific bacteria limited effect or failure of the treatment has been described. Here we studied the survival of Lucilia sericata maggots encountering Pseudomonas aeruginosa PAO1 in a simple assay with emphasis on the quorum-sensing (QS)-regulated virulence. The maggots were challenged with GFP-tagged P. aeruginosa wild-type (WT) PAO1 and a GFP-tagged P. aeruginosa ΔlasR rhlR (ΔRR) QS-deficient mutant in different concentrations. Maggots were killed in the presence of WT PAO1 whereas the challenge with the QS mutant showed a survival reduction of ∼25 % compared to negative controls. Furthermore, bacterial intake by the maggots was lower in the presence of WT PAO1 compared to the PAO1 ΔRR mutant. Maggot excretions/secretions (ES) were assayed for the presence of QS inhibitors; only high doses of ES showed inhibition of QS in P. aeruginosa. Thus P. aeruginosa was shown to be toxic to L. sericata maggots. This, coupled to the preferential feeding by the maggots and reduced ingestion of P. aeruginosa, could explain MDT failure in wounds colonized by P. aeruginosa. Wounds heavily colonized with P. aeruginosa should be a counterindication for MDT unless used in combination with a pre-treatment with other topical therapeutics targeting P. aeruginosa. PMID:19892758

  2. Quorum-sensing effects in the antagonistic rhizosphere bacterium Serratia plymuthica HRO-C48.

    PubMed

    Müller, Henry; Westendorf, Christian; Leitner, Erich; Chernin, Leonid; Riedel, Kathrin; Schmidt, Silvia; Eberl, Leo; Berg, Gabriele

    2009-03-01

    The rhizosphere-associated bacterium Serratia plymuthica HRO-C48 is not only able to suppress symptoms caused by soil-borne pathogens but is also able to stimulate growth of plants. Detailed knowledge about the underlying mechanisms and regulation are crucial for the application in biocontrol strategies. To analyse the influence of N-acyl homoserine lactone (AHL)-mediated communication on the biocontrol activity, the AHL-degrading lactonase AiiA was heterologously expressed in the strain, resulting in abolished AHL production. The comparative analysis of the wild type and AHL negative mutants led to the identification of new AHL-regulated phenotypes. In the pathosystem Verticillium dahliae-oilseed rape, the essential role of AHL-mediated signaling for disease suppression was demonstrated. In vitro, the regulatory function of AHLs in the synthesis of the plant growth hormone indole-3-acetic acid is shown for the first time. Additionally, swimming motility was found to be negatively AHL regulated. In contrast, production of extracellular hydrolytic enzymes is shown to be positively AHL-regulated. HRO-C48 emits a broad spectrum of volatile organic compounds that are involved in antifungal activity and, interestingly, whose relative abundances are influenced by quorum sensing (QS). This study shows that QS is crucial for biocontrol activity of S. plymuthica and discusses the impact for the application of the strain as a biocontrol agent. PMID:19220861

  3. Genes as Early Responders Regulate Quorum-Sensing and Control Bacterial Cooperation in Pseudomonas aeruginosa

    PubMed Central

    Zhao, Kelei; Li, Yi; Yue, Bisong; Wu, Min

    2014-01-01

    Quorum-sensing (QS) allows bacterial communication to coordinate the production of extracellular products essential for population fitness at higher cell densities. It has been generally accepted that a significant time duration is required to reach appropriate cell density to activate the relevant quiescent genes encoding these costly but beneficial public goods. Which regulatory genes are involved and how these genes control bacterial communication at the early phases are largely un-explored. By determining time-dependent expression of QS-related genes of the opportunistic pathogen Pseudomonas aerugionsa, we show that the induction of social cooperation could be critically influenced by environmental factors to optimize the density of population. In particular, small regulatory RNAs (RsmY and RsmZ) serving as early responders, can promote the expression of dependent genes (e.g. lasR) to boost the synthesis of intracellular enzymes and coordinate instant cooperative behavior in bacterial cells. These early responders, acting as a rheostat to finely modulate bacterial cooperation, which may be quickly activated under environment threats, but peter off when critical QS dependent genes are fully functional for cooperation. Our findings suggest that RsmY and RsmZ critically control the timing and levels of public goods production, which may have implications in sociomicrobiology and infection control. PMID:25006971

  4. Global and Phylogenetic Distribution of Quorum Sensing Signals, Acyl Homoserine Lactones, in the Family of Vibrionaceae

    PubMed Central

    Barker Rasmussen, Bastian; Fog Nielsen, Kristian; Machado, Henrique; Melchiorsen, Jette; Gram, Lone; Sonnenschein, Eva C.

    2014-01-01

    Bacterial quorum sensing (QS) and the corresponding signals, acyl homoserine lactones (AHLs), were first described for a luminescent Vibrio species. Since then, detailed knowledge has been gained on the functional level of QS; however, the abundance of AHLs in the family of Vibrionaceae in the environment has remained unclear. Three hundred and one Vibrionaceae strains were collected on a global research cruise and the prevalence and profile of AHL signals in this global collection were determined. AHLs were detected in 32 of the 301 strains using Agrobacterium tumefaciens and Chromobacterium violaceum reporter strains. Ethyl acetate extracts of the cultures were analysed by ultra-high performance liquid chromatography-high resolution mass spectrometry (MS) with automated tandem MS confirmation for AHLs. N-(3-hydroxy-hexanoyl) (OH-C6) and N-(3-hydroxy-decanoyl) (OH-C10) homoserine lactones were the most common AHLs found in 17 and 12 strains, respectively. Several strains produced a diversity of different AHLs, including N-heptanoyl (C7) HL. AHL-producing Vibrionaceae were found in polar, temperate and tropical waters. The AHL profiles correlated with strain phylogeny based on gene sequence homology, however not with geographical location. In conclusion, a wide range of AHL signals are produced by a number of clades in the Vibrionaceae family and these results will allow future investigations of inter- and intra-species interactions within this cosmopolitan family of marine bacteria. PMID:25419995

  5. ω-Hydroxyemodin Limits Staphylococcus aureus Quorum Sensing-Mediated Pathogenesis and Inflammation

    PubMed Central

    Daly, Seth M.; Elmore, Bradley O.; Kavanaugh, Jeffrey S.; Triplett, Kathleen D.; Figueroa, Mario; Raja, Huzefa A.; El-Elimat, Tamam; Crosby, Heidi A.; Femling, Jon K.; Cech, Nadja B.; Horswill, Alexander R.; Oberlies, Nicholas H.

    2015-01-01

    Antibiotic-resistant pathogens are a global health threat. Small molecules that inhibit bacterial virulence have been suggested as alternatives or adjuncts to conventional antibiotics, as they may limit pathogenesis and increase bacterial susceptibility to host killing. Staphylococcus aureus is a major cause of invasive skin and soft tissue infections (SSTIs) in both the hospital and community settings, and it is also becoming increasingly antibiotic resistant. Quorum sensing (QS) mediated by the accessory gene regulator (agr) controls virulence factor production essential for causing SSTIs. We recently identified ω-hydroxyemodin (OHM), a polyhydroxyanthraquinone isolated from solid-phase cultures of Penicillium restrictum, as a suppressor of QS and a compound sought for the further characterization of the mechanism of action. At concentrations that are nontoxic to eukaryotic cells and subinhibitory to bacterial growth, OHM prevented agr signaling by all four S. aureus agr alleles. OHM inhibited QS by direct binding to AgrA, the response regulator encoded by the agr operon, preventing the interaction of AgrA with the agr P2 promoter. Importantly, OHM was efficacious in a mouse model of S. aureus SSTI. Decreased dermonecrosis with OHM treatment was associated with enhanced bacterial clearance and reductions in inflammatory cytokine transcription and expression at the site of infection. Furthermore, OHM treatment enhanced the immune cell killing of S. aureus in vitro in an agr-dependent manner. These data suggest that bacterial disarmament through the suppression of S. aureus QS may bolster the host innate immune response and limit inflammation. PMID:25645827

  6. Bioinformatic Prediction of Gene Functions Regulated by Quorum Sensing in the Bioleaching Bacterium Acidithiobacillus ferrooxidans

    PubMed Central

    Banderas, Alvaro; Guiliani, Nicolas

    2013-01-01

    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. PMID:23959118

  7. Identification of functions linking quorum sensing with biofilm formation in Burkholderia cenocepacia H111

    PubMed Central

    Inhülsen, Silja; Aguilar, Claudio; Schmid, Nadine; Suppiger, Angela; Riedel, Kathrin; Eberl, Leo

    2012-01-01

    Burkholderia cenocepacia has emerged as an important pathogen for patients suffering from cystic fibrosis (CF). Previous work has shown that this organism employs the CepIR quorum-sensing (QS) system to control the expression of virulence factors as well as the formation of biofilms. To date, however, very little is known about the QS-regulated virulence factors and virtually nothing about the factors that link QS and biofilm formation. Here, we have employed a combined transcriptomic and proteomic approach to precisely define the QS regulon in our model strain B. cenocepacia H111, a CF isolate. Among the identified CepR-activated loci, three were analyzed in better detail for their roles in biofilm development: (i) a gene cluster coding for the BclACB lectins, (ii) the large surface protein BapA, and (iii) a type I pilus. The analysis of defined mutants revealed that BapA plays a major role in biofilm formation on abiotic surfaces while inactivation of the type I pilus showed little effect both in a static microtitre dish-based biofilm assay and in flow-through cells. Inactivation of the bclACB lectin genes resulted in biofilms containing hollow microcolonies, suggesting that the lectins are important for biofilm structural development. PMID:22950027

  8. Cystic fibrosis–adapted Pseudomonas aeruginosa quorum sensing lasR mutants cause hyperinflammatory responses

    PubMed Central

    LaFayette, Shantelle L.; Houle, Daniel; Beaudoin, Trevor; Wojewodka, Gabriella; Radzioch, Danuta; Hoffman, Lucas R.; Burns, Jane L.; Dandekar, Ajai A.; Smalley, Nicole E.; Chandler, Josephine R.; Zlosnik, James E.; Speert, David P.; Bernier, Joanie; Matouk, Elias; Brochiero, Emmanuelle; Rousseau, Simon; Nguyen, Dao

    2015-01-01

    Cystic fibrosis lung disease is characterized by chronic airway infections with the opportunistic pathogen Pseudomonas aeruginosa and severe neutrophilic pulmonary inflammation. P. aeruginosa undergoes extensive genetic adaptation to the cystic fibrosis (CF) lung environment, and adaptive mutations in the quorum sensing regulator gene lasR commonly arise. We sought to define how mutations in lasR alter host-pathogen relationships. We demonstrate that lasR mutants induce exaggerated host inflammatory responses in respiratory epithelial cells, with increased accumulation of proinflammatory cytokines and neutrophil recruitment due to the loss of bacterial protease–dependent cytokine degradation. In subacute pulmonary infections, lasR mutant–infected mice show greater neutrophilic inflammation and immunopathology compared with wild-type infections. Finally, we observed that CF patients infected with lasR mutants have increased plasma interleukin-8 (IL-8), a marker of inflammation. These findings suggest that bacterial adaptive changes may worsen pulmonary inflammation and directly contribute to the pathogenesis and progression of chronic lung disease in CF patients. PMID:26457326

  9. Identification of functions linking quorum sensing with biofilm formation in Burkholderia cenocepacia H111.

    PubMed

    Inhülsen, Silja; Aguilar, Claudio; Schmid, Nadine; Suppiger, Angela; Riedel, Kathrin; Eberl, Leo

    2012-06-01

    Burkholderia cenocepacia has emerged as an important pathogen for patients suffering from cystic fibrosis (CF). Previous work has shown that this organism employs the CepIR quorum-sensing (QS) system to control the expression of virulence factors as well as the formation of biofilms. To date, however, very little is known about the QS-regulated virulence factors and virtually nothing about the factors that link QS and biofilm formation. Here, we have employed a combined transcriptomic and proteomic approach to precisely define the QS regulon in our model strain B. cenocepacia H111, a CF isolate. Among the identified CepR-activated loci, three were analyzed in better detail for their roles in biofilm development: (i) a gene cluster coding for the BclACB lectins, (ii) the large surface protein BapA, and (iii) a type I pilus. The analysis of defined mutants revealed that BapA plays a major role in biofilm formation on abiotic surfaces while inactivation of the type I pilus showed little effect both in a static microtitre dish-based biofilm assay and in flow-through cells. Inactivation of the bclACB lectin genes resulted in biofilms containing hollow microcolonies, suggesting that the lectins are important for biofilm structural development. PMID:22950027

  10. Inhibition of quorum sensing, biofilm, and spoilage potential in Shewanella baltica by green tea polyphenols.

    PubMed

    Zhu, Junli; Huang, Xuzheng; Zhang, Fang; Feng, Lifang; Li, Jianrong

    2015-12-01

    We investigated the quorum sensing (QS) system of Shewanella baltica and the anti-QS related activities of green tea polyphenols (TP) against spoilage bacteria in refrigerated large yellow croaker. Autoinducer-2 (AI-2) and the diketopiperazines (DKPs) cyclo-(L-Pro-L-Leu) and cyclo-(L-Pro-L-Phe) were detected in the culture extract of S. baltica XH2, however, no N-acylhomoserine lactones (AHLs) activity was observed. Green TP at sub-inhibitory concentrations interfered with AI-2 and DKPs activities of S. baltica without inhibiting cell growth and promoted degradation of AI-2. The green TP treatment inhibited biofilm development, exopolysaccharide production and swimming motility of S. baltica in a concentration- dependent manner. In addition, green TP decreased extracellular protease activities and trimethylamine production in S. baltica. A transcriptional analysis showed that green TP repressed the luxS and torA genes in S. baltica, which agreed with the observed reductions in QS activity and the spoilage phenotype. Epigallocatechin gallate (EGCG)-enriched in green TP significantly inhibited AI-2 activity of S. baltica. These findings strongly suggest that green TP could be developed as a new QS inhibitor for seafood preservation to enhance shelf life.

  11. Relationships between the Regulatory Systems of Quorum Sensing and Multidrug Resistance

    PubMed Central

    Xu, Gang-Ming

    2016-01-01

    Cell–cell communications, known as quorum sensing (QS) in bacteria, involve the signal molecules as chemical languages and the corresponding receptors as transcriptional regulators. In Gram-negative bacteria, orphan LuxR receptors recognize signals more than just acylhomoserine lactones, and modulate interspecies and interkingdom communications. Whereas, in the Gram-positive Streptomyces, pseudo gamma-butyrolactones (GBLs) receptors bind antibiotics other than GBL signals, and coordinate antibiotics biosynthesis. By interacting with structurally diverse molecules like antibiotics, the TetR family receptors regulate multidrug resistance (MDR) by controlling efflux pumps. Antibiotics at subinhibitory concentration may act as signal molecules; while QS signals also have antimicrobial activity at high concentration. Moreover, the QS and MDR systems may share the same exporters to transport molecules. Among these orphan LuxR, pseudo GBL receptors, and MDR regulators, although only with low sequence homology, they have some structure similarity and function correlation. Therefore, perhaps there might be evolutionary relationship and biological relevance between the regulatory systems of QS and MDR. Since the QS systems become new targets for antimicrobial strategy, it would expand our understanding about the evolutionary history of these regulatory systems. PMID:27379084

  12. The effect of quorum sensing system for growth competitiveness on Shigella flexneri.

    PubMed

    Ping, Xu; Jing, Yang; Lilan, Lu; Erling, Feng; Hengliang, Wang; Ying, Lu; Li, Zhu

    2015-05-01

    Quorum sensing (QS) regulates the onset of bacterial social responses related to cell density. Comparison between the gene sequences of all components of QS system of Escherichia coli and Shigella strains, shows that the QS system is generally lost or mutated in Shigella. Since AI-2 is produced and processed by the lsr operon, we analyzed the potential function of the lsr operon. We first detected AI-2 in Shigella flexneri 2a strain 301 through the reporter bacteria Vibrio harveyi BB170, indicating that S. flexneri can produce AI-2. Then, the lsr operon of E. coli MG1655 was cloned into S. flexneri using the Golden Gate method. Colony counting experiments showed that the QS system recovery strain had growth advantage over the wild-type strain when they were mixed and cultured. The preliminary comparative proteomics analysis showed that the lsr operon could be expressed and the abundance of stress response proteins also changed when the QS system was introduced into S. flexneri. PMID:25998438

  13. Exploiting Quorum Sensing Interfering Strategies in Gram-Negative Bacteria for the Enhancement of Environmental Applications

    PubMed Central

    Zhang, Weiwei; Li, Chenghua

    2016-01-01

    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 10 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. PMID:26779175

  14. Broad spectrum pro-quorum-sensing molecules as inhibitors of virulence in vibrios.

    PubMed

    Ng, Wai-Leung; Perez, Lark; Cong, Jianping; Semmelhack, Martin F; Bassler, Bonnie L

    2012-01-01

    Quorum sensing (QS) is a bacterial cell-cell communication process that relies on the production and detection of extracellular signal molecules called autoinducers. QS allows bacteria to perform collective activities. Vibrio cholerae, a pathogen that causes an acute disease, uses QS to repress virulence factor production and biofilm formation. Thus, molecules that activate QS in V. cholerae have the potential to control pathogenicity in this globally important bacterium. Using a whole-cell high-throughput screen, we identified eleven molecules that activate V. cholerae QS: eight molecules are receptor agonists and three molecules are antagonists of LuxO, the central NtrC-type response regulator that controls the global V. cholerae QS cascade. The LuxO inhibitors act by an uncompetitive mechanism by binding to the pre-formed LuxO-ATP complex to inhibit ATP hydrolysis. Genetic analyses suggest that the inhibitors bind in close proximity to the Walker B motif. The inhibitors display broad-spectrum capability in activation of QS in Vibrio species that employ LuxO. To the best of our knowledge, these are the first molecules identified that inhibit the ATPase activity of a NtrC-type response regulator. Our discovery supports the idea that exploiting pro-QS molecules is a promising strategy for the development of novel anti-infectives. PMID:22761573

  15. Discovery of a nitric oxide responsive quorum sensing circuit in Vibrio harveyi.

    PubMed

    Henares, Bernadette M; Higgins, Kate E; Boon, Elizabeth M

    2012-08-17

    Bacteria use small molecules to assess the density and identity of nearby organisms and formulate a response. This process, called quorum sensing (QS), commonly regulates bioluminescence, biofilm formation, and virulence. Vibrio harveyi have three described QS circuits. Each involves the synthesis of a molecule that regulates phosphorylation of its cognate receptor kinase. Each receptor exchanges phosphate with a common phosphorelay protein, LuxU, which ultimately regulates bioluminescence. Here, we show that another small molecule, nitric oxide (NO), participates in QS through LuxU. V. harveyi display a NO concentration-dependent increase in bioluminescence that is regulated by an hnoX gene. We demonstrate that H-NOX is a NO sensor and NO/H-NOX regulates phosphorylation of a kinase that transfers phosphate to LuxU. This study reveals the discovery of a fourth QS pathway in V. harveyi and suggests that bacteria use QS to integrate not only the density of bacteria but also other diverse information about their environment into decisions about gene expression. PMID:22606970

  16. Relationships between the Regulatory Systems of Quorum Sensing and Multidrug Resistance.

    PubMed

    Xu, Gang-Ming

    2016-01-01

    Cell-cell communications, known as quorum sensing (QS) in bacteria, involve the signal molecules as chemical languages and the corresponding receptors as transcriptional regulators. In Gram-negative bacteria, orphan LuxR receptors recognize signals more than just acylhomoserine lactones, and modulate interspecies and interkingdom communications. Whereas, in the Gram-positive Streptomyces, pseudo gamma-butyrolactones (GBLs) receptors bind antibiotics other than GBL signals, and coordinate antibiotics biosynthesis. By interacting with structurally diverse molecules like antibiotics, the TetR family receptors regulate multidrug resistance (MDR) by controlling efflux pumps. Antibiotics at subinhibitory concentration may act as signal molecules; while QS signals also have antimicrobial activity at high concentration. Moreover, the QS and MDR systems may share the same exporters to transport molecules. Among these orphan LuxR, pseudo GBL receptors, and MDR regulators, although only with low sequence homology, they have some structure similarity and function correlation. Therefore, perhaps there might be evolutionary relationship and biological relevance between the regulatory systems of QS and MDR. Since the QS systems become new targets for antimicrobial strategy, it would expand our understanding about the evolutionary history of these regulatory systems.

  17. Nutrient reduction induced stringent responses promote bacterial quorum-sensing divergence for population fitness

    PubMed Central

    Zhao, Kelei; Zhou, Xikun; Li, Wujiao; Zhang, Xiuyue; Yue, Bisong

    2016-01-01

    Bacteria use a cell-cell communication system termed quorum-sensing (QS) to adjust population size by coordinating the costly but beneficial cooperative behaviors. It has long been suggested that bacterial social conflict for expensive extracellular products may drive QS divergence and cause the “tragedy of the commons”. However, the underlying molecular mechanism of social divergence and its evolutionary consequences for the bacterial ecology still remain largely unknown. By using the model bacterium Pseudomonas aeruginosa PAO1, here we show that nutrient reduction can promote QS divergence for population fitness during evolution but requiring adequate cell density. Mechanically, decreased nutrient supplies can induce RpoS-directed stringent response and enhance the selection pressure on lasR gene, and lasR mutants are evolved in association with the DNA mismatch repair “switch-off”. The lasR mutants have higher relative fitness than QS-intact individuals due to their energy-saving characteristic under nutrient decreased condition. Furthermore an optimal incorporation of lasR mutants is capable of maximizing the fitness of entire population during in vitro culture and the colonization in mouse lung. Consequently, rather than worsen the population health, QS-coordinated social divergence is an elaborate evolutionary strategy that renders the entire bacterial population more fit in tough times. PMID:27713502

  18. Surface enhanced Raman scattering for detection of Pseudomonas aeruginosa quorum sensing compounds

    NASA Astrophysics Data System (ADS)

    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.

  19. Discovery of new diketopiperazines inhibiting Burkholderia cenocepacia quorum sensing in vitro and in vivo

    PubMed Central

    Scoffone, Viola C.; Chiarelli, Laurent R.; Makarov, Vadim; Brackman, Gilles; Israyilova, Aygun; Azzalin, Alberto; Forneris, Federico; Riabova, Olga; Savina, Svetlana; Coenye, Tom; Riccardi, Giovanna; Buroni, Silvia

    2016-01-01

    Burkholderia cenocepacia, an opportunistic respiratory pathogen particularly relevant for cystic fibrosis patients, is difficult to eradicate due to its high level of resistance to most clinically relevant antimicrobials. Consequently, the discovery of new antimicrobials as well as molecules capable of inhibiting its virulence is mandatory. In this regard quorum sensing (QS) represents a good target for anti-virulence therapies, as it has been linked to biofilm formation and is important for the production of several virulence factors, including proteases and siderophores. Here, we report the discovery of new diketopiperazine inhibitors of the B. cenocepacia acyl homoserine lactone synthase CepI, and report their anti-virulence properties. Out of ten different compounds assayed against recombinant CepI, four were effective inhibitors, with IC50 values in the micromolar range. The best compounds interfered with protease and siderophore production, as well as with biofilm formation, and showed good in vivo activity in a Caenorhabditis elegans infection model. These molecules were also tested in human cells and showed very low toxicity. Therefore, they could be considered for in vivo combined treatments with established or novel antimicrobials, to improve the current therapeutic strategies against B. cenocepacia. PMID:27580679

  20. Ajoene, a sulfur-rich molecule from garlic, inhibits genes controlled by quorum sensing.

    PubMed

    Jakobsen, Tim Holm; van Gennip, Maria; Phipps, Richard Kerry; Shanmugham, Meenakshi Sundaram; Christensen, Louise Dahl; Alhede, Morten; Skindersoe, Mette Eline; Rasmussen, Thomas Bovbjerg; Friedrich, Karlheinz; Uthe, Friedrich; Jensen, Peter Østrup; Moser, Claus; Nielsen, Kristian Fog; Eberl, Leo; Larsen, Thomas Ostenfeld; Tanner, David; Høiby, Niels; Bjarnsholt, Thomas; Givskov, Michael

    2012-05-01

    In relation to emerging multiresistant bacteria, development of antimicrobials and new treatment strategies of infections should be expected to become a high-priority research area. Quorum sensing (QS), a communication system used by pathogenic bacteria like Pseudomonas aeruginosa to synchronize the expression of specific genes involved in pathogenicity, is a possible drug target. Previous in vitro and in vivo studies revealed a significant inhibition of P. aeruginosa QS by crude garlic extract. By bioassay-guided fractionation of garlic extracts, we determined the primary QS inhibitor present in garlic to be ajoene, a sulfur-containing compound with potential as an antipathogenic drug. By comprehensive in vitro and in vivo studies, the effect of synthetic ajoene toward P. aeruginosa was elucidated. DNA microarray studies of ajoene-treated P. aeruginosa cultures revealed a concentration-dependent attenuation of a few but central QS-controlled virulence factors, including rhamnolipid. Furthermore, ajoene treatment of in vitro biofilms demonstrated a clear synergistic, antimicrobial effect with tobramycin on biofilm killing and a cease in lytic necrosis of polymorphonuclear leukocytes. Furthermore, in a mouse model of pulmonary infection, a significant clearing of infecting P. aeruginosa was detected in ajoene-treated mice compared to a nontreated control group. This study adds to the list of examples demonstrating the potential of QS-interfering compounds in the treatment of bacterial infections.

  1. Death and survival in Streptococcus mutans: differing outcomes of a quorum-sensing signaling peptide

    PubMed Central

    Leung, Vincent; Dufour, Delphine; Lévesque, Céline M.

    2015-01-01

    Bacteria are considered “social” organisms able to communicate with one another using small hormone-like molecules (pheromones) in a process called quorum-sensing (QS). These signaling molecules increase in concentration as a function of bacterial cell density. For most human pathogens, QS is critical for virulence and biofilm formation, and the opportunity to interfere with bacterial QS 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 (cavities). In S. mutans, its CSP QS signaling peptide does not act as a classical QS signal by accumulating passively in proportion to cell density. In fact, particular stresses such as those encountered in the oral cavity, induce the production of the CSP pheromone, suggesting that the pheromone most probably functions as a stress-inducible alarmone by triggering the signaling 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 QS signaling peptide to regulate two opposite phenotypes. PMID:26557114

  2. Serum Lipoproteins Are Critical for Pulmonary Innate Defense against Staphylococcus aureus Quorum Sensing.

    PubMed

    Manifold-Wheeler, Brett C; Elmore, Bradley O; Triplett, Kathleen D; Castleman, Moriah J; Otto, Michael; Hall, Pamela R

    2016-01-01

    Hyperlipidemia has been extensively studied in the context of atherosclerosis, whereas the potential health consequences of the opposite extreme, hypolipidemia, remain largely uninvestigated. Circulating lipoproteins are essential carriers of insoluble lipid molecules and are increasingly recognized as innate immune effectors. Importantly, severe hypolipidemia, which may occur with trauma or critical illness, is clinically associated with bacterial pneumonia. To test the hypothesis that circulating lipoproteins are essential for optimal host innate defense in the lung, we used lipoprotein-deficient mice and a mouse model of Staphylococcus aureus pneumonia in which invasive infection requires virulence factor expression controlled by the accessory gene regulator (agr) operon. Activation of agr and subsequent virulence factor expression is inhibited by apolipoprotein B, the structural protein of low-density lipoprotein, which binds and sequesters the secreted agr-signaling peptide (AIP). In this article, we report that lipoprotein deficiency impairs early pulmonary innate defense against S. aureus quorum-sensing-dependent pathogenesis. Specifically, apolipoprotein B levels in the lung early postinfection are significantly reduced with lipoprotein deficiency, coinciding with impaired host control of S. aureus agr-signaling and increased agr-dependent morbidity (weight loss) and inflammation. Given that lipoproteins also inhibit LTA- and LPS-mediated inflammation, these results suggest that hypolipidemia may broadly impact posttrauma pneumonia susceptibility to both Gram-positive and -negative pathogens. Together with previous reports demonstrating that hyperlipidemia also impairs lung innate defense, these results suggest that maintenance of normal serum lipoprotein levels is necessary for optimal host innate defense in the lung.

  3. Quorum sensing activity of Citrobacter amalonaticus L8A, a bacterium isolated from dental plaque

    PubMed Central

    Goh, Share-Yuan; Khan, Saad Ahmed; Tee, Kok Keng; Abu Kasim, Noor Hayaty; Yin, Wai-Fong; Chan, Kok-Gan

    2016-01-01

    Cell-cell communication is also known as quorum sensing (QS) that happens in the bacterial cells with the aim to regulate their genes expression in response to increased cell density. In this study, a bacterium (L8A) isolated from dental plaque biofilm was identified as Citrobacter amalonaticus by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). Its N-acylhomoserine-lactone (AHL) production was screened by using two types of AHL biosensors namely Chromobacterium violaceum CV026 and Escherichia coli [pSB401]. Citrobacter amalonaticus strain L8A was identified and confirmed producing numerous types of AHL namely N-butyryl-L-homoserine lactone (C4-HSL), N-hexanoyl-L-homoserine lactone (C6-HSL), N-octanoyl-L-homoserine lactone (C8-HSL) and N-hexadecanoyl-L-homoserine lactone (C16-HSL). We performed the whole genome sequence analysis of this oral isolate where its genome sequence reveals the presence of QS signal synthase gene and our work will pave the ways to study the function of the related QS genes in this bacterium. PMID:26860259

  4. Quorum sensing inhibitory activities of surface immobilized antibacterial dihydropyrrolones via click chemistry.

    PubMed

    Ho, Kitty K K; Chen, Renxun; Willcox, Mark D P; Rice, Scott A; Cole, Nerida; Iskander, George; Kumar, Naresh

    2014-02-01

    Device-related infection remains a major barrier to the use of biomaterial implants as life-saving devices. This study aims to examine the effectiveness and mechanism of action of surface attached dihydropyrrolones (DHPs), a quorum sensing (QS) inhibitor, against bacterial colonization. DHPs were covalently attached on glass surfaces via copper-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) click reaction. The covalent attachment of DHP surfaces was confirmed by X-ray photoelectron spectroscopy (XPS) and contact angle measurements, and the antimicrobial efficacy of the DHP coatings was assessed by confocal laser scanning microscopy (CLSM) and image analysis. The results demonstrated that covalently bound DHP compounds are effective in reducing the adhesion by up to 97% (p < 0.05) for both Pseudomonas aeruginosa and Staphylococcus aureus. Furthermore, using the green fluorescent protein (Gfp)-based reporter technology, it is demonstrated that surface attached DHPs were able to repress the expression of a lasB-gfp reporter fusion of P. aeruginosa by 72% (p < 0.001) without affecting cell viability. This demonstrates the ability of the covalently bound QS inhibitor to inhibit QS and suggests the existence of a membrane-based pathway(s) for QS inhibition. Hence, strategies based on incorporation of QS inhibitors such as DHPs represent a potential approach for prevention of device-related infections. PMID:24345737

  5. Chemical probes of quorum sensing: from compound development to biological discovery.

    PubMed

    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.

  6. Single cell analysis of Vibrio harveyi uncovers functional heterogeneity in response to quorum sensing signals

    PubMed Central

    2012-01-01

    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. PMID:22985329

  7. Synthesis, quorum sensing inhibition and docking studies of 1,5-dihydropyrrol-2-ones.

    PubMed

    Goh, Wai-Kean; Gardner, Christopher R; Chandra Sekhar, Kondapalli V G; Biswas, Nripendra N; Nizalapur, Shashidhar; Rice, Scott A; Willcox, Mark; Black, David StC; Kumar, Naresh

    2015-12-01

    Gram-negative bacteria such as Pseudomonas aeruginosa and Escherichia coli use N-acylated l-homoserine lactones (AHLs) as autoinducers (AIs) for quorum sensing (QS), a chief regulatory and cell-to-cell communication system. QS is responsible for social adaptation, virulence factor production, biofilm production and antibiotic resistance in bacteria. Fimbrolides, a class of halogenated furanones isolated from the red marine alga Delisea pulchra, have been shown to exhibit promising QS inhibitory activity against various Gram-negative and Gram-positive bacterial strains. In this work, various lactam analogues of fimbrolides viz., 1,5-dihydropyrrol-2-ones, were designed and synthesized via an efficient lactamization protocol. All the synthesized analogues were tested for QS inhibition against the E. coli AHL-monitor strain JB357 gfp (ASV). Compound 17a emerged as the most potent compound, followed by 9c, with AIC40 values (the ratio of synthetic inhibitor to natural AHL signaling molecule that is required to lower GFP expression to 40%) of 1.95 and 19.00, respectively. Finally, the potential binding interactions between the synthesized molecules and the LasR QS receptor were studied by molecular docking. Our results indicate that 1,5-dihydropyrrol-2-ones have the ability to serve as potential leads for the further development of novel QS inhibitors as antimicrobial therapeutics. PMID:26547407

  8. Quorum Sensing and Density-Dependent Dispersal in an Aquatic Model System

    PubMed Central

    Fellous, Simon; Duncan, Alison; Coulon, Aurélie; Kaltz, Oliver

    2012-01-01

    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. PMID:23144882

  9. Small Molecules that Modulate Quorum Sensing and Control Virulence in Pseudomonas aeruginosa

    PubMed Central

    Mattmann, Margrith E.; Blackwell, Helen E.

    2010-01-01

    Bacteria use small molecule signals to access their local population densities in a process called quorum sensing (QS). Once a threshold signal concentration is reached, and therefore a certain number of bacteria have assembled, bacteria use QS to change gene expression levels and initiate behaviors that benefit the group. These group processes play central roles in both bacterial virulence and symbiosis, and can have significant impacts on human health, agriculture, and the environment. The dependence of QS on small molecule signals has inspired organic chemists to design non-native molecules that can intercept these signals and thereby perturb bacterial group behaviors. The opportunistic pathogen Pseudomonas aeruginosa has been the target of many of these efforts due to its prevalence in human infections. P. aeruginosa uses at least two N-acyl L-homoserine lactone signals and three homologous LuxR-type receptors to initiate a ran