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1

Recent progresses on AI-2 bacterial quorum sensing inhibitors.  

PubMed

Quorum sensing (QS) is a communication procedure that predominates gene expression in response to cell density and fluctuations in the neighboring environment as a result of discerning molecules termed autoinducers (AIs). It has been embroiled that QS can govern bacterial behaviors such as the secretion of virulence factors, biofilm formation, bioluminescence production, conjugation, sporulation and swarming motility. Autoinducer 2 (AI-2), a QS signaling molecule brought up to be involved in interspecies communication, exists in both gram-negative and -positive bacteria. Therefore, novel approaches to interrupt AI-2 quorum sensing are being recognized as next generation antimicrobials. In the present review article, we summarized recent progresses on AI-2 bacterial quorum sensing inhibitors and discussed their potential as the antibacterial agents. PMID:22320296

Zhu, Peng; Li, Minyong

2012-01-01

2

Evolution of resistance to quorum-sensing inhibitors.  

PubMed

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

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

2014-07-01

3

Treatment of Staphylococcus aureus Biofilm Infection by the Quorum-Sensing Inhibitor RIP?  

PubMed Central

The quorum-sensing inhibitor RIP inhibits staphylococcal TRAP/agr systems and both TRAP- and agr-negative strains are deficient in biofilm formation in vivo, indicating the importance of quorum sensing to biofilms in the host. RIP injected systemically into rats has been found to have strong activity in preventing methicillin-resistant Staphylococcus aureus graft infections, suggesting that RIP can be used as a therapeutic agent. PMID:17371825

Balaban, Naomi; Cirioni, Oscar; Giacometti, Andrea; Ghiselli, Roberto; Braunstein, Joel B.; Silvestri, Carmela; Mocchegiani, Federico; Saba, Vittorio; Scalise, Giorgio

2007-01-01

4

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

PubMed

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

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

2015-04-01

5

Quorum Sensing and Phytochemicals  

PubMed Central

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

Nazzaro, Filomena; Fratianni, Florinda; Coppola, Raffaele

2013-01-01

6

Quorum sensing inhibitors of Staphylococcus aureus from Italian medicinal plants.  

PubMed

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 ?-hemolysin. Quantification of ?-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 ?-hemolysin. Extracts from three medicinal plants (Ballota nigra, Castanea sativa, and Sambucus ebulus) exhibited a dose-dependent response in the production of ?-hemolysin, indicating anti-QS activity in a pathogenic MRSA isolate. PMID:20645243

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

2011-01-01

7

Quorum Sensing Inhibitors for Staphylococcus aureus from Italian Medicinal Plants  

PubMed Central

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 ?-hemolysin. Quantification of ?-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 ?-hemolysin. Extracts from three medicinal plants (Ballota nigra, Castanea sativa, and Sambucus ebulus) exhibited a dose-dependent response in the production of ?-hemolysin, indicating strong anti-QS activity in a pathogenic MRSA isolate. PMID:20645243

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

2010-01-01

8

Bacterial quorum sensing inhibitors: attractive alternatives for control of infectious pathogens showing multiple drug resistance.  

PubMed

Quorum sensing (QS) is a bacterial communication process that depends on the bacterial population density. It involves small diffusible signaling molecules which activate the expression of myriad genes that control diverse array of functions like bioluminescence, virulence, biofilm formation, sporulation, to name a few. Since QS is responsible for virulence in the clinically relevant bacteria, inhibition of QS appears to be a promising strategy to control these pathogenic bacteria. With indiscriminate use of antibiotics, there has been an alarming increase in the number of antibiotic resistant pathogens. Antibiotics are no longer the magic bullets they were once thought to be and therefore there is a need for development of new antibiotics and/or other novel strategies to combat the infections caused by multidrug resistant organisms. Quorum sensing inhibition or quorum quenching has been pursued as one of such novel strategies. While antibiotics kill or slow down the growth of bacteria, quorum sensing inhibitors (QSIs) or quorum quenchers (QQs) attenuate bacterial virulence. A large body of work on QS has been carried out in deadly pathogens like Pseudomonas aeruginosa, Staphylococcus aureus, Vibrio fischeri, V. harveyi, Escherichia coli and V. cholerae etc to unravel the mechanisms of QS as well as identify and study QSIs. This review describes various aspects of QS, QSI, different model systems to study these phenomena and recent patents on various QSIs. It suggests QSIs as attractive alternatives for controlling human, animal and plant pathogens and their utility in agriculture and other industries. PMID:23394143

Bhardwaj, Ashima K; Vinothkumar, Kittappa; Rajpara, Neha

2013-04-01

9

Inhibition of marine biofouling by bacterial quorum sensing inhibitors  

PubMed Central

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

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

2012-01-01

10

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

PubMed

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

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

2006-11-15

11

QUORUM SENSING IN BACTERIA  

Microsoft Academic Search

? Abstract Quorum sensing is the regulation of gene expression in response to fluctuations in cell-population density. Quorum sensing bacteria produce and release chemical signal molecules called autoinducers that increase in concentration as a function of cell density. The detection of a minimal threshold stimulatory con- centration of an autoinducer leads to an alteration in gene expression. Gram-positive and Gram-negative

Melissa B. Miller; Bonnie L. Bassler

2001-01-01

12

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

PubMed Central

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

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

2013-01-01

13

Imidazolines as Non-Classical Bioisosteres of N-Acyl Homoserine Lactones and Quorum Sensing Inhibitors  

PubMed Central

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 ?M 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 ?M. 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 ?M, until reaching 100 ?M, 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 ?M. PMID:22408391

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

2012-01-01

14

At a Supra-Physiological Concentration, Human Sexual Hormones Act as Quorum-Sensing Inhibitors  

PubMed Central

N-Acylhomoserine lactone (AHL)-mediated quorum-sensing (QS) regulates virulence functions in plant and animal pathogens such as Agrobacterium tumefaciens and Pseudomonas aeruginosa. A chemolibrary of more than 3500 compounds was screened using two bacterial AHL-biosensors to identify QS-inhibitors (QSIs). The purity and structure of 15 QSIs selected through this screening were verified using HPLC MS/MS tools and their activity tested on the A. tumefaciens and P. aeruginosa bacterial models. The IC50 value of the identified QSIs ranged from 2.5 to 90 µg/ml, values that are in the same range as those reported for the previously identified QSI 4-nitropyridine-N-oxide (IC50 24 µg/ml). Under the tested culture conditions, most of the identified QSIs did not exhibit bacteriostatic or bactericidal activities. One third of the tested QSIs, including the plant compound hordenine and the human sexual hormone estrone, decreased the frequency of the QS-regulated horizontal transfer of the tumor-inducing (Ti) plasmid in A. tumefaciens. Hordenine, estrone as well as its structural relatives estriol and estradiol, also decreased AHL accumulation and the expression of six QS-regulated genes (lasI, lasR, lasB, rhlI, rhlR, and rhlA) in cultures of the opportunist pathogen P. aeruginosa. Moreover, the ectopic expression of the AHL-receptors RhlR and LasR of P. aeruginosa in E. coli showed that their gene-regulatory activity was affected by the QSIs. Finally, modeling of the structural interactions between the human hormones and AHL-receptors LasR of P. aeruginosa and TraR of A. tumefaciens confirmed the competitive binding capability of the human sexual hormones. This work indicates potential interferences between bacterial and eukaryotic hormonal communications. PMID:24376718

Beury-Cirou, Amélie; Tannières, Mélanie; Minard, Corinne; Soulère, Laurent; Rasamiravaka, Tsiry; Dodd, Robert H.; Queneau, Yves; Dessaux, Yves; Guillou, Catherine; Vandeputte, Olivier M.; Faure, Denis

2013-01-01

15

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

PubMed

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. PMID:25672848

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

2015-04-01

16

Quorum sensing inhibition, relevance to periodontics.  

PubMed

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

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

2015-01-01

17

Quorum Sensing Inhibition, Relevance to Periodontics  

PubMed Central

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

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

2015-01-01

18

Non-antibiotic quorum sensing inhibitors acting against N-acyl homoserine lactone synthase as druggable target  

PubMed Central

N-acylhomoserine lactone (AHL)-based quorum sensing (QS) is important for the regulation of proteobacterial virulence determinants. Thus, the inhibition of AHL synthases offers non-antibiotics-based therapeutic potentials against QS-mediated bacterial infections. In this work, functional AHL synthases of Pseudomonas aeruginosa LasI and RhlI were heterologously expressed in an AHL-negative Escherichia coli followed by assessments on their AHLs production using AHL biosensors and high resolution liquid chromatography–mass spectrometry (LCMS). These AHL-producing E. coli served as tools for screening AHL synthase inhibitors. Based on a campaign of screening synthetic molecules and natural products using our approach, three strongest inhibitors namely are salicylic acid, tannic acid and trans-cinnamaldehyde have been identified. LCMS analysis further confirmed tannic acid and trans-cinnemaldehyde efficiently inhibited AHL production by RhlI. We further demonstrated the application of trans-cinnemaldehyde inhibiting Rhl QS system regulated pyocyanin production in P. aeruginosa up to 42.06%. Molecular docking analysis suggested that trans-cinnemaldehyde binds to the LasI and EsaI with known structures mainly interacting with their substrate binding sites. Our data suggested a new class of QS-inhibiting agents from natural products targeting AHL synthase and provided a potential approach for facilitating the discovery of anti-QS signal synthesis as basis of novel anti-infective approach. PMID:25430794

Chang, Chien-Yi; Krishnan, Thiba; Wang, Hao; Chen, Ye; Yin, Wai-Fong; Chong, Yee-Meng; Tan, Li Ying; Chong, Teik Min; Chan, Kok-Gan

2014-01-01

19

Screening for Quorum-Sensing Inhibitors (QSI) by Use of a Novel Genetic System, the QSI Selector  

Microsoft Academic Search

With the widespread appearance of antibiotic-resistant bacteria, there is an increasing demand for novel strategies to control infectious diseases. Furthermore, it has become apparent that the bacterial life style also contributes significantly to this problem. Bacteria living in the biofilm mode of growth tolerate conventional antimicrobial treatments. The discovery that many bacteria use quorum-sensing (QS) systems to coordinate virulence and

Thomas Bovbjerg Rasmussen; Thomas Bjarnsholt; Mette Elena Skindersoe; Morten Hentzer; Peter Kristoffersen; Manuela Kote; John Nielsen; Leo Eberl; Michael Givskov

2005-01-01

20

Screening for Quorum-Sensing Inhibitors (QSI) by Use of a Novel Genetic System, the QSI Selector  

PubMed Central

With the widespread appearance of antibiotic-resistant bacteria, there is an increasing demand for novel strategies to control infectious diseases. Furthermore, it has become apparent that the bacterial life style also contributes significantly to this problem. Bacteria living in the biofilm mode of growth tolerate conventional antimicrobial treatments. The discovery that many bacteria use quorum-sensing (QS) systems to coordinate virulence and biofilm development has pointed out a new, promising target for antimicrobial drugs. We constructed a collection of screening systems, QS inhibitor (QSI) selectors, which enabled us to identify a number of novel QSIs among natural and synthetic compound libraries. The two most active were garlic extract and 4-nitro-pyridine-N-oxide (4-NPO). GeneChip-based transcriptome analysis revealed that garlic extract and 4-NPO had specificity for QS-controlled virulence genes in Pseudomonas aeruginosa. These two QSIs also significantly reduced P. aeruginosa biofilm tolerance to tobramycin treatment as well as virulence in a Caenorhabditis elegans pathogenesis model. PMID:15716452

Rasmussen, Thomas Bovbjerg; Bjarnsholt, Thomas; Skindersoe, Mette Elena; Hentzer, Morten; Kristoffersen, Peter; Köte, Manuela; Nielsen, John; Eberl, Leo; Givskov, Michael

2005-01-01

21

Honaucins A–C, Potent Inhibitors of Eukaryotic Inflammation and Bacterial Quorum Sensing: Synthetic Derivatives and Structure-Activity Relationships  

PubMed Central

SUMMARY Honaucins A–C were isolated from the cyanobacterium Leptolyngbya crossbyana which was found overgrowing corals on the Hawaiian coast. Honaucin A consists of (S)-3-hydroxy-?-butyrolactone and 4-chlorocrotonic acid which are connected via an ester linkage. Honaucin A and its two natural analogs exhibit potent inhibition of bioluminescence, a quorum sensing-dependent phenotype, in Vibrio harveyi BB120 as well as of lipopolysaccharide-stimulated nitric oxide production in the murine macrophage cell line RAW264.7. The decrease in nitric oxide production was accompanied by a decrease in the transcripts of several pro-inflammatory cytokines, most dramatically interleukin-1?. Synthesis of honaucin A as well as a number of analogs and subsequent evaluation in anti-inflammation and quorum sensing inhibition bioassays revealed the essential structural features for activity in this chemical class, and provided analogs with greater potency in both assays. PMID:22633410

Choi, Hyukjae; Mascuch, Samantha J.; Villa, Francisco A.; Byrum, Tara; Teasdale, Margaret E.; Smith, Jennifer E.; Preskitt, Linda B.; Rowley, David C.; Gerwick, Lena; Gerwick, William H.

2012-01-01

22

Quorum Sensing in Extreme Environments  

PubMed Central

Microbial communication, particularly that of quorum sensing, plays an important role in regulating gene expression in a range of organisms. Although this phenomenon has been well studied in relation to, for example, virulence gene regulation, the focus of this article is to review our understanding of the role of microbial communication in extreme environments. Cell signaling regulates many important microbial processes and may play a pivotal role in driving microbial functional diversity and ultimately ecosystem function in extreme environments. Several recent studies have characterized cell signaling in modern analogs to early Earth communities (microbial mats), and characterization of cell signaling systems in these communities may provide unique insights in understanding the microbial interactions involved in function and survival in extreme environments. Cell signaling is a fundamental process that may have co-evolved with communities and environmental conditions on the early Earth. Without cell signaling, evolutionary pressures may have even resulted in the extinction rather than evolution of certain microbial groups. One of the biggest challenges in extremophile biology is understanding how and why some microbial functional groups are located where logically they would not be expected to survive, and tightly regulated communication may be key. Finally, quorum sensing has been recently identified for the first time in archaea, and thus communication at multiple levels (potentially even inter-domain) may be fundamental in extreme environments. PMID:25371335

Montgomery, Kate; Charlesworth, James C.; LeBard, Rebecca; Visscher, Pieter T.; Burns, Brendan P.

2013-01-01

23

Quorum sensing and bacterial cooperation Anand Pai  

E-print Network

Quorum sensing and bacterial cooperation Anand Pai CTMS Graduate Fellow of cooperation benefits bacteria. Fig. 1: Schematic of bacterial communication The equation depicts the dynamics of population density N under logistic growth. Its

Wolpert, Robert L

24

N,N?-alkylated Imidazolium-Derivatives Act as Quorum-Sensing Inhibitors Targeting the Pectobacterium atrosepticum-Induced Symptoms on Potato Tubers  

PubMed Central

Bacteria belonging to the Pectobacterium genus are the causative agents of the blackleg and soft-rot diseases that affect potato plants and tubers worldwide. In Pectobacterium, the expression of the virulence genes is controlled by quorum-sensing (QS) and N-acylhomoserine lactones (AHLs). In this work, we screened a chemical library of QS-inhibitors (QSIs) and AHL-analogs to find novel QSIs targeting the virulence of Pectobacterium. Four N,N?-bisalkylated imidazolium salts were identified as QSIs; they were active at the ?M range. In potato tuber assays, two of them were able to decrease the severity of the symptoms provoked by P. atrosepticum. This work extends the range of the QSIs acting on the Pectobacterium-induced soft-rot disease. PMID:24108370

des Essarts, Yannick Raoul; Sabbah, Mohamad; Comte, Arnaud; Soulère, Laurent; Queneau, Yves; Dessaux, Yves; Hélias, Valérie; Faure, Denis

2013-01-01

25

Acne, quorum sensing and danger.  

PubMed

Propionibacterium acnes is a ubiquitous skin commensal bacterium, which is normally well tolerated by the immune system in healthy human skin. However, there is increasing evidence to suggest a pivotal role for P. acnes in the inflammatory process underlying the acne pathogenesis. With its features of inflammation and pustulation, acne vulgaris resembles the skin's normal reaction to bacterial pathogens. P. acnes flourishes when sebum production increases in the follicles. Bacteria may undergo behavioural changes based on the surrounding bacterial population, a process called quorum sensing (QS). Evidence from in vitro studies suggests that QS enables P. acnes to upregulate its hydrolysis of sebum triglycerides by its bacterial lipases, secreting free fatty acids (FFAs) such as oleic, palmitic and lauric acids. These FFAs act as danger-associated molecular patterns (DAMPs), and activate Toll-like receptor (TLR)2 and TLR4, leading to selective T-helper (Th)-driven immunity, with subsequent expression of Th1/Th17-associated inflammatory cytokines. To our knowledge, there is currently no explanation as to what determines the shift of recognition by the immune system of P. acnes from being symbiotic to pathogenic. We present a novel hypothesis based on the essence of QS and DAMPs. P. acnes sends no or only 'safety' signals when present in 'controlled' quantities under commensal conditions, but becomes pathogenic and sends 'danger' signals via QS in the form of excess FFA production, which stimulates TLR2 and TLR4 as the bacterial population flourishes. PMID:24524558

Lwin, S M; Kimber, I; McFadden, J P

2014-03-01

26

Quorum sensing and the confusion about diffusion  

E-print Network

Quorum sensing and the confusion about diffusion Stuart A. West1 , Klaus Winzer2 , Andy Gardner1 with both social interactions and a role of diffusion; (v) alternate hypotheses, such as efficiency sensing to cell density. Bacteria produce and release small diffusible molecules, usually termed signals (see

West, Stuart

27

A Strategy for Antagonizing Quorum Sensing  

SciTech Connect

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.

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

2011-12-31

28

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

PubMed

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. PMID:25219871

Zhao, J; Chen, M; Quan, Cs; Fan, Sd

2014-09-15

29

Preliminary results of a novel quorum sensing inhibitor against pneumococcal infection and biofilm formation with special interest to otitis media and cochlear implantation.  

PubMed

The purpose of the study is to assess the effect of a novel quorum sensing inhibitor (QSI), coded as 'yd 47', against otitis media and biofilm formation on Cochlear implants (CIs). Small pieces cut from cochlear implant were implanted under the skin in the retroauricular area on both sides of four guinea pigs. The implant pieces in the study and control sides were implanted in Streptococcus pneumoniae strain solution and saline, respectively. The right and left middle ears were also instilled with a solution containing pneumococci and saline, respectively. The animals were only given an intraperitoneal 'yd 47' twice daily for three months to be assessed later with electron microscopy. Clinical examination with palpation, inspection and otoscopy did not reveal any sign of implant infection or otitis media. In the study and control implant materials, soft tissues around the implant and tympanic membranes, there was no biofilm formation by pneumococci. Contamination by various cells and some rod-shaped bacteria (not diplococcic) were seen in some of the materials. In conclusion, the novel QSI seems promising in the prevention of otitis media and biofilm formation on CIs by pneumococci. PMID:24570174

Cevizci, Ra?it; Düzlü, Mehmet; Dündar, Yasemin; Noyanalpan, Ningur; Sultan, Nedim; Tutar, Hakan; Bayaz?t, Y?ld?r?m A

2014-02-26

30

Collective sensing and collective responses in quorum-sensing bacteria  

PubMed Central

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

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

2015-01-01

31

Exploiting Quorum Sensing To Confuse Bacterial Pathogens  

PubMed Central

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

LaSarre, Breah

2013-01-01

32

Surface coatings that promote rapid release of peptide-based AgrC inhibitors for attenuation of quorum sensing in Staphylococcus aureus.  

PubMed

Staphylococcus aureus is a major human pathogen responsible for a variety of life-threatening infections. The pathogenicity of this organism is attributed to its ability to produce a range of virulence factors and toxins, including the superantigen toxic shock syndrome toxin-1 (TSST-1). While many S. aureus infections can be treated using conventional antibiotics, strains resistant to these bactericidal agents have emerged. Approaches that suppress pathogenicity through mechanisms that are nonbactericidal (i.e., antivirulence approaches) could provide new options for treating infections, including those caused by resistant strains. Here, we report a nonbactericidal approach to suppressing pathogenicity based on the release of macrocyclic peptides (1 and 2) that inhibit the agr quorum sensing (QS) circuit in group-III S. aureus. It is demonstrated that these peptides can be immobilized on planar and complex objects (on glass slides, nonwoven meshes, or within absorbent tampons) using the rapidly dissolving polymer carboxymethylcellulose (CMC). Peptide-loaded CMC films released peptide rapidly (<5 min) and promoted strong (>95%) inhibition of the agr QS circuit without inducing cell death when incubated in the presence of a group-III S. aureus gfp-reporter strain. Peptide 1 is among the most potent inhibitors of QS in S. aureus reported to date, and the group-III QS circuit regulates production of TSST-1, the primary cause of toxic shock syndrome (TSS). These results thus suggest approaches to treat the outer covers of tampons, wound dressings, or other objects to suppress toxin production and reduce the severity of TSS in clinical and personal care contexts. Because peptide 1 also inhibits QS in S. aureus groups-I, -II, and -IV, this approach could also provide a pathway for attenuation of QS and associated virulence phenotypes in a broader range of contexts. PMID:23813683

Broderick, Adam H; Stacy, Danielle M; Tal-Gan, Yftah; Kratochvil, Michael J; Blackwell, Helen E; Lynn, David M

2014-01-01

33

Metagenomic approaches to understanding phylogenetic diversity in quorum sensing  

PubMed Central

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

Kimura, Nobutada

2014-01-01

34

Antibiotic-free nanotherapeutics: ultra-small, mucus-penetrating solid lipid nanoparticles enhance the pulmonary delivery and anti-virulence efficacy of novel quorum sensing inhibitors.  

PubMed

Cystic fibrosis (CF) is a genetic disease mainly manifested in the respiratory tract. Pseudomonas aeruginosa (P. aeruginosa) is the most common pathogen identified in cultures of the CF airways, however, its eradication with antibiotics remains challenging as it grows in biofilms that counterwork human immune response and dramatically decrease susceptibility to antibiotics. P. aeruginosa regulates pathogenicity via a cell-to-cell communication system known as quorum sensing (QS) involving the virulence factor (pyocyanin), thus representing an attractive target for coping with bacterial pathogenicity. The first in vivo potent QS inhibitor (QSI) was recently developed. Nevertheless, its lipophilic nature might hamper its penetration of non-cellular barriers such as mucus and bacterial biofilms, which limits its biomedical application. Successful anti-infective inhalation therapy necessitates proper design of a biodegradable nanocarrier allowing: 1) high loading and prolonged release, 2) mucus penetration, 3) effective pulmonary delivery, and 4) maintenance of the anti-virulence activity of the QSI. In this context, various pharmaceutical lipids were used to prepare ultra-small solid lipid nanoparticles (us-SLNs) by hot melt homogenization. Plain and QSI-loaded SLNs were characterized in terms of colloidal properties, drug loading, in vitro release and acute toxicity on Calu-3 cells. Mucus penetration was studied using a newly-developed confocal microscopy technique based on 3D-time-lapse imaging. For pulmonary application, nebulization efficiency of SLNs and lung deposition using next generation impactor (NGI) were performed. The anti-virulence efficacy was investigated by pyocyanin formation in P. aeruginosa cultures. Ultra-small SLNs (<100nm diameter) provided high encapsulation efficiency (68-95%) according to SLN composition, high burst in phosphate buffer saline compared to prolonged release of the payload over >8h in simulated lung fluid with minor burst. All types and concentrations of plain and QSI-loaded SLNs maintained the viability of Calu-3 cells. 3D time-lapse confocal imaging proved the ability of SLNs to penetrate into artificial sputum model. SLNs were efficiently nebulized; NGI experiments revealed their deposition in the bronchial region. Overall, nanoencapsulated QSI showed up to sevenfold superior anti-virulence activity to the free compound. Most interestingly, the plain SLNs exhibited anti-virulence properties themselves, which was shown to be related to anti-virulence effects of the emulsifiers used. These startling findings represent a new perspective of ultimate significance in the area of nano-based delivery of novel anti-infectives. PMID:24997276

Nafee, Noha; Husari, Ayman; Maurer, Christine K; Lu, Cenbin; de Rossi, Chiara; Steinbach, Anke; Hartmann, Rolf W; Lehr, Claus-Michael; Schneider, Marc

2014-10-28

35

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

SciTech Connect

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.

Gutierrez, J.; Crowder, T; Rinaldo-Matthis, A; Ho, M; Almo, S; Schramm, V

2009-01-01

36

Interspecific Quorum Sensing Mediates the Resuscitation of Viable but Nonculturable Vibrios  

PubMed Central

Entry and exit from dormancy are essential survival mechanisms utilized by microorganisms to cope with harsh environments. Many bacteria, including the opportunistic human pathogen Vibrio vulnificus, enter a form of dormancy known as the viable but nonculturable (VBNC) state. VBNC cells can resuscitate when suitable conditions arise, yet the molecular mechanisms facilitating resuscitation in most bacteria are not well understood. We discovered that bacterial cell-free supernatants (CFS) can awaken preexisting dormant vibrio populations within oysters and seawater, while CFS from a quorum sensing mutant was unable to produce the same resuscitative effect. Furthermore, the quorum sensing autoinducer AI-2 could induce resuscitation of VBNC V. vulnificus in vitro, and VBNC cells of a mutant unable to produce AI-2 were unable to resuscitate unless the cultures were supplemented with exogenous AI-2. The quorum sensing inhibitor cinnamaldehyde delayed the resuscitation of wild-type VBNC cells, confirming the importance of quorum sensing in resuscitation. By monitoring AI-2 production by VBNC cultures over time, we found quorum sensing signaling to be critical for the natural resuscitation process. This study provides new insights into the molecular mechanisms stimulating VBNC cell exit from dormancy, which has significant implications for microbial ecology and public health. PMID:24509922

Ayrapetyan, Mesrop; Williams, Tiffany C.

2014-01-01

37

Electronic Implementation of a Repressilator with Quorum Sensing Feedback  

PubMed Central

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

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

2013-01-01

38

Temporal Quorum-Sensing Induction Regulates Vibrio cholerae Biofilm Architecture?  

PubMed Central

Vibrio cholerae, the pathogen that causes cholera, also survives in aqueous reservoirs, probably in the form of biofilms. Quorum sensing negatively regulates V. cholerae biofilm formation through HapR, whose expression is induced at a high cell density. In this study, we show that the concentration of the quorum-sensing signal molecule CAI-1 is higher in biofilms than in planktonic cultures. By measuring hapR expression and activity, we found that the induction of quorum sensing in biofilm-associated cells occurs earlier. We further demonstrate that the timing of hapR expression is crucial for biofilm thickness, biofilm detachment rates, and intestinal colonization efficiency. These results suggest that V. cholerae is able to regulate its biofilm architecture by temporal induction of quorum-sensing systems. PMID:17074850

Liu, Zhi; Stirling, Fiona R.; Zhu, Jun

2007-01-01

39

Zingerone silences quorum sensing and attenuates virulence of Pseudomonas aeruginosa.  

PubMed

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

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

2015-04-01

40

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

PubMed Central

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

Papaioannou, Evelina; Utari, Putri Dwi; Quax, Wim J.

2013-01-01

41

Quorum sensing in group A Streptococcus  

PubMed Central

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

Jimenez, Juan Cristobal; Federle, Michael J.

2014-01-01

42

Quorum sensing in fungi – a review  

PubMed Central

Quorum sensing (QS) is a mechanism of microbial communication dependent on cell density that can regulate several behaviors in bacteria such as secretion of virulence factors, biofilm formation, competence and bioluminescence. The existence of fungal QS systems was revealed ten years ago after the discovery that farnesol controls filamentation in the pathogenic polymorphic fungus Candida albicans. In the past decade, farnesol has been shown to play multiple roles in C. albicans physiology as a signaling molecule and inducing detrimental effects on host cells and other microbes. In addition to farnesol, the aromatic alcohol tyrosol was also found to be a C. albicans QS molecule (QSM) controlling growth, morphogenesis and biofilm formation. In Saccharomyces cerevisiae, two other aromatic alcohols, phenylethanol and tryptophol were found to be QSMs regulating morphogenesis during nitrogen starvation conditions. Additionally, population density-dependent behaviors that resemble QS have been described in several other fungal species. Although fungal QS research is still in its infancy, its discovery has changed our views about the fungal kingdom and could eventually lead to the development of new antifungal therapeutics. PMID:22268493

ALBUQUERQUE, PATRÍCIA; CASADEVALL, ARTURO

2015-01-01

43

Early development and quorum sensing in bacterial biofilms.  

PubMed

We develop mathematical models to examine the formation, growth and quorum sensing activity of bacterial biofilms. The growth aspects of the model are based on the assumption of a continuum of bacterial cells whose growth generates movement, within the developing biofilm, described by a velocity field. A model proposed in Ward et al. (2001) to describe quorum sensing, a process by which bacteria monitor their own population density by the use of quorum sensing molecules (QSMs), is coupled with the growth model. The resulting system of nonlinear partial differential equations is solved numerically, revealing results which are qualitatively consistent with experimental ones. Analytical solutions derived by assuming uniform initial conditions demonstrate that, for large time, a biofilm grows algebraically with time; criteria for linear growth of the biofilm biomass, consistent with experimental data, are established. The analysis reveals, for a biologically realistic limit, the existence of a bifurcation between non-active and active quorum sensing in the biofilm. The model also predicts that travelling waves of quorum sensing behaviour can occur within a certain time frame; while the travelling wave analysis reveals a range of possible travelling wave speeds, numerical solutions suggest that the minimum wave speed, determined by linearisation, is realised for a wide class of initial conditions. PMID:12827447

Ward, John P; King, John R; Koerber, Adrian J; Croft, Julie M; Sockett, R Elizabeth; Williams, Paul

2003-07-01

44

The Evolution of Quorum Sensing in Bacterial Biofilms  

PubMed Central

Bacteria have fascinating and diverse social lives. They display coordinated group behaviors regulated by quorum-sensing systems that detect the density of other bacteria around them. A key example of such group behavior is biofilm formation, in which communities of cells attach to a surface and envelope themselves in secreted polymers. Curiously, after reaching high cell density, some bacterial species activate polymer secretion, whereas others terminate polymer secretion. Here, we investigate this striking variation in the first evolutionary model of quorum sensing in biofilms. We use detailed individual-based simulations to investigate evolutionary competitions between strains that differ in their polymer production and quorum-sensing phenotypes. The benefit of activating polymer secretion at high cell density is relatively straightforward: secretion starts upon biofilm formation, allowing strains to push their lineages into nutrient-rich areas and suffocate neighboring cells. But why use quorum sensing to terminate polymer secretion at high cell density? We find that deactivating polymer production in biofilms can yield an advantage by redirecting resources into growth, but that this advantage occurs only in a limited time window. We predict, therefore, that down-regulation of polymer secretion at high cell density will evolve when it can coincide with dispersal events, but it will be disfavored in long-lived (chronic) biofilms with sustained competition among strains. Our model suggests that the observed variation in quorum-sensing behavior can be linked to the differing requirements of bacteria in chronic versus acute biofilm infections. This is well illustrated by the case of Vibrio cholerae, which competes within biofilms by polymer secretion, terminates polymer secretion at high cell density, and induces an acute disease course that ends with mass dispersal from the host. More generally, this work shows that the balance of competition within and among biofilms can be pivotal in the evolution of quorum sensing. PMID:18232735

Levin, Simon A; Foster, Kevin R

2008-01-01

45

Biomimicry of quorum sensing using bacterial lifecycle model  

PubMed Central

Background Recent microbiologic studies have shown that quorum sensing mechanisms, which serve as one of the fundamental requirements for bacterial survival, exist widely in bacterial intra- and inter-species cell-cell communication. Many simulation models, inspired by the social behavior of natural organisms, are presented to provide new approaches for solving realistic optimization problems. Most of these simulation models follow population-based modelling approaches, where all the individuals are updated according to the same rules. Therefore, it is difficult to maintain the diversity of the population. Results In this paper, we present a computational model termed LCM-QS, which simulates the bacterial quorum-sensing (QS) mechanism using an individual-based modelling approach under the framework of Agent-Environment-Rule (AER) scheme, i.e. bacterial lifecycle model (LCM). LCM-QS model can be classified into three main sub-models: chemotaxis with QS sub-model, reproduction and elimination sub-model and migration sub-model. The proposed model is used to not only imitate the bacterial evolution process at the single-cell level, but also concentrate on the study of bacterial macroscopic behaviour. Comparative experiments under four different scenarios have been conducted in an artificial 3-D environment with nutrients and noxious distribution. Detailed study on bacterial chemotatic processes with quorum sensing and without quorum sensing are compared. By using quorum sensing mechanisms, artificial bacteria working together can find the nutrient concentration (or global optimum) quickly in the artificial environment. Conclusions Biomimicry of quorum sensing mechanisms using the lifecycle model allows the artificial bacteria endowed with the communication abilities, which are essential to obtain more valuable information to guide their search cooperatively towards the preferred nutrient concentrations. It can also provide an inspiration for designing new swarm intelligence optimization algorithms, which can be used for solving the real-world problems. PMID:23815296

2013-01-01

46

Bacterial Quorum Sensing and Its Interference: Methods and Significance  

Microsoft Academic Search

\\u000a Bacteria use the language of low-molecular-weight ligands to assess their population densities in a process called quorum\\u000a sensing (QS). Different types of quorum sensing pathways are present in Gram-negative and Gram-positive bacteria. Signal molecules\\u000a most commonly used in Gram-negative bacteria are acyl homoserine lactones. In recent years, a substantial amount of literature\\u000a and data have been available on bacterial QS.

Iqbal Ahmad; Mohd Sajjad Ahmad Khan; Fohad Mabood Husain; Maryam Zahin; Mahipal Singh

47

Quorum sensing activity in Pandoraea pnomenusa RB38.  

PubMed

Strain RB38 was recovered from a former dumping area in Malaysia. MALDI-TOF mass spectrometry and genomic analysis identified strain RB-38 as Pandoraea pnomenusa. Various biosensors confirmed its quorum sensing properties. High resolution triple quadrupole liquid chromatography-mass spectrometry analysis was subsequently used to characterize the N-acyl homoserine lactone production profile of P. pnomenusa strain RB38, which validated that this isolate produced N-octanoyl homoserine lactone as a quorum sensing molecule. This is the first report of the production of N-octanoyl homoserine lactone by P. pnomenusa strain RB38. PMID:24919016

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

2014-01-01

48

Inhibiting Effect of Bioactive Metabolites Produced by Mushroom Cultivation on Bacterial Quorum Sensing-Regulated Behaviors  

Microsoft Academic Search

Aims: This study aimed to search for novel quorum sensing (QS) inhibitors from mushroom and to analyze their inhibitory activity, with a view to their possible use in controlling detrimental infections. Methods: The bioactive metabolites produced by mushroom cultivation were tested for their abilities to inhibit QS-regulated behavior. All mushroom strains were cultivated in potato-dextrose medium by large-scale submerged fermentation.

Hu Zhu; Shou-xian Wang; Shuai-shuai Zhang; Chun-xu Cao

2011-01-01

49

Structural Basis for Native Agonist and Synthetic Inhibitor Recognition by the Pseudomonas aeruginosa Quorum Sensing Regulator PqsR (MvfR)  

PubMed Central

Bacterial populations co-ordinate gene expression collectively through quorum sensing (QS), a cell-to-cell communication mechanism employing diffusible signal molecules. The LysR-type transcriptional regulator (LTTR) protein PqsR (MvfR) is a key component of alkyl-quinolone (AQ)-dependent QS in Pseudomonas aeruginosa. PqsR is activated by 2-alkyl-4-quinolones including the Pseudomonas quinolone signal (PQS; 2-heptyl-3-hydroxy-4(1H)-quinolone), its precursor 2-heptyl-4-hydroxyquinoline (HHQ) and their C9 congeners, 2-nonyl-3-hydroxy-4(1H)-quinolone (C9-PQS) and 2-nonyl-4-hydroxyquinoline (NHQ). These drive the autoinduction of AQ biosynthesis and the up-regulation of key virulence determinants as a function of bacterial population density. Consequently, PqsR constitutes a potential target for novel antibacterial agents which attenuate infection through the blockade of virulence. Here we present the crystal structures of the PqsR co-inducer binding domain (CBD) and a complex with the native agonist NHQ. We show that the structure of the PqsR CBD has an unusually large ligand-binding pocket in which a native AQ agonist is stabilized entirely by hydrophobic interactions. Through a ligand-based design strategy we synthesized and evaluated a series of 50 AQ and novel quinazolinone (QZN) analogues and measured the impact on AQ biosynthesis, virulence gene expression and biofilm development. The simple exchange of two isosteres (OH for NH2) switches a QZN agonist to an antagonist with a concomitant impact on the induction of bacterial virulence factor production. We also determined the complex crystal structure of a QZN antagonist bound to PqsR revealing a similar orientation in the ligand binding pocket to the native agonist NHQ. This structure represents the first description of an LTTR-antagonist complex. Overall these studies present novel insights into LTTR ligand binding and ligand-based drug design and provide a chemical scaffold for further anti-P. aeruginosa virulence drug development by targeting the AQ receptor PqsR. PMID:23935486

Ilangovan, Aravindan; Fletcher, Matthew; Rampioni, Giordano; Pustelny, Christian; Rumbaugh, Kendra; Heeb, Stephan; Cámara, Miguel; Truman, Alex; Chhabra, Siri Ram; Emsley, Jonas; Williams, Paul

2013-01-01

50

Quorum-sensing and cheating in bacterial biofilms  

E-print Network

; spatial structure; cooperation; cheating 1. INTRODUCTION The growth and success of bacterial populationsQuorum-sensing and cheating in bacterial biofilms Roman Popat1,, Shanika A. Crusz1, Marco Messina1 is sometimes termed the public goods dilemma. We tested this idea in the opportunistic bacterial patho- gen

West, Stuart

51

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

PubMed Central

Proteobacteria are known to communicate via signaling molecules and this process is known as quorum sensing. The most commonly studied quorum sensing molecules are N-acylhomoserine lactones (AHLs) that consists of a homoserine lactone moiety and an N-acyl side chain with various chain lengths and degrees of saturation at the C-3 position. We have isolated a bacterium, RB-44, from a site which was formally a landfill dumping ground. Using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry analysis, this isolate was identified as a Pandoraea sp.which was then screened for AHL production using biosensors which indicated its quorum sensing properties. To identify the AHL profile of Pandoraea sp. RB-44, we used high resolution tandem mass spectrometry confirming that this isolate produced N-octanoylhomoserine lactone (C8-HSL). To the best of our knowledge, this is the first report that showed quorum sensing activity exhibited by Pandoraea sp. Our data add Pandoraea sp. to the growing number of bacteria that possess QS systems. PMID:24145919

Han-Jen, Robson Ee; Wai-Fong, Yin; Kok-Gan, Chan

2013-01-01

52

Detection of quorum-sensing-related molecules in Vibrio scophthalmi  

PubMed Central

Background Cell-to-cell communication (also referred to as quorum sensing) based on N-acyl-homoserine lactones (AHLs) is a widespread response to environmental change in Gram-negative bacteria. AHLs seem to be highly variable, both in terms of the acyl chain length and in the chemical structure of the radicals. Another quorum sensing pathway, the autoinducer-2-based system, is present both in Gram-positive and Gram-negative bacteria. In this study the presence of signal molecules belonging to both quorum sensing signalling pathways was analysed in the marine symbiotic species Vibrio scophthalmi. Results Three AHL-like signal molecules were detected in V. scophthalmi supernatants with the Agrobacterium tumefaciens sensor assay. This observation was further supported by the decrease in the presence of these signal molecules after cloning and expression of lactonase AiiA from Bacillus cereus in the V. scophthalmi strains. One of the signal molecules was identified as N-(3-hydroxy dodecanoyl)-L-homoserine lactone. V. scophthalmi was also shown to carry a functional LuxS synthase. The coding sequence for a luxS-like gene was obtained showing a maximum similarity of 78% with Vibrio vulnificus. Analysis of the translated sequence revealed that the sequenced luxS gene carried the conserved domain, which is common to luxS sequences found in other species, and which is essential for LuxS enzymatic activity. Conclusion The data are consistent with the presence of quorum-sensing signal molecules from both AHL- and autoinducer 2-based quorum sensing systems in V. scophthalmi, which are homologous to others previously described in various Vibrio species. How this bacterium interacts with other bacteria and eukaryotic cells to compete ecologically with other intestinal bacteria present in the fish Scophthalmus maximus warrants further investigation. PMID:18700048

García-Aljaro, Cristina; Eberl, Leo; Riedel, Kathrin; Blanch, Anicet R

2008-01-01

53

Quorum sensing-controlled gene expression in lactic acid bacteria  

Microsoft Academic Search

Quorum sensing in lactic acid bacteria (LAB) involves peptides that are directly sensed by membrane-located histidine kinases, after which the signal is transmitted to an intracellular response regulator. This regulator in turn activates transcription of target genes, that commonly include the structural gene for the inducer molecule. The two-component signal-transduction machinery has proven to be indispensable for transcription activation and

Oscar P. Kuipers; Michiel Kleerebezem; Willem M. de Vos

1998-01-01

54

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

PubMed Central

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

2013-01-01

55

Substituted Lactam and Cyclic Azahemiacetals Modulate Pseudomonas aeruginosa Quorum Sensing  

PubMed Central

Quorum sensing (QS) is a population-dependent signaling process bacteria use to control multiple processes including virulence that is critical for establishing infection. The most common QS signaling molecule used by Gram-negative bacteria are acylhomoserine lactones. The development of non-native acylhomoserine lactone (AHL) ligands has emerged as a promising new strategy to inhibit QS in Gram-negative bacteria. In this work, we have synthesized a set of optically pure ?-lactams and their reduced cyclic azahemiacetal analogues, bearing the additional alkylthiomethyl substituent, and evaluated their effect on the AHL-dependent Pseudomonas aeruginosa las and rhl QS pathways. The concentration of these ligands and the simple structural modification such as the length of the alkylthio substituent has notable effect on activity. The ?-lactam derivatives with nonylthio or dodecylthio chains acted as inhibitors of las signaling with moderate potency. The cyclic azahemiacetal with shorter propylthio or hexylthio substituent was found to strongly inhibit both las and rhl signaling at higher concentrations while the propylthio analogue strongly stimulated the las QS system at lower concentrations. PMID:21855349

Malladi, Venkata L. A.; Sobczak, Adam J.; Maricic, Natalie; Murugapiran, Senthil Kumar; Schneper, Lisa; Makemson, John; Mathee, Kalai; Wnuk, Stanislaw F.

2011-01-01

56

Inhibition of quorum-sensing signals by essential oils.  

PubMed

The role of quorum sensing (QS) is well known in microbial pathogenicity and antibiotic resistance. QS is responsible for motility, swarming, and biofilm production based on the signal molecules, e.g., acylated homoserine lactones (AHLs) produced by micro-organisms above certain population density. The inhibition of QS may reduce pathogenicity, antibiotic resistance and biofilm formation in systemic and local infections. The homoserine lactones and other transmitters contribute to antibiotic resistance and pathogenicity of several bacteria; consequently the inhibition of QS signals reduces the problem of resistance and virulence. Due to the increasing number of persistent non-treatable infections, there is an urgent need to develop new strategies to combat infections that destabilize bacterial communities in the host. The effect of essential oils on bacterial growth and QS were evaluated using the sensor strain Chromobacterium violaceum CV026 and N-acyl homoserine lactone (AHL) producing Escherichia coli ATTC 31298 and the grapevine colonizing Ezf 10-17 strains. Of the tested oils, rose, geranium, lavender and rosemary oils were the most potent QS inhibitors. Eucalyptus and citrus oils moderately reduced pigment production by CV026, whereas the chamomile, orange and juniper oils were ineffective. PMID:19827025

Szabó, Mira Agnes; Varga, Gábor Zoltán; Hohmann, Judit; Schelz, Zsuzsanna; Szegedi, Erno; Amaral, Leonard; Molnár, József

2010-05-01

57

Transcriptome Analysis of Acetyl-Homoserine Lactone-Based Quorum Sensing Regulation in Yersinia pestis  

PubMed Central

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. PMID:23620823

Horswill, Alexander R.; Parsek, Matthew R.; Minion, F. Chris

2013-01-01

58

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

PubMed

Quorum sensing allows bacteria to sense and respond to changes in population density. Acyl-homoserine lactones serve as quorum-sensing signals for many Proteobacteria, and acyl-homoserine lactone signaling is known to control cooperative activities. Quorum-controlled activities vary from one species to another. Quorum-sensing controls a constellation of genes in the opportunistic pathogen Pseudomonas aeruginosa, which thrives in a number of habitats ranging from soil and water to animal hosts. We hypothesized that there would be significant variation in quorum-sensing regulons among strains of P. aeruginosa isolated from different habitats and that differences in the quorum-sensing regulons might reveal insights about the ecology of P. aeruginosa. As a test of our hypothesis we used RNA-seq to identify quorum-controlled genes in seven P. aeruginosa isolates of diverse origins. Although our approach certainly overlooks some quorum-sensing-regulated genes we found a shared set of genes, i.e., a core quorum-controlled gene set, and we identified distinct, strain-variable sets of quorum-controlled genes, i.e., accessory genes. Some quorum-controlled genes in some strains were not present in the genomes of other strains. We detected a correlation between traits encoded by some genes in the strain-variable subsets of the quorum regulons and the ecology of the isolates. These findings indicate a role for quorum sensing in extension of the range of habitats in which a species can thrive. This study also provides a framework for understanding the molecular mechanisms by which quorum-sensing systems operate, the evolutionary pressures by which they are maintained, and their importance in disparate ecological contexts. PMID:22988113

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

2012-10-01

59

RETRACTED ARTICLE: Quorum-sensing of bacteria and its application  

NASA Astrophysics Data System (ADS)

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.

Jiang, Guoliang; Su, Mingxia

2009-12-01

60

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

PubMed

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. PMID:24936763

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

61

Global Analysis of the Burkholderia thailandensis Quorum Sensing-Controlled Regulon  

PubMed Central

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

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

2014-01-01

62

Analysis of Autoinducer-2 Quorum Sensing in Yersinia pestis  

PubMed Central

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

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

2013-01-01

63

Stationary-Phase Quorum-Sensing Signals Affect Autoinducer-2 and Gene Expression in Escherichia coli  

Microsoft Academic Search

Quorum sensing via autoinducer-2 (AI-2) has been identified in different strains, including those from Escherichia, Vibrio, Streptococcus, and Bacillus species, and previous studies have suggested the existence of additional quorum-sensing signals working in the stationary phase of Escherichia coli cultures. To investigate the presence and global effect of these possible quorum-sensing signals other than AI-2, DNA microarrays were used to

Dacheng Ren; Laura A. Bedzyk; Rick W. Ye; Stuart M. Thomas; Thomas K. Wood

2004-01-01

64

(2) DNA O(n^5) Quorum-Sensing Lux  

E-print Network

- 1 - ( ) ( ) DNA RNA DNA RNA DNA DNA 2 DNA #12;- 2 - 17 6 (1) (2) DNA O(n^5) (3) Quorum-Sensing Lux (4) (5) LMNtal ambient LMNtal (1) (2) DNA (3) DNA (4) DNA (5) DNA (1) DNA ANP-96 (Precision System Science ) (2) RTRACS DNA RTRACS (3) in vivo in vivo (4) DNA trans cis 1/10 (5) DNA-PNA DNA DNA DNA DNA DNA

Hagiya, Masami

65

Regulation of las and rhl Quorum Sensing in Pseudomonas aeruginosa  

Microsoft Academic Search

The production of several virulence factors by Pseudomonas aeruginosa is controlled according to cell density through two quorum-sensing systems, las and rhl. The las system is comprised of the transcriptional activator protein LasR and of LasI, which directs the synthesis of the autoinducer PAI-1. Similarly, the rhl system consists of the transcriptional activator protein RhlR and of RhlI, which directs

EVERETT C. PESCI; JAMES P. PEARSON; PATRICK C. SEED; BARBARA H. IGLEWSKI

1997-01-01

66

A Quorum-Sensing-Induced Bacteriophage Defense Mechanism  

PubMed Central

ABSTRACT One of the key determinants of the size, composition, structure, and development of a microbial community is the predation pressure by bacteriophages. Accordingly, bacteria have evolved a battery of antiphage defense strategies. Since maintaining constantly elevated defenses is costly, we hypothesize that some bacteria have additionally evolved the abilities to estimate the risk of phage infection and to adjust their strategies accordingly. One risk parameter is the density of the bacterial population. Hence, quorum sensing, i.e., the ability to regulate gene expression according to population density, may be an important determinant of phage-host interactions. This hypothesis was investigated in the model system of Escherichia coli and phage ?. We found that, indeed, quorum sensing constitutes a significant, but so far overlooked, determinant of host susceptibility to phage attack. Specifically, E. coli reduces the numbers of ? receptors on the cell surface in response to N-acyl-l-homoserine lactone (AHL) quorum-sensing signals, causing a 2-fold reduction in the phage adsorption rate. The modest reduction in phage adsorption rate leads to a dramatic increase in the frequency of uninfected survivor cells after a potent attack by virulent phages. Notably, this mechanism may apply to a broader range of phages, as AHLs also reduce the risk of ? phage infection through a different receptor. PMID:23422409

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

2013-01-01

67

Quorum Sensing in the Context of Food Microbiology  

PubMed Central

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

Skandamis, Panagiotis N.

2012-01-01

68

Quorum sensing via static coupling demonstrated by Chua's circuits  

NASA Astrophysics Data System (ADS)

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 ?s), 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.

Singh, Harpartap; Parmananda, P.

2013-10-01

69

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

PubMed

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

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

2015-01-01

70

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

PubMed Central

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

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

2015-01-01

71

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

PubMed

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 ?g/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

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

2015-02-01

72

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

PubMed Central

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

2011-01-01

73

Microarray Analysis of Quorum-Sensing Regulated Gene Expression in Campylobacter jejuni  

Technology Transfer Automated Retrieval System (TEKTRAN)

Quorum-sensing (QS) is defined as cell-to-cell communication in response to population density in bacteria. Autoinducer-2 (AI-2)-dependent quorum-sensing has been shown to control a variety of cellular processes such as expression of virulence factors, toxin production, biofilm formation, and swarm...

74

Connecting Quorum Sensing, c-di-GMP, Pel Polysaccharide, and Biofilm Formation in Pseudomonas  

E-print Network

Connecting Quorum Sensing, c-di-GMP, Pel Polysaccharide, and Biofilm Formation in Pseudomonas on homoserine lactones was found to influence biofilm formation. Here we discern a mechanism by which quorum sensing controls biofilm formation by screening 5850 transposon mutants of P. aeruginosa PA14 for altered

Wood, Thomas K.

75

l-Canavanine Made by Medicago sativa Interferes with Quorum Sensing in Sinorhizobium meliloti  

PubMed Central

Sinorhizobium meliloti is a gram-negative soil bacterium, capable of establishing a nitrogen-fixing symbiosis with its legume host, alfalfa (Medicago sativa). Quorum sensing plays a crucial role in this symbiosis, where it influences the nodulation process and the synthesis of the symbiotically important exopolysaccharide II (EPS II). S. meliloti has three quorum-sensing systems (Sin, Tra, and Mel) that use N-acyl homoserine lactones as their quorum-sensing signal molecule. Increasing evidence indicates that certain eukaryotic hosts involved in symbiotic or pathogenic relationships with gram-negative bacteria produce quorum-sensing-interfering (QSI) compounds that can cross-communicate with the bacterial quorum-sensing system. Our studies of alfalfa seed exudates suggested the presence of multiple signal molecules capable of interfering with quorum-sensing-regulated gene expression in different bacterial strains. In this work, we choose one of these QSI molecules (SWI) for further characterization. SWI inhibited violacein production, a phenotype that is regulated by quorum sensing in Chromobacterium violaceum. In addition, this signal molecule also inhibits the expression of the S. meliloti exp genes, responsible for the production of EPS II, a quorum-sensing-regulated phenotype. We identified this molecule as l-canavanine, an arginine analog, produced in large quantities by alfalfa and other legumes. PMID:16321947

Keshavan, Neela D.; Chowdhary, Puneet K.; Haines, Donovan C.; González, Juan E.

2005-01-01

76

Quorum Sensing Regulates Type III Secretion in Vibrio harveyi and Vibrio parahaemolyticus  

PubMed Central

In a process known as quorum sensing, bacteria communicate with one another by producing, releasing, detecting, and responding to signal molecules called autoinducers. Vibrio harveyi, a marine pathogen, uses two parallel quorum-sensing circuits, each consisting of an autoinducer-sensor pair, to control the expression of genes required for bioluminescence and a number of other target genes. Genetic screens designed to discover autoinducer-regulated targets in V. harveyi have revealed genes encoding components of a putative type III secretion (TTS) system. Using transcriptional reporter fusions and TTS protein localization studies, we show that the TTS system is indeed functional in V. harveyi and that expression of the genes encoding the secretion machinery requires an intact quorum-sensing signal transduction cascade. The newly completed genome of the closely related marine bacterium Vibrio parahaemolyticus, which is a human pathogen, shows that it possesses the genes encoding both of the V. harveyi-like quorum-sensing signaling circuits and that it also has a TTS system similar to that of V. harveyi. We show that quorum sensing regulates TTS in V. parahaemolyticus. Previous reports connecting quorum sensing to TTS in enterohemorrhagic and enteropathogenic Escherichia coli show that quorum sensing activates TTS at high cell density. Surprisingly, we find that at high cell density (in the presence of autoinducers), quorum sensing represses TTS in V. harveyi and V. parahaemolyticus. PMID:15175293

Henke, Jennifer M.; Bassler, Bonnie L.

2004-01-01

77

Structure and Inhibition of Quorum Sensing Target from Streptococcus pneumoniae  

SciTech Connect

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-ImmA would predict equal binding, yet most analogues bind 10{sup 3}-10{sup 4}-fold more tightly to the E. coli enzyme. Catalytic site efficiency is primarily responsible for this difference since k{sub cat}/K{sub m} for S. pneumoniae MTAN is decreased 845-fold relative to that of E. coli MTAN.

Singh,V.; Shi, W.; Almo, S.; Evans, G.; Furneaux, R.; Tyler, P.; Painter, G.; Lenz, D.; Mee, S.; et al.

2006-01-01

78

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

PubMed Central

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

Rutherford, Steven T.; Bassler, Bonnie L.

2012-01-01

79

Chemical methods to interrogate bacterial quorum sensing pathways  

PubMed Central

Bacteria frequently manifest distinct phenotypes as a function of cell density in a phenomenon known as quorum sensing (QS). This intercellular signalling process is mediated by “chemical languages comprised of low-molecular weight signals, known as” autoinducers, and their cognate receptor proteins. As many of the phenotypes regulated by QS can have a significant impact on the success of pathogenic or mutualistic prokaryotic–eukaryotic interactions, there is considerable interest in methods to probe and modulate QS pathways with temporal and spatial control. Such methods would be valuable for both basic research in bacterial ecology and in practical medicinal, agricultural, and industrial applications. Toward this goal, considerable recent research has been focused on the development of chemical approaches to study bacterial QS pathways. In this Perspective, we provide an overview of the use of chemical probes and techniques in QS research. Specifically, we focus on: (1) combinatorial approaches for the discovery of small molecule QS modulators, (2) affinity chromatography for the isolation of QS receptors, (3) reactive and fluorescent probes for QS receptors, (4) antibodies as quorum “quenchers,” (5) abiotic polymeric “sinks” and “pools” for QS signals, and (6) the electrochemical sensing of QS signals. The application of such chemical methods can offer unique advantages for both elucidating and manipulating QS pathways in culture and under native conditions. PMID:22948815

Praneenararat, Thanit; Palmer, Andrew G.

2012-01-01

80

Bacterial quorum sensing and metabolic slowing in a cooperative population.  

PubMed

Acyl-homoserine lactone (AHL)-mediated quorum sensing (QS) controls the production of numerous intra- and extracellular products across many species of Proteobacteria. Although these cooperative activities are often costly at an individual level, they provide significant benefits to the group. Other potential roles for QS include the restriction of nutrient acquisition and maintenance of metabolic homeostasis of individual cells in a crowded but cooperative population. Under crowded conditions, QS may function to modulate and coordinate nutrient utilization and the homeostatic primary metabolism of individual cells. Here, we show that QS down-regulates glucose uptake, substrate level and oxidative phosphorylation, and de novo nucleotide biosynthesis via the activity of the QS-dependent transcriptional regulator QsmR (quorum sensing master regulator R) in the rice pathogen Burkholderia glumae. Systematic analysis of glucose uptake and core primary metabolite levels showed that QS deficiency perturbed nutrient acquisition, and energy and nucleotide metabolism, of individuals within the group. The QS mutants grew more rapidly than the wild type at the early exponential stage and outcompeted wild-type cells in coculture. Metabolic slowing of individuals in a QS-dependent manner indicates that QS acts as a metabolic brake on individuals when cells begin to mass, implying a mechanism by which AHL-mediated QS might have evolved to ensure homeostasis of the primary metabolism of individuals under crowded conditions. PMID:25267613

An, Jae Hyung; Goo, Eunhye; Kim, Hongsup; Seo, Young-Su; Hwang, Ingyu

2014-10-14

81

Functional Amyloids Keep Quorum-sensing Molecules in Check.  

PubMed

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

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

2015-03-01

82

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

PubMed

Quorum sensing, a group behaviour coordinated by a diffusible pheromone signal and a cognate receptor, is typical of bacteria that form symbioses with plants and animals. LuxIR-type N-acyl L-homoserine (AHL) quorum sensing is common in Gram-negative Proteobacteria, and many members of this group have additional quorum-sensing networks. The bioluminescent symbiont Vibrio fischeri encodes two AHL signal synthases: AinS and LuxI. AinS-dependent quorum sensing converges with LuxI-dependent quorum sensing at the LuxR regulatory element. Both AinS- and LuxI-mediated signalling are required for efficient and persistent colonization of the squid host, Euprymna scolopes. The basis of the mutualism is symbiont bioluminescence, which is regulated by both LuxI- and AinS-dependent quorum sensing, and is essential for maintaining a colonization of the host. Here, we used chemical and genetic approaches to probe the dynamics of LuxI- and AinS-mediated regulation of bioluminescence during symbiosis. We demonstrate that both native AHLs and non-native AHL analogues can be used to non-invasively and specifically modulate induction of symbiotic bioluminescence via LuxI-dependent quorum sensing. Our data suggest that the first day of colonization, during which symbiont bioluminescence is induced by LuxIR, is a critical period that determines the stability of the V.?fischeri population once symbiosis is established. PMID:24191970

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

2014-08-01

83

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

PubMed Central

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

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

2012-01-01

84

Small Molecule Inhibitors of AI-2 Signaling in Bacteria: State-of-the-Art and Future Perspectives for Anti-Quorum Sensing Agents  

PubMed Central

Bacteria respond to different small molecules that are produced by other neighboring bacteria. These molecules, called autoinducers, are classified as intraspecies (i.e., molecules produced and perceived by the same bacterial species) or interspecies (molecules that are produced and sensed between different bacterial species). AI-2 has been proposed as an interspecies autoinducer and has been shown to regulate different bacterial physiology as well as affect virulence factor production and biofilm formation in some bacteria, including bacteria of clinical relevance. Several groups have embarked on the development of small molecules that could be used to perturb AI-2 signaling in bacteria, with the ultimate goal that these molecules could be used to inhibit bacterial virulence and biofilm formation. Additionally, these molecules have the potential to be used in synthetic biology applications whereby these small molecules are used as inputs to switch on and off AI-2 receptors. In this review, we highlight the state-of-the-art in the development of small molecules that perturb AI-2 signaling in bacteria and offer our perspective on the future development and applications of these classes of molecules. PMID:23994835

Guo, Min; Gamby, Sonja; Zheng, Yue; Sintim, Herman O.

2013-01-01

85

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

PubMed

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

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

2014-01-01

86

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

PubMed Central

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

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

2014-01-01

87

Synchronization and quorum sensing in a swarm of humanoid robots  

E-print Network

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

Bechon, Patrick

2012-01-01

88

Bacterial Autoinducer-2 Detection via an Engineered Quorum Sensing Protein.  

PubMed

Autoinducer-2 (AI-2) is a Quorum Sensing (QS) molecule utilized by bacteria in interspecies communication. More recently, it is identified to be vital in regulating QS pathways in a number of human and foodborne pathogens. Methods to detect AI-2 in a rapid and highly sensitive manner can help in the early detection of bacterial infections. Herein, we describe a rapid, selective, and highly sensitive protein based biosensing system employing the Fluorescence Resonance Energy Transfer (FRET) between a protein fusion LuxP-EGFP and 7-diethylamino-3-[N-(2-maleimidoethyl)carbamoyl]coumarin (MDCC). The developed biosensing system, which can detect AI-2 at subnanomolar levels, was successfully applied to detect AI-2 in clinical samples such as saliva and blood serum. PMID:25654248

Raut, Nilesh; Joel, Smita; Pasini, Patrizia; Daunert, Sylvia

2015-03-01

89

The use of quorum sensing to improve vaccine immune response.  

PubMed

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

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

2013-12-17

90

Modulating Vibrio cholerae Quorum-Sensing-Controlled Communication Using Autoinducer-Loaded Nanoparticles.  

PubMed

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. PMID:25651002

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

91

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

PubMed Central

Bacteria deploy a range of chemistries to regulate their behaviour and respond to their environment. Quorum sensing is one mean by which bacteria use chemical reactions to modulate pre-infection behaviour such as surface attachment. Polymers that can interfere with bacterial adhesion or the chemical reactions used for quorum sensing are thus a potential means to control bacterial population responses. Here we report how polymeric “bacteria sequestrants”, designed to bind to bacteria through electrostatic interactions and thus 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 characterise the feedback between bacteria clustering and quorum sensing signaling. We have also derived design principles and chemical strategies for controlling bacterial behaviour at the population level. PMID:24256871

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

2014-01-01

92

Active regulation of receptor ratios controls integration of quorum-sensing signals in Vibrio harveyi  

PubMed Central

Quorum sensing is a chemical signaling mechanism used by bacteria to communicate and orchestrate group behaviors. Multiple feedback loops exist in the quorum-sensing circuit of the model bacterium Vibrio harveyi. Using fluorescence microscopy of individual cells, we assayed the activity of the quorum-sensing circuit, with a focus on defining the functions of the feedback loops. We quantitatively investigated the signaling input–output relation both in cells with all feedback loops present as well as in mutants with specific feedback loops disrupted. We found that one of the feedback loops regulates receptor ratios to control the integration of multiple signals. Together, the feedback loops affect the input–output dynamic range of signal transmission and the noise in the output. We conclude that V. harveyi employs multiple feedback loops to simultaneously control quorum-sensing signal integration and to ensure signal transmission fidelity. PMID:21613980

Teng, Shu-Wen; Schaffer, Jessica N; Tu, Kimberly C; Mehta, Pankaj; Lu, Wenyun; Ong, N P; Bassler, Bonnie L; Wingreen, Ned S

2011-01-01

93

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

PubMed

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

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

2013-06-01

94

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

NASA Astrophysics Data System (ADS)

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.

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

95

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

PubMed Central

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

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

2015-01-01

96

BACTERIAL ATTRACTION AND QUORUM SENSING INHIBITION IN CAENORHABDITIS ELEGANS EXUDATES  

PubMed Central

Caenorhabditis elegans, a bacterivorous nematode, lives in complex rotting fruit, soil, and compost environments, and chemical interactions are required for mating, monitoring population density, recognition of food, avoidance of pathogenic microbes, and other essential ecological functions. Despite being one of the best-studied model organisms in biology, relatively little is known about the signals that C. elegans uses to chemically interact with its environment or as defense. C. elegans exudates were analyzed using several analytical methods and found to contain 36 common metabolites including organic acids, amino acids and sugars, all in relatively high abundance. Furthermore, the concentrations of amino acids in the exudates were dependent on developmental stage. The C. elegans exudates were tested for bacterial chemotaxis using Pseudomonas putida (KT2440), a plant growth promoting rhizobacterium, Pseudomonas aeruginosa (PAO1), a soil bacterium pathogenic to C. elegans, and E. coli (OP50), a non-motile bacterium tested as a control. The C. elegans exudates attracted the two Psuedomonas species, but had no detectable antibacterial activity against P. aeruginosa. To our surprise, the exudates of young adult and adult life stages of C. elegans exudates inhibited quorum sensing in the reporter system based on the LuxR bacterial quorum sensing (QS) system, which regulates bacterial virulence and other factors in Vibrio fischeri. We were able to fractionate the QS inhibition and bacterial chemotaxis activities, demonstrating that these activities are chemically distinct. Our results demonstrate that C. elegans can attract its bacterial food and has the potential of partially regulating the virulence of bacterial pathogens by inhibiting specific QS systems. PMID:19649780

KAPLAN, FATMA; BADRI, DAYAKAR V.; ZACHARIAH, CHERIAN; AJREDINI, RAMADAN; SANDOVAL, FRANCISCO J; ROJE, SANJA; LEVINE, LANFANG H.; ZHANG, FENGLI; ROBINETTE, STEVEN L.; ALBORN, HANS T.; ZHAO, WEI; STADLER, MICHAEL; NIMALENDRAN, RATHIKA; DOSSEY, AARON T.; BRÜSCHWEILER, RAFAEL; VIVANCO, JORGE M.; EDISON, ARTHUR S.

2014-01-01

97

Three Parallel Quorum-Sensing Systems Regulate Gene Expression in Vibrio harveyi  

Microsoft Academic Search

In a process called quorum sensing, bacteria communicate using extracellular signal molecules termed auto- inducers. Two parallel quorum-sensing systems have been identified in the marine bacterium Vibrio harveyi. System 1 consists of the LuxM-dependent autoinducer HAI-1 and the HAI-1 sensor, LuxN. System 2 consists of the LuxS-dependent autoinducer AI-2 and the AI-2 detector, LuxPQ. The related bacterium, Vibrio cholerae, a

Jennifer M. Henke; Bonnie L. Bassler

2004-01-01

98

Genetic control of quorum-sensing signal turnover in Agrobacterium tumefaciens  

Microsoft Academic Search

A signal turnover system is an essential component of many genetic regulatory mechanisms. The best-known example is the ubiquitin-dependent protein degradation system that exists in many organisms. We found that Agrobacterium tumefaciens adopts a unique signal turnover system to control exiting from a quorum-sensing mode. A. tumefaciens regulates Ti plasmid conjugal transfer by a quorum-sensing signal, N-3-oxo-octanoyl homoserine lactone (3OC8HSL),

Hai-Bao Zhang; Lian-Hui Wang; Lian-Hui Zhang

2002-01-01

99

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

Microsoft Academic Search

Cell-density-dependent gene expression appears to be widely spread in bacteria. This quorum-sensing phenomenon has been well established in Gram-negative bacteria, where N-acyl homoserine lactones are the diffusible communication molecules that modulate cell-density-dependent phenotypes. Similarly, a variety of processes are known to be regulated in a cell-density- or growth-phase-dependent manner in Gram-positive bacteria. Examples of such quorum-sensing modes in Gram-positive bacteria

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

1997-01-01

100

A mathematical model of quorum sensing in a growing bacterial biofilm  

Microsoft Academic Search

  In a process called quorum sensing, bacteria monitor their population density via extracellular signaling molecules and modulate gene expression accordingly. This paper describes a one-dimensional model\\u000a of a growing Pseudomonas aeruginosa biofilm. Quorum sensing has been included in the model by the addition of equations describing the production, degradation,\\u000a and diffusion of acyl-homoserine lactones in the biofilm. In order for

D L Chopp; M J Kirisits; B Moran; M R Parsek

2002-01-01

101

Contribution of quorum-sensing systems to virulence of Pseudomonas aeruginosa in an experimental pyelonephritis model  

Microsoft Academic Search

Background and Purpose: Pseudomonas aeruginosa has been reported to monitor its cell density as well as expression of virulence determinants by quorum-sensing signal mechanisms operative through autoinducers. In the present investigation, we studied the contribution of quorum-sensing signals during the course of P. aeruginosa- induced pyelonephritis in mice. Methods: The standard parent strain of P. aeruginosa (PAO1), possessing functional las

Rahul Mittal; Saroj Sharma; Sanjay Chhibber; Kusum Harjai

2006-01-01

102

DNA Microarray-Based Identification of Genes Controlled by Autoinducer 2Stimulated Quorum Sensing in Escherichia coli  

Microsoft Academic Search

Bacterial cell-to-cell communication facilitates coordinated expression of specific genes in a growth rate-II and cell density-dependent manner, a process known as quorum sensing. While the discovery of a diffusible Escherichia coli signaling pheromone, termed autoinducer 2 (AI-2), has been made along with several quorum sensing genes, the overall number and coordination of genes controlled by quorum sensing through the AI-2

MATTHEW P. DELISA; CHI-FANG WU; LIANG WANG; JAMES J. VALDES; WILLIAM E. BENTLEY

2001-01-01

103

Siamycin Attenuates fsr Quorum Sensing Mediated by a Gelatinase Biosynthesis-Activating Pheromone in Enterococcus faecalis?  

PubMed Central

The expression of two Enterococcus faecalis virulence-related proteases, gelatinase (GelE) and serine protease (SprE), is positively regulated by a quorum-sensing system encoded by the fsr gene cluster. In this system, E. faecalis secretes an autoinducing peptide, gelatinase biosynthesis-activating pheromone (GBAP), which triggers the FsrC-FsrA two-component regulatory system controlling the expression of two transcripts, fsrBDC and gelE-sprE. In the present study, we screened actinomycete metabolites for inhibitors of fsr quorum sensing. E. faecalis was cultured with each actinomycete culture supernatant tested, and the production of gelatinase and the production of GBAP were examined using the first screening and the second screening, respectively. Culture supernatant of Streptomyces sp. strain Y33-1 had the most potent inhibitory effect on both gelatinase production and GBAP production without inhibiting E. faecalis cell growth. The inhibitor in the culture supernatant was identified as a known peptide antibiotic, siamycin I. Siamycin I inhibited both gelatinase production and GBAP production at submicromolar concentrations, and it inhibited E. faecalis cell growth at concentrations above micromolar concentrations. Quantitative analysis of fsrBDC and gelE-sprE transcripts revealed that siamycin I suppressed the expression of both transcripts at a sublethal concentration. Siamycin I attenuated gelatinase production even when an overdose of GBAP was exogenously added to the culture. These results suggested that siamycin I inhibited the GBAP signaling via the FsrC-FsrA two-component regulatory system in a noncompetitive manner. The sublethal concentrations of siamycin I also attenuated biofilm formation. Treatment with siamycin could be a novel means of treating enterococcal infections. PMID:17071762

Nakayama, Jiro; Tanaka, Emi; Kariyama, Reiko; Nagata, Koji; Nishiguchi, Kenzo; Mitsuhata, Ritsuko; Uemura, Yumi; Tanokura, Masaru; Kumon, Hiromi; Sonomoto, Kenji

2007-01-01

104

Cooperation, Quorum Sensing, and Evolution of Virulence in Staphylococcus aureus  

PubMed Central

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

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

2014-01-01

105

Quorum sensing regulatory cascades control Vibrio fluvialis pathogenesis.  

PubMed

Quorum sensing (QS) is a process by which individual bacteria are able to communicate with one another, thereby enabling the population as a whole to coordinate gene regulation and subsequent phenotypic outcomes. Communication is accomplished through production and detection of small molecules in the extracellular milieu. In many bacteria, particularly Vibrio species, multiple QS systems result in multiple signals, as well as cross talk between systems. In this study, we identify two QS systems in the halophilic enteric pathogen Vibrio fluvialis: one acyl-homoserine lactone (AHL) based and one CAI-1/AI-2 based. We show that a LuxI homolog, VfqI, primarily produces 3-oxo-C10-HSL, which is sensed by a LuxR homolog, VfqR. VfqR-AHL is required to activate vfqI expression and autorepress vfqR expression. In addition, we have shown that similar to that in V. cholerae and V. harveyi, V. fluvialis produces CAI-1 and AI-2 signal molecules to activate the expression of a V. cholerae HapR homolog through LuxO. Although VfqR-AHL does not regulate hapR expression, HapR can repress vfqR transcription. Furthermore, we found that QS in V. fluvialis positively regulates production of two potential virulence factors, an extracellular protease and hemolysin. QS also affects cytotoxic activity against epithelial tissue cultures. These data suggest that V. fluvialis integrates QS regulatory pathways to play important physiological roles in pathogenesis. PMID:23749976

Wang, Yunduan; Wang, Hui; Liang, Weili; Hay, Amanda J; Zhong, Zengtao; Kan, Biao; Zhu, Jun

2013-08-01

106

Reversible non-genetic phenotypic heterogeneity in bacterial quorum sensing.  

PubMed

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. PMID:24601980

Pradhan, Binod B; Chatterjee, Subhadeep

2014-05-01

107

Evaluation of anti-quorum sensing activity of silver nanowires.  

PubMed

A menace of antimicrobial resistance with growing difficulties in eradicating clinical pathogens owing to the biofilm has prompted us to take up a facile aqueous-phase approach for the synthesis of silver nanowires (SNWs) by using ethylene glycol as a reducing agent and polyvinylpyrrolidone (PVP) as a capping agent. This synthesis is a reflux reaction seedless process. The obtained SNWs were about 200-250 nm in diameter and up to 3-4 ?m in length. The SNWs were characterized by field emission scanning electron microscopy, transmission electron microscopy, UV-Vis spectroscopy, and X-Ray powder diffraction, and the chemical composition of the sample was examined by energy dispersive X-ray spectrum. The SNWs did not show an antibacterial activity against test organisms, Bacillus subtilis NCIM 2063 and Escherichia coli NCIM 2931; however, it showed a promising property of a quorum sensing-mediated inhibition of biofilm in Pseudomonas aeruginosa NCIM 2948 and violacein synthesis in Chromobacterium violaceum ATCC 12472, which is hitherto unattempted, by polyol approach. PMID:23224498

Wagh Nee Jagtap, Mohini S; Patil, Rajendra H; Thombre, Deepali K; Kulkarni, Milind V; Gade, Wasudev N; Kale, Bharat B

2013-04-01

108

Bacterial quorum sensing and nitrogen cycling in rhizosphere soil  

SciTech Connect

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.

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

2008-10-01

109

Quorum Sensing in Some Representative Species of Halomonadaceae  

PubMed Central

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

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

2013-01-01

110

Identification of quorum sensing-controlled genes in Burkholderia ambifaria.  

PubMed

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

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

2013-04-01

111

Functions and regulation of quorum-sensing in Agrobacterium tumefaciens  

PubMed Central

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

Lang, Julien; Faure, Denis

2014-01-01

112

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

PubMed Central

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

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

2013-01-01

113

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

PubMed

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

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

114

Type 2 quorum sensing monitoring, inhibition and biofilm formation in marine microrganisms.  

PubMed

The quorum sensing (QS) dependent behaviour of micro-organisms, in particular expression of virulence genes, biofilm formation and dispersal, have provided impetus for investigating practical approaches to interfere with microbial QS. This study tests Halomonas pacifica and Marinobacter hydrocarbonoclasticus, two halophilic marine micro-organism, for their AI-2 dependent QS signalling and the effect of two well-known quorum-sensing inhibitors (QSIs), patulin and penicillic acid, on biofilm formation. We report, for the first time, the successful amplification of a putative luxS gene in H. pacifica using degenerated primers and AI-2 dependent QS as well as inhibition using QSIs. Penicillic acid had a strong inhibitory effect on AI-2 induction of H. pacifica at non-growth inhibitory concentrations, while patulin has an adverse effect only at the highest concentration (25 ?M). QSIs effect on biofilm forming capability was isolate specific, with maximum inhibition at 25 ?M of patulin in H. pacifica. In M. hydrocarbonoclasticus, no adverse effects were noted at any tested concentration of either QSIs. Detection of bioluminescence and the presence of a putative luxS gene provide biochemical and genetic evidence for the production of a signalling molecule(s) which is the essential first step in characterizing H. pacifica QS. This study highlights the importance of AI-2 dependent QS in a marine setting, not previously reported. It further suggests that QSI compounds must be selected in the specific system in which they are to function, and they cannot easily be transferred from one QS system to another. PMID:24166155

Liaqat, Iram; Bachmann, Robert Thomas; Edyvean, Robert G J

2014-03-01

115

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

116

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

PubMed Central

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

Paul, Diby

2014-01-01

117

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

PubMed

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

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

2014-01-01

118

Influence of polyphenols on bacterial biofilm formation and quorum-sensing.  

PubMed

Many bacteria utilize sophisticated regulatory systems to ensure that some functions are only expressed when a particular population density has been reached. The term 'quorum-sensing' has been coined to describe this form of density-dependent gene regulation which relies on the production and perception of small signal molecules by bacterial cells. As in many pathogenic bacteria the production of virulence factors is quorum-sensing regulated, it has been suggested that this form of gene regulation allows the bacteria to remain invisible to the defence systems of the host until the population is sufficiently large to successfully establish the infection. Here we present first evidence that polyphenolic compounds can interfere with bacterial quorum-sensing. Since polyphenols are widely distributed in the plant kingdom, they may be important for promoting plant fitness. PMID:14713169

Huber, Birgit; Eberl, Leo; Feucht, Walter; Polster, Jürgen

2003-01-01

119

Increased colonization of indwelling medical devices by quorum-sensing mutants of Staphylococcus epidermidis in vivo.  

PubMed

Infections with the leading nosocomial pathogen Staphylococcus epidermidis are characterized by biofilm development on indwelling medical devices. We demonstrate that the quorum-sensing regulator agr affects the biofilm development of S. epidermidis in an unexpected fashion and is likely involved in promoting biofilm detachment. An isogenic agr mutant showed increased biofilm development and colonization in a rabbit model. In addition, nonfunctional agr occurred more frequently among strains isolated from infections of joint prostheses. Lack of functionality was based on mutations, including insertion of an IS256 element. Relative to other bacterial pathogens, quorum sensing in S. epidermidis thus has a different role during biofilm development and biofilm-associated infection. Our results indicate that disabling agr likely enhances the success of S. epidermidis during infection of indwelling medical devices. The permanent elimination of quorum-sensing regulation used by S. epidermidis represents a surprising and unusual means to adapt to a certain environment and type of infection. PMID:15378444

Vuong, Cuong; Kocianova, Stanislava; Yao, Yufeng; Carmody, Aaron B; Otto, Michael

2004-10-15

120

Quorum Sensing Controls Flagellar Morphogenesis in Burkholderia glumae  

PubMed Central

Burkholderia glumae is a motile plant pathogenic bacterium that has multiple polar flagella and one LuxR/LuxI-type quorum sensing (QS) system, TofR/TofI. A QS-dependent transcriptional regulator, QsmR, activates flagellar master regulator flhDC genes. FlhDC subsequently activates flagellar gene expression in B. glumae at 37°C. Here, we confirm that the interplay between QS and temperature is critical for normal polar flagellar morphogenesis in B. glumae. In the wild-type bacterium, flagellar gene expression and flagellar number were greater at 28°C compared to 37°C. The QS-dependent flhC gene was significantly expressed at 28°C in two QS-defective (tofI::? and qsmR::?) mutants. Thus, flagella were present in both tofI::? and qsmR::? mutants at 28°C, but were absent at 37°C. Most tofI::? and qsmR::? mutant cells possessed polar or nonpolar flagella at 28°C. Nonpolarly flagellated cells processing flagella around cell surface of both tofI::? and qsmR::? mutants exhibited tumbling and spinning movements. The flhF gene encoding GTPase involved in regulating the correct placement of flagella in other bacteria was expressed in QS mutants in a FlhDC-dependent manner at 28°C. However, FlhF was mislocalized in QS mutants, and was associated with nonpolar flagellar formation in QS mutants at 28°C. These results indicate that QS-independent expression of flagellar genes at 28°C allows flagellar biogenesis, but is not sufficient for normal polar flagellar morphogenesis in B. glumae. Our findings demonstrate that QS functions together with temperature to control flagellar morphogenesis in B. glumae. PMID:24416296

Jang, Moon Sun; Goo, Eunhye; An, Jae Hyung; Kim, Jinwoo; Hwang, Ingyu

2014-01-01

121

[Construct a molecular switch based on bacterial quorum sensing].  

PubMed

Engineering the existing or manual assembling biosynthetic pathways involves two important issues: the activity and expression level of key enzymes in the pathway. Concerning the enzyme expression study, the conventional approach is to use strong promoter to initiate the overexpression of the target protein. The excessive expression of the target protein usually result in the intracellular accumulation of a large number of inactive inclusion bodies, thereby seriously affect the physiological state of the cell and the effective functioning of the relevant biological pathways. To solve this problem, we would like to design a molecular switch to precisely manipulate the expression level of key enzymes in the biosynthetic process, which has important practical value for the study of metabolic rhythm of the biosynthetic pathway and to promote the efficiency of the biosynthetic pathway. Based on the basic principles of quorum sensing existing in the bacterial community and combining the dynamic characteristics of the enzymatic catalysis, we first established cell-cell communication mechanisms mediated by signal molecule homoserine lactone (AHL) in the E. coli community and target protein EGFP was expressed under the control of the promoter P(lux1). In the process of cell growth, AHL accumulated to a certain concentration to start the expression of target gene egfp. At the different cell growth stages, AHL-degrading enzyme AiiA was induced and resulted in the degradation of AHL molecule in a controlled environment, thereby controlling the transcription efficiency of target gene egfp and ultimately achieve the precise control of the level of expression of the target protein EGFP. The detection of cell growth state, the mRNA level and protein expression level of the target gene showed the artificially designed molecular switch can control the level of expression of a target gene in a convenient and efficient manner with a spatial and temporal regulation of rigor. The molecular switch is expected to be widely used in the field of metabolic engineering and synthetic biology research areas. PMID:24409693

Zhang, Zhiwei; Wu, Sheng

2013-09-01

122

Anti-quorum sensing potential of Adenanthera pavonina  

PubMed Central

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

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

2015-01-01

123

Assessment of Anti-Quorum Sensing Activity for Some Ornamental and Medicinal Plants Native to Egypt  

PubMed Central

This study investigated the effects of some plant extracts on the bacterial communication system, expressed as quorum sensing (QS) activity. Quorum sensing has a directly proportional effect on the amount of certain compounds, such as pigments, produced by the bacteria. Alcohol extracts of 23 ornamental and medicinal plants were tested for anti-QS activity by the Chromobacterium violaceum assay using the agar cup diffusion method. The screening revealed the anti-QS activity of six plants; namely the leaves of Adhatoda vasica Nees, Bauhinia purpurea L., Lantana camara L., Myoporum laetum G. Forst.; the fruits of Piper longum L.; and the aerial parts of Taraxacum officinale F.H. Wigg. PMID:23641343

Zaki, Ahmed A.; Shaaban, Mona I.; Hashish, Nadia E.; Amer, Mohamed A.; Lahloub, Mohamed-Farid

2013-01-01

124

Assessment of anti-quorum sensing activity for some ornamental and medicinal plants native to egypt.  

PubMed

This study investigated the effects of some plant extracts on the bacterial communication system, expressed as quorum sensing (QS) activity. Quorum sensing has a directly proportional effect on the amount of certain compounds, such as pigments, produced by the bacteria. Alcohol extracts of 23 ornamental and medicinal plants were tested for anti-QS activity by the Chromobacterium violaceum assay using the agar cup diffusion method. The screening revealed the anti-QS activity of six plants; namely the leaves of Adhatoda vasica Nees, Bauhinia purpurea L., Lantana camara L., Myoporum laetum G. Forst.; the fruits of Piper longum L.; and the aerial parts of Taraxacum officinale F.H. Wigg. PMID:23641343

Zaki, Ahmed A; Shaaban, Mona I; Hashish, Nadia E; Amer, Mohamed A; Lahloub, Mohamed-Farid

2013-03-01

125

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

PubMed Central

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

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

2014-01-01

126

Whole-Genome Analysis of Aeromonas hydrophila Strain 187, Exhibiting Quorum-Sensing Activity  

PubMed Central

Aeromonas hydrophila is a quorum-sensing (QS) bacterium that causes diarrhea in humans upon infection. Here, we report the genome of pathogenic Aeromonas hydrophila strain 187, which possesses a QS gene responsible for signaling molecule N-acyl homoserine lactone (AHL) synthesis and has been found to be located at contig 36. PMID:25540357

Chan, Xin-Yue; Chua, Kek Heng; Yin, Wai-Fong; Puthucheary, S. D.

2014-01-01

127

Natural Genome Diversity of AI-2 Quorum Sensing in Escherichia coli: Conserved Signal Production but Labile  

E-print Network

Natural Genome Diversity of AI-2 Quorum Sensing in Escherichia coli: Conserved Signal Production an important impact in virulence. Autoinducer-2 (AI-2) is a signal that has the peculiarity of mediating both intra- and interspecies bacterial QS. We analyzed the diversity of all components of AI-2 QS across 44

Gordo, Isabel

128

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

PubMed

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

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

2015-01-01

129

Whole-Genome Sequence of Quorum-Sensing Vibrio tubiashii Strain T33  

PubMed Central

Vibrio tubiashii strain T33 was isolated from the coastal waters of Morib, Malaysia, and was shown to possess quorum-sensing activity similar to that of its famous relative Vibrio fischeri. Here, the assembly and annotation of its genome are presented. PMID:25555738

Izzati Mohamad, Nur; Yin, Wai-Fong

2015-01-01

130

Nickel and cadmium ions inhibit quorum sensing and biofilm formation without affecting viability in Burkholderia multivorans  

E-print Network

Nickel and cadmium ions inhibit quorum sensing and biofilm formation without affecting viability transcriptase polymerase chain reaction (q-PCR) assays, we show that sub-millimolar concentrations of nickel (Ni2þ ) and cadmium (Cd2þ ) inhibit biofilm formation by the bacterium Burkholderia multivorans through

Alvarez, Pedro J.

131

Transcriptional control of the quorum sensing response in yeastw Arthur Wuster* and M. Madan Babu*  

E-print Network

analysis upon deletion and over-expression of transcriptional factors, we predict CAT8 and MIG1 as keyTranscriptional control of the quorum sensing response in yeastw Arthur Wuster* and M. Madan Babu transcriptional regulators that control the differential expression of the genes affected by aromatic alcohol

Babu, M. Madan

132

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

PubMed Central

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

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

2015-01-01

133

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

PubMed Central

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

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

2015-01-01

134

LuxU connects quorum sensing to biofilm formation in Vibrio fischeri  

E-print Network

LuxU connects quorum sensing to biofilm formation in Vibrio fischeri Valerie A. Ray and Karen L, USA. Summary Biofilm formation by Vibrio fischeri is a complex process involving multiple regulators polysaccha- ride (syp) locus. To identify other regulators of biofilm formation in V. fischeri, we screened

McFall-Ngai, Margaret

135

Visualizing Bacteria Quorum Sensing Maria Schwarz, Daniela Romano and Marian Gheorghe1  

E-print Network

Visualizing Bacteria Quorum Sensing Maria Schwarz, Daniela Romano and Marian Gheorghe1 12 Abstract. Large populations of bacteria communicate by sending into the environment some specific signalling is presented in [1]. Bacteria use QS to coordinate different behaviours. For example the light emission

Romano, Daniela

136

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

PubMed Central

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 ?agr 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 ?agr 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 S. aureus to promote host defense while sparing agr signaling in S. epidermidis and limiting resistance development. PMID:24945495

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

137

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

PubMed

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. PMID:25448450

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

138

Thiolactone modulators of quorum sensing revealed through library design and screening  

PubMed Central

Quorum sensing (QS) is a process by which bacteria use small molecules or peptidic signals to assess their local population densities. At sufficiently high density, bacteria can alter gene expression levels to regulate group behaviors involved in a range of important and diverse phenotypes, including virulence factor production, biofilm formation, root nodulation, and bioluminescence. Gram-negative bacteria most commonly use N-acylated L-homoserine lactones (AHLs) as their QS signals. The AHL lactone ring is hydrolyzed relatively rapidly at biological pH, and the ring-opened product is QS inactive. We seek to identify AHL analogues with heightened hydrolytic stability, and thereby potentially heightened activity, for use as non-native modulators of bacterial QS. As part of this effort, we probed the utility of thiolactone analogues in the current study as QS agonists and antagonists in Gram-negative bacteria. A focused library of thiolactone analogs was designed and rapidly synthesized in solution. We examined the activity of the library as agonists and antagonists of LuxR-type QS receptors in Pseudomonas aeruginosa (LasR), Vibrio fischeri (LuxR), and Agrobacterium tumefaciens (TraR) using bacterial reporter strains. The thiolactone library contained several highly active compounds, including some of the most active LuxR inhibitors and the most active synthetic TraR agonist reported to date. Analysis of a representative thiolactone analog revealed that its hydrolysis half-life was almost double that of its parent AHL in bacterial growth medium. PMID:21798746

McInnis, Christine E.; Blackwell, Helen E.

2011-01-01

139

Specificity grouping of the accessory gene regulator quorum-sensing system of Staphylococcus epidermidis is linked to infection.  

PubMed

Staphylococcus epidermidis represents the most frequent pathogen involved in nosocomial infections and infections of indwelling medical devices. The strain-to-strain variation of the gene encoding the quorum-sensing pheromone of S. epidermidis as well as the correlation between specificity groups and origin from infection were determined. The pro-pheromone gene was highly conserved and showed infrequent, non-synonymous, single-nucleotide polymorphisms that led to conservative amino acid exchanges only. Importantly, one specificity group was significantly more frequent among strains isolated from infection. The finding that quorum-sensing specificity groups are linked to infection demonstrates the relevance of quorum-sensing for virulence in this critical human pathogen and contributes to the scientific basis needed for the development of quorum-sensing-targeting drugs. PMID:14714104

Carmody, A B; Otto, Michael

2004-03-01

140

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

SciTech Connect

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.

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

2006-01-01

141

Quorum-Sensing Dysbiotic Shifts in the HIV-Infected Oral Metabiome  

PubMed Central

We implemented a Systems Biology approach using Correlation Difference Probability Network (CDPN) analysis to provide insights into the statistically significant functional differences between HIV-infected patients and uninfected individuals. The analysis correlates bacterial microbiome (“bacteriome”), fungal microbiome (“mycobiome”), and metabolome data to model the underlying biological processes comprising the Human Oral Metabiome. CDPN highlights the taxa-metabolite-taxa differences between the cohorts that frequently capture quorum-sensing modifications that reflect communication disruptions in the dysbiotic HIV cohort. The results also highlight the significant role of cyclic mono and dipeptides as quorum-sensing (QS) mediators between oral bacteria and fungal genus. The developed CDPN approach allowed us to model the interactions of taxa and key metabolites, and hypothesize their possible contribution to the etiology of Oral Candidiasis (OC). PMID:25886290

Brown, Robert E.; Ghannoum, Mahmoud A.; Mukherjee, Pranab K.; Gillevet, Patrick M.; Sikaroodi, Masoumeh

2015-01-01

142

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

PubMed Central

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

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

2014-01-01

143

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

PubMed

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. PMID:24823895

Rampioni, Giordano; Leoni, Livia; Williams, Paul

2014-08-01

144

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

PubMed Central

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

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

2012-01-01

145

Chromosomal Arrangement of AHL-Driven Quorum Sensing Circuits in Pseudomonas  

PubMed Central

Pseudomonas spp. are able to colonize a large variety of environments due to their wide adaptability which is also associated with an N-acyl homoserine lactone (AHL) gene regulation mechanism called quorum sensing (QS). In this article we present a systematic overview of the genomic arrangement patterns of quorum sensing genes found in Pseudomonas and compare the topologies with those found in other bacterial genomes. We find that the topological arrangement of QS genes is more variable than previously thought but there are a few unifying features that occur in many of the topological arrangements. We hypothesize that the negative regulators of QS that are often found between the canonical luxR/ and luxI-family genes may be crucial for stabilizing the output of QS circuits. PMID:23724324

Gelencsér, Zsolt; Galbáts, Borisz; Gonzalez, Juan F.; Choudhary, K. Sonal; Hudaiberdiev, Sanjarbek; Venturi, Vittorio; Pongor, Sándor

2012-01-01

146

Dynamical quorum-sensing in oscillators coupled through an external medium  

PubMed Central

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 BZ catalytic particles as well as synthetically engineered bacteria. PMID:23087494

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

2012-01-01

147

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

PubMed

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. PMID:25716005

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

148

Regulation of Uptake and Processing of the Quorum-Sensing Autoinducer AI2 in Escherichia coli  

Microsoft Academic Search

AI-2 is a quorum-sensing signaling molecule proposed to be involved in interspecies communication. In Escherichia coli and Salmonella enterica serovar Typhimurium, extracellular AI-2 accumulates in exponential phase, but the amount decreases drastically upon entry into stationary phase. In S. enterica serovar Typhi- murium, the reduction in activity is due to import and processing of AI-2 by the Lsr transporter. We

Karina B. Xavier; Bonnie L. Bassler

2005-01-01

149

Siamycin Attenuates fsr Quorum Sensing Mediated by a Gelatinase Biosynthesis-Activating Pheromone in Enterococcus faecalis  

Microsoft Academic Search

The expression of two Enterococcus faecalis virulence-related proteases, gelatinase (GelE) and serine protease (SprE), is positively regulated by a quorum-sensing system encoded by the fsr gene cluster. In this system, E. faecalis secretes an autoinducing peptide, gelatinase biosynthesis-activating pheromone (GBAP), which trig- gers the FsrC-FsrA two-component regulatory system controlling the expression of two transcripts, fsrBDC and gelE-sprE. In the present

Jiro Nakayama; Emi Tanaka; Reiko Kariyama; Koji Nagata; Kenzo Nishiguchi; Ritsuko Mitsuhata; Yumi Uemura; Masaru Tanokura; Hiromi Kumon; Kenji Sonomoto

2007-01-01

150

Quorum Sensing as a Target for Novel Biocontrol Strategies Directed at Pectobacterium  

Microsoft Academic Search

\\u000a Members of the species Pectobacterium carotovorum and P. atrosepticum are pathogenic bacteria that are responsible for tissue maceration on various host plants. Pathogenicity essentially relies\\u000a upon the production of plant cell wall degradation enzymes, the synthesis of which is regulated in a bacterial cell density\\u000a dependent fashion, a process called quorum sensing (QS). This process involves key low molecular weight

Amélie Cirou; Stéphane Uroz; Emilie Chapelle; Xavier Latour; Nicole Orange; Denis Faure; Yves Dessaux

151

Pseudomonas aeruginosa activates the quorum sensing LuxR response regulator through secretion of 2-aminoacetophenone.  

PubMed

In this study we identify a volatile compound produced by Pseudomonas aeruginosa, which can specifically activate the LuxR quorum-sensing response regulator of Vibrio fischeri. Comparative gas-chromatography analysis between P. aeruginosa wild type and a ?lasR mutant strain implied that the active volatile is 2-aminoacetophenone. The use of synthetic 2-aminoacetophenone and in silico docking analyses verified the activity of the molecule and provided putative interacting residues within the binding site. PMID:25614099

Kviatkovski, I; Chernin, L; Yarnitzky, T; Frumin, I; Sobel, N; Helman, Y

2015-02-01

152

Quorum-Sensing-Negative (lasR) Mutants of Pseudomonas aeruginosa Avoid Cell Lysis and Death  

Microsoft Academic Search

In Pseudomonas aeruginosa, N-acylhomoserine lactone signals regulate the expression of several hundreds of genes, via the transcriptional regulator LasR and, in part, also via the subordinate regulator RhlR. This regulatory network termed quorum sensing contributes to the virulence of P. aeruginosa as a pathogen. The fact that two supposed PAO1 wild-type strains from strain collections were found to be defective

Karin Heurlier; Valerie Denervaud; Marisa Haenni; Lionel Guy; Viji Krishnapillai; Dieter Haas

2005-01-01

153

Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms  

Microsoft Academic Search

The bacterium Pseudomonas aeruginosa permanently colonizes cystic fibrosis lungs despite aggressive antibiotic treatment. This suggests that P. aeruginosa might exist as biofilms-structured communities of bacteria encased in a self-produced polymeric matrix-in the cystic fibrosis lung. Consistent with this hypothesis, microscopy of cystic fibrosis sputum shows that P. aeruginosa are in biofilm-like structures. P. aeruginosa uses extracellular quorum-sensing signals (extracellular chemical

Pradeep K. Singh; Amy L. Schaefer; Matthew R. Parsek; Thomas O. Moninger; Michael J. Welsh; E. P. Greenberg

2000-01-01

154

Robust and sensitive control of a quorum-sensing circuit by two interlocked feedback loops  

Microsoft Academic Search

The quorum-sensing (QS) response of Vibrio fischeri involves a rapid switch between low and high induction states of the lux operon over a narrow concentration range of the autoinducer (AI) 3-oxo-hexanoyl-L-homoserine lactone. In this system, LuxR is an AI-dependent positive regulator of the lux operon, which encodes the AI synthase. This creates a positive feedback loop common in many bacterial

Joshua W Williams; Xiaohui Cui; Andre Levchenko; Ann M Stevens

2008-01-01

155

Diversity of biofilms produced by quorum-sensing-deficient clinical isolates of Pseudomonas aeruginosa  

Microsoft Academic Search

The quorum-sensing (QS) systems control several virulence attributes of Pseudomonas aeruginosa. Five QS-deficient P. aeruginosa clinical isolates (CI) that were obtained from wound (CI-1), tracheal (CI-2, CI-3, CI-4) and urinary tract (CI-5) infections had previously been characterized. In this study, a flow-through continuous-culture system was utilized to examine in detail the biofilms formed by these isolates in comparison with the

J. Andy Schaber; Adrienne Hammond; Nancy L. Carty; Simon C. Williams; Jane A. Colmer-Hamood; Ben H. Burrowes; Vijian Dhevan; John A. Griswold; Abdul N. Hamood

2007-01-01

156

A Cysteine-Rich Extracellular Protein Containing a PA14 Domain Mediates Quorum Sensing in Dictyostelium discoideum  

PubMed Central

Much remains to be understood about quorum-sensing factors that allow cells to sense their local density. Dictyostelium discoideum is a simple eukaryote that grows as single-celled amoebae and switches to multicellular development when food becomes limited. As the growing cells reach a high density, they begin expressing discoidin genes. The cells secrete an unknown factor, and at high cell densities the concomitant high levels of the factor induce discoidin expression. We report here the enrichment of discoidin-inducing complex (DIC), an ?400-kDa protein complex that induces discoidin expression during growth and development. Two proteins in the DIC preparation, DicA1 and DicB, were identified by sequencing proteolytic digests. DicA1 and DicB were expressed in Escherichia coli and tested for their ability to induce discoidin during growth and development. Recombinant DicB was unable to induce discoidin expression, while recombinant DicA1 was able to induce discoidin expression. This suggests that DicA1 is an active component of DIC and indicates that posttranslational modification is dispensable for activity. DicA1 mRNA is expressed in vegetative and developing cells. The mature secreted form of DicA1 has a molecular mass of 80 kDa and has a 24-amino-acid cysteine-rich repeat that is similar to repeats in Dictyostelium proteins, such as the extracellular matrix protein ecmB/PstA, the prespore cell-inducing factor PSI, and the cyclic AMP phosphodiesterase inhibitor PDI. Together, the data suggest that DicA1 is a component of a secreted quorum-sensing signal regulating discoidin gene expression during Dictyostelium growth and development. PMID:15947191

Kolbinger, Alexandra; Gao, Tong; Brock, Debbie; Ammann, Robin; Kisters, Axel; Kellermann, Joseph; Hatton, Diane; Gomer, Richard H.; Wetterauer, Birgit

2005-01-01

157

A cysteine-rich extracellular protein containing a PA14 domain mediates quorum sensing in Dictyostelium discoideum.  

PubMed

Much remains to be understood about quorum-sensing factors that allow cells to sense their local density. Dictyostelium discoideum is a simple eukaryote that grows as single-celled amoebae and switches to multicellular development when food becomes limited. As the growing cells reach a high density, they begin expressing discoidin genes. The cells secrete an unknown factor, and at high cell densities the concomitant high levels of the factor induce discoidin expression. We report here the enrichment of discoidin-inducing complex (DIC), an approximately 400-kDa protein complex that induces discoidin expression during growth and development. Two proteins in the DIC preparation, DicA1 and DicB, were identified by sequencing proteolytic digests. DicA1 and DicB were expressed in Escherichia coli and tested for their ability to induce discoidin during growth and development. Recombinant DicB was unable to induce discoidin expression, while recombinant DicA1 was able to induce discoidin expression. This suggests that DicA1 is an active component of DIC and indicates that posttranslational modification is dispensable for activity. DicA1 mRNA is expressed in vegetative and developing cells. The mature secreted form of DicA1 has a molecular mass of 80 kDa and has a 24-amino-acid cysteine-rich repeat that is similar to repeats in Dictyostelium proteins, such as the extracellular matrix protein ecmB/PstA, the prespore cell-inducing factor PSI, and the cyclic AMP phosphodiesterase inhibitor PDI. Together, the data suggest that DicA1 is a component of a secreted quorum-sensing signal regulating discoidin gene expression during Dictyostelium growth and development. PMID:15947191

Kolbinger, Alexandra; Gao, Tong; Brock, Debbie; Ammann, Robin; Kisters, Axel; Kellermann, Joseph; Hatton, Diane; Gomer, Richard H; Wetterauer, Birgit

2005-06-01

158

Production of the antifungal compound pyrrolnitrin is quorum sensing-regulated in members of the Burkholderia cepacia complex  

Microsoft Academic Search

Summary Members of the genus Burkholderia are known for their ability to suppress soil-borne fungal pathogens by the production of various antibiotic compounds. In this study we investigated the role of N-acylhomoserine lactone (AHL)-dependent quorum sensing (QS) in the expression of antifungal traits. Using a quorum quenching approach, that is, by heterologous expression of the Bacillus sp. AiiA lactonase, we

Silvia Schmidt; Judith F. Blom; Jakob Pernthaler; Gabriele Berg; Adam Baldwin; Eshwar Mahenthiralingam; Leo Eberl

2009-01-01

159

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

PubMed

Coordinated organ behavior is crucial for an effective response to environmental stimuli. By studying regeneration of hair follicles in response to patterned hair plucking, we demonstrate that organ-level quorum sensing allows coordinated responses to skin injury. Plucking hair at different densities leads to a regeneration of up to five 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-?-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

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

2015-04-01

160

Investigating the effect of antibiotics on quorum sensing with whole-cell biosensing systems.  

PubMed

Quorum sensing (QS) allows bacteria to communicate with one another by means of QS signaling molecules and control certain behaviors in a group-based manner, including pathogenicity and biofilm formation. Bacterial gut microflora may play a role in inflammatory bowel disease pathogenesis, and antibiotics are one of the available therapeutic options for Crohn's disease. In the present study, we employed genetically engineered bioluminescent bacterial whole-cell sensing systems as a tool to evaluate the ability of antibiotics commonly employed in the treatment of chronic inflammatory conditions to interfere with QS. We investigated the effect of ciprofloxacin, metronidazole, and tinidazole on quorum sensing. Several concentrations of individual antibiotics were allowed to interact with two different types of bacterial sensing cells, in both the presence and absence of a fixed concentration of N-acylhomoserine lactone (AHL) QS molecules. The antibiotic effect was then determined by monitoring the biosensor's bioluminescence response. Ciprofloxacin, metronidazole, and tinidazole exhibited a dose-dependent augmentation in the response of both bacterial sensing systems, thus showing an AHL-like effect. Additionally, such an augmentation was observed, in both the presence and absence of AHL. The data obtained indicate that ciprofloxacin, metronidazole, and tinidazole may interfere with bacterial communication systems. The results suggest that these antibiotics, at the concentrations tested, may themselves act as bacterial signaling molecules. The beneficial effect of these antibiotics in the treatment of intestinal inflammation may be due, at least in part, to their effect on QS-related bacterial behavior in the gut. PMID:22290388

Struss, Anjali K; Pasini, Patrizia; Flomenhoft, Deborah; Shashidhar, Harohalli; Daunert, Sylvia

2012-04-01

161

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

PubMed Central

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

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

2015-01-01

162

Streptomyces-derived quorum-sensing systems engineered for adjustable transgene expression in mammalian cells and mice  

PubMed Central

Prokaryotic transcriptional regulatory elements have been adopted for controlled expression of cloned genes in mammalian cells and animals, the cornerstone for gene-function correlations, drug discovery, biopharmaceutical manufacturing as well as advanced gene therapy and tissue engineering. Many prokaryotes have evolved specific molecular communication systems known as quorum-sensing to coordinate population-wide responses to physiological and/or physicochemical signals. A generic bacterial quorum-sensing system is based on a diffusible signal molecule that prevents binding of a repressor to corresponding operator sites thus resulting in derepression of a target regulon. In Streptomyces, a family of butyrolactones and their corresponding receptor proteins, serve as quorum-sensing systems that control morphological development and antibiotic biosynthesis. Fusion of the Streptomyces coelicolor quorum-sensing receptor (ScbR) to a eukaryotic transactivation domain (VP16) created a mammalian transactivator (SCA) which binds and adjusts transcription from chimeric promoters containing an SCA-specific operator module (PSPA). Expression of erythropoietin or the human secreted alkaline phosphatase (SEAP) by this quorum-sensor-regulated gene expression system (QuoRex) could be fine-tuned by non-toxic butyrolactones in a variety of mammalian cells including human primary and mouse embryonic stem cells. Following intraperitoneal implantation of microencapsulated Chinese hamster ovary cells transgenic for QuoRex-controlled SEAP expression into mice, the serum levels of this model glycoprotein could be adjusted to desired concentrations using different butyrolactone dosing regimes. PMID:12853648

Weber, Wilfried; Schoenmakers, Ronald; Spielmann, Manuela; El-Baba, Marie Daoud; Folcher, Marc; Keller, Bettina; Weber, Cornelia C.; Link, Nils; van de Wetering, Petra; Heinzen, Christoph; Jolivet, Benoît; Séquin, Urs; Aubel, Dominique; Thompson, Charles J.; Fussenegger, Martin

2003-01-01

163

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

PubMed

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.The ISME Journal advance online publication, 14 November 2014; doi:10.1038/ismej.2014.214. PMID:25397946

Pérez-Rodríguez, Ileana; Bolognini, Marie; Ricci, Jessica; Bini, Elisabetta; Vetriani, Costantino

2014-11-14

164

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

NASA Astrophysics Data System (ADS)

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.

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

2014-03-01

165

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

PubMed

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. PMID:25455678

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

2014-11-13

166

A tangled web: regulatory connections between quorum sensing and cyclic Di-GMP.  

PubMed

Bacteria sense and respond to environmental cues to control important developmental processes. Two widely conserved and important strategies that bacteria employ to sense changes in population density and local environmental conditions are quorum sensing (QS) and cyclic di-GMP (c-di-GMP) signaling, respectively. The importance of these pathways in controlling a broad variety of functions, including virulence, biofilm formation, and motility, has been recognized in many species. Recent research has shown that these pathways are intricately intertwined. Here we review the regulatory connections between QS and c-di-GMP signaling. We propose that the integration of QS with c-di-GMP allows bacteria to assimilate information about the local bacterial population density with other physicochemical environmental signals within the broader c-di-GMP signaling network. PMID:22661686

Srivastava, Disha; Waters, Christopher M

2012-09-01

167

A Tangled Web: Regulatory Connections between Quorum Sensing and Cyclic Di-GMP  

PubMed Central

Bacteria sense and respond to environmental cues to control important developmental processes. Two widely conserved and important strategies that bacteria employ to sense changes in population density and local environmental conditions are quorum sensing (QS) and cyclic di-GMP (c-di-GMP) signaling, respectively. The importance of these pathways in controlling a broad variety of functions, including virulence, biofilm formation, and motility, has been recognized in many species. Recent research has shown that these pathways are intricately intertwined. Here we review the regulatory connections between QS and c-di-GMP signaling. We propose that the integration of QS with c-di-GMP allows bacteria to assimilate information about the local bacterial population density with other physicochemical environmental signals within the broader c-di-GMP signaling network. PMID:22661686

Srivastava, Disha

2012-01-01

168

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

PubMed Central

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

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

169

Oregano essential oil-pectin edible films as anti-quorum sensing and food antimicrobial agents  

PubMed Central

Edible films can be used as carriers for antimicrobial compounds to assure food safety and quality; in addition, pathogenesis of food bacteria is related to a cell to cell communication mechanism called quorum sensing (QS). Oregano essential oil (OEO) has proved to be useful as food antimicrobial; however, its food applications can be compromised by the volatile character of its active constituents. Therefore, formulation of edible films containing OEO can be an alternative to improve its food usages. QS inhibitory activity of OEO and pectin-OEO films was evaluated using Chromobacterium violaceum as bacterial model. Additionally, antibacterial activity was tested against Escherichia coli O157:H7, Salmonella Choleraesuis, Staphylococcus aureus, and Listeria monocytogenes. OEO was effective to inhibit bacterial growth at MIC of 0.24 mg/mL for all tested bacteria and MBC of 0.24, 0.24, 0.48, and 0.24 mg/mL against E. coli O157:H7, S. Choleraesuis, S. aureus, and L. monocytogenes, respectively. Pectin-films incorporated with 36.1 and 25.9 mg/mL of OEO showed inhibition diameters of 16.3 and 15.2 mm for E. coli O157:H7; 18.1 and 24.2 mm for S. Choleraesuis; 20.8 and 20.3 mm for S. aureus; 21.3 and 19.3 mm for L. monocytogenes, respectively. Pectin-OEO film (15.7 mg/mL) was effective against E. coli O157:H7 (9.3 mm), S. aureus (9.7 mm), and L. monocytogenes (9.2 mm), but not for S. Choleraesuis. All concentrations of OEO (0.0156, 0.0312, 0.0625 and 0.125 mg/mL) and pectin-OEO films (15.7, 25.9 and 36.1 mg/mL) showed a significant anti-QS activity expressed as inhibition of violacein production by C. violaceum. Additionally, the application of pectin-OEO films was effective reducing total coliforms, yeast, and molds of shrimp and cucumber slices stored at 4°C during 15 d. These results demonstrated the potential of pectin films enriched with OEO as food related microorganisms and QS inhibitors. PMID:25566215

Alvarez, Maria V.; Ortega-Ramirez, Luis A.; Gutierrez-Pacheco, M. Melissa; Bernal-Mercado, A. Thalia; Rodriguez-Garcia, Isela; Gonzalez-Aguilar, Gustavo A.; Ponce, Alejandra; Moreira, Maria del R.; Roura, Sara I.; Ayala-Zavala, J. Fernando

2014-01-01

170

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

PubMed

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

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

2015-04-01

171

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

NASA Astrophysics Data System (ADS)

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.

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

2008-03-01

172

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

PubMed

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. PMID:23214663

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

2012-10-01

173

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

PubMed Central

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

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

2011-01-01

174

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

PubMed

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

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

2014-01-01

175

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

SciTech Connect

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 used to regulate virulence in Y. pestis. It is known that many bacteria use intercellular signaling molecules to orchestrate gene expression and cellular function. A fair amount is known about production and uptake of signaling molecules, but very little is known about how intercellular signaling regulates other pathways. Although several studies demonstrate that intercellular signaling plays a role in regulating virulence in other pathogens, the link between signaling and regulation of virulence has not been established. Very little work had been done directly with Y. pestis intercellular signaling apart from the work carried out at LLNL. The research we proposed was intended to both establish a causative link between AI-2 intercellular signaling and regulation of virulence in Y. pestis and elucidate the fate of the AI-2 signaling molecule after it is taken up and processed by Y. pestis. Elucidating the fate of AI-2 was expected to lead directly to the understanding of how AI-2 signal processing regulates other pathways as well as provide new insights in this direction.

Segelke, B; Hok, S; Lao, V; Corzett, M; Garcia, E

2010-03-29

176

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

PubMed

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. PMID:25673159

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

2015-02-24

177

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

PubMed Central

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

Tan, Wen-Si

2015-01-01

178

Draft Genome Sequence of a Quorum-Sensing Bacterium, Dickeya sp. Strain 2B12, Isolated from a Freshwater Lake  

PubMed Central

Dickeya sp. strain 2B12 was isolated from a freshwater lake in Malaysia. Here, we report the draft genome sequence of Dickeya sp. 2B12 sequenced by the Illumina MiSeq platform. With the genome sequence available, this genome sequence will be useful for the study of quorum-sensing activity in this isolate. PMID:25657288

Tan, Kian-Hin; Sheng, Kit-Yeng; Chang, Chien-Yi; Yin, Wai-Fong

2015-01-01

179

Modulation of quorum sensing controlled behaviour of bacteria by growing seedling, seed and seedling extracts of leguminous plants  

Microsoft Academic Search

Effect of growing seedling, seeds and seedlings extracts from seven leguminous plants (Pisum sativum, Vigna radiata, Vigna mungo, Cajanus cajan, Lentil culinaris, Cicer arietinum and Trigonella foenum graecum) were screened for their ability to influence quorum sensing controlled pigment production in Chromobacterium violaceum indicator strains (CV12472 and CVO26). Germinating seedling and seedling extracts of only P. sativum (pea) showed inhibition

Qaseem Fatima; Maryam Zahin; Mohd Sajjad Ahmad Khan; Iqbal Ahmad

2010-01-01

180

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...

181

A LuxR/LuxI-Type Quorum-Sensing System in a Plant Bacterium, Mesorhizobium tianshanense, Controls Symbiotic Nodulation  

PubMed Central

The ability of rhizobia to symbiotically fix nitrogen from the atmosphere when forming nodules on their plant hosts requires various signal transduction pathways. LuxR-LuxI-type quorum-sensing systems have been shown to be one of the players in a number of rhizobium species. In this study, we found that Mesorhizobium tianshanense, a moderate-growth Rhizobium that forms nodules on a number of licorice plants, produces multiple N-acyl homoserine lactone (AHL)-like molecules. A simple screen for AHL synthase genes using an M. tianshanense genomic expression library in Escherichia coli, coupled with a sensitive AHL detector, uncovered a LuxI-type synthase, MrtI, and a LuxR-type regulator, MrtR, in M. tianshanense. Deletions of the mrtI or mrtR locus completely abolished AHL production in M. tianshanense. Using lacZ transcriptional fusions, we found that expression of the quorum-sensing regulators is autoinduced, as mrtI gene expression requires MrtR and cognate AHLs and mrtR expression is dependent on AHLs. Compared with the wild-type strains, quorum-sensing-deficient mutants showed a marked reduction in the efficiency of root hair adherence and, more importantly, were defective in nodule formation on their host plant, Glycyrrhiza uralensis. These data provide strong evidence that quorum sensing plays a critical role in the M. tianshanense symbiotic process. PMID:16484206

Zheng, Huiming; Zhong, Zengtao; Lai, Xin; Chen, Wen-Xin; Li, Shunpeng; Zhu, Jun

2006-01-01

182

Complete Genome Sequence of Pandoraea pnomenusa 3kgm, a Quorum-Sensing Strain Isolated from a Former Landfill Site.  

PubMed

Pandoraea pnomenusa strain 3kgm has been identified as a quorum-sensing strain isolated from soil. Here, we report the complete genome sequence of P. pnomenusa strain 3kgm by using the Pacific Biosciences single-molecule real-time (PacBio RS SMRT) sequencer high-resolution technology. PMID:24812228

Chan, Kok-Gan; Yin, Wai-Fong; Goh, Share-Yuan

2014-01-01

183

Vibrio fischeri Uses Two Quorum-Sensing Systems for the Regulation of Early and Late Colonization Factors  

Microsoft Academic Search

Vibrio fischeri possesses two quorum-sensing systems, ain and lux, using acyl homoserine lactones as signaling molecules. We have demonstrated previously that the ain system activates luminescence gene ex- pression at lower cell densities than those required for lux system activation and that both systems are essential for persistent colonization of the squid host, Euprymna scolopes. Here, we asked whether the

Claudia Lupp; Edward G. Ruby

2005-01-01

184

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

PubMed

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 quorum sensing involves the spoilage of refrigerated Litopenaeus vannamei. PMID:25305441

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

2015-01-01

185

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

PubMed Central

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

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

2014-01-01

186

Anti-quorum sensing activity of selected sponge extracts: a case study of Pseudomonas aeruginosa.  

PubMed

The anti-quorum sensing activities towards the bacterium Pseudomonas aeruginosa PA01 (pyocyanin production, biofilm formation and twitching and flagella motility) of two crude extracts (methanol and acetone) of the freshwater sponge Ochridaspongia rotunda (Arndt, 1937) were evaluated in vitro for the first time. Both extracts demonstrated P. aeruginosa pyocyanin inhibitory activity, reducing its production for 49.90% and 42.44%, respectively. In addition, they both showed higher anti-biofilm activity (48.29% and 53.99%, respectively) than ampicillin (30.84%). Finally, O. rotunda extracts effectively reduced twitching and flagella motility of P. aeruginosa. Taken all together, these results suggest that endemic sponge species from the oldest lake in Europe may offer novel bioactive natural products with promising medicinal potential towards P. aeruginosa infections. PMID:25039944

Pejin, Boris; Talevska, Aleksandra; Ciric, Ana; Glamoclija, Jasmina; Nikolic, Milos; Talevski, Trajce; Sokovic, Marina

2014-01-01

187

6-Gingerol reduces Pseudomonas aeruginosa biofilm formation and virulence via quorum sensing inhibition  

PubMed Central

Pseudomonas aeruginosa is a well-known pathogenic bacterium that forms biofilms and produces virulence factors via quorum sensing (QS). Interfering with normal QS interactions between signal molecules and their cognate receptors is a developing strategy for attenuating its virulence. Here we tested the hypothesis that 6-gingerol, a pungent oil of fresh ginger, reduces biofilm formation and virulence by antagonistically binding to P. aeruginosa QS receptors. In silico studies demonstrated molecular binding occurs between 6-gingerol and the QS receptor LasR through hydrogen bonding and hydrophobic interactions. Experimentally 6-gingerol reduced biofilm formation, several virulence factors (e.g., exoprotease, rhamnolipid, and pyocyanin), and mice mortality. Further transcriptome analyses demonstrated that 6-gingerol successfully repressed QS-induced genes, specifically those related to the production of virulence factors. These results strongly support our hypothesis and offer insight into the molecular mechanism that caused QS gene repression. PMID:25728862

Kim, Han-Shin; Lee, Sang-Hoon; Byun, Youngjoo; Park, Hee-Deung

2015-01-01

188

6-Gingerol reduces Pseudomonas aeruginosa biofilm formation and virulence via quorum sensing inhibition.  

PubMed

Pseudomonas aeruginosa is a well-known pathogenic bacterium that forms biofilms and produces virulence factors via quorum sensing (QS). Interfering with normal QS interactions between signal molecules and their cognate receptors is a developing strategy for attenuating its virulence. Here we tested the hypothesis that 6-gingerol, a pungent oil of fresh ginger, reduces biofilm formation and virulence by antagonistically binding to P. aeruginosa QS receptors. In silico studies demonstrated molecular binding occurs between 6-gingerol and the QS receptor LasR through hydrogen bonding and hydrophobic interactions. Experimentally 6-gingerol reduced biofilm formation, several virulence factors (e.g., exoprotease, rhamnolipid, and pyocyanin), and mice mortality. Further transcriptome analyses demonstrated that 6-gingerol successfully repressed QS-induced genes, specifically those related to the production of virulence factors. These results strongly support our hypothesis and offer insight into the molecular mechanism that caused QS gene repression. PMID:25728862

Kim, Han-Shin; Lee, Sang-Hoon; Byun, Youngjoo; Park, Hee-Deung

2015-01-01

189

Anti-quorum sensing activity of medicinal plants in southern Florida.  

PubMed

Bacterial intercellular communication, or quorum sensing (QS), controls the pathogenesis of many medically important organisms. Anti-QS compounds are known to exist in marine algae and have the ability to attenuate bacterial pathogenicity. We hypothesized that terrestrial plants traditionally used as medicines may also produce anti-QS compounds. To test this hypothesis, 50 medicinal plants from southern Florida were screened for anti-QS activity using two biomonitor strains, Chromobacterium violaceum and Agrobacterium tumefaciens. Of these plants, six showed QS inhibition: Conocarpus erectus L. (Combretaceae), Chamaecyce hypericifolia (L.) Millsp. (Euphorbiaceae), Callistemon viminalis (Sol. ex Gaertn.) G. Don (Myrtaceae), Bucida burceras L. (Combretaceae), Tetrazygia bicolor (Mill.) Cogn. (Melastomataceae), and Quercus virginiana Mill. (Fagaceae). This study introduces not only a new mode of action and possible validation for traditional plant use, but also a potentially new therapeutic direction for the treatment of bacterial infections. PMID:16406418

Adonizio, Allison L; Downum, Kelsey; Bennett, Bradley C; Mathee, Kalai

2006-05-24

190

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

PubMed Central

During our search for new natural products from the marine environment, we discovered a wide range of cyclic peptides from a marine Photobacterium, closely related to P. halotolerans. The chemical fingerprint of the bacterium showed primarily non-ribosomal peptide synthetase (NRPS)-like compounds, including the known pyrrothine antibiotic holomycin and a wide range of peptides, from diketopiperazines to cyclodepsipeptides of 500–900 Da. Purification of components from the pellet fraction led to the isolation and structure elucidation of four new cyclodepsipeptides, ngercheumicin F, G, H, and I. The ngercheumicins interfered with expression of virulence genes known to be controlled by the agr quorum sensing system of Staphylococcus aureus, although to a lesser extent than the previously described solonamides from the same strain of Photobacterium. PMID:24351904

Kjaerulff, Louise; Nielsen, Anita; Mansson, Maria; Gram, Lone; Larsen, Thomas O.; Ingmer, Hanne; Gotfredsen, Charlotte H.

2013-01-01

191

Identification of four new agr quorum sensing-interfering cyclodepsipeptides from a marine Photobacterium.  

PubMed

During our search for new natural products from the marine environment, we discovered a wide range of cyclic peptides from a marine Photobacterium, closely related to P. halotolerans. The chemical fingerprint of the bacterium showed primarily non-ribosomal peptide synthetase (NRPS)-like compounds, including the known pyrrothine antibiotic holomycin and a wide range of peptides, from diketopiperazines to cyclodepsipeptides of 500-900 Da. Purification of components from the pellet fraction led to the isolation and structure elucidation of four new cyclodepsipeptides, ngercheumicin F, G, H, and I. The ngercheumicins interfered with expression of virulence genes known to be controlled by the agr quorum sensing system of Staphylococcus aureus, although to a lesser extent than the previously described solonamides from the same strain of Photobacterium. PMID:24351904

Kjaerulff, Louise; Nielsen, Anita; Mansson, Maria; Gram, Lone; Larsen, Thomas O; Ingmer, Hanne; Gotfredsen, Charlotte H

2013-12-01

192

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

PubMed Central

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

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

193

Quorum-Sensing Regulation of the Biofilm Matrix Genes (pel) of Pseudomonas aeruginosa?  

PubMed Central

Quorum sensing (QS) has been previously shown to play an important role in the development of Pseudomonas aeruginosa biofilms (D. G. Davies et al., Science 280:295-298, 1998). Although QS regulation of swarming and DNA release has been shown to play important roles in biofilm development, regulation of genes directly involved in biosynthesis of biofilm matrix has not been described. Here, transcription of the pel operon, essential for the production of a glucose-rich matrix exopolysaccharide, is shown to be greatly reduced in lasI and rhlI mutants. Chemical complementation of the lasI mutant with 3-oxo-dodecanoyl homoserine lactone restores pel transcription to the wild-type level and biofilm formation ability. These findings thus connect QS signaling and transcription of genes responsible for biofilm matrix biosynthesis. PMID:17496081

Sakuragi, Yumiko; Kolter, Roberto

2007-01-01

194

Synthesis and biological evaluation of novel N-?-haloacylated homoserine lactones as quorum sensing modulators  

PubMed Central

Summary Novel N-?-haloacylated homoserine lactones, in which a halogen atom was introduced at the ?-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 ?-chloro, ?-bromo and ?-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 ?-iodo lactones being the less active ones and the ?-chloro AHLs the most potent QS agonists. Most of the ?-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

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

2014-01-01

195

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

PubMed Central

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

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

2012-01-01

196

Antagonistic Rgg Regulators Mediate Quorum Sensing via Competitive DNA Binding in Streptococcus pyogenes  

PubMed Central

ABSTRACT Recent studies have established the fact that multiple members of the Rgg family of transcriptional regulators serve as key components of quorum sensing (QS) pathways that utilize peptides as intercellular signaling molecules. We previously described a novel QS system in Streptococcus pyogenes which utilizes two Rgg-family regulators (Rgg2 and Rgg3) that respond to neighboring signaling peptides (SHP2 and SHP3) to control gene expression and biofilm formation. We have shown that Rgg2 is a transcriptional activator of target genes, whereas Rgg3 represses expression of these genes, and that SHPs function to activate the QS system. The mechanisms by which Rgg proteins regulate both QS-dependent and QS-independent processes remain poorly defined; thus, we sought to further elucidate how Rgg2 and Rgg3 mediate gene regulation. Here we provide evidence that S. pyogenes employs a unique mechanism of direct competition between the antagonistic, peptide-responsive proteins Rgg2 and Rgg3 for binding at target promoters. The highly conserved, shared binding sites for Rgg2 and Rgg3 are located proximal to the ?35 nucleotide in the target promoters, and the direct competition between the two regulators results in concentration-dependent, exclusive occupation of the target promoters that can be skewed in favor of Rgg2 in vitro by the presence of SHP. These results suggest that exclusionary binding of target promoters by Rgg3 may prevent Rgg2 binding under SHP-limiting conditions, thereby preventing premature induction of the quorum sensing circuit. PMID:23188510

LaSarre, Breah; Aggarwal, Chaitanya; Federle, Michael J.

2012-01-01

197

Methylthioadenosine deaminase in an alternative quorum sensing pathway in Pseudomonas aeruginosa.  

PubMed

Pseudomonas aeruginosa possesses an unusual pathway for 5'-methylthioadenosine (MTA) metabolism involving deamination to 5'-methylthioinosine (MTI) followed by N-ribosyl phosphorolysis to hypoxanthine and 5-methylthio-?-d-ribose 1-phosphate. The specific MTI phosphorylase of P. aeruginosa has been reported [Guan, R., Ho, M. C., Almo, S. C., and Schramm, V. L. (2011) Biochemistry 50, 1247-1254], and here we characterize MTA deaminase from P. aeruginosa (PaMTADA). Genomic analysis indicated the PA3170 locus to be a candidate for MTA deaminase (MTADA). Protein encoded by PA3170 was expressed and shown to deaminate MTA with 40-fold greater catalytic efficiency for MTA than for adenosine. The k(cat)/K(m) value of 1.6 × 10(7) M(-1) s(-1) for MTA is the highest catalytic efficiency known for an MTA deaminase. 5'-Methylthiocoformycin (MTCF) is a 4.8 pM transition state analogue for PaMTADA but causes no significant inhibition of human adenosine deaminase or MTA phosphorylase. MTCF is permeable to P. aeruginosa and exhibits an IC(50) of 3 nM on cellular PaMTADA activity. PaMTADA is the only activity in P. aeruginosa extracts to act on MTA. MTA and 5-methylthio-?-d-ribose are involved in quorum sensing pathways; thus, PaMTADA is a potential target for quorum sensing. The crystal structure of PaMTADA in complex with MTCF shows the transition state mimic 8(R)-hydroxyl group in contact with a catalytic site Zn(2+), the 5'-methylthio group in a hydrophobic pocket, and the transition state mimic of the diazepine ring in contact with a catalytic site Glu. PMID:23050701

Guan, Rong; Ho, Meng-Chiao; Fröhlich, Richard F G; Tyler, Peter C; Almo, Steven C; Schramm, Vern L

2012-11-13

198

Connecting Quorum Sensing, c-di-GMP, Pel Polysaccharide, and Biofilm Formation in Pseudomonas aeruginosa through Tyrosine Phosphatase TpbA (PA3885)  

Microsoft Academic Search

With the opportunistic pathogen Pseudomonas aeruginosa, quorum sensing based on homoserine lactones was found to influence biofilm formation. Here we discern a mechanism by which quorum sensing controls biofilm formation by screening 5850 transposon mutants of P. aeruginosa PA14 for altered biofilm formation. This screen identified the PA3885 mutant, which had 147-fold more biofilm than the wild-type strain. Loss of

Akihiro Ueda; Thomas K. Wood

2009-01-01

199

The Stringent Response Modulates 4-Hydroxy-2-Alkylquinoline Biosynthesis and Quorum-Sensing Hierarchy in Pseudomonas aeruginosa  

PubMed Central

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 (?SR) 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 ?SR 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

Schafhauser, James; Lepine, Francois; McKay, Geoffrey; Ahlgren, Heather G.; Khakimova, Malika

2014-01-01

200

Quorum-sensing-deficient (lasR) mutants emerge at high frequency from a Pseudomonas aeruginosa mutS strain  

Microsoft Academic Search

In Pseudomonas aeruginosa, quorum sensing constitutes a highly complex cell-to-cell communication system that, along with the cognate acylhomoserine lactone signals and regulators LasR and RhlR, modulates the production of virulence factors and a wide range of metabolic functions. In a previous paper, the authors reported that mismatch repair disruption inP. aeruginosa results in the spontaneous and reproducible emergence of defined

Adela M. Lujan; Alejandro J. Moyano; Ignacio Segura; Carlos E. Argarana; Andrea M. Smania

2007-01-01

201

Quorum sensing signalling and biofilm formation of brewery-derived bacteria, and inhibition of signalling by natural compounds.  

PubMed

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

Priha, O; Virkajärvi, V; Juvonen, R; Puupponen-Pimiä, R; Nohynek, L; Alakurtti, S; Pirttimaa, M; Storgårds, E

2014-11-01

202

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

PubMed

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. PMID:25113857

Helman, Yael; Chernin, Leonid

2015-04-01

203

Functional Analysis of the Quorum-Sensing Streptococcal Invasion Locus (sil)  

PubMed Central

Group A streptococcus (GAS) causes a wide variety of human diseases, and at the same time, GAS can also circulate without producing symptoms, similar to its close commensal relative, group G streptococcus (GGS). We previously identified, by transposon-tagged mutagenesis, the streptococcal invasion locus (sil). sil is a quorum-sensing regulated locus which is activated by the autoinducer peptide SilCR through the two-component system SilA-SilB. Here we characterize the DNA promoter region necessary for SilA-mediated activation. This site is composed of two direct repeats of 10 bp, separated by a spacer of 11 bp. Fusion of this site to gfp allowed us to systematically introduce single-base substitutions in the repeats region and to assess the relative contribution of various positions to promoter strength. We then developed an algorithm giving different weights to these positions, and performed a chromosome-wide bioinformatics search which was validated by transcriptome analysis. We identified 13 genes, mostly bacteriocin related, that are directly under the control of SilA. Having developed the ability to quantify SilCR signaling via GFP accumulation prompted us to search for GAS and GGS strains that sense and produce SilCR. While the majority of GAS strains lost sil, all GGS strains examined still possess the locus and ?63% are able to respond to exogenously added SilCR. By triggering the autoinduction circle using a minute concentration of synthetic SilCR, we identified GAS and GGS strains that are capable of sensing and naturally producing SilCR, and showed that SilCR can be sensed across these streptococci species. These findings suggest that sil may be involved in colonization and establishment of commensal host-bacterial relationships. PMID:19893632

Belotserkovsky, Ilia; Baruch, Moshe; Peer, Asaf; Dov, Eran; Ravins, Miriam; Mishalian, Inbal; Persky, Merav; Smith, Yoav; Hanski, Emanuel

2009-01-01

204

Inhibition of Quorum Sensing-Controlled Virulence Factor Production in Pseudomonas aeruginosa by South Florida Plant Extracts?  

PubMed Central

Quorum sensing (QS) is a key regulator of virulence and biofilm formation in Pseudomonas aeruginosa and other medically relevant bacteria. Aqueous extracts of six plants, Conocarpus erectus, Chamaesyce hypericifolia, Callistemon viminalis, Bucida buceras, Tetrazygia bicolor, and Quercus virginiana, were examined in this study for their effects on P. aeruginosa virulence factors and the QS system. C. erectus, B. buceras, and C. viminalis caused a significant inhibition of LasA protease, LasB elastase, pyoverdin production, and biofilm formation. Additionally, each plant presented a distinct effect profile on the las and rhl QS genes and their respective signaling molecules, suggesting that different mechanisms are responsible for efficacy. Extracts of all plants caused the inhibition of QS genes and QS-controlled factors, with marginal effects on bacterial growth, suggesting that the quorum-quenching mechanisms are unrelated to static or cidal effects. PMID:17938186

Adonizio, Allison; Kong, Kok-Fai; Mathee, Kalai

2008-01-01

205

?-Hydroxyemodin Limits Staphylococcus aureus Quorum Sensing-Mediated Pathogenesis and Inflammation.  

PubMed

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 ?-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

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; Hall, Pamela R

2015-04-01

206

AHL-type quorum sensing and its regulation on symplasmata formation in Pantoea agglomerans YS19.  

PubMed

Pantoea agglomerans YS19, an endophytic diazotrophic bacterium isolated from rice, is characterized by the formation of multicellular aggregate structure called symplasmata, which not only bestow the strong stress-resistance of the bacterium, but also contribute to the specific adaptation in the endophyte-host association. Acyl-homoserine lactones (AHLs), as the important signal molecule in the quorum sensing (QS) system of gram-negative bacteria, were demonstrated to regulate motility, cell-aggregation, and other bacterial behaviors. Here, the production of AHL by P. agglomerans YS19 and its regulation on the symplasmata formation were studied. It was revealed that the production of AHL by YS19 was initiated at the exponential growth stage and from then on, reached the peak values at the stationary growth stage in LB medium. The AHL was identified as N-3-oxooctanoyl-L-homoserine lactone (OOHL) by MALDI-TOF-MS analysis. The AHL synthesis gene pagI and receptor gene pagR in YS19 were cloned and phylogenetic analysis showed that they were high conservative among strains in species of P. agglomerans. It was revealed that AHL promoted the bacterial growth and symplasmata formation of YS19. Meanwhile, the colonization ability and growth-promoting effect of YS19 on the host plant were also enhanced by AHL. These results strongly suggest the pleiotropic effects of the AHL-type QS system in endophytic life of the strain. PMID:25283544

Jiang, Jing; Wu, Suisui; Wang, Jieru; Feng, Yongjun

2014-10-01

207

Influence of quorum sensing in multiple phenotypes of the bacterial pathogen Chromobacterium violaceum.  

PubMed

Chromobacterium violaceum is a bacterial pathogen that communicates through quorum sensing (QS), via the C6-homoserine lactone signal (C6-HSL). It is well known that the production of the pigment violacein is controlled by QS in this microorganism, in fact QS-dependent violacein production is widely used as a marker to evaluate the efficiency of potential anti-QS molecules, such as those extracted from plants. In addition to violacein, the production of chitinase is also known to be controlled by QS, but besides those two phenotypes there is a lack of experimental studies aimed to discover additional process controlled by QS in this organism; therefore, in this work the production of exoprotease, aggregation, biofilm formation, swarming motility, H2O2 resistance as well as carbon and nitrogen utilization was determined in the wild-type strain and the QS negative mutant CVO26. Our results indicate that alkaline exoprotease activity is QS controlled in this organism, that QS increases aggregation, biofilm formation, swarming, that may increase H2O2 stress tolerance, and that it may influence the utilization of several carbon and nitrogen sources. PMID:25722489

de Oca-Mejía, Marielba Montes; Castillo-Juárez, Israel; Martínez-Vázquez, Mariano; Soto-Hernandez, Marcos; García-Contreras, Rodolfo

2015-03-01

208

Quorum sensing activity and control of yeast-mycelium dimorphism in Ophiostoma floccosum.  

PubMed

Quorum sensing (QS) activity in Ophiostoma fungi has not been described. We have examined the growth conditions on the control of dimorphism in Ophiostoma floccosum, an attractive biocontrol agent against blue-stain fungi, and its relationship with QS activity. In a defined culture medium with L-proline as the N source, a high inoculum size (10(7) c.f.u. ml(-1)) was the principal factor that promoted yeast-like growth. Inoculum size effect can be explained by the secretion of a QS molecule(s) (QSMs) responsible for inducing yeast morphology. QSM candidates were extracted from spent medium and their structure was determined by GC-MS. Three cyclic sesquiterpenes were found. The most abundant molecule, and therefore the principal candidate to be the QSM responsible for yeast growth of O. floccosum, was 1,1,4a-trimethyl-5,6-dimethylene-decalin (C15H24). Other two compounds were also detected. PMID:24737073

Berrocal, Alexander; Oviedo, Claudia; Nickerson, Kenneth W; Navarrete, José

2014-07-01

209

Caenorhabditis elegans recognizes a bacterial quorum-sensing signal molecule through the AWCON neuron.  

PubMed

In a process known as quorum sensing, bacteria use chemicals called autoinducers for cell-cell communication. Population-wide detection of autoinducers enables bacteria to orchestrate collective behaviors. In the animal kingdom detection of chemicals is vital for success in locating food, finding hosts, and avoiding predators. This behavior, termed chemotaxis, is especially well studied in the nematode Caenorhabditis elegans. Here we demonstrate that the Vibrio cholerae autoinducer (S)-3-hydroxytridecan-4-one, termed CAI-1, influences chemotaxis in C. elegans. C. elegans prefers V. cholerae that produces CAI-1 over a V. cholerae mutant defective for CAI-1 production. The position of the CAI-1 ketone moiety is the key feature driving CAI-1-directed nematode behavior. CAI-1 is detected by the C. elegans amphid sensory neuron AWC(ON). Laser ablation of the AWC(ON) cell, but not other amphid sensory neurons, abolished chemoattraction to CAI-1. These analyses define the structural features of a bacterial-produced signal and the nematode chemosensory neuron that permit cross-kingdom interaction. PMID:25092291

Werner, Kristen M; Perez, Lark J; Ghosh, Rajarshi; Semmelhack, Martin F; Bassler, Bonnie L

2014-09-19

210

Quorum Sensing Contributes to Natural Transformation of Vibrio cholerae in a Species-Specific Manner?  

PubMed Central

Although it is a human pathogen, Vibrio cholerae is a regular member of aquatic habitats, such as coastal regions and estuaries. Within these environments, V. cholerae often takes advantage of the abundance of zooplankton and their chitinous molts as a nutritious surface on which the bacteria can form biofilms. Chitin also induces the developmental program of natural competence for transformation in several species of the genus Vibrio. In this study, we show that V. cholerae does not distinguish between species-specific and non-species-specific DNA at the level of DNA uptake. This is in contrast to what has been shown for other Gram-negative bacteria, such as Neisseria gonorrhoeae and Haemophilus influenzae. However, species specificity with respect to natural transformation still occurs in V. cholerae. This is based on a positive correlation between quorum sensing and natural transformation. Using mutant-strain analysis, cross-feeding experiments, and synthetic cholera autoinducer-1 (CAI-1), we provide strong evidence that the species-specific signaling molecule CAI-1 plays a major role in natural competence for transformation. We suggest that CAI-1 can be considered a competence pheromone. PMID:21784943

Suckow, Gaia; Seitz, Patrick; Blokesch, Melanie

2011-01-01

211

Quorum sensing restrains growth and is rapidly inactivated during domestication of Sinorhizobium meliloti.  

PubMed

Microbial cooperative behaviours, such as quorum sensing (QS), improve survival and this explains their prevalence throughout the microbial world. However, relatively little is known about the mechanisms by which cooperation promotes survival. Furthermore, cooperation typically requires costly contributions, e.g. exopolysaccharides, which are produced from limited resources. Inevitably, cooperation is vulnerable to damaging mutations which results in mutants that are relieved of the burden of contributing but nonetheless benefit from the contributions of their parent. Unless somehow prevented, such mutants may outcompete and replace the parent. The bacterium Sinorhizobium meliloti uses QS to activate the production of copious levels of exopolysaccharide (EPS). Domestication of this bacterium is typified by the appearance of spontaneous mutants incapable of EPS production, which take advantage of EPS production by the parent and outcompete the parent. We found that all of the mutants were defect in QS, implying that loss of QS is a typical consequence of the domestication of this bacterium. This instability was traced to several QS-regulated processes, including a QS-dependent restraint of growth, providing the mutant with a significant growth advantage. A model is proposed whereby QS restrains population growth to prevent overcrowding and prepares the population for the survival of severe conditions. PMID:25534533

Charoenpanich, Pornsri; Soto, Maria J; Becker, Anke; McIntosh, Matthew

2015-04-01

212

Crystal Structure of the Vibrio Cholerae Quorum-Sensing Regulatory Protein HapR  

SciTech Connect

Quorum sensing in Vibrio cholerae involves signaling between two-component sensor protein kinases and the response regulator LuxO to control the expression of the master regulator HapR. HapR, in turn, plays a central role in regulating a number of important processes, such as virulence gene expression and biofilm formation. We have determined the crystal structure of HapR to 2.2- Angstroms resolution. Its structure reveals a dimeric, two-domain molecule with an all-helical structure that is strongly conserved with members of the TetR family of transcriptional regulators. The N-terminal DNA-binding domain contains a helix-turn-helix DNA-binding motif and alteration of certain residues in this domain completely abolishes the ability of HapR to bind to DNA, alleviating repression of both virulence gene expression and biofilm formation. The C-terminal dimerization domain contains a unique solvent accessible tunnel connected to an amphipathic cavity, which by analogy with other TetR regulators, may serve as a binding pocket for an as-yet-unidentified ligand.

DeSilva,R.; Kovacikova, G.; Lin, W.; Taylor, R.; Skorupski, K.; Kull, F.

2007-01-01

213

Global and phylogenetic distribution of quorum sensing signals, acyl homoserine lactones, in the family of vibrionaceae.  

PubMed

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

Rasmussen, Bastian Barker; Nielsen, Kristian Fog; Machado, Henrique; Melchiorsen, Jette; Gram, Lone; Sonnenschein, Eva C

2014-11-01

214

Freshwater-borne bacteria isolated from a Malaysian rainforest waterfall exhibiting quorum sensing properties.  

PubMed

One obvious requirement for concerted action by a bacterial population is for an individual to be aware of and respond to the other individuals of the same species in order to form a response in unison. The term "quorum sensing" (QS) was coined to describe bacterial communication that is able to stimulate expression of a series of genes when the concentration of the signaling molecules has reached a threshold level. Here we report the isolation from aquatic environment of a bacterium that was later identified as Enterobacter sp.. Chromobacterium violaceum CV026 and Escherichia coli [pSB401] were used for preliminary screening of N-acyl homoserine lactone (AHL) production. The Enterobacter sp. isolated was shown to produce two types of AHLs as confirmed by analysis using high resolution tandem mass spectrometry. To the best of our knowledge, this is the first documentation of an Enterobacter sp. that produced both 3-oxo-C6-HSL and 3-oxo-C8-HSL as QS signaling molecules. PMID:24932870

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

2014-01-01

215

Combinatorial quorum sensing allows bacteria to resolve their social and physical environment  

PubMed Central

Quorum sensing (QS) is a cell–cell communication system that controls gene expression in many bacterial species, mediated by diffusible signal molecules. Although the intracellular regulatory mechanisms of QS are often well-understood, the functional roles of QS remain controversial. In particular, the use of multiple signals by many bacterial species poses a serious challenge to current functional theories. Here, we address this challenge by showing that bacteria can use multiple QS signals to infer both their social (density) and physical (mass-transfer) environment. Analytical and evolutionary simulation models show that the detection of, and response to, complex social/physical contrasts requires multiple signals with distinct half-lives and combinatorial (nonadditive) responses to signal concentrations. We test these predictions using the opportunistic pathogen Pseudomonas aeruginosa and demonstrate significant differences in signal decay between its two primary signal molecules, as well as diverse combinatorial responses to dual-signal inputs. QS is associated with the control of secreted factors, and we show that secretome genes are preferentially controlled by synergistic “AND-gate” responses to multiple signal inputs, ensuring the effective expression of secreted factors in high-density and low mass-transfer environments. Our results support a new functional hypothesis for the use of multiple signals and, more generally, show that bacteria are capable of combinatorial communication. PMID:24594597

Cornforth, Daniel M.; Popat, Roman; McNally, Luke; Gurney, James; Scott-Phillips, Thomas C.; Ivens, Alasdair; Diggle, Stephen P.; Brown, Sam P.

2014-01-01

216

The Organization of the Quorum Sensing luxI/R Family Genes in Burkholderia  

PubMed Central

Members of the Burkholderia genus of Proteobacteria are capable of living freely in the environment and can also colonize human, animal and plant hosts. Certain members are considered to be clinically important from both medical and veterinary perspectives and furthermore may be important modulators of the rhizosphere. Quorum sensing via N-acyl homoserine lactone signals (AHL QS) is present in almost all Burkholderia species and is thought to play important roles in lifestyle changes such as colonization and niche invasion. Here we present a census of AHL QS genes retrieved from public databases and indicate that the local arrangement (topology) of QS genes, their location within chromosomes and their gene neighborhoods show characteristic patterns that differ between the known Burkholderia clades. In sequence phylogenies, AHL QS genes seem to cluster according to the local gene topology rather than according to the species, which suggests that the basic topology types were present prior to the appearance of current Burkholderia species. The data are available at http://net.icgeb.org/burkholderia/. PMID:23820583

Choudhary, Kumari Sonal; Hudaiberdiev, Sanjarbek; Gelencsér, Zsolt; Coutinho, Bruna Gonçalves; Venturi, Vittorio; Pongor, Sándor

2013-01-01

217

Discovery of a nitric oxide responsive quorum sensing circuit in Vibrio harveyi.  

PubMed

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

Henares, Bernadette M; Higgins, Kate E; Boon, Elizabeth M

2012-08-17

218

Solonamide B Inhibits Quorum Sensing and Reduces Staphylococcus aureus Mediated Killing of Human Neutrophils  

PubMed Central

Methicillin-resistant Staphylococcus aureus (MRSA) continues to be a serious human pathogen, and particularly the spread of community associated (CA)-MRSA strains such as USA300 is a concern, as these strains can cause severe infections in otherwise healthy adults. Recently, we reported that a cyclodepsipeptide termed Solonamide B isolated from the marine bacterium, Photobacterium halotolerans strongly reduces expression of RNAIII, the effector molecule of the agr quorum sensing system. Here we show that Solonamide B interferes with the binding of S. aureus autoinducing peptides (AIPs) to sensor histidine kinase, AgrC, of the agr two-component system. The hypervirulence of USA300 has been linked to increased expression of central virulence factors like ?-hemolysin and the phenol soluble modulins (PSMs). Importantly, in strain USA300 Solonamide B dramatically reduced the activity of ?-hemolysin and the transcription of psma encoding PSMs with an 80% reduction in toxicity of supernatants towards human neutrophils and rabbit erythrocytes. To our knowledge this is the first report of a compound produced naturally by a Gram-negative marine bacterium that interferes with agr and affects both RNAIII and AgrA controlled virulence gene expression in S. aureus. PMID:24416329

Nielsen, Anita; Månsson, Maria; Bojer, Martin S.; Gram, Lone; Larsen, Thomas O.; Novick, Richard P.; Frees, Dorte; Frøkiær, Hanne; Ingmer, Hanne

2014-01-01

219

Global and Phylogenetic Distribution of Quorum Sensing Signals, Acyl Homoserine Lactones, in the Family of Vibrionaceae  

PubMed Central

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

Barker Rasmussen, Bastian; Fog Nielsen, Kristian; Machado, Henrique; Melchiorsen, Jette; Gram, Lone; Sonnenschein, Eva C.

2014-01-01

220

Solonamide B inhibits quorum sensing and reduces Staphylococcus aureus mediated killing of human neutrophils.  

PubMed

Methicillin-resistant Staphylococcus aureus (MRSA) continues to be a serious human pathogen, and particularly the spread of community associated (CA)-MRSA strains such as USA300 is a concern, as these strains can cause severe infections in otherwise healthy adults. Recently, we reported that a cyclodepsipeptide termed Solonamide B isolated from the marine bacterium, Photobacterium halotolerans strongly reduces expression of RNAIII, the effector molecule of the agr quorum sensing system. Here we show that Solonamide B interferes with the binding of S. aureus autoinducing peptides (AIPs) to sensor histidine kinase, AgrC, of the agr two-component system. The hypervirulence of USA300 has been linked to increased expression of central virulence factors like ?-hemolysin and the phenol soluble modulins (PSMs). Importantly, in strain USA300 Solonamide B dramatically reduced the activity of ?-hemolysin and the transcription of psma encoding PSMs with an 80% reduction in toxicity of supernatants towards human neutrophils and rabbit erythrocytes. To our knowledge this is the first report of a compound produced naturally by a Gram-negative marine bacterium that interferes with agr and affects both RNAIII and AgrA controlled virulence gene expression in S. aureus. PMID:24416329

Nielsen, Anita; Månsson, Maria; Bojer, Martin S; Gram, Lone; Larsen, Thomas O; Novick, Richard P; Frees, Dorte; Frøkiær, Hanne; Ingmer, Hanne

2014-01-01

221

Bacillus marcorestinctum sp. nov., a Novel Soil Acylhomoserine Lactone Quorum-Sensing Signal Quenching Bacterium  

PubMed Central

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

Han, Yan; Chen, Fang; Li, Nuo; Zhu, Bo; Li, Xianzhen

2010-01-01

222

Density-dependent fitness benefits in quorum-sensing bacterial populations.  

PubMed

It has been argued that bacteria communicate using small diffusible signal molecules to coordinate, among other things, the production of factors that are secreted outside of the cells in a process known as quorum sensing (QS). The underlying assumption made to explain QS is that the secretion of these extracellular factors is more beneficial at higher cell densities. However, this fundamental assumption has never been tested experimentally. Here, we directly test this by independently manipulating population density and the induction and response to the QS signal, using the opportunistic pathogen Pseudomonas aeruginosa as a model organism. We found that the benefit of QS was relatively greater at higher population densities, and that this was because of more efficient use of QS-dependent extracellular "public goods." In contrast, the benefit of producing "private goods," which are retained within the cell, does not vary with cell density. Overall, these results support the idea that QS is used to coordinate the switching on of social behaviors at high densities when such behaviors are more efficient and will provide the greatest benefit. PMID:22566647

Darch, Sophie E; West, Stuart A; Winzer, Klaus; Diggle, Stephen P

2012-05-22

223

Methylobacterium-plant interaction genes regulated by plant exudate and quorum sensing molecules.  

PubMed

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

Dourado, Manuella Nóbrega; Bogas, Andrea Cristina; Pomini, Armando M; Andreote, Fernando Dini; Quecine, Maria Carolina; Marsaioli, Anita J; Araújo, Welington Luiz

2013-12-01

224

Quorum Sensing Activity of a Kluyvera sp. Isolated from a Malaysian Waterfall  

PubMed Central

In many species of bacteria, the quorum sensing mechanism is used as a unique communication system which allows them to regulate gene expression and behavior in accordance with their population density. N-Acylhomoserine lactones (AHLs) are known as diffusible autoinducer molecules involved in this communication network. This finding aimed to characterize the production of AHL of a bacterial strain ND04 isolated from a Malaysian waterfall. Strain ND04 was identified as Kluyvera sp. as confirmed by molecular analysis of its 16S ribosomal RNA gene sequence. Kluyvera sp. is closely related to the Enterobacteriaceae family. Chromobacterium violaceum CV026 was used as a biosensor to detect the production of AHL by strain ND04. High resolution triple quadrupole liquid chromatography-mass spectrometry analysis of strain ND04 showed our isolate produced two AHLs which are N-(3-oxohexanoyl)homoserine lactone (3-oxo-C6 HSL) and N-3-oxo-octanoyl-L-homoserine lactone (3-oxo-C8 HSL). PMID:24815680

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

2014-01-01

225

Freshwater-Borne Bacteria Isolated from a Malaysian Rainforest Waterfall Exhibiting Quorum Sensing Properties  

PubMed Central

One obvious requirement for concerted action by a bacterial population is for an individual to be aware of and respond to the other individuals of the same species in order to form a response in unison. The term “quorum sensing” (QS) was coined to describe bacterial communication that is able to stimulate expression of a series of genes when the concentration of the signaling molecules has reached a threshold level. Here we report the isolation from aquatic environment of a bacterium that was later identified as Enterobacter sp.. Chromobacterium violaceum CV026 and Escherichia coli [pSB401] were used for preliminary screening of N-acyl homoserine lactone (AHL) production. The Enterobacter sp. isolated was shown to produce two types of AHLs as confirmed by analysis using high resolution tandem mass spectrometry. To the best of our knowledge, this is the first documentation of an Enterobacter sp. that produced both 3-oxo-C6-HSL and 3-oxo-C8-HSL as QS signaling molecules. PMID:24932870

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

2014-01-01

226

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

PubMed Central

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 ?g 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

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

227

Protease IV, a quorum sensing-dependent protease of Pseudomonas aeruginosa modulates insect innate immunity.  

PubMed

In Pseudomonas aeruginosa, quorum sensing (QS) plays an essential role in pathogenesis and the QS response controls many virulence factors. Using a mealworm, Tenebrio molitor as a host model, we found that Protease IV, a QS-regulated exoprotease of P. aeruginosa functions as a key virulence effector causing the melanization and death of T. molitor larvae. Protease IV was able to degrade zymogens of spätzle processing enzyme (SPE) and SPE-activating enzyme (SAE) without the activation of the antimicrobial peptide (AMP) production. Since SPE and SAE function to activate spätzle, a ligand of Toll receptor in the innate immune system of T. molitor, we suggest that Protease IV may interfere with the activation of the Toll signaling. Independently of the Toll pathway, the melanization response, another innate immunity was still generated, since Protease IV directly converted Tenebrio prophenoloxidase into active phenoloxidase. Protease IV also worked as an important factor in the virulence to brine shrimp and nematode. These results suggest that Protease IV provides P. aeruginosa with a sophisticated way to escape the immune attack of host by interfering with the production of AMPs. PMID:25315216

Park, Su-Jin; Kim, Soo-Kyoung; So, Yong-In; Park, Ha-Young; Li, Xi-Hui; Yeom, Doo Hwan; Lee, Mi-Nan; Lee, Bok-Luel; Lee, Joon-Hee

2014-12-01

228

Altering Plant–Microbe Interaction Through Artificially Manipulating Bacterial Quorum Sensing  

PubMed Central

Many bacteria regulate diverse physiological processes in concert with their population size. Bacterial cell?to?cell communication utilizes small diffusible signal molecules, which the bacteria both produce and perceive. The bacteria couple gene expression to cell density by eliciting a response only when the signalling molecules reach a critical threshold (a point at which the population is said to be ‘quorate’). The population as a whole is thus able to modify its behaviour as a single unit. Amongst Gram?negative bacteria, the quorum sensing signals most commonly used are N?acylhomoserine lactones (AHLs). It is now apparent that AHLs are used for regulating diverse behaviours in epiphytic, rhizosphere?inhabiting and plant pathogenic bacteria and that plants may produce their own metabolites that interfere with this signalling. Transgenic plants that produce high levels of AHLs or which can degrade bacterial?produced AHLs have been made. These plants have dramatically altered susceptibilities to infection by pathogenic Erwinia species. In addition, such plants will prove useful tools in determining the roles of AHL?regulated density?dependent behaviour in growth promoting, biological control and pathogenic plant?associated bacterial species. PMID:12096736

FRAY, RUPERT G.

2002-01-01

229

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

PubMed

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 ?g 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

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

2014-11-01

230

Quorum sensing triggers the stochastic escape of individual cells from Pseudomonas putida biofilms  

PubMed Central

The term ‘quorum sensing’ (QS) is generally used to describe the phenomenon that bacteria release and perceive signal molecules to coordinate cooperative behaviour in response to their population size. QS-based communication has therefore been considered a social trait. Here we show that QS signals (N-acyl-homoserine lactones, AHLs) are stochastically produced in young biofilms of Pseudomonas putida and act mainly as self-regulatory signals rather than inducing neighbouring cells. We demonstrate that QS induces the expression of putisolvin biosurfactants that are not public goods, thereby triggering asocial motility of induced cells out of microcolonies. Phenotypic heterogeneity is most prominent in the early stages of biofilm development, whereas at later stages behaviour patterns across cells become more synchronized. Our findings broaden our perspective on QS by showing that AHLs can control the expression of asocial (self-directed) traits, and that heterogeneity in QS can serve as a mechanism to drive phenotypic heterogeneity in self-directed behaviour. PMID:25592773

Cárcamo-Oyarce, Gerardo; Lumjiaktase, Putthapoom; Kümmerli, Rolf; Eberl, Leo

2015-01-01

231

Antibiotic-Mediated Selection of Quorum-Sensing-Negative Staphylococcus aureus  

PubMed Central

ABSTRACT Staphylococcus aureus is a human commensal that at times turns into a serious bacterial pathogen causing life-threatening infections. For the delicate control of virulence, S. aureus employs the agr quorum-sensing system that, via the intracellular effector molecule RNAIII, regulates virulence gene expression. We demonstrate that the presence of the agr locus imposes a fitness cost on S. aureus that is mediated by the expression of RNAIII. Further, we show that exposure to sublethal levels of the antibiotics ciprofloxacin, mupirocin, and rifampin, each targeting separate cellular functions, markedly increases the agr-mediated fitness cost by inducing the expression of RNAIII. Thus, the extensive use of antibiotics in hospitals may explain why agr-negative variants are frequently isolated from hospital-acquired S. aureus infections but rarely found among community-acquired S. aureus strains. Importantly, agr deficiency correlates with increased duration of and mortality due to bacteremia during antibiotic treatment and with a higher frequency of glycopeptide resistance than in agr-carrying strains. Our results provide an explanation for the frequent isolation of agr-defective strains from hospital-acquired S. aureus infections and suggest that the adaptability of S. aureus to antibiotics involves the agr locus. PMID:23143800

Paulander, Wilhelm; Nissen Varming, Anders; Bæk, Kristoffer T.; Haaber, Jakob; Frees, Dorte; Ingmer, Hanne

2012-01-01

232

Negative Regulation of Quorum-Sensing Systems in Pseudomonas aeruginosa by ATP-Dependent Lon Protease?  

PubMed Central

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. PMID:18408026

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

2008-01-01

233

Inhibition of quorum sensing mediated biofilm development and virulence in uropathogens by Hyptis suaveolens.  

PubMed

Bacterial urinary tract infections (UTIs) are the most common nosocomial infections, accounting for about 40 % of all hospital-acquired infections. The bacterial spectrum of nosocomial UTIs is broad and the treatment of UTIs is becoming difficult owing to the emergence of drug resistance. Therefore, it is reasonable to investigate novel and alternative therapeutic strategies to treat UTIs. Since UTIs are caused by uropathogens with quorum sensing (QS)-dependent biofilm forming abilities, interruption of QS systems may be a novel approach to combat drug resistance. In the present study, a methanol extract (and hexane extract derived from it) of the medicinal plant Hyptis suaveolens (L.) were shown to have anti-QS activity against the biosensor strain Chromobacterium violaceum (ATCC 12472). Furthermore, the hexane extract of H. suaveolens (HEHS) inhibited biofilm formation by uropathogens such as Escherichia coli, Proteus vulgaris, Proteus mirabilis, Klebsiella pneumoniae and Serratia marcescens. HEHS promotes the loosening of biofilm architecture and strongly inhibits in vitro biofilm formation by uropathogens, which was more apparent from microscopic images. In addition to this, HEHS reduces the production of QS-dependent virulence factors like protease and hemolysin, along with motility. The partial purification and GC-MS analysis of the active fraction revealed the presence of several therapeutically important compounds which may synergistically act on the uropathogens and possibly reduce the QS-dependent phenotypes. These findings suggest HEHS as potential phytotherapeutic agent which can be employed to formulate protective strategies against biofilm linked infections caused by uropathogens. PMID:25656290

Salini, Ramesh; Sindhulakshmi, Muthukrishnan; Poongothai, Thirumaran; Pandian, Shunmugiah Karutha

2015-04-01

234

Inhibition of quorum sensing in Chromobacterium violaceum by Syzygium cumini L. and Pimenta dioica L.  

PubMed Central

Objective To investigated into the anti-quorum sensing (QS) activity of Syzygium cumini L. (S. cumini) and Pimenta dioica L. (P. dioica) using Chromobacterium violaceum (C. violaceum) strains. Methods In this study, anti-QS activity of ethanol extract of Syzygium cumini L. and Pimenta dioica L. were screened using C. violaceum CV026 biosensor bioassay. By bioassay guided fractionation of S. cumini and P. dioica, ethyl acetate fraction (EAF) with strong anti-QS activity was separated. Inhibition of QS regulated violacein production in C. violaceum ATCC12472 by EAF was assessed at different concentrations. The effect of EAF on the synthesis of autoinducer like N-acyl homoserine lactone (AHL) was studied in C. violaceum ATCC31532 using its mutant C. violaceum CV026 by standard methods. Results EAF inhibited violacein production in C. violaceum ATCC12472 in a concentration dependent manner without significant reduction in bacterial growth. Complete inhibition of violacein production was evidenced in 0.75-1.0 mg/mL concentration of EAF without inhibiting the synthesis of the AHL. TLC biosensor overlay profile of EAF revealed two translucent spots in S. cumini and P. dioica that inhibited C6-AHL mediated violacein production in C. violaceum CV026. Conclusions This study indicates the anti-QS activity of the tested medicinal plants against C. violaceum. PMID:24093786

Vasavi, Halkare Suryanarayana; Arun, Ananthapadmanabha Bhagwath; Rekha, Punchapady Devasya

2013-01-01

235

Identification of an rsh gene from a Novosphingobium sp. necessary for quorum-sensing signal accumulation.  

PubMed

The stringent response is a mechanism by which bacteria adapt to environmental stresses and nutritional deficiencies through the synthesis and hydrolysis of (p)ppGpp by RelA/SpoT enzymes. Alphaproteobacteria and plants contain a single Rsh enzyme (named for RelA/SpoT homolog) that is bifunctional. Here we report the identification of a new species of bacteria belonging to the genus Novosphingobium and characterization of an rsh mutation in this plant tumor-associated isolate. Isolate Rr 2-17, from a grapevine crown gall tumor, is a member of the Novosphingobium genus that produces the N-acyl-homoserine lactone (AHL) quorum-sensing (QS) signals. A Tn5 mutant, Hx 699, deficient in AHL production was found to have an insertion in an rsh gene. The Rsh protein showed significant percent sequence identity to Rsh proteins of alphaproteobacteria. The Novosphingobium sp. rsh gene (rsh(Nsp)) complemented the multiple amino acid requirements of the Escherichia coli relA spoT double mutant by restoring the growth on selection media. Besides QS signal production, the rsh mutation also affects soluble polysaccharide production and cell aggregation. Genetic complementation of the Hx 699 mutant with the rsh(Nsp) gene restored these phenotypes. This is the first discovery of a functional rsh gene in a member of the Novosphingobium genus. PMID:19201802

Gan, Han Ming; Buckley, Larry; Szegedi, Erno; Hudson, André O; Savka, Michael A

2009-04-01

236

Detecting the molecular signature of social conflict: theory and a test with bacterial quorum sensing genes.  

PubMed

Extending social evolution theory to the molecular level opens the door to an unparalleled abundance of data and statistical tools for testing alternative hypotheses about the long-term evolutionary dynamics of cooperation and conflict. To this end, we take a collection of known sociality genes (bacterial quorum sensing [QS] genes), model their evolution in terms of patterns that are detectable using gene sequence data, and then test model predictions using available genetic data sets. Specifically, we test two alternative hypotheses of social conflict: (1) the "adaptive" hypothesis that cheaters are maintained in natural populations by frequency-dependent balancing selection as an evolutionarily stable strategy and (2) the "evolutionary null" hypothesis that cheaters are opposed by purifying kin selection yet exist transiently because of their recurrent introduction into populations by mutation (i.e., kin selection-mutation balance). We find that QS genes have elevated within- and among-species sequence variation, nonsignificant signatures of natural selection, and putatively small effect sizes of mutant alleles, all patterns predicted by our evolutionary null model but not by the stable cheater hypothesis. These empirical findings support our theoretical prediction that QS genes experience relaxed selection due to nonclonality of social groups, conditional expression, and the individual-level advantage enjoyed by cheaters. Furthermore, cheaters are evolutionarily transient, persisting in populations because of their recurrent introduction by mutation and not because they enjoy a frequency-dependent fitness advantage. PMID:22437174

Van Dyken, J David; Wade, Michael J

2012-04-01

237

Methylobacterium-plant interaction genes regulated by plant exudate and quorum sensing molecules  

PubMed Central

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

Dourado, Manuella Nóbrega; Bogas, Andrea Cristina; Pomini, Armando M.; Andreote, Fernando Dini; Quecine, Maria Carolina; Marsaioli, Anita J.; Araújo, Welington Luiz

2013-01-01

238

Targeting agr- and agr-Like Quorum Sensing Systems for Development of Common Therapeutics to Treat Multiple Gram-Positive Bacterial Infections  

PubMed Central

Invasive infection by the Gram-positive pathogen Staphylococcus aureus is controlled by a four gene operon, agr that encodes a quorum sensing system for the regulation of virulence. While agr has been well studied in S. aureus, the contribution of agr homologues and analogues in other Gram-positive pathogens is just beginning to be understood. Intriguingly, other significant human pathogens, including Clostridium perfringens, Listeria monocytogenes, and Enterococcus faecalis contain agr or analogues linked to virulence. Moreover, other significant human Gram-positive pathogens use peptide based quorum sensing systems to establish or maintain infection. The potential for commonality in aspects of these signaling systems across different species raises the prospect of identifying therapeutics that could target multiple pathogens. Here, we review the status of research into these agr homologues, analogues, and other peptide based quorum sensing systems in Gram-positive pathogens as well as the potential for identifying common pathways and signaling mechanisms for therapeutic discovery. PMID:23598501

Gray, Brian; Hall, Pamela; Gresham, Hattie

2013-01-01

239

Synthetic analogs of bacterial quorum sensors  

DOEpatents

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

Iyer, Rashi S.; Ganguly, Kumkum; Silks, Louis A.

2013-01-08

240

Synthetic analogs of bacterial quorum sensors  

SciTech Connect

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

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

2011-12-06

241

Pyocyanin Stimulates Quorum Sensing-Mediated Tolerance to Oxidative Stress and Increases Persister Cell Populations in Acinetobacter baumannii  

PubMed Central

Acinetobacter baumannii and Pseudomonas aeruginosa are nosocomial pathogens with overlapping sites of infection. This work reports that the two can coexist stably in mixed-culture biofilms. In a study intended to improve our understanding of the mechanism of their coexistence, it was found that pyocyanin, produced by P. aeruginosa that generally eliminates competition from other pathogens, led to the generation of reactive oxygen species (ROS) in A. baumannii cells, which in response showed a significant (P ? 0.05) increase in production of enzymes, specifically, catalase and superoxide dismutase (SOD). This work shows for the first time that the expression of catalase and SOD is under the control of a quorum-sensing system in A. baumannii. In support of this observation, a quorum-sensing mutant of A. baumannii (abaI::Km) was found to be sensitive to pyocyanin compared to its wild type and showed significantly (P ? 0.001) lower levels of the antioxidant enzymes, which increased on addition of 5 ?M N-(3-hydroxydodecanoyl)-l-homoserine lactone. Likewise, in wild-type A. baumannii, there was a significant (P < 0.01) decrease in the level of anti-oxidant enzymes in the presence of salicylic acid, a known quencher of quorum sensing. In the presence of amikacin and carbenicillin, A. baumannii formed 0.07 and 0.02% persister cells, which increased 4- and 3-fold, respectively, in the presence of pyocyanin. These findings show that pyocyanin induces a protective mechanism in A. baumannii against oxidative stress and also increases its persistence against antibiotics which could be of clinical significance in the case of coinfections with A. baumannii and P. aeruginosa. PMID:24891106

Bhargava, Nidhi; Sharma, Prince

2014-01-01

242

Marine-Derived Quorum-Sensing Inhibitory Activities Enhance the Antibacterial Efficacy of Tobramycin against Pseudomonas aeruginosa  

PubMed Central

Bacterial epiphytes isolated from marine eukaryotes were screened for the production of quorum sensing inhibitory compounds (QSIs). Marine isolate KS8, identified as a Pseudoalteromonas sp., was found to display strong quorum sensing inhibitory (QSI) activity against acyl homoserine lactone (AHL)-based reporter strains Chromobacterium violaceum ATCC 12472 and CV026. KS8 supernatant significantly reduced biofilm biomass during biofilm formation (?63%) and in pre-established, mature P. aeruginosa PAO1 biofilms (?33%). KS8 supernatant also caused a 0.97-log reduction (?89%) and a 2-log reduction (?99%) in PAO1 biofilm viable counts in the biofilm formation assay and the biofilm eradication assay respectively. The crude organic extract of KS8 had a minimum inhibitory concentration (MIC) of 2 mg/mL against PAO1 but no minimum bactericidal concentration (MBC) was observed over the concentration range tested (MBC > 16 mg/mL). Sub-MIC concentrations (1 mg/mL) of KS8 crude organic extract significantly reduced the quorum sensing (QS)-dependent production of both pyoverdin and pyocyanin in P. aeruginosa PAO1 without affecting growth. A combinatorial approach using tobramycin and the crude organic extract at 1 mg/mL against planktonic P. aeruginosa PAO1 was found to increase the efficacy of tobramycin ten-fold, decreasing the MIC from 0.75 to 0.075 µg/mL. These data support the validity of approaches combining conventional antibiotic therapy with non-antibiotic compounds to improve the efficacy of current treatments. PMID:25546516

Busetti, Alessandro; Shaw, George; Megaw, Julianne; Gorman, Sean P.; Maggs, Christine A.; Gilmore, Brendan F.

2014-01-01

243

Disruption of a Quorum Sensing mechanism triggers tumorigenesis: a simple discrete model corroborated by experiments in mammary cancer stem cells  

PubMed Central

Background The balance between self-renewal and differentiation of stem cells is expected to be tightly controlled in order to maintain tissue homeostasis throughout life, also in the face of environmental hazards. Theory, predicting that homeostasis is maintained by a negative feedback on stem cell proliferation, implies a Quorum Sensing mechanism in higher vertebrates. Results Application of this theory to a cellular automata model of stem cell development in disrupted environments shows a sharply dichotomous growth dynamics: maturation within 50-400 cell cycles, or immortalization. This dichotomy is mainly driven by intercellular communication, low intensity of which causes perpetual proliferation. Another driving force is the cells' kinetic parameters. Reduced tissue life span of differentiated cells results in uncontrolled proliferation. Model's analysis, showing that under the Quorum Sensing control, stem cell fraction within a steady state population is fixed, is corroborated by experiments in breast carcinoma cells. Experimental results show that the plating densities of CD44+ cells and of CD44+/24lo/ESA+ cells do not affect stem cell fraction near confluence. Conclusions This study suggests that stem cell immortalization may be triggered by reduced intercellular communication, rather than exclusively result from somatic evolution, and implies that stem cell proliferation can be attenuated by signal manipulation, or enhanced by cytotoxics targeted to differentiated cells. In vivo verification and identification of the Quorum Sensing mediating molecules will pave the way to a higher level control of stem cell proliferation in cancer and in tissue engineering. Reviewers This article was reviewed by Glenn Webb and Marek Kimmel. PMID:20406437

2010-01-01

244

Ribosomal frameshifting and dual-target antiactivation restrict quorum-sensing-activated transfer of a mobile genetic element.  

PubMed

Symbiosis islands are integrative and conjugative mobile genetic elements that convert nonsymbiotic rhizobia into nitrogen-fixing symbionts of leguminous plants. Excision of the Mesorhizobium loti symbiosis island ICEMlSym(R7A) is indirectly activated by quorum sensing through TraR-dependent activation of the excisionase gene rdfS. Here we show that a +1 programmed ribosomal frameshift (PRF) fuses the coding sequences of two TraR-activated genes, msi172 and msi171, producing an activator of rdfS expression named Frameshifted excision activator (FseA). Mass-spectrometry and mutational analyses indicated that the PRF occurred through +1 slippage of the tRNA(phe) from UUU to UUC within a conserved msi172-encoded motif. FseA activated rdfS expression in the absence of ICEMlSym(R7A), suggesting that it directly activated rdfS transcription, despite being unrelated to any characterized DNA-binding proteins. Bacterial two-hybrid and gene-reporter assays demonstrated that FseA was also bound and inhibited by the ICEMlSym(R7A)-encoded quorum-sensing antiactivator QseM. Thus, activation of ICEMlSym(R7A) excision is counteracted by TraR antiactivation, ribosomal frameshifting, and FseA antiactivation. This robust suppression likely dampens the inherent biological noise present in the quorum-sensing autoinduction circuit and ensures that ICEMlSym(R7A) transfer only occurs in a subpopulation of cells in which both qseM expression is repressed and FseA is translated. The architecture of the ICEMlSym(R7A) transfer regulatory system provides an example of how a set of modular components have assembled through evolution to form a robust genetic toggle that regulates gene transcription and translation at both single-cell and cell-population levels. PMID:25787256

Ramsay, Joshua P; Tester, Laura G L; Major, Anthony S; Sullivan, John T; Edgar, Christina D; Kleffmann, Torsten; Patterson-House, Jackson R; Hall, Drew A; Tate, Warren P; Hynes, Michael F; Ronson, Clive W

2015-03-31

245

Development of a Mimotope Vaccine Targeting the Staphylococcus aureus Quorum Sensing Pathway  

PubMed Central

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

Triplett, Kathleen D.; Peabody, David; Chackerian, Bryce

2014-01-01

246

Phylogenetically novel LuxI/LuxR-type quorum sensing systems isolated using a metagenomic approach.  

PubMed

A great deal of research has been done to understand bacterial cell-to-cell signaling systems, but there is still a large gap in our current knowledge because the majority of microorganisms in natural environments do not have cultivated representatives. Metagenomics is one approach to identify novel quorum sensing (QS) systems from uncultured bacteria in environmental samples. In this study, fosmid metagenomic libraries were constructed from a forest soil and an activated sludge from a coke plant, and the target genes were detected using a green fluorescent protein (GFP)-based Escherichia coli biosensor strain whose fluorescence was screened by spectrophotometry. DNA sequence analysis revealed two pairs of new LuxI family N-acyl-L-homoserine lactone (AHL) synthases and LuxR family transcriptional regulators (clones N16 and N52, designated AubI/AubR and AusI/AusR, respectively). AubI and AusI each produced an identical AHL, N-dodecanoyl-L-homoserine lactone (C(12)-HSL), as determined by nuclear magnetic resonance (NMR) and mass spectrometry. Phylogenetic analysis based on amino acid sequences suggested that AusI/AusR was from an uncultured member of the Betaproteobacteria and AubI/AubR was very deeply branched from previously described LuxI/LuxR homologues in isolates of the Proteobacteria. The phylogenetic position of AubI/AubR indicates that they represent a QS system not acquired recently from the Proteobacteria by horizontal gene transfer but share a more ancient ancestry. We demonstrated that metagenomic screening is useful to provide further insight into the phylogenetic diversity of bacterial QS systems by describing two new LuxI/LuxR-type QS systems from uncultured bacteria. PMID:22983963

Nasuno, Eri; Kimura, Nobutada; Fujita, Masaki J; Nakatsu, Cindy H; Kamagata, Yoichi; Hanada, Satoshi

2012-11-01

247

What Does the Talking?: Quorum Sensing Signalling Genes Discovered in a Bacteriophage Genome  

PubMed Central

The transfer of novel genetic material into the genomes of bacterial viruses (phages) has been widely documented in several host-phage systems. Bacterial genes are incorporated into the phage genome and, if retained, subsequently evolve within them. The expression of these phage genes can subvert or bolster bacterial processes, including altering bacterial pathogenicity. The phage phiCDHM1 infects Clostridium difficile, a pathogenic bacterium that causes nosocomial infections and is associated with antibiotic treatment. Genome sequencing and annotation of phiCDHM1 shows that despite being closely related to other C. difficile myoviruses, it has several genes that have not been previously reported in any phage genomes. Notably, these include three homologs of bacterial genes from the accessory gene regulator (agr) quorum sensing (QS) system. These are; a pre-peptide (AgrD) of an autoinducing peptide (AIP), an enzyme which processes the pre-peptide (AgrB) and a histidine kinase (AgrC) that detects the AIP to activate a response regulator. Phylogenetic analysis of the phage and C. difficile agr genes revealed that there are three types of agr loci in this species. We propose that the phage genes belonging to a third type, agr3, and have been horizontally transferred from the host. AgrB and AgrC are transcribed during the infection of two different strains. In addition, the phage agrC appears not to be confined to the phiCDHM1 genome as it was detected in genetically distinct C. difficile strains. The discovery of QS gene homologs in a phage genome presents a novel way in which phages could influence their bacterial hosts, or neighbouring bacterial populations. This is the first time that these QS genes have been reported in a phage genome and their distribution both in C. difficile and phage genomes suggests that the agr3 locus undergoes horizontal gene transfer within this species. PMID:24475037

Hargreaves, Katherine R.; Kropinski, Andrew M.; Clokie, Martha R. J.

2014-01-01

248

Acyl-Homoserine Lactone Recognition and Response Hindering the Quorum-Sensing Regulator EsaR  

PubMed Central

During quorum sensing in the plant pathogen Pantoea stewartii subsp. stewartii, EsaI, an acyl-homoserine lactone (AHL) synthase, and the transcription factor EsaR coordinately control capsular polysaccharide production. The capsule is expressed only at high cell density when AHL levels are high, leading to inactivation of EsaR. In lieu of detailed structural information, the precise mechanism whereby EsaR recognizes AHL and is hindered by it, in a response opposite to that of most other LuxR homologues, remains unresolved. Hence, a random mutagenesis genetic approach was designed to isolate EsaR* variants that are immune to the effects of AHL. Error-prone PCR was used to generate the desired mutants, which were subsequently screened for their ability to repress transcription in the presence of AHL. Following sequencing, site-directed mutagenesis was used to generate all possible mutations of interest as single, rather than multiple amino acid substitutions. Eight individual amino acids playing a critical role in the AHL-insensitive phenotype have been identified. The ability of EsaR* variants to bind AHL and the effect of individual substitutions on the overall conformation of the protein were examined through in vitro assays. Six EsaR* variants had a decreased ability to bind AHL. Fluorescence anisotropy was used to examine the relative DNA binding affinity of the final two EsaR* variants, which retained some AHL binding capability but remained unresponsive to it, perhaps due to an inability of the N-terminal domain to transduce information to the C-terminal domain. PMID:25238602

Schu, Daniel J.; Scruggs, Jessica M.; Geissinger, Jared S.; Michel, Katherine G.; Stevens, Ann M.

2014-01-01

249

Physiological Framework for the Regulation of Quorum Sensing-Dependent Public Goods in Pseudomonas aeruginosa  

PubMed Central

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. PMID:24375105

Mellbye, Brett

2014-01-01

250

Quorum sensing controls hyphal initiation in Candida albicans through Ubr1-mediated protein degradation  

PubMed Central

Candida albicans is the most common cause of invasive fungal infections in humans. Its ability to undergo the morphological transition from yeast to hyphal growth forms is critical for its pathogenesis. Hyphal initiation requires the activation of the cAMP-PKA pathway, which down-regulates the expression of NRG1, the major repressor of hyphal development. Hyphal initiation also requires inoculation of a small amount of C. albicans cells from overnight culture to fresh medium. This inoculation releases the inhibition from farnesol, a quorum-sensing molecule of C. albicans, that accumulated in the spent medium. Here, we show that farnesol inhibits hyphal initiation mainly through blocking the protein degradation of Nrg1. Through screening a kinase mutant library, we identified Sok1 as the kinase required for Nrg1 degradation during inoculation. SOK1 expression is transiently activated on inoculation during hyphal initiation, and overexpression of SOK1 overcomes the farnesol-mediated inhibition of hyphal initiation. Screening a collection of transcription factor mutants, the homeodomain-containing transcription repressor Cup9 is found to be responsible for the repression of SOK1 expression in response to farnesol inhibition. Interestingly, farnesol inhibits Cup9 degradation mediated by the N-end rule E3 ubiquitin ligase, Ubr1. Therefore, hyphal initiation requires both the cAMP-PKA pathway-dependent transcriptional down-regulation of NRG1 and Sok1-mediated degradation of Nrg1 protein. The latter is triggered by the release from farnesol inhibition of Cup9 degradation and consequently, derepression of SOK1 transcription. Neither pathway alone is sufficient for hyphal initiation. PMID:24449897

Lu, Yang; Su, Chang; Unoje, Ohimai; Liu, Haoping

2014-01-01

251

Private link between signal and response in Bacillus subtilis quorum sensing  

PubMed Central

Bacteria coordinate their behavior using quorum sensing (QS), whereby cells secrete diffusible signals that generate phenotypic responses associated with group living. The canonical model of QS is one of extracellular signaling, where signal molecules bind to cognate receptors and cause a coordinated response across many cells. Here we study the link between QS input (signaling) and QS output (response) in the ComQXPA QS system of Bacillus subtilis by characterizing the phenotype and fitness of comQ null mutants. These lack the enzyme to produce the ComX signal and do not activate the ComQXPA QS system in other cells. In addition to the activation effect of the signal, however, we find evidence of a second, repressive effect of signal production on the QS system. Unlike activation, which can affect other cells, repression acts privately: the de-repression of QS in comQ cells is intracellular and only affects mutant cells lacking ComQ. As a result, the QS signal mutants have an overly responsive QS system and overproduce the secondary metabolite surfactin in the presence of the signal. This surfactin overproduction is associated with a strong fitness cost, as resources are diverted away from primary metabolism. Therefore, by acting as a private QS repressor, ComQ may be protected against evolutionary competition from loss-of-function mutations. Additionally, we find that surfactin participates in a social selection mechanism that targets signal null mutants in coculture with signal producers. Our study shows that by pleiotropically combining intracellular and extracellular signaling, bacteria may generate evolutionarily stable QS systems. PMID:24425772

Oslizlo, Anna; Stefanic, Polonca; Dogsa, Iztok; Mandic-Mulec, Ines

2014-01-01

252

Regulation of universal stress protein genes by quorum sensing and RpoS in Burkholderia glumae.  

PubMed

Burkholderia glumae possesses a quorum-sensing (QS) system mediated by N-octanoyl-homoserine lactone (C(8)-HSL) and its cognate receptor TofR. TofR/C(8)-HSL regulates the expression of a transcriptional regulator, qsmR. We identified one of the universal stress proteins (Usps), Usp2, from a genome-wide analysis of QS-dependent proteomes of B. glumae. In the whole genome of B. glumae BGR1, 11 usp genes (usp1 to usp11) were identified. Among the stress conditions tested, usp1 and usp2 mutants died 1 h after heat shock stress, whereas the other usp mutants and the wild-type strain survived for more than 3 h at 45°C. The expressions of all usp genes were positively regulated by QS, directly by QsmR. In addition, the expressions of usp1 and usp2 were dependent on RpoS in the stationary phase, as confirmed by the direct binding of RpoS-RNA holoenzyme to the promoter regions of the usp1 and usp2 genes. The expression of usp1 was upregulated upon a temperature shift from 37°C to either 28°C or 45°C, whereas the expression of usp2 was independent of temperature stress. This indicates that the regulation of usp1 and usp2 expression is different from what is known about Escherichia coli. Compared to the diverse roles of Usps in E. coli, Usps in B. glumae are dedicated to heat shock stress. PMID:22178971

Kim, Hongsup; Goo, Eunhye; Kang, Yongsung; Kim, Jinwoo; Hwang, Ingyu

2012-03-01

253

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

PubMed

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

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

2015-04-01

254

Prediction and Analysis of Quorum Sensing Peptides Based on Sequence Features  

PubMed Central

Quorum sensing peptides (QSPs) are the signaling molecules used by the Gram-positive bacteria in orchestrating cell-to-cell communication. In spite of their enormous importance in signaling process, their detailed bioinformatics analysis is lacking. In this study, QSPs and non-QSPs were examined according to their amino acid composition, residues position, motifs and physicochemical properties. Compositional analysis concludes that QSPs are enriched with aromatic residues like Trp, Tyr and Phe. At the N-terminal, Ser was a dominant residue at maximum positions, namely, first, second, third and fifth while Phe was a preferred residue at first, third and fifth positions from the C-terminal. A few motifs from QSPs were also extracted. Physicochemical properties like aromaticity, molecular weight and secondary structure were found to be distinguishing features of QSPs. Exploiting above properties, we have developed a Support Vector Machine (SVM) based predictive model. During 10-fold cross-validation, SVM achieves maximum accuracy of 93.00%, Mathew’s correlation coefficient (MCC) of 0.86 and Receiver operating characteristic (ROC) of 0.98 on the training/testing dataset (T200p+200n). Developed models performed equally well on the validation dataset (V20p+20n). The server also integrates several useful analysis tools like “QSMotifScan”, “ProtFrag”, “MutGen” and “PhysicoProp”. Our analysis reveals important characteristics of QSPs and on the basis of these unique features, we have developed a prediction algorithm “QSPpred” (freely available at: http://crdd.osdd.net/servers/qsppred). PMID:25781990

Rajput, Akanksha; Gupta, Amit Kumar; Kumar, Manoj

2015-01-01

255

Use of Bacterial Quorum-Sensing Components to Regulate Gene Expression in Plants1[W  

PubMed Central

We describe an efficient inducible system to regulate gene expression in plants based on quorum-sensing components found in Gram-negative bacteria such as Agrobacterium tumefaciens. These bacteria monitor their own population density by utilizing members of the N-acyl homoserine lactone family as inducers and a transcriptional activator as its receptor. In our study, we utilize the components from A. tumefaciens (i.e. 3-oxooctanyl-l-homoserine lactone [OOHL]) synthesized by the TraI protein and its receptor, TraR. When OOHL binds to TraR, it recognizes its specific cis-element, the tra box. We translationally fused the eukaryotic VP16 activation domain to the N terminus of TraR. In the presence of OOHL, the chimeric VP16:TraR transcriptional regulator induces reporter gene expression in moss (Physcomitrella patens), barley (Hordeum vulgare), and carrot (Daucus carota) cells, as well as in transgenic Arabidopsis (Arabidopsis thaliana) seedlings. The inducible system shows a low level of reporter gene expression in the absence of the inducer. Foliar application and a floating-leaf assay in the presence of the inducer shows a 30- and 200-fold induction, respectively. Induction by foliar application of the inducer to whole seedlings is achieved within 8 h. The VP16:TraR activator also shows specificity for binding to its cognate inducer, OOHL. Based on microarray analyses, endogenous gene expression is not significantly affected due to overexpression of the TraR protein or presence of OOHL in either wild-type or lactone-inducible transgenic plants. PMID:16607032

You, Young-Sook; Marella, Heather; Zentella, Rodolfo; Zhou, Yiyong; Ulmasov, Tim; Ho, Tuan-Hua David; Quatrano, Ralph S.

2006-01-01

256

Quercetin Sensitizes Fluconazole-Resistant Candida albicans To Induce Apoptotic Cell Death by Modulating Quorum Sensing.  

PubMed

Quorum sensing (QS) regulates group behaviors of Candida albicans such as biofilm, hyphal growth, and virulence factors. The sesquiterpene alcohol farnesol, a QS molecule produced by C. albicans, is known to regulate the expression of virulence weapons of this fungus. Fluconazole (FCZ) is a broad-spectrum antifungal drug that is used for the treatment of C. albicans infections. While FCZ can be cytotoxic at high concentrations, our results show that at much lower concentrations, quercetin (QC), a dietary flavonoid isolated from an edible lichen (Usnea longissima), can be implemented as a sensitizing agent for FCZ-resistant C. albicans NBC099, enhancing the efficacy of FCZ. QC enhanced FCZ-mediated cell killing of NBC099 and also induced cell death. These experiments indicated that the combined application of both drugs was FCZ dose dependent rather than QC dose dependent. In addition, we found that QC strongly suppressed the production of virulence weapons-biofilm formation, hyphal development, phospholipase, proteinase, esterase, and hemolytic activity. Treatment with QC also increased FCZ-mediated cell death in NBC099 biofilms. Interestingly, we also found that QC enhances the anticandidal activity of FCZ by inducing apoptotic cell death. We have also established that this sensitization is reliant on the farnesol response generated by QC. Molecular docking studies also support this conclusion and suggest that QC can form hydrogen bonds with Gln969, Thr1105, Ser1108, Arg1109, Asn1110, and Gly1061 in the ATP binding pocket of adenylate cyclase. Thus, this QS-mediated combined sensitizer (QC)-anticandidal agent (FCZ) strategy may be a novel way to enhance the efficacy of FCZ-based therapy of C. albicans infections. PMID:25645848

Singh, B N; Upreti, D K; Singh, B R; Pandey, G; Verma, S; Roy, S; Naqvi, A H; Rawat, A K S

2015-04-01

257

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

PubMed Central

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

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

2015-01-01

258

Staphylococcus epidermidis agr Quorum-Sensing System: Signal Identification, Cross Talk, and Importance in Colonization  

PubMed Central

Staphylococcus epidermidis is an opportunistic pathogen that is one of the leading causes of medical device infections. Global regulators like the agr quorum-sensing system in this pathogen have received a limited amount of attention, leaving important questions unanswered. There are three agr types in S. epidermidis strains, but only one of the autoinducing peptide (AIP) signals has been identified (AIP-I), and cross talk between agr systems has not been tested. We structurally characterized all three AIP types using mass spectrometry and discovered that the AIP-II and AIP-III signals are 12 residues in length, making them the largest staphylococcal AIPs identified to date. S. epidermidis agr reporter strains were developed for each system, and we determined that cross-inhibitory interactions occur between the agr type I and II systems and between the agr type I and III systems. In contrast, no cross talk was observed between the type II and III systems. To further understand the outputs of the S. epidermidis agr system, an RNAIII mutant was constructed, and microarray studies revealed that exoenzymes (Ecp protease and Geh lipase) and low-molecular-weight toxins were downregulated in the mutant. Follow-up analysis of Ecp confirmed the RNAIII is required to induce protease activity and that agr cross talk modulates Ecp activity in a manner that mirrors the agr reporter results. Finally, we demonstrated that the agr system enhances skin colonization by S. epidermidis using a porcine model. This work expands our knowledge of S. epidermidis agr system function and will aid future studies on cell-cell communication in this important opportunistic pathogen. PMID:25070736

Olson, Michael E.; Todd, Daniel A.; Schaeffer, Carolyn R.; Paharik, Alexandra E.; Van Dyke, Michael J.; Büttner, Henning; Dunman, Paul M.; Rohde, Holger; Cech, Nadja B.; Fey, Paul D.

2014-01-01

259

A Novel Signal Transduction Pathway that Modulates rhl Quorum Sensing and Bacterial Virulence in Pseudomonas aeruginosa  

PubMed Central

The rhl quorum-sensing (QS) system plays critical roles in the pathogenesis of P. aeruginosa. However, the regulatory effects that occur directly upstream of the rhl QS system are poorly understood. Here, we show that deletion of gene encoding for the two-component sensor BfmS leads to the activation of its cognate response regulator BfmR, which in turn directly binds to the promoter and decreases the expression of the rhlR gene that encodes the QS regulator RhlR, causing the inhibition of the rhl QS system. In the absence of bfmS, the Acka-Pta pathway can modulate the regulatory activity of BfmR. In addition, BfmS tunes the expression of 202 genes that comprise 3.6% of the P. aeruginosa genome. We further demonstrate that deletion of bfmS causes substantially reduced virulence in lettuce leaf, reduced cytotoxicity, enhanced invasion, and reduced bacterial survival during acute mouse lung infection. Intriguingly, specific missense mutations, which occur naturally in the bfmS gene in P. aeruginosa cystic fibrosis (CF) isolates such as DK2 strains and RP73 strain, can produce BfmS variants (BfmSL181P, BfmSL181P/E376Q, and BfmSR393H) that no longer repress, but instead activate BfmR. As a result, BfmS variants, but not the wild-type BfmS, inhibit the rhl QS system. This study thus uncovers a previously unexplored signal transduction pathway, BfmS/BfmR/RhlR, for the regulation of rhl QS in P. aeruginosa. We propose that BfmRS TCS may have an important role in the regulation and evolution of P. aeruginosa virulence during chronic infection in CF lungs. PMID:25166864

Chen, Feifei; Xia, Yongjie; Lou, Jingyu; Zhang, Xue; Yang, Nana; Sun, Xiaoxu; Zhang, Qin; Zhuo, Chao; Huang, Xi; Deng, Xin; Yang, Cai-Guang; Ye, Yan; Zhao, Jing; Wu, Min; Lan, Lefu

2014-01-01

260

Quorum-sensing inhibitory compounds from extremophilic microorganisms isolated from a hypersaline cyanobacterial mat.  

PubMed

In this study, extremely halophilic and moderately thermophilic microorganisms from a hypersaline microbial mat were screened for their ability to produce antibacterial, antidiatom, antialgal, and quorum-sensing (QS) inhibitory compounds. Five bacterial strains belonging to the genera Marinobacter and Halomonas and one archaeal strain belonging to the genus Haloterrigena were isolated from a microbial mat. The strains were able to grow at a maximum salinity of 22-25 % and a maximum temperature of 45-60 °C. Hexanes, dichloromethane, and butanol extracts from the strains inhibited the growth of at least one out of nine human pathogens. Only butanol extracts of supernatants of Halomonas sp. SK-1 inhibited growth of the microalga Dunaliella salina. Most extracts from isolates inhibited QS of the acyl homoserine lactone producer and reporter Chromobacterium violaceum CV017. Purification of QS inhibitory dichloromethane extracts of Marinobacter sp. SK-3 resulted in isolation of four related diketopiperazines (DKPs): cyclo(L-Pro-L-Phe), cyclo(L-Pro-L-Leu), cyclo(L-Pro-L-isoLeu), and cyclo(L-Pro-D-Phe). QS inhibitory properties of these DKPs were tested using C. violaceum CV017 and Escherichia coli-based QS reporters (pSB401 and pSB1075) deficient in AHL production. Cyclo(L-Pro-L-Phe) and cyclo(L-Pro-L-isoLeu) inhibited QS-dependent production of violacein by C. violaceum CV017. Cyclo(L-Pro-L-Phe), cyclo(L-Pro-L-Leu), and cyclo(L-Pro-L-isoLeu) reduced QS-dependent luminescence of the reporter E. coli pSB401 induced by 3-oxo-C6-HSL. Our study demonstrated the ability of halophilic and moderately thermophilic strains from a hypersaline microbial mat to produce biotechnologically relevant compounds that could be used as antifouling agents. PMID:23645384

Abed, Raeid M M; Dobretsov, Sergey; Al-Fori, Marwan; Gunasekera, Sarath P; Sudesh, Kumar; Paul, Valerie J

2013-07-01

261

QsrO a Novel Regulator of Quorum-Sensing and Virulence in Pseudomonas aeruginosa  

PubMed Central

In Pseudomonas aeruginosa, the production of many secreted virulence factors is controlled by a quorum-sensing (QS) circuit, constituted of transcriptional activators (LasR, RhlR, PqsR) and their cognate signaling molecules (3-oxo-C12-HSL, C4-HSL, PQS). QS is a cooperative behavior that is beneficial to a population but can be exploited by “QS-cheaters”, individuals which do not respond to the QS-signal, but can use public goods produced by QS-cooperators. In order to identify QS-deficient clones we designed a genetic screening based on a lasB-lacZ fusion. We isolated one clone (PT1617) deficient in QS-dependent gene expression and virulence factor production despite wild type lasR, rhlR and pqsR alleles. Whole genome sequencing of PT1617 revealed a 3,552 bp deletion encompassing ORFs PA2228-PA2229-PA2230 and the pslA gene. However, complementation of PT1617 by plasmid-encoded copies of these ORFs, did not restore QS. Unexpectedly, gene expression levels of ORFs PA2228, PA2227 (vqsM) and PA2222, located adjacent to the deletion, were 10 to 100 fold higher in mutant PT1617 than in PAO1. When expressed from a constitutive promoter on a plasmid, PA2226, alone was found to be sufficient to confer a QS-negative phenotype on PAO1 as well as on PA14. Co-expression of PA2226 and PA2225 in PAO1 further prevented induction of the type III secretion system. In summary, we have identified a novel genetic locus including ORF2226 termed qsrO (QS-repressing ORF), capable of down-regulating all three known QS-systems in P. aeruginosa. PMID:24551066

Köhler, Thilo; Ouertatani-Sakouhi, Hajer; Cosson, Pierre; van Delden, Christian

2014-01-01

262

Expanding dialogues: from natural autoinducers to non-natural analogues that modulate quorum sensing in Gram-negative bacteria†  

PubMed Central

Bacteria are capable of “communicating” their local population densities via a process termed quorum sensing (QS). Gram-negative bacteria use N-acylated l-homoserine lactones (AHLs), in conjunction with their cognate LuxR-type receptors, as their primary signalling circuit for QS. In this critical review, we examine AHL signalling in Gram-negative bacteria with a primary focus on the design of non-natural AHLs, their structure-activity relationships, and their application in chemical biological approaches to study QS. PMID:18568169

Geske, Grant D.; O’Neill, Jennifer C.; Blackwell, Helen E.

2008-01-01

263

Emergent dynamics from quorum eavesdropping.  

PubMed

Numerous bacterial species utilize quorum sensing to communicate, but crosstalk often complicates the dynamics of mixed populations. In this issue of Chemistry & Biology, Wu and colleagues take advantage of synthetic gene circuits to elucidate interactions between two quorum sensing systems, with potential applications to fields from infectious diseases to biosynthesis. PMID:25525988

Srimani, Jaydeep K; You, Lingchong

2014-12-18

264

Guava Leaf Extract Inhibits Quorum-Sensing and Chromobacterium violaceum Induced Lysis of Human Hepatoma Cells: Whole Transcriptome Analysis Reveals Differential Gene Expression  

PubMed Central

Quorum sensing (QS) is a process mediated via small molecules termed autoinducers (AI) that allow bacteria to respond and adjust according to the cell population density by altering the expression of multitudinous genes. Since QS governs numerous bioprocesses in bacteria, including virulence, its inhibition promises to be an ideal target for the development of novel therapeutics. We found that the aqueous leaf extract of Psidium guajava (GLE) exhibited anti-QS properties as evidenced by inhibition of violacein production in Chromobacterium violaceum and swarming motility of Pseudomonas aeruginosa. The gram-negative bacterium, C. violaceum is a rare pathogen with high mortality rate. In this study, perhaps for the first time, we identified the target genes of GLE in C. violaceum MTCC 2656 by whole transcriptome analysis on Ion Torrent. Our data revealed that GLE significantly down-regulated 816 genes at least three fold, with p value?0.01, which comprises 19% of the C. violaceum MTCC 2656 genome. These genes were distributed throughout the genome and were associated with virulence, motility and other cellular processes, many of which have been described as quorum regulated in C. violaceum and other gram negative bacteria. Interestingly, GLE did not affect the growth of the bacteria. However, consistent with the gene expression pattern, GLE treated C. violaceum cells were restrained from causing lysis of human hepatoma cell line, HepG2, indicating a positive relationship between the QS-regulated genes and pathogenicity. Overall, our study proposes GLE as a QS inhibitor (QSI) with the ability to attenuate virulence without affecting growth. To the best of our knowledge, this is the first report which provides with a plausible set of candidate genes regulated by the QS system in the neglected pathogen C. violaceum. PMID:25229331

Tiwary, Bipransh Kumar; Kumar, Anoop

2014-01-01

265

Quorum quenching enzymes.  

PubMed

Bacteria use cell-to-cell communication systems based on chemical signal molecules to coordinate their behavior within the population. These quorum sensing systems are potential targets for antivirulence therapies, because many bacterial pathogens control the expression of virulence factors via quorum sensing networks. Since biofilm maturation is also usually influenced by quorum sensing, quenching these systems may contribute to combat biofouling. One possibility to interfere with quorum sensing is signal inactivation by enzymatic degradation or modification. Such quorum quenching enzymes are wide-spread in the bacterial world and have also been found in eukaryotes. Lactonases and acylases that hydrolyze N-acyl homoserine lactone (AHL) signaling molecules have been investigated most intensively, however, different oxidoreductases active toward AHLs or 2-alkyl-4(1H)-quinolone signals as well as other signal-converting enzymes have been described. Several approaches have been assessed which aim at alleviating virulence, or biofilm formation, by reducing the signal concentration in the bacterial environment. These involve the application or stimulation of signal-degrading bacteria as biocontrol agents in the protection of crop plants against soft-rot disease, the use of signal-degrading bacteria as probiotics in aquaculture, and the immobilization or entrapment of quorum quenching enzymes or bacteria to control biofouling in membrane bioreactors. While most approaches to use quorum quenching as antivirulence strategy are still in the research phase, the growing number of organisms and enzymes known to interfere with quorum sensing opens up new perspectives for the development of innovative antibacterial strategies. PMID:25220028

Fetzner, Susanne

2015-05-10

266

Enterobacter asburiae strain L1: complete genome and whole genome optical mapping analysis of a quorum sensing bacterium.  

PubMed

Enterobacter asburiae L1 is a quorum sensing bacterium isolated from lettuce leaves. In this study, for the first time, the complete genome of E. asburiae L1 was sequenced using the single molecule real time sequencer (PacBio RSII) and the whole genome sequence was verified by using optical genome mapping (OpGen) technology. In our previous study, E. asburiae L1 has been reported to produce AHLs, suggesting the possibility of virulence factor regulation which is quorum sensing dependent. This evoked our interest to study the genome of this bacterium and here we present the complete genome of E. asburiae L1, which carries the virulence factor gene virK, the N-acyl homoserine lactone-based QS transcriptional regulator gene luxR and the N-acyl homoserine lactone synthase gene which we firstly named easI. The availability of the whole genome sequence of E. asburiae L1 will pave the way for the study of the QS-mediated gene expression in this bacterium. Hence, the importance and functions of these signaling molecules can be further studied in the hope of elucidating the mechanisms of QS-regulation in E. asburiae. To the best of our knowledge, this is the first documentation of both a complete genome sequence and the establishment of the molecular basis of QS properties of E. asburiae. PMID:25196111

Lau, Yin Yin; Yin, Wai-Fong; Chan, Kok-Gan

2014-01-01

267

Deducing receptor signaling parameters from in vivo analysis: LuxN/AI-1 quorum sensing in Vibrio harveyi  

PubMed Central

Summary Quorum sensing, a process of bacterial cell-cell communication, relies on production, detection, and response to autoinducer signaling molecules. Here we focus on LuxN, a nine transmembrane domain protein from Vibrio harveyi, and the founding example of membrane-bound receptors for acyl-homoserine lactone (AHL) autoinducers. Previously, nothing was known about signal recognition by membrane-bound AHL receptors. We used mutagenesis and suppressor analyses to identify the AHL-binding domain of LuxN, and discovered LuxN mutants that confer decreased and increased AHL sensitivity. Our analysis of dose-response curves of multiple LuxN mutants pins these inverse phenotypes on quantifiable opposing shifts in the free-energy bias of LuxN for its kinase and phosphatase states. To extract signaling parameters, we exploited a strong LuxN antagonist, one of fifteen small-molecule antagonists we identified. We find that quorum-sensing-mediated communication can be manipulated positively and negatively to control bacterial behavior, and that signaling parameters can be deduced from in vivo data. PMID:18692469

Swem, Lee R.; Swem, Danielle L.; Wingreen, Ned S.; Bassler, Bonnie L.

2008-01-01

268

The Vibrio cholerae quorum-sensing autoinducer CAI-1: analysis of the biosynthetic enzyme CqsA  

SciTech Connect

Vibrio cholerae, the bacterium that causes the disease cholera, controls virulence factor production and biofilm development in response to two extracellular quorum-sensing molecules, called autoinducers. The strongest autoinducer, called CAI-1 (for cholera autoinducer-1), was previously identified as (S)-3-hydroxytridecan-4-one. Biosynthesis of CAI-1 requires the enzyme CqsA. Here, we determine the CqsA reaction mechanism, identify the CqsA substrates as (S)-2-aminobutyrate and decanoyl coenzyme A, and demonstrate that the product of the reaction is 3-aminotridecan-4-one, dubbed amino-CAI-1. CqsA produces amino-CAI-1 by a pyridoxal phosphate-dependent acyl-CoA transferase reaction. Amino-CAI-1 is converted to CAI-1 in a subsequent step via a CqsA-independent mechanism. Consistent with this, we find cells release {ge}100 times more CAI-1 than amino-CAI-1. Nonetheless, V. cholerae responds to amino-CAI-1 as well as CAI-1, whereas other CAI-1 variants do not elicit a quorum-sensing response. Thus, both CAI-1 and amino-CAI-1 have potential as lead molecules in the development of an anticholera treatment.

Kelly, R.; Bolitho, M; Higgins, D; Lu, W; Ng, W; Jeffrey, P; Rabinowitz, J; Semmelhack, M; Hughson, F; Bassler, B

2009-01-01

269

ComQXPA Quorum Sensing Systems May Not Be Unique to Bacillus subtilis: A Census in Prokaryotic Genomes  

PubMed Central

The comQXPA locus of Bacillus subtilis encodes a quorum sensing (QS) system typical of Gram positive bacteria. It encodes four proteins, the ComQ isoprenyl transferase, the ComX pre-peptide signal, the ComP histidine kinase, and the ComA response regulator. These are encoded by four adjacent genes all situated on the same chromosome strand. Here we present results of a comprehensive census of comQXPA-like gene arrangements in 2620 complete and 6970 draft prokaryotic genomes (sequenced by the end of 2013). After manually checking the data for false-positive and false-negative hits, we found 39 novel com-like predictions. The census data show that in addition to B. subtilis and close relatives, 20 comQXPA-like loci are predicted to occur outside the B. subtilis clade. These include some species of Clostridiales order, but none outside the phylum Firmicutes. Characteristic gene-overlap patterns were observed in comQXPA loci, which were different for the B. subtilis-like and non-B. subtilis-like clades. Pronounced sequence variability associated with the ComX peptide in B. subtilis clade is evident also in the non-B. subtilis clade suggesting grossly similar evolutionary constraints in the underlying quorum sensing systems. PMID:24788106

Marsetic, Ziva; Hudaiberdiev, Sanjarbek; Vera, Roberto; Pongor, Sándor; Mandic-Mulec, Ines

2014-01-01

270

A Modular View of the Diversity of Cell-Density-Encoding Schemes in Bacterial Quorum-Sensing Systems  

PubMed Central

Certain environmental parameters are accessible to cells only indirectly and require an encoding step for cells to retrieve the relevant information. A prominent example is the phenomenon of quorum sensing by microorganisms, where information about cell density is encoded by means of secreted signaling molecules. The mapping of cell density to signal molecule concentration and the corresponding network modules involved have been at least partially characterized in many bacteria, and vary markedly between different systems. In this study, we investigate theoretically how differences in signal transport, signal modification, and site of signal detection shape the encoding function and affect the sensitivity and the noise characteristics of the cell-density-encoding process. We find that different modules are capable of implementing both fairly basic as well as more complex encoding schemes, whose qualitative characteristics vary with cell density and are linked to network architecture, providing the basis for a hierarchical classification scheme. We exploit the tight relationship between encoding behavior and network architecture to constrain the network topology of partially characterized natural systems, and verify one such prediction by showing experimentally that Vibrio harveyi is capable of importing Autoinducer 2. The framework developed in this research can serve not only to guide reverse engineering of natural systems but also to stimulate the design of synthetic systems and generally facilitate a better understanding of the complexities arising in the quorum-sensing process because of variations in the physical organization of the encoder network module. PMID:24988360

Drees, Bastian; Reiger, Matthias; Jung, Kirsten; Bischofs, Ilka B.

2014-01-01

271

Alveolar epithelium protects macrophages from quorum sensing-induced cytotoxicity in a three-dimensional co-culture model.  

PubMed

The quorum sensing signal N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C(12) HSL), produced by Pseudomonas aeruginosa, exerts cytotoxic effects in macrophages in vitro, which is believed to affect host innate immunity in vivo. However, the medical significance of this finding to pulmonary disease remains unclear since the multicellular complexity of the lung was not considered in the assessment of macrophage responses to 3-oxo-C(12) HSL. We developed a novel three-dimensional co-culture model of alveolar epithelium and macrophages using the rotating wall vessel (RWV) bioreactor, by adding undifferentiated monocytes to RWV-derived alveolar epithelium. Our three-dimensional model expressed important architectural/phenotypic hallmarks of the parental tissue, as evidenced by highly differentiated epithelium, spontaneous differentiation of monocytes to functional macrophage-like cells, localization of these cells on the alveolar surface and a macrophage-to-epithelial cell ratio relevant to the in vivo situation. Co-cultivation of macrophages with alveolar epithelium counteracted 3-oxo-C(12) HSL-induced cytotoxicity via removal of quorum sensing molecules by alveolar cells. Furthermore, 3-oxo-C(12) HSL induced the intercellular adhesion molecule ICAM-1 in both alveolar epithelium and macrophages. These data stress the importance of multicellular organotypic models to integrate the role of different cell types in overall lung homeostasis and disease development in response to external factors. PMID:21054742

Crabbé, Aurélie; Sarker, Shameema F; Van Houdt, Rob; Ott, C Mark; Leys, Natalie; Cornelis, Pierre; Nickerson, Cheryl A

2011-03-01

272

Dynamics of the quorum sensing switch: stochastic and non-stationary effects  

PubMed Central

Background A wide range of bacteria species are known to communicate through the so called quorum sensing (QS) mechanism by means of which they produce a small molecule that can freely diffuse in the environment and in the cells. Upon reaching a threshold concentration, the signalling molecule activates the QS-controlled genes that promote phenotypic changes. This mechanism, for its simplicity, has become the model system for studying the emergence of a global response in prokaryotic cells. Yet, how cells precisely measure the signal concentration and act coordinately, despite the presence of fluctuations that unavoidably affects cell regulation and signalling, remains unclear. Results We propose a model for the QS signalling mechanism in Vibrio fischeri based on the synthetic strains lux01 and lux02. Our approach takes into account the key regulatory interactions between LuxR and LuxI, the autoinducer transport, the cellular growth and the division dynamics. By using both deterministic and stochastic models, we analyze the response and dynamics at the single-cell level and compare them to the global response at the population level. Our results show how fluctuations interfere with the synchronization of the cell activation and lead to a bimodal phenotypic distribution. In this context, we introduce the concept of precision in order to characterize the reliability of the QS communication process in the colony. We show that increasing the noise in the expression of LuxR helps cells to get activated at lower autoinducer concentrations but, at the same time, slows down the global response. The precision of the QS switch under non-stationary conditions decreases with noise, while at steady-state it is independent of the noise value. Conclusions Our in silico experiments show that the response of the LuxR/LuxI system depends on the interplay between non-stationary and stochastic effects and that the burst size of the transcription/translation noise at the level of LuxR controls the phenotypic variability of the population. These results, together with recent experimental evidences on LuxR regulation in wild-type species, suggest that bacteria have evolved mechanisms to regulate the intensity of those fluctuations. PMID:23324134

2013-01-01

273

The influence of quorum sensing in compartment II of the MELiSSA loop  

NASA Astrophysics Data System (ADS)

MELiSSA (Micro-Ecological Life Support System Alternative) has been conceived as a 5 compartments microorganisms and higher plants recycling system for long haul space flights. Rhodospirillum rubrum S1H colonizes compartment II. Previous work reported that continuous culture of the bacterium in a photobioreactor could lead to thick biofilm formation, leading to bioreactor arrest. Our aim is to investigate the unknown quorum sensing (QS) system of R. rubrum S1H, specifically under MELiSSA relevant culture conditions meaning light anaerobic (LAN) and using acetate as carbon source. In that purpose an autoinducer synthase gene (Rru_A3396) knockout mutant was constructed by allelic exchange generating strain M68. In addition phenotypic comparison between wild type (WT) and M68 was performed. Results of thin layer chromatography assay where Agrobacterium tumefaciens NT1 have been used as reporter strain showed that WT produces acyl-homoserine lactones (AHLs) from C4 to C12 acyl carbon chain length; however, in M68 no AHLs were detected confirming that gene Rru_A3396 (named rruI) encodes an autoinducer synthase. Interestingly under a low shear or static environment M68 showed cell aggregation similar as reported in a closely related bacterium Rhodobacter sphaeroides (cerI mutant). In contrast to WT, M68 did not form biofilm and exhibited a decreased motility and pigment content. M68 vs wild type transcriptomics results showed that 326 genes were statistically significant differentially expressed. Downregulation of genes related to photosynthesis e.g., reaction center subunits, light harvesting complex and photosynthetic assembly proteins was observed. Similar results were obtained for preliminary proteomic analysis. Results obtained showed that in R. rubrum S1H the AHL-based QS system regulates almost 8% of the genome which is linked to biofilm formation among other biological processes described above. Since strain M68 could not be used in compartment II due to its less effective photosynthetic apparatus (among other cellular functions) we are investigating other alternatives to avoid biofilm formation.

Condori, Sandra; Mastroleo, Felice; Wattiez, Ruddy; Leys, Natalie

274

Enterohemorrhagic Escherichia coli O157:H7 requires quorum sensing transcriptional regulators QseA and SdiA for colonization and persistence in the bovine intestinal tract  

Technology Transfer Automated Retrieval System (TEKTRAN)

QseA and SdiA are two of several transcriptional regulators that regulate virulence gene expression of enterohemorrhagic Escherichia coli (EHEC) O157:H7 via quorum sensing (QS). QseA regulates the expression of the locus of enterocyte effacement (LEE). LEE encodes for a type III secretion (T3S) sys...

275

Quorum Sensing in Bacillus thuringiensis Is Required for Completion of a Full Infectious Cycle in the Insect  

PubMed Central

Bacterial cell-cell communication or quorum sensing (QS) is a biological process commonly described as allowing bacteria belonging to a same pherotype to coordinate gene expression to cell density. In Gram-positive bacteria, cell-cell communication mainly relies on cytoplasmic sensors regulated by secreted and re-imported signaling peptides. The Bacillus quorum sensors Rap, NprR, and PlcR were previously identified as the first members of a new protein family called RNPP. Except for the Rap proteins, these RNPP regulators are transcription factors that directly regulate gene expression. QS regulates important biological functions in bacteria of the Bacillus cereus group. PlcR was first characterized as the main regulator of virulence in B. thuringiensis and B. cereus. More recently, the PlcR-like regulator PlcRa was characterized for its role in cysteine metabolism and in resistance to oxidative stress. The NprR regulator controls the necrotrophic properties allowing the bacteria to survive in the infected host. The Rap proteins negatively affect sporulation via their interaction with a phosphorelay protein involved in the activation of Spo0A, the master regulator of this differentiation pathway. In this review we aim at providing a complete picture of the QS systems that are sequentially activated during the lifecycle of B. cereus and B. thuringiensis in an insect model of infection. PMID:25089349

Slamti, Leyla; Perchat, Stéphane; Huillet, Eugénie; Lereclus, Didier

2014-01-01

276

Quorum sensing in Bacillus thuringiensis is required for completion of a full infectious cycle in the insect.  

PubMed

Bacterial cell-cell communication or quorum sensing (QS) is a biological process commonly described as allowing bacteria belonging to a same pherotype to coordinate gene expression to cell density. In Gram-positive bacteria, cell-cell communication mainly relies on cytoplasmic sensors regulated by secreted and re-imported signaling peptides. The Bacillus quorum sensors Rap, NprR, and PlcR were previously identified as the first members of a new protein family called RNPP. Except for the Rap proteins, these RNPP regulators are transcription factors that directly regulate gene expression. QS regulates important biological functions in bacteria of the Bacillus cereus group. PlcR was first characterized as the main regulator of virulence in B. thuringiensis and B. cereus. More recently, the PlcR-like regulator PlcRa was characterized for its role in cysteine metabolism and in resistance to oxidative stress. The NprR regulator controls the necrotrophic properties allowing the bacteria to survive in the infected host. The Rap proteins negatively affect sporulation via their interaction with a phosphorelay protein involved in the activation of Spo0A, the master regulator of this differentiation pathway. In this review we aim at providing a complete picture of the QS systems that are sequentially activated during the lifecycle of B. cereus and B. thuringiensis in an insect model of infection. PMID:25089349

Slamti, Leyla; Perchat, Stéphane; Huillet, Eugénie; Lereclus, Didier

2014-08-01

277

The phosphotransferase VanU represses expression of four qrr genes antagonizing VanO-mediated quorum-sensing regulation in Vibrio anguillarum  

PubMed Central

Vibrio anguillarum utilizes quorum sensing to regulate stress responses required for survival in the aquatic environment. Like other Vibrio species, V. anguillarum contains the gene qrr1, which encodes the ancestral quorum regulatory RNA Qrr1, and phosphorelay quorum-sensing systems that modulate the expression of small regulatory RNAs (sRNAs) that destabilize mRNA encoding the transcriptional regulator VanT. In this study, three additional Qrr sRNAs were identified. All four sRNAs were positively regulated by ?54 and the ?54-dependent response regulator VanO, and showed a redundant activity. The Qrr sRNAs, together with the RNA chaperone Hfq, destabilized vanT mRNA and modulated expression of VanT-regulated genes. Unexpectedly, expression of all four qrr genes peaked at high cell density, and exogenously added N-acylhomoserine lactone molecules induced expression of the qrr genes at low cell density. The phosphotransferase VanU, which phosphorylates and activates VanO, repressed expression of the Qrr sRNAs and stabilized vanT mRNA. A model is presented proposing that VanU acts as a branch point, aiding cross-regulation between two independent phosphorelay systems that activate or repress expression of the Qrr sRNAs, giving flexibility and precision in modulating VanT expression and inducing a quorum-sensing response to stresses found in a constantly changing aquatic environment. PMID:21948044

Weber, Barbara; Lindell, Kristoffer; El Qaidi, Samir; Hjerde, Erik; Willassen, Nils-Peder

2011-01-01

278

The quorum sensing transcriptional regulator TraR has separate binding sites for DNA and the anti-activator  

SciTech Connect

Highlights: Black-Right-Pointing-Pointer Quorum sensing transcription factor TraR is inhibited by forming TraR-TraM complex. Black-Right-Pointing-Pointer K213 is a key DNA binding residue, but not involved in interaction with TraM. Black-Right-Pointing-Pointer Mutations of TraM-interacting TraR residues did not affect DNA-binding of TraR. Black-Right-Pointing-Pointer Mutations of TraR residues reduced the TraR-TraM interaction more than those of TraM. Black-Right-Pointing-Pointer TraM inhibition on DNA-binding of TraR is driven by thermodynamics. -- Abstract: Quorum sensing represents a mechanism by which bacteria control their genetic behaviors via diffusible signals that reflect their population density. TraR, a quorum sensing transcriptional activator in the Rhizobiaceae family, is regulated negatively by the anti-activator TraM via formation of a TraR-TraM heterocomplex. Prior structural analysis suggests that TraM and DNA bind to TraR in distinct sites. Here we combined isothermal titration calorimetry (ITC) and electrophoretic mobility shift assays (EMSA) to investigate roles of TraR residues from Rhizobium sp. NGR234 in binding of both TraM and DNA. We found that K213A mutation of TraR{sub NGR} abolished DNA binding, however, did not alter TraM binding. Mutations of TraM-interfacing TraR{sub NGR} residues decreased the TraR-TraM interaction, but did not affect the DNA-binding activity of TraR{sub NGR}. Thus, our biochemical studies support the independent binding sites on TraR for TraM and DNA. We also found that point mutations in TraR{sub NGR} appeared to decrease the TraR-TraM interaction more effectively than those in TraM{sub NGR}, consistent with structural observations that individual TraR{sub NGR} residues contact with more TraM{sub NGR} residues than each TraM{sub NGR} residues with TraR{sub NGR} residues. Finally, we showed that TraM inhibition on DNA-binding of TraR was driven thermodynamically. We discussed subtle mechanistic differences in TraM anti-activation on TraR activity between homologous systems.

Zheng, Zhida; Fuqua, Clay [Department of Molecular and Cellular Biochemistry, 212 S. Hawthorne Dr. Simon Hall 400A, Indiana University, Bloomington, IN 47405 (United States)] [Department of Molecular and Cellular Biochemistry, 212 S. Hawthorne Dr. Simon Hall 400A, Indiana University, Bloomington, IN 47405 (United States); Chen, Lingling, E-mail: linchen@indiana.edu [Department of Molecular and Cellular Biochemistry, 212 S. Hawthorne Dr. Simon Hall 400A, Indiana University, Bloomington, IN 47405 (United States)] [Department of Molecular and Cellular Biochemistry, 212 S. Hawthorne Dr. Simon Hall 400A, Indiana University, Bloomington, IN 47405 (United States)

2012-02-10

279

The Quorum Sensing Peptides PhrG, CSP and EDF Promote Angiogenesis and Invasion of Breast Cancer Cells In Vitro  

PubMed Central

The role of the human microbiome on cancer progression remains unclear. Therefore, in this study, we investigated the influence of some quorum sensing peptides, produced by diverse commensal or pathogenic bacteria, on breast cancer cell invasion and thus cancer outcome. Based on microscopy, transcriptome and Chick Chorioallantoic Membrane (CAM) analyses, four peptides (PhrG from B. subtilis, CSP from S. mitis and EDF from E. coli, together with its tripeptide analogue) were found to promote tumour cell invasion and angiogenesis, thereby potentially influencing tumour metastasis. Our results offer not only new insights on the possible role of the microbiome, but also further opportunities in cancer prevention and therapy by competing with these endogenous molecules and/or by modifying people’s life style. PMID:25780927

De Spiegeleer, Bart; Verbeke, Frederick; D’Hondt, Matthias; Hendrix, An; Van De Wiele, Christophe; Burvenich, Christian; Peremans, Kathelijne; De Wever, Olivier; Bracke, Marc; Wynendaele, Evelien

2015-01-01

280

[Quorum sensing in class II bacteriocin-producing lactic acid bacteria and its application--a review].  

PubMed

Quorum sensing (QS) refers to the behavior of microorganisms to control gene expression through detection the concentration of certain signal molecules, which is correlated with cell density. In many class II bacteriocin-producing lactic acid bacteria (LAB), bacteriocin production is regulated by peptide pheromones via a QS mechanism. We reviewed, QS regulated class II bacteriocin production in LAB and its regulation mechanism, components of the QS system, as well as the application of QS mechanism. The study of QS mechanism of class II bacteriocin-producing LAB may provide a new platform for revealing the mechanism of fermentation control and regulating fermentation process. It also offers an alternative to the exploitation of food grade gene expression system. PMID:22126069

Zhang, Xiangmei; Li, Pinglan

2011-09-01

281

Disrupting the luxS quorum sensing gene does not significantly affect Bacillus anthracis virulence in mice or guinea pigs  

PubMed Central

Many bacterial species use secreted quorum-sensing autoinducer molecules to regulate cell density- and growth phase-dependent gene expression, including virulence factor production, as sufficient environmental autoinducer concentrations are achieved. Bacillus anthracis, the causative agent of anthrax, contains a functional autoinducer (AI-2) system, which appears to regulate virulence gene expression. To determine if the AI-2 system is necessary for disease, we constructed a LuxS AI-2 synthase-deficient mutant in the virulent Ames strain of B. anthracis. We found that growth of the LuxS-deficient mutant was inhibited and sporulation was delayed when compared with the parental strain. However, spores of the Ames luxS mutant remained fully virulent in both mice and guinea pigs. PMID:23076278

Bozue, Joel; Powell, Bradford S.; Cote, Christopher K.; Moody, Krishna L.; Gelhaus, H. Carl; Vietri, Nicholas J.; Rozak, David A.

2012-01-01

282

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

PubMed Central

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

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

2014-01-01

283

Draft Genome Sequence of the Quorum-Sensing and Biofilm-Producing Pseudomonas aeruginosa Strain Pae221, Belonging to the Epidemic High-Risk Clone Sequence Type 274  

PubMed Central

Pseudomonas aeruginosa Pae221 is a clinical isolate from blood culture. Pae221 was found to be a strong quorum-sensing and biofilm-producing strain and also demonstrates a notable production of phenazines. This strain belongs to sequence type 274 (ST274), an epidemic high-risk clone. Here, we report the draft genome sequence of P. aeruginosa Pae221. PMID:25593247

Fernández-Martínez, Marta; Cabot, Gabriel; Tubau, Fé; Oliver, Antonio; Martínez-Martínez, Luis

2015-01-01

284

Rhomboid protease AarA mediates quorum-sensing in Providencia stuartii by activating TatA of the twin-arginine translocase  

Microsoft Academic Search

The Providencia stuartii AarA protein is a member of the rhomboid family of intramembrane serine proteases and is required for the production of an unknown quorum-sensing molecule. In a screen to identify rhomboid-encoding genes from Proteus mirabilis, tatA was identified as a multicopy suppressor and restored extracellular signal production as well as complementing all other phenotypes of a Prov. stuartii

L. G. Stevenson; Kvido Strisovsky; K. M. Clemmer; Shantanu Bhatt; Matthew Freeman

2007-01-01

285

Secondary Metabolites Produced by the Marine Bacterium Halobacillus salinus That Inhibit Quorum Sensing-Controlled Phenotypes in Gram-Negative Bacteria  

Microsoft Academic Search

Certain bacteria use cell-to-cell chemical communication to coordinate community-wide phenotypic expres- sion, including swarming motility, antibiotic biosynthesis, and biofilm production. Here we present a marine gram-positive bacterium that secretes secondary metabolites capable of quenching quorum sensing-controlled behaviors in several gram-negative reporter strains. Isolate C42, a Halobacillus salinus strain obtained from a sea grass sample, inhibits bioluminescence production by Vibrio harveyi

Margaret E. Teasdale; Jiayuan Liu; Joselynn Wallace; Fatemeh Akhlaghi; David C. Rowley

2009-01-01

286

Draft Genome Sequence of Cellulophaga sp. E6, a Marine Algal Epibiont That Produces a Quorum-Sensing Inhibitory Compound Active against Pseudomonas aeruginosa  

PubMed Central

The genus Cellulophaga is composed of obligate aerobic Gram-negative bacteria commonly found in association with marine algae. We report the approximately 4.42-Mbp draft genome sequence of Cellulophaga sp. E6, which inhibits N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C12-HSL)–mediated quorum sensing (QS), lasB transcription, and biofilm formation by Pseudomonas aeruginosa. PMID:25676769

Lafleur, J. E.; Costa, S. K.; Bitzer, A. S.

2015-01-01

287

The Formation of Streptococcus mutans Persisters Induced by the Quorum-Sensing Peptide Pheromone Is Affected by the LexA Regulator.  

PubMed

The presence of multidrug-tolerant persister cells within microbial populations has been implicated in the resiliency of bacterial survival against antibiotic treatments and is a major contributing factor in chronic infections. The mechanisms by which these phenotypic variants are formed have been linked to stress response pathways in various bacterial species, but many of these mechanisms remain unclear. We have previously shown that in the cariogenic organism Streptococcus mutans, the quorum-sensing peptide CSP (competence-stimulating peptide) pheromone was a stress-inducible alarmone that triggered an increased formation of multidrug-tolerant persisters. In this study, we characterized SMU.2027, a CSP-inducible gene encoding a LexA ortholog. We showed that in addition to exogenous CSP exposure, stressors, including heat shock, oxidative stress, and ofloxacin antibiotic, were capable of triggering expression of lexA in an autoregulatory manner akin to that of LexA-like transcriptional regulators. We demonstrated the role of LexA and its importance in regulating tolerance toward DNA damage in a noncanonical SOS mechanism. We showed its involvement and regulatory role in the formation of persisters induced by the CSP-ComDE quorum-sensing regulatory system. We further identified key genes involved in sugar and amino acid metabolism, the clustered regularly interspaced short palindromic repeat (CRISPR) system, and autolysin from transcriptomic analyses that contribute to the formation of quorum-sensing-induced persister cells. PMID:25583974

Leung, Vincent; Ajdic, Dragana; Koyanagi, Stephanie; Lévesque, Céline M

2015-03-15

288

A Second Quorum-Sensing System Regulates Cell Surface Properties but Not Phenazine Antibiotic Production in Pseudomonas aureofaciens  

PubMed Central

The root-associated biological control bacterium Pseudomonas aureofaciens 30-84 produces a range of exoproducts, including protease and phenazines. Phenazine antibiotic biosynthesis by phzXYFABCD is regulated in part by the PhzR-PhzI quorum-sensing system. Mutants defective in phzR or phzI produce very low levels of phenazines but wild-type levels of exoprotease. In the present study, a second genomic region of strain 30-84 was identified that, when present in trans, increased ?-galactosidase activity in a genomic phzB::lacZ reporter and partially restored phenazine production to a phzR mutant. Sequence analysis identified two adjacent genes, csaR and csaI, that encode members of the LuxR-LuxI family of regulatory proteins. No putative promoter region is present upstream of the csaI start codon and no lux box-like element was found in either the csaR promoter or the 30-bp intergenic region between csaR and csaI. Both the PhzR-PhzI and CsaR-CsaI systems are regulated by the GacS-GacA two-component regulatory system. In contrast to the multicopy effects of csaR and csaI in trans, a genomic csaR mutant (30-84R2) and a csaI mutant (30-84I2) did not exhibit altered phenazine production in vitro or in situ, indicating that the CsaR-CsaI system is not involved in phenazine regulation in strain 30-84. Both mutants also produced wild-type levels of protease. However, disruption of both csaI and phzI or both csaR and phzR eliminated both phenazine and protease production completely. Thus, the two quorum-sensing systems do not interact for phenazine regulation but do interact for protease regulation. Additionally, the CsaI N-acylhomoserine lactone (AHL) signal was not recognized by the phenazine AHL reporter 30-84I/Z but was recognized by the AHL reporters Chromobacterium violaceum CV026 and Agrobacterium tumefaciens A136(pCF240). Inactivation of csaR resulted in a smooth mucoid colony phenotype and formation of cell aggregates in broth, suggesting that CsaR is involved in regulating biosynthesis of cell surface components. Strain 30-84I/I2 exhibited mucoid colony and clumping phenotypes similar to those of 30-84R2. Both phenotypes were reversed by complementation with csaR-csaI or by the addition of the CsaI AHL signal. Both quorum-sensing systems play a role in colonization by strain 30-84. Whereas loss of PhzR resulted in a 6.6-fold decrease in colonization by strain 30-84 on wheat roots in natural soil, a phzR csaR double mutant resulted in a 47-fold decrease. These data suggest that gene(s) regulated by the CsaR-CsaI system also plays a role in the rhizosphere competence of P. aureofaciens 30-84. PMID:11526037

Zhang, Zhongge; Pierson, Leland S.

2001-01-01

289

Necrotrophism Is a Quorum-Sensing-Regulated Lifestyle in Bacillus thuringiensis  

PubMed Central

How pathogenic bacteria infect and kill their host is currently widely investigated. In comparison, the fate of pathogens after the death of their host receives less attention. We studied Bacillus thuringiensis (Bt) infection of an insect host, and show that NprR, a quorum sensor, is active after death of the insect and allows Bt to survive in the cadavers as vegetative cells. Transcriptomic analysis revealed that NprR regulates at least 41 genes, including many encoding degradative enzymes or proteins involved in the synthesis of a nonribosomal peptide named kurstakin. These degradative enzymes are essential in vitro to degrade several substrates and are specifically expressed after host death suggesting that Bt has an active necrotrophic lifestyle in the cadaver. We show that kurstakin is essential for Bt survival during necrotrophic development. It is required for swarming mobility and biofilm formation, presumably through a pore forming activity. A nprR deficient mutant does not develop necrotrophically and does not sporulate efficiently in the cadaver. We report that necrotrophism is a highly regulated mechanism essential for the Bt infectious cycle, contributing to spore spreading. PMID:22511867

Perchat, Stéphane; Lemy, Christelle; Buisson, Christophe; Nielsen-LeRoux, Christina; Gohar, Michel; Jacques, Philippe; Ramarao, Nalini; Kolstø, Anne-Brit; Lereclus, Didier

2012-01-01

290

Specificity and polymorphism of the PlcR-PapR quorum-sensing system in the Bacillus cereus group.  

PubMed

The expression of extracellular virulence factors in various species of the Bacillus cereus group is controlled by the plcR and papR genes, which encode a transcriptional regulator and a cell-cell signaling peptide, respectively. A processed form of PapR, presumably a pentapeptide, specifically interacts with PlcR to facilitate its binding to its DNA targets. This activating mechanism is strain specific, with this specificity being determined by the first residue of the pentapeptide. We carried out in vivo complementation assays and compared the PlcR-PapR sequences of 29 strains from the B. cereus group. Our findings suggested that the fifth amino acid of the pentapeptide is also involved in the specificity of activation. We identified four classes of PlcR-PapR pairs, defining four distinct pherotypes in the B. cereus group. We used these findings to look at the evolution of the PlcR-PapR quorum-sensing system with regard to the phylogeny of the species forming the B. cereus group. PMID:15659693

Slamti, Leyla; Lereclus, Didier

2005-02-01

291

The impact of the competence quorum sensing system on Streptococcus pneumoniae biofilms varies depending on the experimental model  

PubMed Central

Background Different models for biofilm in Streptococcus pneumoniae have been described in literature. To permit comparison of experimental data, we characterised the impact of the pneumococcal quorum-sensing competence system on biofilm formation in three models. For this scope, we used two microtiter and one continuous culture biofilm system. Results In both microtiter models the competence system influences stability and structure of biofilm in the late attachment phase and synthetic competence stimulating peptide (CSP) restored wild type phenotypes in the comC mutants unable to produce the peptide. Early attachment of single cells to well bottoms was found for both systems to be competence independent, while later phases, including microcolony formation correlated to an intact competence system. The continuous culture biofilm model was not affected by mutations in the competence locus, but deletion of capsule had a significant impact in this model. Conclusions Since biofilm remains a largely uncharacterised multi-parameter phenotype it appears to be advisable to exploit more than one model in order to draw conclusion of possible relevance of specific genotypes on pneumococcal physiology. PMID:21492426

2011-01-01

292

Design, synthesis, and biological evaluation of abiotic, non-lactone modulators of LuxR-type quorum sensing  

PubMed Central

Quorum sensing (QS) is a cell-cell signaling mechanism that allows bacteria to monitor their population size and alter their behavior at high cell densities. Gram-negative bacteria use N-acylated L-homoserine lactones (AHLs) as their primary signals for QS. These signals are susceptible to lactone hydrolysis in biologically relevant media, and the ring-opened products are inactive QS signals. We have previously identified a range of non-native AHLs capable of strongly agonizing and antagonizing QS in Gram-negative bacteria. However, these abiotic AHLs are also prone to hydrolysis and inactivation and thereby have a relatively short time window for use (~12–48 h). Non-native QS modulators with reduced or no hydrolytic instability could have enhanced potencies and would be valuable as tools to study the mechanisms of QS in a range of environments (for example, on eukaryotic hosts). This study reports the design and synthesis of two libraries of new, non-hydrolyzable AHL mimics. The libraries were screened for QS modulatory activity using LasR, LuxR, and TraR bacterial reporter strains, and several new, abiotic agonists and antagonists of these receptors were identified. PMID:21798749

McInnis, Christine E.; Blackwell, Helen E.

2011-01-01

293

Investigation of quorum sensing-dependent gene expression in Burkholderia gladioli BSR3 through RNA-seq analyses.  

PubMed

The plant pathogen Burkholderia gladioli, which has a broad host range that includes rice and onion, causes bacterial panicle blight and sheath rot. Based on the complete genome sequence of B. gladioli BSR3 isolated from infected rice sheaths, the genome of B. gladioli BSR3 contains the luxI/luxR family of genes. Members of this family encode N-acyl-homoserine lactone (AHL) quorum sensing (QS) signal synthase and the LuxR-family AHL signal receptor, which are similar to B. glumae BGR1. In B. glumae, QS has been shown to play pivotal roles in many bacterial behaviors. In this study, we compared the QS-dependent gene expression between B. gladioli BSR3 and a QS-defective B. gladioli BSR3 mutant in two different culture states (10 and 24 h after incubation, corresponding to an exponential phase and a stationary phase) using RNA sequencing (RNA-seq). RNA-seq analyses including gene ontology and pathway enrichment revealed that the B. gladioli BSR3 QS system regulates genes related to motility, toxin production, and oxalogenesis, which were previously reported in B. glumae. Moreover, the uncharacterized polyketide biosynthesis is activated by QS, which was not detected in B. glumae. Thus, we observed not only common QS-dependent genes between B. glumae BGR1 and B. gladioli BSR3, but also unique QS-dependent genes in B. gladioli BSR3. PMID:25223327

Kim, Sunyoung; Park, Jungwook; Choi, Okhee; Kim, Jinwoo; Seo, Young-Su

2014-12-28

294

Quorum sensing influences growth and photosynthetic membrane production in high-cell-density cultivations of Rhodospirillum rubrum  

PubMed Central

Background The facultative anoxygenic photosynthetic bacterium Rhodospirillum rubrum exhibits versatile metabolic activity allowing the adaptation to rapidly changing growth conditions in its natural habitat, the microaerobic and anoxic zones of stagnant waters. The microaerobic growth mode is of special interest as it allows the high-level expression of photosynthetic membranes when grown on succinate and fructose in the dark, which could significantly simplify the industrial production of compounds associated with PM formation. However, recently we showed that PM synthesis is no longer inducible when R. rubrum cultures are grown to high cell densities under aerobic conditions. In addition a reduction of the growth rate and the continued accumulation of precursor molecules for bacteriochlorophyll synthesis were observed under high cell densities conditions. Results In the present work, we demonstrate that the cell density-dependent effects are reversible if the culture supernatant is replaced by fresh medium. We identified six N-acylhomoserine lactones and show that four of them are produced in varying amounts according to the growth phase and the applied growth conditions. Further, we demonstrate that N-acylhomoserine lactones and tetrapyrrole compounds released into the growth medium affect the growth rate and PM expression in high cell density cultures. Conclusions In summary, we provide evidence that R. rubrum possesses a Lux-type quorum sensing system which influences the biosynthesis of PM and the growth rate and is thus likely to be involved in the phenotypes of high cell density cultures and the rapid adaptation to changing environmental conditions. PMID:23927486

2013-01-01

295

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

PubMed Central

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

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

2015-01-01

296

Characterisation of a Marine Bacterium Vibrio Brasiliensis T33 Producing N-acyl Homoserine Lactone Quorum Sensing Molecules  

PubMed Central

N-acylhomoserine lactones (AHL) plays roles as signal molecules in quorum sensing (QS) in most Gram-negative bacteria. QS regulates various physiological activities in relation with population density and concentration of signal molecules. With the aim of isolating marine water-borne bacteria that possess QS properties, we report here the preliminary screening of marine bacteria for AHL production using Chromobacterium violaceum CV026 as the AHL biosensor. Strain T33 was isolated based on preliminary AHL screening and further identified by using 16S rDNA sequence analysis as a member of the genus Vibrio closely related to Vibrio brasiliensis. The isolated Vibrio sp. strain T33 was confirmed to produce N-hexanoyl-l-homoserine lactone (C6-HSL) and N-(3-oxodecanoyl)-l-homoserine lactone (3-oxo-C10 HSL) through high resolution tandem mass spectrometry analysis. We demonstrated that this isolate formed biofilms which could be inhibited by catechin. To the best of our knowledge, this is the first report that documents the production of these AHLs by Vibrio brasiliensis strain T33. PMID:25006994

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

2014-01-01

297

Isolation and Molecular Characterization of Biofouling Bacteria and Profiling of Quorum Sensing Signal Molecules from Membrane Bioreactor Activated Sludge  

PubMed Central

The formation of biofilm in a membrane bioreactor depends on the production of various signaling molecules like N-acyl homoserine lactones (AHLs). In the present study, a total of 200 bacterial strains were isolated from membrane bioreactor activated sludge and screened for AHLs production using two biosensor systems, Chromobacterium violaceum CV026 and Agrobacterium tumefaciens A136. A correlation between AHLs production and biofilm formation has been made among screened AHLs producing strains. The 16S rRNA gene sequence analysis revealed the dominance of Aeromonas and Enterobacter sp. in AHLs production; however few a species of Serratia, Leclercia, Pseudomonas, Klebsiella, Raoultella and Citrobacter were also identified. The chromatographic characterization of sludge extract showed the presence of a broad range of quorum sensing signal molecules. Further identification of sludge AHLs by thin layer chromatography bioassay and high performance liquid chromatography confirms the presence of C4-HSL, C6-HSL, C8-HSL, 3-oxo-C8-HSL, C10-HSL, C12-HSL, 3-oxo-C12-HSL and C14-HSL. The occurrence of AHLs in sludge extract and dominance of Aeromonas and Enterobacter sp. in activated sludge suggests the key role of these bacterial strains in AHLs production and thereby membrane fouling. PMID:24499972

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

2014-01-01

298

Effect of quorum sensing signals produced by seaweed-associated bacteria on carpospore liberation from Gracilaria dura  

PubMed Central

Epiphytic and endophytic bacteria associated with green macroalgae Ulva (U. fasciata and U. lactuca) and red macroalgae Gracilaria (G. corticata and G. dura) have been identified from three different seasons to evaluate the effect of quorum sensing (QS) molecules on carpospores liberation from Gracilaria dura. The bacterial isolates belonging to the orders Bacillales, Pseudomonadales, Alteromonadales, and Vibrionales were present in all seasons, whereas Actinomycetales and Enterobacteriales were confined to pre-monsoon and post-monsoon seasons, respectively. Among all the Gram-negative bacteria, seven isolates were found to produce different types of N-acyl homoserine lactones (AHLs). Interestingly, Shewanella algae produced five types of AHL: C4-HSL, HC4-HSL, C6-HSL, 3-oxo-C6-HSL, and 3-oxo-C12-HSL. Subsequently, the AHLs producing bacterial isolates were screened for carpospore liberation from G. dura and these isolates were found to positively induce carpospore liberation over the control. Also, observed that carpospore liberation increased significantly in C4- and C6-HSL treated cystocarps. Sodium dodecyl sulfate and native polyacrylamide gel electrophoresis of the total protein of the C4- and C6-HSL treated cystocarps showed two specific peptide bands of different molecular weights (50 kDa and 60 kDa) as compared to the control, confirming their indirect effect on carpospore liberation. PMID:25788899

Singh, Ravindra Pal; Baghel, Ravi S.; Reddy, C. R. K.; Jha, Bhavanath

2015-01-01

299

Real-time monitoring of quorum sensing in 3D-printed bacterial aggregates using scanning electrochemical microscopy.  

PubMed

Microbes frequently live in nature as small, densely packed aggregates containing ?10(1)-10(5) cells. These aggregates not only display distinct phenotypes, including resistance to antibiotics, but also, serve as building blocks for larger biofilm communities. Aggregates within these larger communities display nonrandom spatial organization, and recent evidence indicates that this spatial organization is critical for fitness. Studying single aggregates as well as spatially organized aggregates remains challenging because of the technical difficulties associated with manipulating small populations. Micro-3D printing is a lithographic technique capable of creating aggregates in situ by printing protein-based walls around individual cells or small populations. This 3D-printing strategy can organize bacteria in complex arrangements to investigate how spatial and environmental parameters influence social behaviors. Here, we combined micro-3D printing and scanning electrochemical microscopy (SECM) to probe quorum sensing (QS)-mediated communication in the bacterium Pseudomonas aeruginosa. Our results reveal that QS-dependent behaviors are observed within aggregates as small as 500 cells; however, aggregates larger than 2,000 bacteria are required to stimulate QS in neighboring aggregates positioned 8 ?m away. These studies provide a powerful system to analyze the impact of spatial organization and aggregate size on microbial behaviors. PMID:25489085

Connell, Jodi L; Kim, Jiyeon; Shear, Jason B; Bard, Allen J; Whiteley, Marvin

2014-12-23

300

Effect of quorum sensing signals produced by seaweed-associated bacteria on carpospore liberation from Gracilaria dura.  

PubMed

Epiphytic and endophytic bacteria associated with green macroalgae Ulva (U. fasciata and U. lactuca) and red macroalgae Gracilaria (G. corticata and G. dura) have been identified from three different seasons to evaluate the effect of quorum sensing (QS) molecules on carpospores liberation from Gracilaria dura. The bacterial isolates belonging to the orders Bacillales, Pseudomonadales, Alteromonadales, and Vibrionales were present in all seasons, whereas Actinomycetales and Enterobacteriales were confined to pre-monsoon and post-monsoon seasons, respectively. Among all the Gram-negative bacteria, seven isolates were found to produce different types of N-acyl homoserine lactones (AHLs). Interestingly, Shewanella algae produced five types of AHL: C4-HSL, HC4-HSL, C6-HSL, 3-oxo-C6-HSL, and 3-oxo-C12-HSL. Subsequently, the AHLs producing bacterial isolates were screened for carpospore liberation from G. dura and these isolates were found to positively induce carpospore liberation over the control. Also, observed that carpospore liberation increased significantly in C4- and C6-HSL treated cystocarps. Sodium dodecyl sulfate and native polyacrylamide gel electrophoresis of the total protein of the C4- and C6-HSL treated cystocarps showed two specific peptide bands of different molecular weights (50 kDa and 60 kDa) as compared to the control, confirming their indirect effect on carpospore liberation. PMID:25788899

Singh, Ravindra Pal; Baghel, Ravi S; Reddy, C R K; Jha, Bhavanath

2015-01-01

301

Molecular mechanisms of master regulator VqsM mediating quorum-sensing and antibiotic resistance in Pseudomonas aeruginosa  

PubMed Central

The Pseudomonas aeruginosa quorum-sensing (QS) systems contribute to bacterial homeostasis and pathogenicity. Although the AraC-family transcription factor VqsM has been characterized to control the production of virulence factors and QS signaling molecules, its detailed regulatory mechanisms still remain elusive. Here, we report that VqsM directly binds to the lasI promoter region, and thus regulates its expression. To identify additional targets of VqsM in P. aeruginosa PAO1, we performed chromatin immunoprecipitation (ChIP) followed by high-throughput DNA sequencing (ChIP-seq) and detected 48 enriched loci harboring VqsM-binding peaks in the P. aeruginosa genome. The direct regulation of these genes by VqsM has been confirmed by electrophoretic mobility shift assays and quantitative real-time polymerase chain reactions. A VqsM-binding motif was identified by using the MEME suite and verified by footprint assays in vitro. In addition, VqsM directly bound to the promoter regions of the antibiotic resistance regulator NfxB and the master type III secretion system (T3SS) regulator ExsA. Notably, the vqsM mutant displayed more resistance to two types of antibiotics and promoted bacterial survival in a mouse model, compared to wild-type PAO1. Collectively, this work provides new cues to better understand the detailed regulatory networks of QS systems, T3SS, and antibiotic resistance. PMID:25034696

Liang, Haihua; Deng, Xin; Li, Xuefeng; Ye, Yan; Wu, Min

2014-01-01

302

Synthesis and Biological Evaluation of Triazole-Containing N-Acyl Homoserine Lactones as Quorum Sensing Modulators  

PubMed Central

Many bacterial species are capable of assessing their local population densities through a cell-cell signaling mechanism termed quorum sensing (QS). This intercellular communication process is mediated by small molecule or peptide ligands and their cognate protein receptors. Numerous pathogens use QS to initiate virulence once they achieve a threshold cell number on a host. Consequently, approaches to intercept QS have attracted considerable attention as potential anti-infective therapies. Our interest in the development of small molecule tools to modulate QS pathways motivated us to evaluate triazole-containing analogs of natural N-acyl L-homoserine lactone (AHL) signals as non-native QS agonists and antagonists in Gram-negative bacteria. We synthesized 72 triazole derivatives of five broad structure types in high yields and purities using efficient Cu(I)-catalyzed azide-alkyne couplings. These compounds were evaluated for their ability to activate or inhibit two QS receptors from two prevalent pathogens – LasR from Pseudomonas aeruginosa and AbaR from Acinetobacter baumannii – using bacterial reporter strains. Several triazole derivatives were identified that were capable of strongly modulating the activity of LasR and AbaR. These compounds represent a new and synthetically accessible class of AHL analogs, and could find utility as chemical tools to study QS and its role in bacterial virulence. PMID:23258305

Stacy, Danielle M.; Le Quement, Sebastian T.; Hansen, Casper L.; Clausen, Janie W.; Tolker-Nielsen, Tim; Brummond, Jacob W.; Givskov, Michael; Nielsen, Thomas E.; Blackwell, Helen E.

2013-01-01

303

Natural Genome Diversity of AI-2 Quorum Sensing in Escherichia coli: Conserved Signal Production but Labile Signal Reception  

PubMed Central

Quorum sensing (QS) regulates the onset of bacterial social responses in function to cell density having an important impact in virulence. Autoinducer-2 (AI-2) is a signal that has the peculiarity of mediating both intra- and interspecies bacterial QS. We analyzed the diversity of all components of AI-2 QS across 44 complete genomes of Escherichia coli and Shigella strains. We used phylogenetic tools to study its evolution and determined the phenotypes of single-deletion mutants to predict phenotypes of natural strains. Our analysis revealed many likely adaptive polymorphisms both in gene content and in nucleotide sequence. We show that all natural strains possess the signal emitter (the luxS gene), but many lack a functional signal receptor (complete lsr operon) and the ability to regulate extracellular signal concentrations. This result is in striking contrast with the canonical species-specific QS systems where one often finds orphan receptors, without a cognate synthase, but not orphan emitters. Our analysis indicates that selection actively maintains a balanced polymorphism for the presence/absence of a functional lsr operon suggesting diversifying selection on the regulation of signal accumulation and recognition. These results can be explained either by niche-specific adaptation or by selection for a coercive behavior where signal-blind emitters benefit from forcing other individuals in the population to haste in cooperative behaviors. PMID:23246794

Brito, Patrícia H.; Rocha, Eduardo P.C.; Xavier, Karina B.; Gordo, Isabel

2013-01-01

304

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

PubMed Central

Background Antibiotics are not only small molecules with therapeutic activity in killing or inhibiting microbial growth, but can also act as signaling molecules affecting gene expression in bacterial communities. A few studies have demonstrated the effect of tobramycin as a signal molecule on gene expression at the transcriptional level and its effect on bacterial physiology and virulence. These have shown that subinhibitory concentrations (SICs) of tobramycin induce biofilm formation and enhance the capabilities of P. aeruginosa to colonize specific environments. Methods Environmental P. aeruginosa strain PUPa3 was grown in the presence of different concentrations of tobramycin and it was determined at which highest concentration SIC, growth, total protein levels and translation efficiency were not affected. At SIC it was then established if phenotypes related to cell-cell signaling known as quorum sensing were altered. Results In this study it was determined whether tobramycin sensing/response at SICs was affecting the two independent AHL QS systems in an environmental P. aeruginosa strain. It is reasonable to assume that P. aeruginosa encounters tobramycin in nature since it is produced by niche mate Streptomyces tenebrarius. It was established that SICs of tobramycin inhibited the RhlI/R system by reducing levels of C4-HSL production. This effect was not due to a decrease of rhlI transcription and required tobramycin-ribosome interaction. Conclusions Tobramycin signaling in P. aeruginosa occurs and different strains can have a different response. Understanding the tobramycin response by an environmental P. aeruginosa will highlight possible inter-species signalling taking place in nature and can possible also have important implications in the mode of utilization for human use of this very important antibiotic. PMID:20525206

2010-01-01

305

Quorum Quenching Revisited—From Signal Decays to Signalling Confusion  

PubMed Central

In a polymicrobial community, while some bacteria are communicating with neighboring cells (quorum sensing), others are interrupting the communication (quorum quenching), thus creating a constant arms race between intercellular communication. In the past decade, numerous quorum quenching enzymes have been found and initially thought to inactivate the signalling molecules. Though this is widely accepted, the actual roles of these quorum quenching enzymes are now being uncovered. Recent evidence extends the role of quorum quenching to detoxification or metabolism of signalling molecules as food and energy source; this includes “signalling confusion”, a term coined in this paper to refer to the phenomenon of non-destructive modification of signalling molecules. While quorum quenching has been explored as a novel anti-infective therapy targeting, quorum sensing evidence begins to show the development of resistance against quorum quenching. PMID:22666051

Hong, Kar-Wai; Koh, Chong-Lek; Sam, Choon-Kook; Yin, Wai-Fong; Chan, Kok-Gan

2012-01-01

306

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

PubMed

Recent reports have shown that several strains of Pseudomonas putida produce N-acylhomoserine lactones (AHLs). These signal molecules enable bacteria to coordinately express certain phenotypic traits in a density-dependent manner in a process referred to as quorum sensing. In this study we have cloned a genomic region of the plant growth-promoting P. putida strain IsoF that, when present in trans, provoked induction of a bioluminescent AHL reporter plasmid. Sequence analysis identified a gene cluster consisting of four genes: ppuI and ppuR, whose predicted amino acid sequences are highly similar to proteins of the LuxI-LuxR family, an open reading frame (ORF) located in the intergenic region between ppuI and ppuR with significant homology to rsaL from Pseudomonas aeruginosa, and a gene, designated ppuA, present upstream of ppuR, the deduced amino acid sequence of which shows similarity to long-chain fatty acid coenzyme A ligases from various organisms. Using a transcriptional ppuA::luxAB fusion we demonstrate that expression of ppuA is AHL dependent. Furthermore, transcription of the AHL synthase ppuI is shown to be subject to quorum-sensing regulation, creating a positive feedback loop. Sequencing of the DNA regions flanking the ppu gene cluster indicated that the four genes form an island in the suhB-PA3819 intergenic region of the currently sequenced P. putida strain KT2440. Moreover, we provide evidence that the ppu genes are not present in other AHL-producing P. putida strains, indicating that this gene cluster is so far unique for strain IsoF. While the wild-type strain formed very homogenous biofilms, both a ppuI and a ppuA mutant formed structured biofilms with characteristic microcolonies and water-filled channels. These results suggest that the quorum-sensing system influences biofilm structural development. PMID:12450862

Steidle, Anette; Allesen-Holm, Marie; Riedel, Kathrin; Berg, Gabriele; Givskov, Michael; Molin, Søren; Eberl, Leo

2002-12-01

307

Identification and Characterization of an N-Acylhomoserine Lactone-Dependent Quorum-Sensing System in Pseudomonas putida Strain IsoF  

PubMed Central

Recent reports have shown that several strains of Pseudomonas putida produce N-acylhomoserine lactones (AHLs). These signal molecules enable bacteria to coordinately express certain phenotypic traits in a density-dependent manner in a process referred to as quorum sensing. In this study we have cloned a genomic region of the plant growth-promoting P. putida strain IsoF that, when present in trans, provoked induction of a bioluminescent AHL reporter plasmid. Sequence analysis identified a gene cluster consisting of four genes: ppuI and ppuR, whose predicted amino acid sequences are highly similar to proteins of the LuxI-LuxR family, an open reading frame (ORF) located in the intergenic region between ppuI and ppuR with significant homology to rsaL from Pseudomonas aeruginosa, and a gene, designated ppuA, present upstream of ppuR, the deduced amino acid sequence of which shows similarity to long-chain fatty acid coenzyme A ligases from various organisms. Using a transcriptional ppuA::luxAB fusion we demonstrate that expression of ppuA is AHL dependent. Furthermore, transcription of the AHL synthase ppuI is shown to be subject to quorum-sensing regulation, creating a positive feedback loop. Sequencing of the DNA regions flanking the ppu gene cluster indicated that the four genes form an island in the suhB-PA3819 intergenic region of the currently sequenced P. putida strain KT2440. Moreover, we provide evidence that the ppu genes are not present in other AHL-producing P. putida strains, indicating that this gene cluster is so far unique for strain IsoF. While the wild-type strain formed very homogenous biofilms, both a ppuI and a ppuA mutant formed structured biofilms with characteristic microcolonies and water-filled channels. These results suggest that the quorum-sensing system influences biofilm structural development. PMID:12450862

Steidle, Anette; Allesen-Holm, Marie; Riedel, Kathrin; Berg, Gabriele; Givskov, Michael; Molin, Søren; Eberl, Leo

2002-01-01

308

The Mucoid Switch in Pseudomonas aeruginosa Represses Quorum Sensing Systems and Leads to Complex Changes to Stationary Phase Virulence Factor Regulation  

PubMed Central

The opportunistic pathogen Pseudomonas aeruginosa chronically infects the airways of Cystic Fibrosis (CF) patients during which it adapts and undergoes clonal expansion within the lung. It commonly acquires inactivating mutations of the anti-sigma factor MucA leading to a mucoid phenotype, caused by excessive production of the extracellular polysaccharide alginate that is associated with a decline in lung function. Alginate production is believed to be the key benefit of mucA mutations to the bacterium in the CF lung. A phenotypic and gene expression characterisation of the stationary phase physiology of mucA22 mutants demonstrated complex and subtle changes in virulence factor production, including cyanide and pyocyanin, that results in their down-regulation upon entry into stationary phase but, (and in contrast to wildtype strains) continued production in prolonged stationary phase. These findings may have consequences for chronic infection if mucoid P. aeruginosa were to continue to make virulence factors under non-growing conditions during infection. These changes resulted in part from a severe down-regulation of both AHL-and AQ (PQS)-dependent quorum sensing systems. In trans expression of the cAMP-dependent transcription factor Vfr restored both quorum sensing defects and virulence factor production in early stationary phase. Our findings have implications for understanding the evolution of P. aeruginosa during CF lung infection and it demonstrates that mucA22 mutation provides a second mechanism, in addition to the commonly occurring lasR mutations, of down-regulating quorum sensing during chronic infection this may provide a selection pressure for the mucoid switch in the CF lung. PMID:24852379

Ryall, Ben; Carrara, Marta; Zlosnik, James E. A.; Behrends, Volker; Lee, Xiaoyun; Wong, Zhen; Lougheed, Kathryn E.; Williams, Huw D.

2014-01-01

309

The mucoid switch in Pseudomonas aeruginosa represses quorum sensing systems and leads to complex changes to stationary phase virulence factor regulation.  

PubMed

The opportunistic pathogen Pseudomonas aeruginosa chronically infects the airways of Cystic Fibrosis (CF) patients during which it adapts and undergoes clonal expansion within the lung. It commonly acquires inactivating mutations of the anti-sigma factor MucA leading to a mucoid phenotype, caused by excessive production of the extracellular polysaccharide alginate that is associated with a decline in lung function. Alginate production is believed to be the key benefit of mucA mutations to the bacterium in the CF lung. A phenotypic and gene expression characterisation of the stationary phase physiology of mucA22 mutants demonstrated complex and subtle changes in virulence factor production, including cyanide and pyocyanin, that results in their down-regulation upon entry into stationary phase but, (and in contrast to wildtype strains) continued production in prolonged stationary phase. These findings may have consequences for chronic infection if mucoid P. aeruginosa were to continue to make virulence factors under non-growing conditions during infection. These changes resulted in part from a severe down-regulation of both AHL-and AQ (PQS)-dependent quorum sensing systems. In trans expression of the cAMP-dependent transcription factor Vfr restored both quorum sensing defects and virulence factor production in early stationary phase. Our findings have implications for understanding the evolution of P. aeruginosa during CF lung infection and it demonstrates that mucA22 mutation provides a second mechanism, in addition to the commonly occurring lasR mutations, of down-regulating quorum sensing during chronic infection this may provide a selection pressure for the mucoid switch in the CF lung. PMID:24852379

Ryall, Ben; Carrara, Marta; Zlosnik, James E A; Behrends, Volker; Lee, Xiaoyun; Wong, Zhen; Lougheed, Kathryn E; Williams, Huw D

2014-01-01

310

Role of Pseudomonas aeruginosa quorum sensing (QS) molecules on the viability and cytokine profile of human mesenchymal stem cells  

PubMed Central

Pseudomonas aeruginosa infections represent one of the major threats for injured or transplanted lungs and for their healing. Considering that the mesenchymal stem cells (MSCs) are a major tool for the regenerative medicine, including therapy of lung damaging diseases, the aim of this paper was to investigate the effects of P. aeruginosa quorum sensing signaling molecules (QSSMs) on human MSCs death signaling pathways and cytokine profile. Our data revealed that N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL), N-butanoyl-L-homoserine lactone (C4-HSL), 2-heptyl-3-hydroxy-4(1H)-quinolone (PQS), and its precursor, 2-heptyl-4-quinolone (HHQ), significantly impact on several core signaling mechanisms of MSCs in a specific and time-dependent manner. Even if all tested autoinducers interfered with the MSCs apoptotic genes expression, only OdDHL and HHQ significantly promoted MSCs apoptosis, by 14- and 23-fold respectively, this aspect being confirmed by the flow cytometry assay. The tested QSSMs induced a heterogeneous cytokine profile of the treated MSCs. The level of IL-1? was increased by OdDHL, IL-8 production was stimulated by all tested autoinducers, IL-6 was modulated mostly by PQS and IL-10 by HHQ. The significant influence of the purified bacterial autoinducers on the MSCs signaling pathways may suggest that the accumulation of these mediators could interfere with the normal function of these cells in the human body, and eventually, impair or abolish the success of the stem cells therapy during P. aeruginosa infections. PMID:24398422

Holban, Alina-Maria; Bleotu, Coralia; Chifiriuc, Mariana Carmen; Bezirtzoglou, Eugenia; Lazar, Veronica

2014-01-01

311

Transcriptome of the quorum-sensing signal-degrading Rhodococcus erythropolis responds differentially to virulent and avirulent Pectobacterium atrosepticum.  

PubMed

Social bacteria use chemical communication to coordinate and synchronize gene expression via the quorum-sensing (QS) regulatory pathway. In Pectobacterium, a causative agent of the blackleg and soft-rot diseases on potato plants and tubers, expression of the virulence factors is collectively controlled by the QS-signals N-acylhomoserine lactones (NAHLs). Several soil bacteria, such as the actinobacterium Rhodococcus erythropolis, are able to degrade NAHLs, hence quench the chemical communication and virulence of Pectobacterium. Here, next-generation sequencing was used to investigate structural and functional genomics of the NAHL-degrading R. erythropolis strain R138. The R. erythropolis R138 genome (6.7?Mbp) contained a single circular chromosome, one linear (250?kbp) and one circular (84?kbp) plasmid. Growth of R. erythropolis and P. atrosepticum was not altered in mixed-cultures as compared with monocultures on potato tuber slices. HiSeq-transcriptomics revealed that no R. erythropolis genes were differentially expressed when R. erythropolis was cultivated in the presence vs absence of the avirulent P. atrosepticum mutant expI, which is defective for QS-signal synthesis. By contrast 50 genes (<1% of the R. erythropolis genome) were differentially expressed when R. erythropolis was cultivated in the presence vs absence of the NAHL-producing virulent P. atrosepticum. Among them, quantitative real-time reverse-transcriptase-PCR confirmed that the expression of some alkyl-sulfatase genes decreased in the presence of a virulent P. atrosepticum, as well as deprivation of organic sulfur such as methionine, which is a key precursor in the synthesis of NAHL by P. atrosepticum. PMID:25585922

Kwasiborski, A; Mondy, S; Chong, T-M; Barbey, C; Chan, K-G; Beury-Cirou, A; Latour, X; Faure, D

2015-05-01

312

Amino Acid Residues in LuxR Critical for Its Mechanism of Transcriptional Activation during Quorum Sensing in Vibrio fischeri  

PubMed Central

PCR-based site-directed mutagenesis has been used to generate 38 alanine-substitution mutations in the C-terminal 41 amino acid residues of LuxR. This region plays a critical role in the mechanism of LuxR-dependent transcriptional activation of the Vibrio fischeri lux operon during quorum sensing. The ability of the variant forms of LuxR to activate transcription of the lux operon was examined by using in vivo assays in recombinant Escherichia coli. Eight recombinant strains produced luciferase at levels less than 50% of that of a strain expressing wild-type LuxR. Western immunoblotting analysis verified that the altered forms of LuxR were expressed at levels equivalent to those of the wild type. An in vivo DNA binding-repression assay in recombinant E. coli was subsequently used to measure the ability of the variant forms of LuxR to bind to the lux box, the binding site of LuxR at the lux operon promoter. All eight LuxR variants found to affect cellular luciferase levels were unable to bind to the lux box. An additional 11 constructs that had no effect on cellular luciferase levels were also found to exhibit a defect in DNA binding. None of the alanine substitutions in LuxR affected activation of transcription of the lux operon without also affecting DNA binding. These results support the conclusion that the C-terminal 41 amino acids of LuxR are important for DNA recognition and binding of the lux box rather than positive control of the process of transcription initiation. PMID:11114940

Trott, Amy E.; Stevens, Ann M.

2001-01-01

313

Post-transcriptional activation of a diguanylate cyclase by quorum sensing small RNAs promotes biofilm formation in Vibrio cholerae  

PubMed Central

Summary Biofilms promote attachment of Vibrio cholerae in aquatic ecosystems and aid in transmission. Intracellular c-di-GMP levels that control biofilm development positively correlate with expression of Qrr sRNAs, which are transcribed when quorum sensing (QS) autoinducer levels are low. The Qrr sRNA base-pair with and repress translation of hapR encoding the QS “master regulator”, hence increased c-di-GMP and biofilm development at low density were believed to be solely a consequence of Qrr/hapR pairing. We show that Qrr sRNAs also base-pair with and activate translation of the mRNA of a diguanylate cyclase (DGC), Vca0939; relieving an inhibitory structure in vca0939 that occludes the ribosome binding site. A nucleotide substitution in vca0939 disrupted sRNA/mRNA base-pairing and prevented vca0939 translation, while a compensating Qrr sRNA substitution restored pairing and Vca0939 levels. Qrr-dependent DGC activation led to c-di-GMP accumulation and biofilm development in V. cholerae. This represents the first description of 1) a DGC post-transcriptionally activated by direct pairing with an Hfq-dependent sRNA, and 2) control of a V. cholerae QS phenotype, independent of HapR. Thus, direct interactions of the same sRNAs with two mRNAs promote c-di-GMP-dependent biofilm formation by complementary mechanisms in V. cholerae; by negatively regulating HapR, and positively regulating the DGC Vca0939. PMID:23841714

Zhao, Xiaonan; Koestler, Benjamin J.; Waters, Christopher M.; Hammer, Brian K.

2013-01-01

314

Analysis of quorum sensing-dependent virulence factor production and its relationship with antimicrobial susceptibility in Pseudomonas aeruginosa respiratory isolates.  

PubMed

Pseudomonas aeruginosa is an opportunistic pathogen causing severe respiratory infections. The pathogenesis of these infections is multifactorial and the production of many virulence factors is regulated by quorum sensing (QS), a cell-to-cell communication mechanism. The two well defined QS systems in P. aeruginosa, the las and rhl systems, rely on N-acyl homoserine lactone signal molecules, also termed autoinducers. We assessed the activity of QS-dependent virulence factors (including elastase, alkaline protease, pyocyanin and biofilm production) in respiratory isolates of P. aeruginosa and their relationship with antimicrobial susceptibility. We identified sixteen isolates displaying impaired phenotypic activity; among them, eleven isolates were also defective in autoinducer production, and therefore considered QS-deficient. Six of the QS-deficient isolates failed to amplify one or more of the four QS regulatory genes (lasI, lasR, rhlI, rhlR) with PCR: one isolate was negative for rhlR, two isolates were negative for rhlI and rhlR and three isolates were negative for all four genes. The isolates that were negative for virulence factor production were generally less susceptible to the antimicrobials and statistically significant correlations were observed between the lack of elastase production and resistance to piperacillin and ceftazidime; between failure in alkaline protease production and resistance to tobramycin, piperacillin, piperacillin-tazobactam, cefepime, imipenem and ciprofloxacin; and between failure in pyocyanin production and resistance to amikacin, tobramycin, ceftazidime, ciprofloxacin and ofloxacin. The results obtained indicate that, despite the pivotal role of QS in the pathogenesis of P. aeruginosa respiratory infections, QS-deficient strains are still capable of causing infections and tend to be less susceptible to antimicrobials. PMID:20132256

Karatuna, O; Yagci, A

2010-12-01

315

Transcriptome-based analysis of the Pantoea stewartii quorum-sensing regulon and identification of EsaR direct targets.  

PubMed

Pantoea stewartii subsp. stewartii is a proteobacterium that causes Stewart's wilt disease in corn plants. The bacteria form a biofilm in the xylem of infected plants and produce capsule that blocks water transport, eventually causing wilt. At low cell densities, the quorum-sensing (QS) regulatory protein EsaR is known to directly repress expression of esaR itself as well as the genes for the capsular synthesis operon transcription regulator, rcsA, and a 2,5-diketogluconate reductase, dkgA. It simultaneously directly activates expression of genes for a putative small RNA, esaS, the glycerol utilization operon, glpFKX, and another transcriptional regulator, lrhA. At high bacterial cell densities, all of this regulation is relieved when EsaR binds an acylated homoserine lactone signal, which is synthesized constitutively over growth. QS-dependent gene expression is critical for the establishment of disease in the plant. However, the identity of the full set of genes controlled by EsaR/QS is unknown. A proteomic approach previously identified around 30 proteins in the QS regulon. In this study, a whole-transcriptome, next-generation sequencing analysis of rRNA-depleted RNA from QS-proficient and -deficient P. stewartii strains was performed to identify additional targets of EsaR. EsaR-dependent transcriptional regulation of a subset of differentially expressed genes was confirmed by quantitative reverse transcription-PCR (qRT-PCR). Electrophoretic mobility shift assays demonstrated that EsaR directly bound 10 newly identified target promoters. Overall, the QS regulon of P. stewartii orchestrates three major physiological responses: capsule and cell envelope biosynthesis, surface motility and adhesion, and stress response. PMID:25015891

Ramachandran, Revathy; Burke, Alison Kernell; Cormier, Guy; Jensen, Roderick V; Stevens, Ann M

2014-09-01

316

Proteomic analysis of the quorum-sensing regulon in Pantoea stewartii and identification of direct targets of EsaR.  

PubMed

The proteobacterium Pantoea stewartii subsp. stewartii causes Stewart's wilt disease in maize when it colonizes the xylem and secretes large amounts of stewartan, an exopolysaccharide. The success of disease pathogenesis lies in the timing of bacterial virulence factor expression through the different stages of infection. Regulation is achieved through a quorum-sensing (QS) system consisting of the acyl-homoserine lactone (AHL) synthase, EsaI, and the transcription regulator EsaR. At low cell densities, EsaR represses transcription of itself and of rcsA, an activator of the stewartan biosynthesis operon; it also activates esaS, which encodes a small RNA (sRNA). Repression or activation ceases at high cell densities when EsaI synthesizes sufficient levels of the AHL ligand N-3-oxo-hexanoyl-L-homoserine lactone to bind and inactivate EsaR. This study aims to identify other genes activated or repressed by EsaR during the QS response. Proteomic analysis identified a QS regulon of more than 30 proteins. Electrophoretic mobility shift assays of promoters of genes encoding differentially expressed proteins distinguished direct targets of EsaR from indirect targets. Additional quantitative reverse transcription-PCR (qRT-PCR) and DNA footprinting analysis established that EsaR directly regulates the promoters of dkgA, glpF, and lrhA. The proteins encoded by dkgA, glpF, and lrhA are a 2,5-diketogluconate reductase, glycerol facilitator, and transcriptional regulator of chemotaxis and motility, respectively, indicating a more global QS response in P. stewartii than previously recognized. PMID:23913428

Ramachandran, Revathy; Stevens, Ann M

2013-10-01

317

Quorum sensing-dependent metalloprotease VvpE is important in the virulence of Vibrio vulnificus to invertebrates.  

PubMed

Vibrio vulnificus, a Gram-negative bacterium, is an opportunistic human pathogen responsible for fatal septicemia caused by contaminated sea foods in eastern Asia. Quorum sensing (QS) is a cell-density dependent gene regulation mechanism that controls the expression of many virulence genes in various bacteria and V. vulnificus has been also suggested to express their virulence genes through the QS system. In this study, we investigated the role of QS system and QS-regulated exoproteases in the virulence of V. vulnificus using several invertebrate host models, Tenebrio molitor, an insect, Caenorhabditis elegans, a nematode, and brine shrimp (Artemia), an aquatic crustacean. When the culture supernatant of smcR (major QS regulator of V. vulnificus) mutant was injected to T. molitor larvae, it failed to induce the melanization of T. molitor larvae, while the culture supernatant of luxO (upstream negative regulator of smcR) mutant more strongly induced the melanization than wild type. These results demonstrated that QS system of V. vulnificus is crucial for virulence to T. molitor larvae. Among several QS-dependently expressed exoproteases of V. vulnificus, vvpE encoding a metalloprotease was mainly responsible for the melanization of T. molitor larvae, in that the culture supernatant of vvpE mutant failed to induce the melanization. This result was confirmed using the C. elegans and Artemia salina model systems, in which the vvpE mutant strains were attenuated in killing C. elegans and A. salina, compared with wild type, indicating that VvpE is important in the infection of V. vulnificus. In conclusion, we suggest that QS system and a QS-dependent exoprotease, VvpE are crucial for the V. vulnificus virulence to invertebrates. PMID:24769338

Ha, Changwan; Kim, Soo-Kyoung; Lee, Mi-Nan; Lee, Joon-Hee

2014-01-01

318

Quorum Sensing Signal Production and Microbial Interactions in a Polymicrobial Disease of Corals and the Coral Surface Mucopolysaccharide Layer  

PubMed Central

Black band disease (BBD) of corals is a complex polymicrobial disease considered to be a threat to coral reef health, as it can lead to mortality of massive reef-building corals. The BBD community is dominated by gliding, filamentous cyanobacteria with a highly diverse population of heterotrophic bacteria. Microbial interactions such as quorum sensing (QS) and antimicrobial production may be involved in BBD disease pathogenesis. In this study, BBD (whole community) samples, as well as 199 bacterial isolates from BBD, the surface mucopolysaccharide layer (SML) of apparently healthy corals, and SML of apparently healthy areas of BBD-infected corals were screened for the production of acyl homoserine lactones (AHLs) and for autoinducer-2 (AI-2) activity using three bacterial reporter strains. AHLs were detected in all BBD (intact community) samples tested and in cultures of 5.5% of BBD bacterial isolates. Over half of a subset (153) of the isolates were positive for AI-2 activity. AHL-producing isolates were further analyzed using LC-MS/MS to determine AHL chemical structure and the concentration of (S)-4,5-dihydroxy-2,3-pentanedione (DPD), the biosynthetic precursor of AI-2. C6-HSL was the most common AHL variant detected, followed by 3OC4-HSL. In addition to QS assays, 342 growth challenges were conducted among a subset of the isolates, with 27% of isolates eliciting growth inhibition and 2% growth stimulation. 24% of BBD isolates elicited growth inhibition as compared to 26% and 32% of the bacteria from the two SML sources. With one exception, only isolates that exhibited AI-2 activity or produced DPD inhibited growth of test strains. These findings demonstrate for the first time that AHLs are present in an active coral disease. It is possible that AI-2 production among BBD and coral SML bacteria may structure the microbial communities of both a polymicrobial infection and the healthy coral microbiome. PMID:25268348

Zimmer, Beth L.; May, Amanda L.; Bhedi, Chinmayee D.; Dearth, Stephen P.; Prevatte, Carson W.; Pratte, Zoe; Campagna, Shawn R.; Richardson, Laurie L.

2014-01-01

319

Functional Characterization of the Quorum Sensing Regulator RsaL in the Plant-Beneficial Strain Pseudomonas putida WCS358  

PubMed Central

In many bacteria, quorum sensing (QS) systems rely on a signal receptor and a synthase producing N-acyl-homoserine lactone(s) as the signal molecule(s). In some species, the rsaL gene, located between the signal receptor and synthase genes, encodes a repressor limiting signal synthase expression and hence signal molecule production. Here we investigate the molecular mechanism of action of the RsaL protein in the plant growth-promoting rhizobacterium Pseudomonas putida WCS358 (RsaLWCS). In P. putida WCS358, RsaLWCS displayed a strong repressive effect on the promoter of the QS signal synthase gene, ppuI, while it did not repress the same promoter in Pseudomonas aeruginosa. DNase I protection assays showed that purified RsaLWCS specifically binds to ppuI on a DNA region overlapping the predicted ?70-binding site, but such protection was observed only at high protein concentrations. Accordingly, electrophoretic mobility shift assays showed that the RsaLWCS protein was not able to form stable complexes efficiently with a probe encompassing the ppuI promoter, while it formed stable complexes with the promoter of lasI, the gene orthologous to ppuI in P. aeruginosa. This difference seems to be dictated by the lower dyad symmetry of the RsaLWCS-binding sequence on the ppuI promoter relative to that on the lasI promoter. Comparison of the results obtained in vivo and in vitro suggests that RsaLWCS needs a molecular interactor/cofactor specific for P. putida WCS358 to repress ppuI transcription. We also demonstrate that RsaLWCS regulates siderophore-mediated growth limitation of plant pathogens and biofilm formation, two processes relevant for plant growth-promoting activity. PMID:22113916

Rampioni, Giordano; Bertani, Iris; Pillai, Cejoice Ramachandran; Venturi, Vittorio; Zennaro, Elisabetta

2012-01-01

320

Bacterial virulence analysis using brine shrimp as an infection model in relation to the importance of quorum sensing and proteases.  

PubMed

Brine shrimp are aquatic crustaceans belonging to a genus of Artemia. This organism is widely used for testing the toxicity of chemicals. In this study, brine shrimp were evaluated as an infection model organism to study bacterial virulence. Artemia nauplii were infected with various pathogenic bacteria, such as Vibrio vulnificus, Pseudomonas aeruginosa, Burkholderia vietnamiensis, Staphylococcus aureus, and Escherichia coli, and the susceptibility to these bacteria was investigated by counting the survival of the infected nauplii. While all of the tested bacteria have significant virulence to brine shrimp, killing the nauplii in a few days, V. vulnificus showed the strongest virulence. P. aeruginosa also showed a dose-dependent virulence to brine shrimp, but the virulence was weaker than that of V. vulnificus. The virulence tests using the virulence-attenuated mutants of V. vulnificus and P. aeruginosa, such as quorum sensing (QS) mutants or protease-deficient mutants showed a significant attenuation of virulence, demonstrating that the QS mechanism is important in the virulence of these bacteria to brine shrimp. B. vietnamiensis, S. aureus, and E. coli were also virulent to brine shrimp and the virulence was correlated with dosage within 24 h under our conditions. Salmonella enterica Typhimurium and Bacillus subtilis were also virulent to brine shrimp, but the virulence was weak and slowly exerted compared with that of other bacteria. Taken together, we suggest that brine shrimp are a good infection model to assay bacterial virulence, especially for V. vulnificus and P. aeruginosa, and QS is important in the bacterial virulence to brine shrimp. PMID:25420421

Lee, Mi-Nan; Kim, Soo-Kyoung; Li, Xi-Hui; Lee, Joon-Hee

2014-01-01

321

Burdock root extracts limit quorum-sensing-controlled phenotypes and biofilm architecture in major urinary tract pathogens.  

PubMed

Bacterial biofilms are serious concern in patients infected with urinary tract infections, complicated urinary tract infections and other device-associated infections. Microbes within the biofilms are effectively shielded from antibiotics and host immune cells, hence can be treated only with agents which has the potential to disassemble the biofilms. The study is focused on the root extracts of Arctium lappa Linn. as a source for complementary medicine against three major biofilm forming clinical isolates of Escherichia coli, Proteus mirabilis, and Serratia marcescens. Methanol extracts of burdock roots (BR) showed no bactericidal activity (p > 0.05) against the uropathogens, whereas restrained the biofilms (p < 0.05) on polystyrene and glass surfaces at a biofilm inhibitory concentration of 100 µg/mL. The 3D confocal laser scanning microscopy was used to analyze the biofilm architecture which showed significant reduction in the surface area. Z-stack analysis has also revealed substantial reduction in the biofilm thickness (E. coli-50.79%, P. mirabilis-69.49%, and S. marcescens-75.84%). Further, BR extracts also inhibited quorum-sensing (QS)-controlled cellular phenotypes such as violacein, prodigiosin, swarming motility, and cell surface hydrophobicity. LC-MS/MS analysis of BR extracts identified the presence of two major quercetin derivatives (miquelianin and peltatoside) along with few other constituent components. Exploring such phytocompounds will provide potential agents to treat infections caused by biofilm forming uropathogens. The antibiofilm and anti-QS agents will ultimately serve as armor, facilitating the host immune system to fight infections. PMID:25226848

Rajasekharan, Satish Kumar; Ramesh, Samiraj; Bakkiyaraj, Dhamodharan; Elangomathavan, Ramaraj; Kamalanathan, Chakkaravarthi

2015-02-01

322

ExpR Coordinates the Expression of Symbiotically Important, Bundle-Forming Flp Pili with Quorum Sensing in Sinorhizobium meliloti  

PubMed Central

Type IVb pili in enteropathogenic bacteria function as a host colonization factor by mediating tight adherence to host cells, but their role in bacterium-plant symbiosis is currently unknown. The genome of the symbiotic soil bacterium Sinorhizobium meliloti contains two clusters encoding proteins for type IVb pili of the Flp (fimbrial low-molecular-weight protein) subfamily. To establish the role of Flp pili in the symbiotic interaction of S. meliloti and its host, Medicago sativa, we deleted pilA1, which encodes the putative pilin subunit in the chromosomal flp-1 cluster and conducted competitive nodulation assays. The pilA1 deletion strain formed 27% fewer nodules than the wild type. Transmission electron microscopy revealed the presence of bundle-forming pili protruding from the polar and lateral region of S. meliloti wild-type cells. The putative pilus assembly ATPase CpaE1 fused to mCherry showed a predominantly unilateral localization. Transcriptional reporter gene assays demonstrated that expression of pilA1 peaks in early stationary phase and is repressed by the quorum-sensing regulator ExpR, which also controls production of exopolysaccharides and motility. Binding of acyl homoserine lactone-activated ExpR to the pilA1 promoter was confirmed with electrophoretic mobility shift assays. A 17-bp consensus sequence for ExpR binding was identified within the 28-bp protected region by DNase I footprinting analyses. Our results show that Flp pili are important for efficient symbiosis of S. meliloti with its plant host. The temporal inverse regulation of exopolysaccharides and pili by ExpR enables S. meliloti to achieve a coordinated expression of cellular processes during early stages of host interaction. PMID:24509921

Zatakia, Hardik M.; Nelson, Cassandra E.; Syed, Umair J.

2014-01-01

323

Transcriptome-Based Analysis of the Pantoea stewartii Quorum-Sensing Regulon and Identification of EsaR Direct Targets  

PubMed Central

Pantoea stewartii subsp. stewartii is a proteobacterium that causes Stewart's wilt disease in corn plants. The bacteria form a biofilm in the xylem of infected plants and produce capsule that blocks water transport, eventually causing wilt. At low cell densities, the quorum-sensing (QS) regulatory protein EsaR is known to directly repress expression of esaR itself as well as the genes for the capsular synthesis operon transcription regulator, rcsA, and a 2,5-diketogluconate reductase, dkgA. It simultaneously directly activates expression of genes for a putative small RNA, esaS, the glycerol utilization operon, glpFKX, and another transcriptional regulator, lrhA. At high bacterial cell densities, all of this regulation is relieved when EsaR binds an acylated homoserine lactone signal, which is synthesized constitutively over growth. QS-dependent gene expression is critical for the establishment of disease in the plant. However, the identity of the full set of genes controlled by EsaR/QS is unknown. A proteomic approach previously identified around 30 proteins in the QS regulon. In this study, a whole-transcriptome, next-generation sequencing analysis of rRNA-depleted RNA from QS-proficient and -deficient P. stewartii strains was performed to identify additional targets of EsaR. EsaR-dependent transcriptional regulation of a subset of differentially expressed genes was confirmed by quantitative reverse transcription-PCR (qRT-PCR). Electrophoretic mobility shift assays demonstrated that EsaR directly bound 10 newly identified target promoters. Overall, the QS regulon of P. stewartii orchestrates three major physiological responses: capsule and cell envelope biosynthesis, surface motility and adhesion, and stress response. PMID:25015891

Ramachandran, Revathy; Burke, Alison Kernell; Cormier, Guy; Jensen, Roderick V.

2014-01-01

324

Cloning and characterizations of the Serratia marcescens metK and pfs genes involved in AI2-dependent quorum-sensing system  

Microsoft Academic Search

Serratia\\u000a marcescens utilizes two types of quorum-sensing signal molecules: N-acyl homoserine lactones and furanosyl borate diester (AI-2). S-adenosylmethionine synthetase (METK), S-adenosylhomocysteine nucleosidase (PFS), and S-ribosylhomocysteinase (LUXS) are three key enzymes in the biosynthetic pathway leading to AI-2 production. The sequence of\\u000a luxS gene was published at NCBI (Accession number: EF164926). So in this study, Serratia marcescens\\u000a metK and pfs genes

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

2008-01-01

325

Connecting Quorum Sensing, c-di-GMP, Pel Polysaccharide, and Biofilm Formation in Pseudomonas aeruginosa through Tyrosine Phosphatase TpbA (PA3885)  

PubMed Central

With the opportunistic pathogen Pseudomonas aeruginosa, quorum sensing based on homoserine lactones was found to influence biofilm formation. Here we discern a mechanism by which quorum sensing controls biofilm formation by screening 5850 transposon mutants of P. aeruginosa PA14 for altered biofilm formation. This screen identified the PA3885 mutant, which had 147-fold more biofilm than the wild-type strain. Loss of PA3885 decreased swimming, abolished swarming, and increased attachment, although this did not affect production of rhamnolipids. The PA3885 mutant also had a wrinkly colony phenotype, formed pronounced pellicles, had substantially more aggregation, and had 28-fold more exopolysaccharide production. Expression of PA3885 in trans reduced biofilm formation and abolished aggregation. Whole transcriptome analysis showed that loss of PA3885 activated expression of the pel locus, an operon that encodes for the synthesis of extracellular matrix polysaccharide. Genetic screening identified that loss of PelABDEG and the PA1120 protein (which contains a GGDEF-motif) suppressed the phenotypes of the PA3885 mutant, suggesting that the function of the PA3885 protein is to regulate 3,5-cyclic diguanylic acid (c-di-GMP) concentrations as a phosphatase since c-di-GMP enhances biofilm formation by activating PelD, and c-di-GMP inhibits swarming. Loss of PA3885 protein increased cellular c-di-GMP concentrations; hence, PA3885 protein is a negative regulator of c-di-GMP production. Purified PA3885 protein has phosphatase activity against phosphotyrosine peptides and is translocated to the periplasm. Las-mediated quorum sensing positively regulates expression of the PA3885 gene. These results show that the PA3885 protein responds to AHL signals and likely dephosphorylates PA1120, which leads to reduced c-di-GMP production. This inhibits matrix exopolysaccharide formation, which leads to reduced biofilm formation; hence, we provide a mechanism for quorum sensing control of biofilm formation through the pel locus and suggest PA3885 should be named TpbA for tyrosine phosphatase related to biofilm formation and PA1120 should be TpbB. PMID:19543378

Ueda, Akihiro; Wood, Thomas K.

2009-01-01

326

Simultaneous quantitative profiling of N -acyl- l -homoserine lactone and 2-alkyl-4(1 H )-quinolone families of quorum-sensing signaling molecules using LCMS\\/MS  

Microsoft Academic Search

An LC-MS\\/MS method, using positive mode electrospray ionization, for the simultaneous, quantitative and targeted profiling\\u000a of the N-acyl-l-homoserine lactone (AHL) and 2-alkyl 4-(1H)-quinolone (AQ) families of bacterial quorum-sensing signaling molecules (QSSMs) is presented. This LC-MS\\/MS technique was\\u000a applied to determine the relative molar ratios of AHLs and AQs produced by Pseudomonas aeruginosa and the consequences of mutating individual or multiple

Catharine A. Ortori; Jean-Frédéric Dubern; Siri Ram Chhabra; Miguel Cámara; Kim Hardie; Paul Williams; David A. Barrett

2011-01-01

327

Effect of salinity and incubation time of planktonic cells on biofilm formation, motility, exoprotease production, and quorum sensing of Aeromonas hydrophila.  

PubMed

The aim of this study was to determine the effect of salinity and age of cultures on quorum sensing, exoprotease production, and biofilm formation by Aeromonas hydrophila on stainless steel (SS) and crab shell as substrates. Biofilm formation was assessed at various salinities, from fresh (0%) to saline water (3.0%). For young and old cultures, planktonic cells were grown at 30 °C for 24 h and 96 h, respectively. Biofilm formation was assessed on SS, glass, and crab shell; viable counts were determined in R2A agar for SS and glass, but Aeromonas-selective media was used for crab shell samples to eliminate bacterial contamination. Exoprotease activity was assessed using a Fluoro™ protease assay kit. Quantification of acyl-homoserine lactone (AHL) was performed using the bioreporter strain Chromobacterium violaceum CV026 and the concentration was confirmed using high-performance liquid chromatography (HPLC). The concentration of autoinducer-2 (AI-2) was determined with Vibrio harveyi BB170. The biofilm structure at various salinities (0-3 %) was assessed using field emission electron microscopy (FESEM). Young cultures of A. hydrophila grown at 0-0.25% salinity showed gradual increasing of biofilm formation on SS, glass and crab shell; swarming and swimming motility; exoproteases production, AHL and AI-2 quorum sensing; while all these phenotypic characters reduced from 0.5 to 3.0% salinity. The FESEM images also showed that from 0 to 0.25% salinity stimulated formation of three-dimensional biofilm structures that also broke through the surface by utilizing the chitin surfaces of crab, while 3% salinity stimulated attachment only for young cultures. However, in marked contrast, salinity (0.1-3%) had no effect on the stimulation of biofilm formation or on phenotypic characters for old cultures. However, all concentrations reduced biofilm formation, motility, protease production and quorum sensing for old culture. Overall, 0-0.25% salinity enhanced biofilm formation and expression of quorum sensing regulatory genes in young cultures, whereas these responses were reduced when salinity was >0.25%. In old cultures, salinity at any concentrations (0.1-3%) induced stress in A. hydrophila. The present study provides insight into the ecology of A. hydrophila growing on fish and crustaceans such as shrimp and crabs in estuarine and seawater. PMID:25846924

Jahid, Iqbal Kabir; Mizan, Md Furkanur Rahaman; Ha, Angela J; Ha, Sang-Do

2015-08-01

328

Clustering in Sensor Networks using Quorum Sensing Ibiso Wokoma, Dr. Lionel Sacks, Dr. Ian Marshall  

E-print Network

of purposes. Vibrio fischeri is a type of bacteria that can be found living symbiotically in association Sensing (QS) is a type of intercellular signalling used by bacteria to monitor cell density for a variety the gene expression of the luminescent bacteria is regulated according to cell-density [4

Haddadi, Hamed

329

Quorum sensing and bacterial cross-talk in biotechnology John C March and William E Bentley  

E-print Network

-sensing systems has ensued, with sightings ranging from virulence in human and plant pathogens to degradative a signalling molecule, a compound has to effect a reaction in a population of cells that is distinct from]. A recent review of cell-to-cell signalling in Escherichia coli and Salmonella enterica has a conc

Jacob, Eshel Ben

330

Structural Insights into a Novel Interkingdom Signaling Circuit by Cartography of the Ligand-Binding Sites of the Homologous Quorum Sensing LuxR-Family  

PubMed Central

Recent studies have identified a novel interkingdom signaling circuit, via plant signaling molecules, and a bacterial sub-family of LuxR proteins, bridging eukaryotes and prokaryotes. Indeed pivotal plant-bacteria interactions are regulated by the so called Plant Associated Bacteria (PAB) LuxR solo regulators that, although closely related to the quorum sensing (QS) LuxR family, do not bind or respond to canonical quorum sensing N-acyl homoserine lactones (AHLs), but only to specific host plant signal molecules. The large body of structural data available for several members of the QS LuxR family complexed with different classes of ligands (AHLs and other compounds), has been exploited to dissect the cartography of their regulatory domains through structure-based multiple sequence alignments, structural superimposition and a comparative analysis of the contact residues involved in ligand binding. In the absence of experimentally determined structures of members of the PAB LuxR solos subfamily, an homology model of its prototype OryR is presented, aiming to elucidate the architecture of its ligand-binding site. The obtained model, in combination with the cartography of the regulatory domains of the homologous QS LuxRs, provides novel insights into the 3D structure of its ligand-binding site and unveils the probable molecular determinants responsible for differences in selectivity towards specific host plant signal molecules, rather than to canonical QS compounds. PMID:24132148

Covaceuszach, Sonia; Degrassi, Giuliano; Venturi, Vittorio; Lamba, Doriano

2013-01-01

331

Opposite effects of cefoperazone and ceftazidime on S-ribosylhomocysteine lyase/autoinducer-2 quorum sensing and biofilm formation by an Escherichia coli clinical isolate  

PubMed Central

To investigate the effects of subminimum inhibitory concentrations of cephalosporins on bacterial biofilm formation, the biofilm production of 52 Escherichia (E.) coli strains was examined following treatment with cephalosporin compounds at 1/4 minimum inhibitory concentrations (MICs). Ceftazidime (CAZ) inhibited biofilm formation in seven isolates, while cefoperazone (CFP) enhanced biofilm formation in 18 isolates. Biofilm formation of E. coli E42 was inhibited by CAZ and induced by CFP. Therefore, using reverse transcription-polymerase chain reaction, the expression of the biofilm-modulating genes of this isolate was investigated. To monitor the production of the autoinducer of quorum sensing in E. coli, autoinducer-2 (AI-2) production was detected by measuring the bioluminescence response of Vibrio harveyi BB170. Antisense oligonucleotides (AS-ODNs) targeting S-ribosylhomocysteine lyase (luxS) inhibited the expression of the luxS gene in E. coli. CAZ at 1/4 MIC reduced luxS mRNA levels and the production of AI-2, whereas CFP at 1/4 MIC had the opposite effect. AS-ODNs targeting luxS significantly decreased the aforementioned inhibitory effects of CAZ and the induction effects of CFP on E. coli biofilm formation. Therefore, biofilm formation by the E. coli clinical isolate E42 was evoked by CFP but attenuated by CAZ at sub-MICs, via a luxS/AI-2-based quorum sensing system. PMID:25189202

SHI, HUI-QING; SUN, FENG-JUN; CHEN, JIAN-HONG; YONG, XIAO-LAN; OU, QIAN-YI; FENG, WEI; XIA, PEI-YUAN

2014-01-01

332

Identification and Characterization of a GDSL Esterase Gene Located Proximal to the swr Quorum-Sensing System of Serratia liquefaciens MG1  

PubMed Central

Serratia liquefaciens MG1 employs the swr quorum-sensing system to control various functions, including production of extracellular enzymes and swarming motility. Here we report the sequencing of the swr flanking DNA regions. We identified a gene upstream of swrR and transcribed in the same direction, designated estA, which encodes an esterase that belongs to family II of lipolytic enzymes. EstA was heterologously expressed in Escherichia coli, and the substrate specificity of the enzyme was determined in crude extracts. With the aid of zymograms visualizing EstA on polyacrylamide gels and by the analysis of a transcriptional fusion of the estA promoter to the promoterless luxAB genes, we showed that expression of the esterase is not regulated by the swr quorum-sensing system. An estA mutant was generated and was found to exhibit growth defects on minimal medium containing Tween 20 or Tween 80 as the sole carbon source. Moreover, we show that the mutant produces greatly reduced amounts of N-acyl-homoserine lactone (AHL) signal molecules on Tween-containing medium compared with the wild type, suggesting that under certain growth conditions EstA may be important for providing the cell with precursors required for AHL biosynthesis. PMID:12839759

Riedel, Kathrin; Talker-Huiber, Daniela; Givskov, Michael; Schwab, Helmut; Eberl, Leo

2003-01-01

333

Quorum Sensing Signaling Molecules Produced by Reference and Emerging Soft-Rot Bacteria (Dickeya and Pectobacterium spp.)  

PubMed Central

Background Several small diffusible molecules are involved in bacterial quorum sensing and virulence. The production of autoinducers-1 and -2, quinolone, indole and ?-amino butyrate signaling molecules was investigated in a set of soft-rot bacteria belonging to six Dickeya or Pectobacterium species including recent or emerging potato isolates. Methodology/Principal Findings Using bacterial biosensors, immunoassay, and chromatographic analysis, we showed that soft-rot bacteria have the common ability to produce transiently during their exponential phase of growth the N-3-oxo-hexanoyl- or the N-3-oxo-octanoyl-l-homoserine lactones and a molecule of the autoinducer-2 family. Dickeya spp. produced in addition the indole-3-acetic acid in tryptophan-rich conditions. All these signaling molecules have been identified for the first time in the novel Dickeya solani species. In contrast, quinolone and ?-amino butyrate signals were not identified and the corresponding synthases are not present in the available genomes of soft-rot bacteria. To determine if the variations of signal production according to growth phase could result from expression modifications of the corresponding synthase gene, the respective mRNA levels were estimated by reverse transcriptase-PCR. While the N-acyl-homoserine lactone production is systematically correlated to the synthase expression, that of the autoinducer-2 follows the expression of an enzyme upstream in the activated methyl cycle and providing its precursor, rather than the expression of its own synthase. Conclusions/Significance Despite sharing the S-adenosylmethionine precursor, no strong link was detected between the production kinetics or metabolic pathways of autoinducers-1 and -2. In contrast, the signaling pathway of autoinducer-2 seems to be switched off by the indole-3-acetic acid pathway under tryptophan control. It therefore appears that the two genera of soft-rot bacteria have similarities but also differences in the mechanisms of communication via the diffusible molecules. Our results designate autoinducer-1 lactones as the main targets for a global biocontrol of soft-rot bacteria communications, including those of emerging isolates. PMID:22539957

Crépin, Alexandre; Barbey, Corinne; Beury-Cirou, Amélie; Hélias, Valérie; Taupin, Laure; Reverchon, Sylvie; Nasser, William; Faure, Denis; Dufour, Alain; Orange, Nicole; Feuilloley, Marc; Heurlier, Karin; Burini, Jean-François; Latour, Xavier

2012-01-01

334

Biofilm formation of Pseudomonas putida IsoF: the role of quorum sensing as assessed by proteomics.  

PubMed

Pseudomonas putida strains are frequently isolated from the rhizosphere of plants and many strains promote plant-growth, exhibit antagonistic activities against plant pathogens and have the capacity to degrade pollutants. Factors that appear to contribute to the rhizosphere fitness are the ability of the organism to form biofilms and the utilization of cell-to-cell-communication systems (quorum sensing, QS) to co-ordinate the expression of certain phenotypes in a cell density dependent manner. Recently, the ppu QS locus of the tomato rhizosphere isolate P. putida Iso F was characterized and an isogenic QS-negative ppuI mutant P. putida F117 was generated. In the present study we investigated the impact of QS and biofilm formation on the protein profile of surface-associated proteins of P. putida IsoF. This was accomplished by comparative proteome analyses of the P. putida wild type IsoF and the QS-deficient mutant F117 grown either in planktonic cultures or in 60 h old mature biofilms. Differentially expressed proteins were identified by peptide mass fingerprinting and database search in the completed P. putida KT2440 genome sequence. The sessile life style affected 129 out of 496 surface proteins, suggesting that a significant fraction of the bacterial genome is involved in biofilm physiology. In surface-attached cells 53 out of 484 protein spots were controlled by the QS system, emphasizing its importance as global regulator of gene expression in P. putida IsoF. Most interestingly, the impact of QS was dependent on whether cells were grown on a surface or in suspension; about 50% of the QS-controlled proteins identified in planktonic cultures were found to be oppositely regulated when the cells were grown as biofilms. Fifty-seven percent of all identified surface-controlled proteins were also regulated by the ppu QS system. In conclusion, our data provide strong evidence that the set of QS-regulated proteins overlaps substantially with the set of proteins differentially expressed in sessile cells. PMID:15830802

Arevalo-Ferro, Catalina; Reil, Gerold; Görg, Angelika; Eberl, Leo; Riedel, Kathrin

2005-03-01

335

Quorum vs. diffusion sensing: a quantitative analysis of the relevance of absorbing or reflecting boundaries.  

PubMed

The consequences of the boundary conditions (signal reflecting vs. signal adsorbing) on bacterial intercellular communication were addressed by a combined physics and microbiology approach. A predictive biophysical model was devised that considered system size, diffusion from given points, signal molecule decay and boundary properties. The theoretical predictions were tested with two experimental agarose-gel-based set-ups for reflecting or absorbing boundaries. N-acyl homoserine lactone (AHL) concentration profiles were measured using the Agrobacterium tumefaciens NTL4 bioassay and found to agree with model predictions. The half-life of AHL was estimated to be 7 days. The absorbing vs. reflecting nature of the boundaries drastically changed AHL concentration profiles. The effect of a single nonreflecting boundary side was equivalent to a 100-fold lower cell concentration. Results suggest that the kinetics of signal accumulation vs. signal removal and their threshold-mediated phenotypic consequences are directly linked to the properties of biofilm boundaries, stressing the relevance of the diffusion sensing component in bacterial communication. PMID:24484313

Trovato, Antonio; Seno, Flavio; Zanardo, Marina; Alberghini, Sara; Tondello, Alessandra; Squartini, Andrea

2014-03-01

336

Crystallization and preliminary crystallographic analysis of an Enterococcus faecalis repressor protein, CylR2, involved in regulating cytolysin production through quorum-sensing  

SciTech Connect

CylR2 is one of the two regulatory proteins associated with the quorum-sensing-dependent synthesis of cytolysin for the common pathogen Enterococcus faecalis. The protein was expressed with a C-terminal 6-histidine tag and purified to homogeneity with a cobalt affinity column followed by another size exclusion column. Both native and SeMet proteins were crystallized. A complete X-ray diffraction data set from the native crystal was collected to 2.3 resolution. The crystal was tetragonal, belonging to space group P41/43, with unit-cell dimensions a=b=66.2 , c=40.9 and a=b=g=90. The asymmetric unit contained two molecules of CylR2.

Ni, Shuisong; McAteer, Kathleen; Bussiere, Dirksen E.; Kennedy, Michael A.

2004-06-01

337

Novel quorum-sensing-controlled genes in Erwinia carotovora subsp. carotovora: identification of a fungal elicitor homologue in a soft-rotting bacterium.  

PubMed

Seven new genes controlled by the quorum-sensing signal molecule N-(3-oxohexanoyl)-L-homoserine lactone (OHHL) have been identified in Erwinia carotovora subsp. carotovora. Using TnphoA as a mutagen, we enriched for mutants defective in proteins that could play a role in the interaction between E. carotovora subsp. carotovora and its plant hosts, and identified NipEcc and its counterpart in E. carotovora subsp. atroseptica. These are members of a growing family of proteins related to Nep1 from Fusarium oxysporum which can induce necrotic responses in a variety of dicotyledonous plants. NipEcc produced necrosis in tobacco, NipEca affected potato stem rot, and both affected virulence in potato tubers. In E. carotovora subsp. carotovora, nip was shown to be subject to weak repression by the LuxR family regulator, EccR, and may be regulated by the negative global regulator RsmA. PMID:15828686

Pemberton, C L; Whitehead, N A; Sebaihia, M; Bell, K S; Hyman, L J; Harris, S J; Matlin, A J; Robson, N D; Birch, P R J; Carr, J P; Toth, I K; Salmond, G P C

2005-04-01

338

A Complex LuxR-LuxI Type Quorum Sensing Network in a Roseobacterial Marine Sponge Symbiont Activates Flagellar Motility and Inhibits Biofilm Formation  

PubMed Central

Summary Bacteria isolated from marine sponges, including the Silicibacter-Ruegeria (SR) subgroup of the Roseobacter clade, produce N-acylhomoserine lactone (AHL) quorum sensing signal molecules. This study is the first detailed analysis of AHL quorum sensing in sponge-associated bacteria, specifically Ruegeria sp. KLH11, from the sponge Mycale laxissima. Two pairs of luxR and luxI homologues and one solo luxI homologue were identified and designated ssaRI, ssbRI, and sscI (sponge-associated symbiont locus A, B, and C, luxRI or luxI homologue). SsaI produced predominantly long-chain 3-oxo-AHLs and both SsbI and SscI specified 3-OH-AHLs. Addition of exogenous AHLs to KLH11 increased the expression of ssaI but not ssaR, ssbI or ssbR, and genetic analyses revealed a complex interconnected arrangement between SsaRI and SsbRI systems. Interestingly, flagellar motility was abolished in the ssaI and ssaR mutants, with the flagellar biosynthesis genes under strict SsaRI control, and active motility only at high culture density. Conversely, ssaI and ssaR mutants formed more robust biofilms than wild type KLH11. AHLs and transcript of the ssaI gene were detected in M. laxissima extracts suggesting that AHL signaling contributes to the decision between motility and sessility and that it also may facilitate acclimation to different environments including the sponge host. PMID:22742196

Zan, Jindong; Cicirelli, Elisha M.; Mohamed, Naglaa M.; Sibhatu, Hiruy; Kroll, Stephanie; Choi, Ohkee; Uhlson, Charis L.; Wysoczinski, Christina L.; Murphy, Robert C.; Churchill, Mair E.A.; Hill, Russell T.; Fuqua, Clay

2012-01-01

339

Quorum-Sensing Systems LuxS/Autoinducer 2 and Com Regulate Streptococcus pneumoniae Biofilms in a Bioreactor with Living Cultures of Human Respiratory Cells  

PubMed Central

Streptococcus pneumoniae forms organized biofilms in the human upper respiratory tract that may play an essential role in both persistence and acute respiratory infection. However, the production and regulation of biofilms on human cells is not yet fully understood. In this work, we developed a bioreactor with living cultures of human respiratory epithelial cells (HREC) and a continuous flow of nutrients, mimicking the microenvironment of the human respiratory epithelium, to study the production and regulation of S. pneumoniae biofilms (SPB). SPB were also produced under static conditions on immobilized HREC. Our experiments demonstrated that the biomass of SPB increased significantly when grown on HREC compared to the amount on abiotic surfaces. Additionally, pneumococcal strains produced more early biofilms on lung cells than on pharyngeal cells. Utilizing the bioreactor or immobilized human cells, the production of early SPB was found to be regulated by two quorum-sensing systems, Com and LuxS/AI-2, since a mutation in either comC or luxS rendered the pneumococcus unable to produce early biofilms on HREC. Interestingly, while LuxS/autoinducer 2 (AI-2) regulated biofilms on both HREC and abiotic surfaces, Com control was specific for those structures produced on HREC. The biofilm phenotypes of strain D39-derivative ?comC and ?luxS QS mutants were reversed by genetic complementation. Of note, SPB formed on immobilized HREC and incubated under static conditions were completely lysed 24 h postinoculation. Biofilm lysis was also regulated by the Com and LuxS/AI-2 quorum-sensing systems. PMID:23403556

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

2013-01-01

340

Quorum Quenching Agents: Resources for Antivirulence Therapy  

PubMed Central

The continuing emergence of antibiotic-resistant pathogens is a concern to human health and highlights the urgent need for the development of alternative therapeutic strategies. Quorum sensing (QS) regulates virulence in many bacterial pathogens, and thus, is a promising target for antivirulence therapy which may inhibit virulence instead of cell growth and division. This means that there is little selective pressure for the evolution of resistance. Many natural quorum quenching (QQ) agents have been identified. Moreover, it has been shown that many microorganisms are capable of producing small molecular QS inhibitors and/or macromolecular QQ enzymes, which could be regarded as a strategy for bacteria to gain benefits in competitive environments. More than 30 species of marine QQ bacteria have been identified thus far, but only a few of them have been intensively studied. Recent studies indicate that an enormous number of QQ microorganisms are undiscovered in the highly diverse marine environments, and these marine microorganism-derived QQ agents may be valuable resources for antivirulence therapy. PMID:24886865

Tang, Kaihao; Zhang, Xiao-Hua

2014-01-01

341

Transcriptional Control of the Hydrogen Cyanide Biosynthetic Genes hcnABC by the Anaerobic Regulator ANR and the Quorum-Sensing Regulators LasR and RhlR in Pseudomonas aeruginosa  

PubMed Central

Virulence factors of Pseudomonas aeruginosa include hydrogen cyanide (HCN). This secondary metabolite is maximally produced at low oxygen tension and high cell densities during the transition from exponential to stationary growth phase. The hcnABC genes encoding HCN synthase were identified on a genomic fragment complementing an HCN-deficient mutant of P. aeruginosa PAO1. The hcnA promoter was found to be controlled by the FNR-like anaerobic regulator ANR and by the quorum-sensing regulators LasR and RhlR. Primer extension analysis revealed two transcription starts, T1 and T2, separated by 29 bp. Their function was confirmed by transcriptional lacZ fusions. The promoter sequence displayed an FNR/ANR box at ?42.5 bp upstream of T2 and a lux box centered around ?42.5 bp upstream of T1. Expression of the hcn genes was completely abolished when this lux box was deleted or inactivated by two point mutations in conserved nucleotides. The lux box was recognized by both LasR [activated by N-(oxododecanoyl)-homoserine lactone] and RhlR (activated by N-butanoyl-homoserine lactone), as shown by expression experiments performed in quorum-sensing-defective P. aeruginosa mutants and in the N-acyl-homoserine lactone-negative heterologous host P. fluorescens CHA0. A second, less conserved lux box lying 160 bp upstream of T1 seems to account for enhanced quorum-sensing-dependent expression. Without LasR and RhlR, ANR could not activate the hcn promoter. Together, these data indicate that expression of the hcn promoter from T1 can occur under quorum-sensing control alone. Enhanced expression from T2 appears to rely on a synergistic action between LasR, RhlR, and ANR. PMID:11092854

Pessi, Gabriella; Haas, Dieter

2000-01-01

342

The Pseudomonas aeruginosa Lectins PA-IL and PA-IIL Are Controlled by Quorum Sensing and by RpoS  

PubMed Central

In Pseudomonas aeruginosa, many exoproduct virulence determinants are regulated via a hierarchical quorum-sensing cascade involving the transcriptional regulators LasR and RhlR and their cognate activators, N-(3-oxododecanoyl)-l-homoserine lactone (3O-C12-HSL) and N-butanoyl-l-homoserine lactone (C4-HSL). In this paper, we demonstrate that the cytotoxic lectins PA-IL and PA-IIL are regulated via quorum sensing. Using immunoblot analysis, the production of both lectins was found to be directly dependent on the rhl locus while, in a lasR mutant, the onset of lectin synthesis was delayed but not abolished. The PA-IL structural gene, lecA, was cloned and sequenced. Transcript analysis indicated a monocistronic organization with a transcriptional start site 70 bp upstream of the lecA translational start codon. A lux box-type element together with RpoS (?S) consensus sequences was identified upstream of the putative promoter region. In Escherichia coli, expression of a lecA::lux reporter fusion was activated by RhlR/C4-HSL, but not by LasR/3O-C12-HSL, confirming direct regulation by RhlR/C4-HSL. Similarly, in P. aeruginosa PAO1, the expression of a chromosomal lecA::lux fusion was enhanced but not advanced by the addition of exogenous C4-HSL but not 3O-C12-HSL. Furthermore, mutation of rpoS abolished lectin synthesis in P. aeruginosa, demonstrating that both RpoS and RhlR/C4-HSL are required. Although the C4-HSL-dependent expression of the lecA::lux reporter in E. coli could be inhibited by the presence of 3O-C12-HSL, this did not occur in P. aeruginosa. This suggests that, in the homologous genetic background, 3O-C12-HSL does not function as a posttranslational regulator of the RhlR/C4-HSL-dependent activation of lecA expression. PMID:11053384

Winzer, Klaus; Falconer, Colin; Garber, Nachman C.; Diggle, Stephen P.; Camara, Miguel; Williams, Paul

2000-01-01

343

Phosphate availability regulates biosynthesis of two antibiotics, prodigiosin and carbapenem, in Serratia via both quorum-sensing-dependent and -independent pathways.  

PubMed

Serratia sp. ATCC 39006 produces two secondary metabolite antibiotics, 1-carbapen-2-em-3-carboxylic acid (Car) and the red pigment, prodigiosin (Pig). We have previously reported that production of Pig and Car is controlled by N-acyl homoserine lactone (N-AHL) quorum sensing, with synthesis of N-AHLs directed by the LuxI homologue SmaI, and is also regulated by Rap, a member of the SlyA family. We now describe further characterization of the SmaI quorum-sensing system and its connection with other regulatory mechanisms. We show that the genes responsible for biosynthesis of Pig, pigA-O, are transcribed as a single polycistronic message in an N-AHL-dependent manner. The smaR gene, transcribed convergently with smaI and predicted to encode the LuxR homologue partner of SmaI, was shown to possess a negative regulatory function, which is uncommon among the LuxR-type transcriptional regulators. SmaR represses transcription of both the pig and car gene clusters in the absence of N-AHLs. Specifically, we show that SmaIR exerts its effect on car gene expression via transcriptional control of carR, encoding a pheromone-independent LuxR homologue. Transcriptional activation of the pig and car gene clusters also requires a functional Rap protein, but Rap dependency can be bypassed by secondary mutations. Transduction of these suppressor mutations into wild-type backgrounds confers a hyper-Pig phenotype. Multiple mutations cluster in a region upstream of the pigA gene, suggesting this region may represent a repressor target site. Two mutations mapped to genes encoding pstS and pstA homologues, which are parts of a high-affinity phosphate transport system (Pst) in Escherichia coli. Disruption of pstS mimicked phosphate limitation and caused concomitant hyper-production of Pig and Car, which was mediated, in part, through increased transcription of the smaI gene. The Pst and SmaIR systems define distinct, yet overlapping, regulatory circuits which form part of a complex regulatory network controlling the production of secondary metabolites in Serratia ATCC 39006. PMID:12519208

Slater, Holly; Crow, Matthew; Everson, Lee; Salmond, George P C

2003-01-01

344

Nox2 Modification of LDL Is Essential for Optimal Apolipoprotein B-mediated Control of agr Type III Staphylococcus aureus Quorum-sensing  

PubMed Central

Staphylococcus aureus contains an autoinducing quorum-sensing system encoded within the agr operon that coordinates expression of virulence genes required for invasive infection. Allelic variation within agr has generated four agr specific groups, agr I–IV, each of which secretes a distinct autoinducing peptide pheromone (AIP1-4) that drives agr signaling. Because agr signaling mediates a phenotypic change in this pathogen from an adherent colonizing phenotype to one associated with considerable tissue injury and invasiveness, we postulated that a significant contribution to host defense against tissue damaging and invasive infections could be provided by innate immune mechanisms that antagonize agr signaling. We determined whether two host defense factors that inhibit AIP1-induced agrI signaling, Nox2 and apolipoprotein B (apoB), also contribute to innate control of AIP3-induced agrIII signaling. We hypothesized that apoB and Nox2 would function differently against AIP3, which differs from AIP1 in amino acid sequence and length. Here we show that unlike AIP1, AIP3 is resistant to direct oxidant inactivation by Nox2 characteristic ROS. Rather, the contribution of Nox2 to defense against agrIII signaling is through oxidation of LDL. ApoB in the context of oxLDL, and not LDL, provides optimal host defense against S. aureus agrIII infection by binding the secreted signaling peptide, AIP3, and preventing expression of the agr-driven virulence factors which mediate invasive infection. ApoB within the context of oxLDL also binds AIP 1-4 and oxLDL antagonizes agr signaling by all four agr alleles. Our results suggest that Nox2-mediated oxidation of LDL facilitates a conformational change in apoB to one sufficient for binding and sequestration of all four AIPs, demonstrating the interdependence of apoB and Nox2 in host defense against agr signaling. These data reveal a novel role for oxLDL in host defense against S. aureus quorum-sensing signaling. PMID:23459693

Hall, Pamela R.; Elmore, Bradley O.; Spang, Cynthia H.; Alexander, Susan M.; Manifold-Wheeler, Brett C.; Castleman, Moriah J.; Daly, Seth M.; Peterson, M. Michal; Sully, Erin K.; Femling, Jon K.; Otto, Michael; Horswill, Alexander R.; Timmins, Graham S.; Gresham, Hattie D.

2013-01-01

345

Lack of genomic evidence of AI-2 receptors suggests a non-quorum sensing role for luxS in most bacteria  

PubMed Central

Background Great excitement accompanied discoveries over the last decade in several Gram-negative and Gram-positive bacteria of the LuxS protein, which catalyzes production of the AI-2 autoinducer molecule for a second quorum sensing system (QS-2). Since the luxS gene was found to be widespread among the most diverse bacterial taxa, it was hypothesized that AI-2 may constitute the basis of a universal microbial language, a kind of bacterial Esperanto. Many of the studies published in this field have drawn a direct correlation between the occurrence of the luxS gene in a given organism and the presence and functionality of a QS-2 therein. However, rarely hathe existence of potential AI-2 receptors been examined. This is important, since it is now well recognized that LuxS also holds a central role as a metabolic enzyme in the activated methyl cycle which is responsible for the generation of S-adenosyl-L-methionine, the major methyl donor in the cell. Results In order to assess whether the role of LuxS in these bacteria is indeed related to AI-2 mediated quorum sensing we analyzed genomic databases searching for established AI-2 receptors (i.e., LuxPQ-receptor of Vibrio harveyi and Lsr ABC-transporter of Salmonella typhimurium) and other presumed QS-related proteins and compared the outcome with published results about the role of QS-2 in these organisms. An unequivocal AI-2 related behavior was restricted primarily to organisms bearing known AI-2 receptor genes, while phenotypes of luxS mutant bacteria lacking these genes could often be explained simply by assuming deficiencies in sulfur metabolism. Conclusion Genomic analysis shows that while LuxPQ is restricted to Vibrionales, the Lsr-receptor complex is mainly present in pathogenic bacteria associated with endotherms. This suggests that QS-2 may play an important role in interactions with animal hosts. In most other species, however, the role of LuxS appears to be limited to metabolism, although in a few cases the presence of yet unknown receptors or the adaptation of pre-existent effectors to QS-2 must be postulated. PMID:18803868

Rezzonico, Fabio; Duffy, Brion

2008-01-01

346

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

PubMed Central

Background N-acylhomoserine lactone (AHL)-based quorum sensing (QS) systems have been described in many plant-associated Gram-negative bacteria to control certain beneficial phenotypic traits, such as production of biocontrol factors and plant growth promotion. However, the role of AHL-mediated signalling in the endophytic strains of plant-associated Serratia is still poorly understood. An endophytic Serratia sp. G3 with biocontrol potential and high levels of AHL signal production was isolated from the stems of wheat and the role of QS in this isolate was determined. Results Strain G3 classified as Serratia plymuthica based on 16S rRNA was subjected to phylogenetic analysis. Using primers to conserved sequences of luxIR homologues from the Serratia genus, splIR and spsIR from the chromosome of strain G3 were cloned and sequenced. AHL profiles from strain G3 and Escherichia coli DH5? expressing splI or spsI from recombinant plasmids were identified by liquid chromatography-tandem mass spectrometry. This revealed that the most abundant AHL signals produced by SplI in E. coli were N-3-oxo-hexanoylhomoserine lactone (3-oxo-C6-HSL), N-3-oxo-heptanoylhomoserine lactone (3-oxo-C7-HSL), N-3-hydroxy-hexanoylhomoserine lactone (3-hydroxy-C6-HSL), N-hexanoylhomoserine lactone (C6-HSL), and N-heptanoyl homoserine lactone (C7-HSL); whereas SpsI was primarily responsible for the synthesis of N-butyrylhomoserine lactone (C4-HSL) and N-pentanoylhomoserine lactone (C5-HSL). Furthermore, a quorum quenching analysis by heterologous expression of the Bacillus A24 AiiA lactonase in strain G3 enabled the identification of the AHL-regulated biocontrol-related traits. Depletion of AHLs with this lactonase resulted in altered adhesion and biofilm formation using a microtiter plate assay and flow cells coupled with confocal laser scanning microscopy respectively. This was different from the closely related S. plymuthica strains HRO-C48 and RVH1, where biofilm formation for both strains is AHL-independent. In addition, QS in G3 positively regulated antifungal activity, production of exoenzymes, but negatively regulated production of indol-3-acetic acid (IAA), which is in agreement with previous reports in strain HRO-C48. However, in contrast to HRO-C48, swimming motility was not controlled by AHL-mediated QS. Conclusions This is the first report of the characterisation of two AHL-based quorum sensing systems in the same isolate of the genus Serratia. Our results show that the QS network is involved in the global regulation of biocontrol-related traits in the endophytic strain G3. However, although free-living and endophytic S. plymuthica share some conservation on QS phenotypic regulation, the control of motility and biofilm formation seems to be strain-specific and possible linked to the life-style of this organism. PMID:21284858

2011-01-01

347

Diffusible signal factor (DSF) quorum sensing signal and structurally related molecules enhance the antimicrobial efficacy of antibiotics against some bacterial pathogens  

PubMed Central

Background Extensive use of antibiotics has fostered the emergence of superbugs that are resistant to multidrugs, which becomes a great healthcare and public concern. Previous studies showed that quorum sensing signal DSF (diffusible signal factor) not only modulates bacterial antibiotic resistance through intraspecies signaling, but also affects bacterial antibiotic tolerance through interspecies communication. These findings motivate us to exploit the possibility of using DSF and its structurally related molecules as adjuvants to influence antibiotic susceptibility of bacterial pathogens. Results In this study, we have demonstrated that DSF signal and its structurally related molecules could be used to induce bacterial antibiotic susceptibility. Exogenous addition of DSF signal (cis-11-methyl-2-dodecenoic acid) and its structural analogues could significantly increase the antibiotic susceptibility of Bacillus cereus, possibly through reducing drug-resistant activity, biofilm formation and bacterial fitness. The synergistic effect of DSF and its structurally related molecules with antibiotics on B. cereus is dosage-dependent. Combination of DSF with gentamicin showed an obviously synergistic effect on B. cereus pathogenicity in an in vitro model. We also found that DSF could increase the antibiotic susceptibility of other bacterial species, including Bacillus thuringiensis, Staphylococcus aureus, Mycobacterium smegmatis, Neisseria subflava and Pseudomonas aeruginosa. Conclusion The results indicate a promising potential of using DSF and its structurally related molecules as novel adjuvants to conventional antibiotics for treatment of infectious diseases caused by bacterial pathogens. PMID:24575808

2014-01-01

348

2(5H)-Furanone, epigallocatechin gallate, and a citric-based disinfectant disturb quorum-sensing activity and reduce motility and biofilm formation of Campylobacter jejuni.  

PubMed

Brominated furanone and epigallocatechin gallate (EGCG) are naturally occurring polyphenolic compounds that can be derived from sources such as Delisea pulchra algae and green tea, respectively. These compounds may have potential health benefits and antimicrobial properties. Biofilm formation and bacterial motility are virulence factors that seem to be involved in the autoinducer 2 (AI-2)-mediated quorum sensing (QS) response of Campylobacter. In this study, the anti-QS activities of 2(5H)-furanone, EGCG, and a citric-based disinfectant were tested against Campylobacter jejuni. The minimal bactericidal concentration (MBC) was determined by a microdilution method, and the AI-2 activity was measured by bioluminescence. For motility tests, subinhibitory concentrations of each compound were mixed with semisolid Muller Hinton agar. Biofilm formation was quantified in broth-containing microplates after staining with safranin. The MBC of tested compounds ranged from 0.3 to 310 ?g/mL. Subinhibitory concentrations of all of the antimicrobial compounds significantly decreased (19 to 62 %) the bacterial motility and reduced biofilm formation. After treatment with EGCG, furanone, and the disinfectant, AI-2 activity was decreased by 60 to 99 % compared to control. In conclusion, 2(5H)-furanone, EGCG, and the disinfectant exert bactericidal effects against C. jejuni and disturb QS activity and reduce motility and biofilm formation. These compounds may be naturally occurring alternatives to control C. jejuni. PMID:25231135

Castillo, Sandra; Heredia, Norma; García, Santos

2015-01-01

349

Bioactive composition, antimicrobial activities and the influence of Agrocybe aegerita (Brig.) Sing on certain quorum-sensing-regulated functions and biofilm formation by Pseudomonas aeruginosa.  

PubMed

Agrocybe aegerita (Brig.) Sing is a basidiomycete, white rot fungus. Antimicrobial activities and the antiqourum effect on Pseudomonas aeruginosa of an A. aegerita methanolic extract were investigated. The extract showed very good antimicrobial activity against all the tested microorganisms in a dose dependent manner. Effects of the Sub-MIC, MIC and 2MIC of the A. aegerita methanolic extract regulated the virulence factors in the quorum sensing (QS) test, as well as biofilm formation on P. aeruginosa. Sub-inhibitory and inhibitory concentrations of the extract demonstrated the reduction of virulence factors such as pyocyanin production, twitching and swimming motility. The biofilm forming capability of P. aeruginosa PAO1 was also reduced in a concentration-dependent manner. Furthermore, the chemical composition of the methanolic extract was determined considering its phenolic composition. The methanolic extract of A. aegerita can be a very good source of bioactive substances. This research is of great importance due to the prevalence of drug-resistant microorganisms. PMID:25367459

Petrovi?, Jovana; Glamo?lija, Jasmina; Stojkovi?, Dejan; Nikoli?, Miloš; ?iri?, Ana; Fernandes, Angela; Ferreira, Isabel C F R; Sokovi?, Marina

2014-12-01

350

The Acyl-Homoserine Lactone-Type Quorum-Sensing System Modulates Cell Motility and Virulence of Erwinia chrysanthemi pv. zeae?  

PubMed Central

Erwinia chrysanthemi pv. zeae is one of the Erwinia chrysanthemi pathovars that infects on both dicotyledons and monocotyledons. However, little is known about the molecular basis and regulatory mechanisms of its virulence. By using a transposon mutagenesis approach, we cloned the genes coding for an E. chrysanthemi pv. zeae synthase of acyl-homoserine lactone (AHL) quorum-sensing signals (expIEcz) and a cognate response regulator (expREcz). Chromatography analysis showed that expIEcz encoded production of the AHL signal N-(3-oxo-hexanoyl)-homoserine lactone (OHHL). Null mutation of expIEcz in the E. chrysanthemi pv. zeae strain EC1 abolished AHL production, increased bacterial swimming and swarming motility, disabled formation of multicell aggregates, and attenuated virulence of the pathogen on potato tubers. The mutation also marginally reduced the inhibitory activity of E. chrysanthemi pv. zeae on rice seed germination. The mutant phenotypes were rescued by either exogenous addition of AHL signal or in trans expression of expIEcz. These data demonstrate that the AHL-type QS signal plays an essential role in modulation of E. chrysanthemi pv. zeae cell motility and the ability to form multicell aggregates and is involved in regulation of bacterial virulence. PMID:18083823

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

2008-01-01

351

Bismuth-thiol incorporation enhances biological activities of liposomal tobramycin against bacterial biofilm and quorum sensing molecules production by Pseudomonas aeruginosa.  

PubMed

Recurrent pulmonary infection and inflammation are major risk factors for high morbidity and mortality in patients with cystic fibrosis (CF). As such, frequent antibiotic use and drug resistant bacterial strains are main concerns in individuals with CF. Bacterial virulence and resistance are influenced by unique CF airways fluid lining and Pseudomonas aeruginosa quorum sensing (QS) and biofilm formation. We have developed a novel liposome formulation consist of bismuth-thiol and tobramycin (LipoBiEDT-TOB) that is non-toxic and highly effective against planktonic bacteria. In this study, we examined the effect of LipoBiEDT-TOB on QS molecule N-acyl homoserine lactone (AHL) secretion by P. aeruginosa isolates in the presence of Agrobacterium tumefaciens reporter strain (A136). LipoBiEDT-TOB activity against biofilm forming P. aeruginosa was compared to free tobramycin using the Calgary Biofilm Device (CBD). Our data indicate that LipoBiEDT-TOB prevents AHL production at low tobramycin concentration (as low as 0.012 mg/l) and stops biofilm forming P. aeruginosa growth at 64 mg/l. The formulation is stable in different biological environments (biofilm, sputum, and bronchoalveolar lavage) and is able to penetrate CF sputum. Taken together, co-encapsulation of bismuth-thiol metal with tobramycin in liposome improves its antimicrobial activities in vitro. PMID:19429299

Halwani, Majed; Hebert, Stéphanie; Suntres, Zacharias E; Lafrenie, Robert M; Azghani, Ali O; Omri, Abdelwahab

2009-05-21

352

Bacterial quorum sensing molecule N-3-oxo-dodecanoyl-L-homoserine lactone causes direct cytotoxicity and reduced cell motility in human pancreatic carcinoma cells.  

PubMed

In spite of chemotherapeutic and surgical advances, pancreatic cancer continues to have a dismal prognosis. Metastasis due to tumor cell migration remains the most critical challenge in treating pancreatic cancer, and conventional chemotherapy is rarely curative. In the quest for more novel molecules to fight this disease, we tested the hypothesis that the Pseudomonas aeruginosa quorum sensing signal molecule N-3-oxo-dodecanoyl-L-homoserine lactone (O-DDHSL) would be cytotoxic to and reduce mobility of pancreatic carcinoma cells (Panc-1 and Aspc-1). Results showed a decrease in cell viability from apoptosis, diminished colony formation, and inhibition of migration of the evaluated pancreatic carcinoma cell lines. Also, cell viability decreased in the presence of O-DDHSL when cells were grown in matrigel basement membrane matrix. While messenger RNA for IQGAP-1 decreased in Panc-1 and HPDE cells upon exposure to O-DDHSL, no change was observed in Aspc-1 cells. Cofilin mRNA expression was found to be increased in both HPDE and Panc-1 cells with marginal decrease in Aspc-1 cells. RhoC, a Rho-family GTPase involved in cell motility, increased in the presence of O-DDHSL, suggesting a possible compensatory response to alteration in other migration associated genes. Our results indicate that O-DDHSL could be an effective biomolecule in eukaryotic systems with multimodal function for essential molecular targeting in pancreatic cancer. PMID:25188245

Kumar, Ashwath S; Bryan, Jeffrey N; Kumar, Senthil R

2014-01-01

353

LitR of Vibrio salmonicida Is a Salinity-Sensitive Quorum-Sensing Regulator of Phenotypes Involved in Host Interactions and Virulence  

PubMed Central

Vibrio (Aliivibrio) salmonicida is the causal agent of cold-water vibriosis, a fatal bacterial septicemia primarily of farmed salmonid fish. The molecular mechanisms of invasion, colonization, and growth of V. salmonicida in the host are still largely unknown, and few virulence factors have been identified. Quorum sensing (QS) is a cell-to-cell communication system known to regulate virulence and other activities in several bacterial species. The genome of V. salmonicida LFI1238 encodes products presumably involved in several QS systems. In this study, the gene encoding LitR, a homolog of the master regulator of QS in V. fischeri, was deleted. Compared to the parental strain, the litR mutant showed increased motility, adhesion, cell-to-cell aggregation, and biofilm formation. Furthermore, the litR mutant produced less cryptic bioluminescence, whereas production of acylhomoserine lactones was unaffected. Our results also indicate a salinity-sensitive regulation of LitR. Finally, reduced mortality was observed in Atlantic salmon infected with the litR mutant, implying that the fish were more susceptible to infection with the wild type than with the mutant strain. We hypothesize that LitR inhibits biofilm formation and favors planktonic growth, with the latter being more adapted for pathogenesis in the fish host. PMID:22371373

Bjelland, Ane Mohn; Sørum, Henning; Tegegne, Daget Ayana; Winther-Larsen, Hanne C.; Willassen, Nils Peder

2012-01-01

354

A quorum sensing-associated virulence gene of Pseudomonas aeruginosa encodes a LysR-like transcription regulator with a unique self-regulatory mechanism  

PubMed Central

The human opportunistic pathogen Pseudomonas aeruginosa strain PA14 infects both plants and animals. Previously, using plants to screen directly for P. aeruginosa virulence-attenuated mutants, we identified a locus, pho34B12, relevant in mammalian pathogenesis. Here, nonsense point mutations in the two opposing ORFs identified in the pho34B12 locus revealed that one of them, mvfR (multiple virulence factor Regulator), is able to control all of the phenotypes that mutant phoA34B12 displays. Both genetic and biochemical evidence demonstrate that the mvfR gene encodes a LysR-like transcriptional factor that positively regulates the production of elastase, phospholipase, and of the autoinducers, 3oxo-dodecanoyl homoserine lactone (PAI I) and 2-heptyl-3-hydroxy-4-quinolone (PQS), as well as the expression of the phnAB operon, involved in phenazine biosynthesis. We demonstrate that the MvfR protein is membrane-associated and acts as a transcriptional activator until cells reach stationary phase, when a unique negative feedback mechanism is activated to signal the down-regulation of the MvfR protein. This work reveals an unprecedented virulence mechanism of P. aeruginosa and identifies a unique indispensable player in the P. aeruginosa quorum-sensing cascade. PMID:11724939

Cao, Hui; Krishnan, Gomathi; Goumnerov, Boyan; Tsongalis, John; Tompkins, Ronald; Rahme, Laurence G.

2001-01-01

355

LitR of Vibrio salmonicida is a salinity-sensitive quorum-sensing regulator of phenotypes involved in host interactions and virulence.  

PubMed

Vibrio (Aliivibrio) salmonicida is the causal agent of cold-water vibriosis, a fatal bacterial septicemia primarily of farmed salmonid fish. The molecular mechanisms of invasion, colonization, and growth of V. salmonicida in the host are still largely unknown, and few virulence factors have been identified. Quorum sensing (QS) is a cell-to-cell communication system known to regulate virulence and other activities in several bacterial species. The genome of V. salmonicida LFI1238 encodes products presumably involved in several QS systems. In this study, the gene encoding LitR, a homolog of the master regulator of QS in V. fischeri, was deleted. Compared to the parental strain, the litR mutant showed increased motility, adhesion, cell-to-cell aggregation, and biofilm formation. Furthermore, the litR mutant produced less cryptic bioluminescence, whereas production of acylhomoserine lactones was unaffected. Our results also indicate a salinity-sensitive regulation of LitR. Finally, reduced mortality was observed in Atlantic salmon infected with the litR mutant, implying that the fish were more susceptible to infection with the wild type than with the mutant strain. We hypothesize that LitR inhibits biofilm formation and favors planktonic growth, with the latter being more adapted for pathogenesis in the fish host. PMID:22371373

Bjelland, Ane Mohn; Sørum, Henning; Tegegne, Daget Ayana; Winther-Larsen, Hanne C; Willassen, Nils Peder; Hansen, Hilde

2012-05-01

356

Ellagic Acid Derivatives from Terminalia chebula Retz. Downregulate the Expression of Quorum Sensing Genes to Attenuate Pseudomonas aeruginosa PAO1 Virulence  

PubMed Central

Background Burgeoning antibiotic resistance in Pseudomonas aeruginosa has necessitated the development of anti pathogenic agents that can quench acylhomoserine lactone (AHL) mediated QS with least risk of resistance. This study explores the anti quorum sensing potential of T. chebula Retz. and identification of probable compounds(s) showing anti QS activity and the mechanism of attenuation of P. aeruginosa PAO1 virulence factors. Methods and Results Methanol extract of T. chebula Retz. fruit showed anti QS activity using Agrobacterium tumefaciens A136. Bioactive fraction (F7), obtained by fractionation of methanol extract using Sephadex LH20, showed significant reduction (p<0.001) in QS regulated production of extracellular virulence factors in P. aeruginosa PAO1. Biofilm formation and alginate were significantly (p<0.05) reduced with enhanced (20%) susceptibility to tobramycin. Real Time PCR of F7 treated P. aeruginosa showed down regulation of autoinducer synthase (lasI and rhlI) and their cognate receptor (lasR and rhlR) genes by 89, 90, 90 and 93%, respectively. Electrospray Ionization Mass Spectrometry also showed 90 and 64% reduction in the production of 3-oxo-C12HSL and C4HSL after treatment. Decrease in AHLs as one of the mechanisms of quorum quenching by F7 was supported by the reversal of inhibited swarming motility in F7-treated P. aeruginosa PAO1 on addition of C4HSL. F7 also showed antagonistic activity against 3-oxo-C12HSL-dependent QS in E. coli bioreporter. C. elegans fed on F7-treated P. aeruginosa showed enhanced survival with LT50 increasing from 24 to 72 h. LC-ESI-MS of F7 revealed the presence of ellagic acid derivatives responsible for anti QS activity in T. chebula extract. Conclusions This is the first report on anti QS activity of T. chebula fruit linked to EADs which down regulate the expression of lasIR and rhlIR genes with concomitant decrease in AHLs in P. aeruginosa PAO1 causing attenuation of its virulence factors and enhanced sensitivity of its biofilm towards tobramycin. PMID:23320085

Sarabhai, Sajal; Sharma, Prince; Capalash, Neena

2013-01-01

357

The Symbiotic Biofilm of Sinorhizobium fredii SMH12, Necessary for Successful Colonization and Symbiosis of Glycine max cv Osumi, Is Regulated by Quorum Sensing Systems and Inducing Flavonoids via NodD1  

PubMed Central

Bacterial surface components, especially exopolysaccharides, in combination with bacterial Quorum Sensing signals are crucial for the formation of biofilms in most species studied so far. Biofilm formation allows soil bacteria to colonize their surrounding habitat and survive common environmental stresses such as desiccation and nutrient limitation. This mode of life is often essential for survival in bacteria of the genera Mesorhizobium, Sinorhizobium, Bradyrhizobium, and Rhizobium. The role of biofilm formation in symbiosis has been investigated in detail for Sinorhizobium meliloti and Bradyrhizobium japonicum. However, for S. fredii this process has not been studied. In this work we have demonstrated that biofilm formation is crucial for an optimal root colonization and symbiosis between S. fredii SMH12 and Glycine max cv Osumi. In this bacterium, nod-gene inducing flavonoids and the NodD1 protein are required for the transition of the biofilm structure from monolayer to microcolony. Quorum Sensing systems are also required for the full development of both types of biofilms. In fact, both the nodD1 mutant and the lactonase strain (the lactonase enzyme prevents AHL accumulation) are defective in soybean root colonization. The impairment of the lactonase strain in its colonization ability leads to a decrease in the symbiotic parameters. Interestingly, NodD1 together with flavonoids activates certain quorum sensing systems implicit in the development of the symbiotic biofilm. Thus, S. fredii SMH12 by means of a unique key molecule, the flavonoid, efficiently forms biofilm, colonizes the legume roots and activates the synthesis of Nod factors, required for successfully symbiosis. PMID:25166872

Pérez-Montaño, Francisco; Jiménez-Guerrero, Irene; Del Cerro, Pablo; Baena-Ropero, Irene; López-Baena, Francisco Javier; Ollero, Francisco Javier; Bellogín, Ramón; Lloret, Javier; Espuny, Rosario

2014-01-01

358

Escherichia coli O157:H7 Lacking the qseBC-Encoded Quorum-Sensing System Outcompetes the Parental Strain in Colonization of Cattle Intestines  

PubMed Central

The qseBC-encoded quorum-sensing system regulates the motility of Escherichia coli O157:H7 in response to bacterial autoinducer 3 (AI-3) and the mammalian stress hormones epinephrine (E) and norepinephrine (NE). The qseC gene encodes a sensory kinase that autophosphorylates in response to AI-3, E, or NE and subsequently phosphorylates its cognate response regulator QseB. In the absence of QseC, QseB downregulates bacterial motility and virulence in animal models. In this study, we found that 8- to 10-month-old calves orally inoculated with a mixture of E. coli O157:H7 and its isogenic qseBC mutant showed significantly higher fecal shedding of the qseBC mutant. In vitro analysis revealed similar growth profiles and motilities of the qseBC mutant and the parental strain in the presence or absence of NE. The magnitudes of the response to NE and expression of flagellar genes flhD and fliC were also similar for the qseBC mutant and the parental strain. The expression of ler (a positive regulator of the locus of enterocyte effacement [LEE]), the ler-regulated espA gene, and the csgA gene (encoding curli fimbriae) was increased in the qseBC mutant compared to the parental strain. On the other hand, growth, motility, and transcription of flhD, fliC, ler, espA, and csgA were significantly reduced in the qseBC mutant complemented with a plasmid-cloned copy of the qseBC genes. Thus, in vitro motility and gene expression data indicate that the near-parental level of motility, ability to respond to NE, and enhanced expression of LEE and curli genes might in part be responsible for increased colonization and fecal shedding of the qseBC mutant in calves. PMID:24413602

Casey, T. A.

2014-01-01

359

Structural basis for the activation mechanism of the PlcR virulence regulator by the quorum-sensing signal peptide PapR  

PubMed Central

The quorum-sensing regulator PlcR is the master regulator of most known virulence factors in Bacillus cereus. It is a helix-turn-helix (HTH)-type transcription factor activated upon binding of its cognate signaling peptide PapR on a tetratricopeptide repeat-type regulatory domain. The structural and functional properties of PlcR have defined a new family of sensor regulators, called the RNPP family (for Rap, NprR, PrgX, and PlcR), in Gram-positive bacteria. To fully understand the activation mechanism of PlcR, we took a closer look at the conformation changes induced upon binding of PapR and of its target DNA, known as PlcR-box. For that purpose we have determined the structures of the apoform of PlcR (Apo PlcR) and of the ternary complex of PlcR with PapR and the PlcR-box from the plcA promoter. Comparison of the apoform of PlcR with the previously published structure of the PlcR–PapR binary complex shows how a small conformational change induced in the C-terminal region of the tetratricopeptide repeat (TPR) domain upon peptide binding propagates via the linker helix to the N-terminal HTH DNA-binding domain. Further comparison with the PlcR–PapR–DNA ternary complex shows how the activation of the PlcR dimer allows the linker helix to undergo a drastic conformational change and subsequent proper positioning of the HTH domains in the major groove of the two half sites of the pseudopalindromic PlcR-box. Together with random mutagenesis experiments and interaction measurements using peptides from distinct pherogroups, this structural analysis allows us to propose a molecular mechanism for this functional switch. PMID:23277548

Grenha, Rosa; Slamti, Leyla; Nicaise, Magali; Refes, Yacine; Lereclus, Didier; Nessler, Sylvie

2013-01-01

360

PlcRa, a New Quorum-Sensing Regulator from Bacillus cereus, Plays a Role in Oxidative Stress Responses and Cysteine Metabolism in Stationary Phase  

PubMed Central

We characterized a new quorum-sensing regulator, PlcRa, which is present in various members of the B. cereus group and identified a signaling heptapeptide for PlcRa activity: PapRa7. We demonstrated that PlcRa is a 3D structural paralog of PlcR using sequence analysis and homology modeling. A comparison of the transcriptomes at the onset of stationary phase of a ?plcRa mutant and the wild-type B. cereus ATCC 14579 strain showed that 68 genes were upregulated and 49 genes were downregulated in the ?plcRa mutant strain (>3-fold change). Genes involved in the cysteine metabolism (putative CymR regulon) were downregulated in the ?plcRa mutant strain. We focused on the gene with the largest difference in expression level between the two conditions, which encoded -AbrB2- a new regulator of the AbrB family. We demonstrated that purified PlcRa bound specifically to the abrB2 promoter in the presence of synthetic PapRa7, in an electrophoretic mobility shift assay. We further showed that the AbrB2 regulator controlled the expression of the yrrT operon involved in methionine to cysteine conversion. We found that the ?plcRa mutant strain was more sensitive to hydrogen peroxide- and disulfide-induced stresses than the wild type. When cystine was added to the culture of the ?plcRa mutant, challenged with hydrogen peroxide, growth inhibition was abolished. In conclusion, we identified a new RNPP transcriptional regulator in B. cereus that activated the oxidative stress response and cysteine metabolism in transition state cells. PMID:23239999

Huillet, Eugénie; Tempelaars, Marcel H.; André-Leroux, Gwenaëlle; Wanapaisan, Pagakrong; Bridoux, Ludovic; Makhzami, Samira; Panbangred, Watanalai; Martin-Verstraete, Isabelle; Abee, Tjakko; Lereclus, Didier

2012-01-01

361

Structural basis for the activation mechanism of the PlcR virulence regulator by the quorum-sensing signal peptide PapR.  

PubMed

The quorum-sensing regulator PlcR is the master regulator of most known virulence factors in Bacillus cereus. It is a helix-turn-helix (HTH)-type transcription factor activated upon binding of its cognate signaling peptide PapR on a tetratricopeptide repeat-type regulatory domain. The structural and functional properties of PlcR have defined a new family of sensor regulators, called the RNPP family (for Rap, NprR, PrgX, and PlcR), in Gram-positive bacteria. To fully understand the activation mechanism of PlcR, we took a closer look at the conformation changes induced upon binding of PapR and of its target DNA, known as PlcR-box. For that purpose we have determined the structures of the apoform of PlcR (Apo PlcR) and of the ternary complex of PlcR with PapR and the PlcR-box from the plcA promoter. Comparison of the apoform of PlcR with the previously published structure of the PlcR-PapR binary complex shows how a small conformational change induced in the C-terminal region of the tetratricopeptide repeat (TPR) domain upon peptide binding propagates via the linker helix to the N-terminal HTH DNA-binding domain. Further comparison with the PlcR-PapR-DNA ternary complex shows how the activation of the PlcR dimer allows the linker helix to undergo a drastic conformational change and subsequent proper positioning of the HTH domains in the major groove of the two half sites of the pseudopalindromic PlcR-box. Together with random mutagenesis experiments and interaction measurements using peptides from distinct pherogroups, this structural analysis allows us to propose a molecular mechanism for this functional switch. PMID:23277548

Grenha, Rosa; Slamti, Leyla; Nicaise, Magali; Refes, Yacine; Lereclus, Didier; Nessler, Sylvie

2013-01-15

362

A proteomic analysis of Arabidopsis thaliana seedling responses to 3-oxo-octanoyl-homoserine lactone, a bacterial quorum-sensing signal  

SciTech Connect

Highlights: Black-Right-Pointing-Pointer 3OC8-HSL can change the expression of diverse proteins in Arabidopsis. Black-Right-Pointing-Pointer 3OC8-HSL responsive proteins were identified using MALDI-TOF-MS. Black-Right-Pointing-Pointer Plant could have an extensive range of functional responses to bacterial AHL. -- Abstract: N-acyl-homoserine lactones (AHLs) are a class of bacterial quorum-sensing (QS) signals that are commonly used by Gram-negative bacteria for cell-to-cell communication. Recently, it has become evident that AHLs can regulate plant root growth and trigger plant defense responses; however, little is known about the plant response mechanisms to bacterial QS signals. In this study, we used a proteomic approach to investigate the responses of Arabidopsis thaliana seedlings to N-3-oxo-octanoyl-homoserine lactone (3OC8-HSL), a bacterial QS signal. The results revealed that the abundance of 53 protein spots was significantly altered; two thirds of these proteins were found to be up-regulated after 3OC8-HSL treatment. Thirty-four proteins were identified using MALDI-TOF-MS. These 3OC8-HSL-responsive proteins, in addition to one protein of unknown function, are implicated in a variety of physiological processes, including metabolism of carbohydrate and energy, protein biosynthesis and quality control systems, defense response and signal transduction and cytoskeleton remodeling. Our bioinformatic analysis indicated that the chloroplasts are the intracellular organelles most influenced by the exposure to 3OC8-HSL. Our data indicate that plants have an extensive range of functional responses to bacterial AHLs that may play important roles in the interaction between plants and bacteria.

Miao, Chunjuan, E-mail: chunjuanjay@163.com [Biology Institute, Hebei Academy of Sciences, Shijiazhuang 050051 (China) [Biology Institute, Hebei Academy of Sciences, Shijiazhuang 050051 (China); Hebei Engineering and Technology Center of Microbiological Control on Main Crop Disease, Shijiazhuang 050051 (China); Liu, Fang, E-mail: liufang830818@126.com [Biology Institute, Hebei Academy of Sciences, Shijiazhuang 050051 (China) [Biology Institute, Hebei Academy of Sciences, Shijiazhuang 050051 (China); Hebei Engineering and Technology Center of Microbiological Control on Main Crop Disease, Shijiazhuang 050051 (China); Zhao, Qian, E-mail: zhqbluesea@163.com [Biology Institute, Hebei Academy of Sciences, Shijiazhuang 050051 (China) [Biology Institute, Hebei Academy of Sciences, Shijiazhuang 050051 (China); Hebei Engineering and Technology Center of Microbiological Control on Main Crop Disease, Shijiazhuang 050051 (China); Jia, Zhenhua, E-mail: zhenhuaj@hotmail.com [Biology Institute, Hebei Academy of Sciences, Shijiazhuang 050051 (China) [Biology Institute, Hebei Academy of Sciences, Shijiazhuang 050051 (China); Hebei Engineering and Technology Center of Microbiological Control on Main Crop Disease, Shijiazhuang 050051 (China); Song, Shuishan, E-mail: shuishans@hotmail.com [Biology Institute, Hebei Academy of Sciences, Shijiazhuang 050051 (China) [Biology Institute, Hebei Academy of Sciences, Shijiazhuang 050051 (China); Hebei Engineering and Technology Center of Microbiological Control on Main Crop Disease, Shijiazhuang 050051 (China)

2012-10-19

363

The Pseudomonas aeruginosa quorum sensing signal molecule N-(3-oxododecanoyl) homoserine lactone enhances keratinocyte migration and induces Mmp13 gene expression in vitro  

SciTech Connect

Highlights: Black-Right-Pointing-Pointer An evidence of the positive effect of AHL on epithelialization process is provided. Black-Right-Pointing-Pointer AHL enhances keratinocyte's ability to migrate in an in vitro scratch wound model. Black-Right-Pointing-Pointer AHL induces the expression of Mmp13. Black-Right-Pointing-Pointer Topical application of AHL represents a possible strategy to treat chronic wounds. -- Abstract: Re-epithelialization is an essential step of wound healing involving three overlapping keratinocyte functions: migration, proliferation and differentiation. While quorum sensing (QS) is a cell density-dependent signaling system that enables bacteria to regulate the expression of certain genes, the QS molecule N-(3-oxododecanoyl) homoserine lactone (AHL) exerts effects also on mammalian cells in a process called inter-kingdom signaling. Recent studies have shown that AHL improves epithelialization in in vivo wound healing models but detailed understanding of the molecular and cellular mechanisms are needed. The present study focused on the AHL as a candidate reagent to improve wound healing through direct modulation of keratinocyte's activity in the re-epithelialization process. Results indicated that AHL enhances the keratinocyte's ability to migrate in an in vitro scratch wound healing model probably due to the high Mmp13 gene expression analysis after AHL treatment that was revealed by real-time RT-PCR. Inhibition of activator protein 1 (AP-1) signaling pathway completely prevented the migration of keratinocytes, and also resulted in a diminished Mmp13 gene expression, suggesting that AP-1 might be essential in the AHL-induced migration. Taken together, these results imply that AHL is a promising candidate molecule to improve re-epithelialization through the induction of migration of keratinocytes. Further investigation is needed to clarify the mechanism of action and molecular pathway of AHL on the keratinocyte migration process.

Paes, Camila, E-mail: camilaquinetti@gmail.com [University of Tokyo, Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)] [University of Tokyo, Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Nakagami, Gojiro, E-mail: gojiron-tky@umin.ac.jp [University of Tokyo, Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)] [University of Tokyo, Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Minematsu, Takeo, E-mail: tminematsu-tky@umin.ac.jp [University of Tokyo, Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)] [University of Tokyo, Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Nagase, Takashi, E-mail: tnagase@fb3.so-net.ne.jp [University of Tokyo, Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)] [University of Tokyo, Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Huang, Lijuan, E-mail: koureikenhlj@gmail.com [University of Tokyo, Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)] [University of Tokyo, Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Sari, Yunita, E-mail: yunita-tky@umin.ac.jp [University of Tokyo, Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)] [University of Tokyo, Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Sanada, Hiromi, E-mail: hsanada-tky@umin.ac.jp [University of Tokyo, Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)] [University of Tokyo, Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)

2012-10-19

364

The plant pathogen Pseudomonas fuscovaginae contains two conserved quorum sensing systems involved in virulence and negatively regulated by RsaL and the novel regulator RsaM.  

PubMed

Pseudomonas fuscovaginae is a Gram-negative fluorescent pseudomonad pathogenic towards several plant species. Despite its importance as a plant pathogen, no molecular studies of virulence have thus far been reported. In this study we show that P. fuscovaginae possesses two conserved N-acyl homoserine lactone (AHL) quorum sensing (QS) systems which we designated PfsI/R and PfvI/R. The PfsI/R system is homologous to the BviI/R system of Burkholderia vietnamiensis and produces and responds to C10-HSL and C12-HSL whereas PfvI/R is homologous to the LasI/R system of Pseudomonas aeruginosa and produces several long-chain 3-oxo-HSLs and responds to 3-oxo-C10-HSL and 3-oxo-C12-HSL and at high AHL concentrations can also respond to structurally different long-chain AHLs. Both systems were found to be negatively regulated by a repressor protein which was encoded by a gene located intergenically between the AHL synthase and LuxR-family response regulator. The pfsI/R system was regulated by a novel repressor designated RsaM while the pfvI/R system was regulated by both the RsaL repressor and by RsaM. The two systems are not transcriptionally hierarchically organized but share a common AHL response and both are required for plant virulence. Pseudomonas fuscovaginae has therefore a unique complex regulatory network composed of at least two different repressors which directly regulate the AHL QS systems and pathogenicity. PMID:20701623

Mattiuzzo, Maura; Bertani, Iris; Ferluga, Sara; Cabrio, Laura; Bigirimana, Joseph; Guarnaccia, Corrado; Pongor, Sandor; Maraite, Henri; Venturi, Vittorio

2011-01-01

365

Immunomodulatory and Protective Roles of Quorum-Sensing Signaling Molecules N-Acyl Homoserine Lactones during Infection of Mice with Aeromonas hydrophila ? †  

PubMed Central

Aeromonas hydrophila leads to both intestinal and extraintestinal infections in animals and humans, and the underlying mechanisms leading to mortality are largely unknown. By using a septicemic mouse model of infection, we showed that animals challenged with A. hydrophila die because of kidney and liver damage, hypoglycemia, and thrombocytopenia. Pretreatment of animals with quorum-sensing-associated signaling molecules N-acyl homoserine lactones (AHLs), such as butanoyl and hexanoyl homoserine lactones (C4- and C6-HSLs), as well as N-3-oxododecanoyl (3-oxo-C12)-HSL, prevented clinical sequelae, resulting in increased survivability of mice. Since little is known as to how different AHLs modulate the immune response during infection, we treated mice with the above AHLs prior to lethal A. hydrophila infection. When we compared results in such animals to those in controls, the treated animals exhibited a significantly reduced bacterial load in the blood and other mouse organs, as well as various levels of cytokines/chemokines. Importantly, neutrophil numbers were significantly elevated in the blood of C6-HSL-treated mice compared to those in animals given phosphate-buffered saline and then infected with the bacteria. These findings coincided with the fact that neutropenic animals were more susceptible to A. hydrophila infection than normal mice. Our data suggested that neutrophils quickly cleared bacteria by either phagocytosis or possibly another mechanism(s) during infection. In a parallel study, we indeed showed that other predominant immune cells inflicted during A. hydrophila infections, such as murine macrophages, when they were pretreated with AHLs, rapidly phagocytosed bacteria, whereas untreated cells phagocytosed fewer bacteria. This study is the first to report that AHL pretreatment modulates the innate immune response in mice and enhances their survivability during A. hydrophila infection. PMID:21536794

Khajanchi, Bijay K.; Kirtley, Michelle L.; Brackman, Sheri M.; Chopra, Ashok K.

2011-01-01

366

Paraoxonase 2 Serves a Proapopotic Function in Mouse and Human Cells in Response to the Pseudomonas aeruginosa Quorum-sensing Molecule N-(3-Oxododecanoyl)-homoserine Lactone.  

PubMed

Pseudomonas aeruginosa use quorum-sensing molecules, including N-(3-oxododecanoyl)-homoserine lactone (C12), for intercellular communication. C12 activated apoptosis in mouse embryo fibroblasts (MEF) from both wild type (WT) and Bax/Bak double knock-out mice (WT MEF and DKO MEF that were responsive to C12, DKOR MEF): nuclei fragmented; mitochondrial membrane potential (??mito) depolarized; Ca(2+) was released from the endoplasmic reticulum (ER), increasing cytosolic [Ca(2+)] (Cacyto); and caspase 3/7 was activated. DKOR MEF had been isolated from a nonclonal pool of DKO MEF that were non-responsive to C12 (DKONR MEF). RNAseq analysis, quantitative PCR, and Western blots showed that WT and DKOR MEF both expressed genes associated with cancer, including paraoxonase 2 (PON2), whereas DKONR MEF expressed little PON2. Adenovirus-mediated expression of human PON2 in DKONR MEF rendered them responsive to C12: ??mito depolarized, Cacyto increased, and caspase 3/7 activated. Human embryonic kidney 293T (HEK293T) cells expressed low levels of endogenous PON2, and these cells were also less responsive to C12. Overexpression of PON2, but not PON2-H114Q (no lactonase activity) in HEK293T cells caused them to become sensitive to C12. Because [C12] may reach high levels in biofilms in lungs of cystic fibrosis (CF) patients, PON2 lactonase activity may control ??mito, Ca(2+) release from the ER, and apoptosis in CF airway epithelia. Coupled with previous data, these results also indicate that PON2 uses its lactonase activity to prevent Bax- and Bak-dependent apoptosis in response to common proapoptotic drugs like doxorubicin and staurosporine, but activates Bax- and Bak-independent apoptosis in response to C12. PMID:25627690

Schwarzer, Christian; Fu, Zhu; Morita, Takeshi; Whitt, Aaron G; Neely, Aaron M; Li, Chi; Machen, Terry E

2015-03-13

367

A widely conserved molecular switch controls quorum sensing and symbiosis island transfer in Mesorhizobium loti through expression of a novel antiactivator.  

PubMed

ICEMlSym(R7A) of Mesorhizobium loti is an integrative and conjugative element (ICE) that confers the ability to form a nitrogen-fixing symbiosis with Lotus species. Horizontal transfer is activated by TraR and N-acyl-homoserine lactone (AHL), which can stimulate ICE excision in 100% of cells. However, in wild-type cultures, the ICE is excised at low frequency. Here we show that QseM, a widely conserved ICE-encoded protein, is an antiactivator of TraR. Mutation of qseM resulted in TraR-dependent activation of AHL production and excision, but did not affect transcription of traR. QseM and TraR directly interacted in a bacterial two-hybrid assay in the presence of AHL. qseM expression was repressed by a DNA-binding protein QseC, which also activated qseC expression from a leaderless transcript. QseC differentially bound two adjacent operator sites, the lower affinity of which overlapped the -35 regions of the divergent qseC-qseM promoters. QseC homologues were identified on ICEs, TraR/TraM-regulated plasmids and restriction-modification cassettes, suggesting a conserved mode of regulation. Six QseC variants with distinct operators were identified that showed evidence of reassortment between mobile elements. We propose that QseC and QseM comprise a bimodal switch that restricts quorum sensing and ICEMlSym(R7A) transfer to a small proportion of cells in the population. PMID:23106190

Ramsay, Joshua P; Major, Anthony S; Komarovsky, Victor M; Sullivan, John T; Dy, Ron L; Hynes, Michael F; Salmond, George P C; Ronson, Clive W

2013-01-01

368

The Pseudomonas aeruginosa Global Regulator VqsR Directly Inhibits QscR To Control Quorum-Sensing and Virulence Gene Expression  

PubMed Central

The opportunistic pathogen Pseudomonas aeruginosa has at least three quorum-sensing (QS) systems, including the acyl-homoserine lactone (acyl-HSL)-mediated las and rhl systems, as well as the 2-alkyl-4(1H)-quinolone (AHQ) signal-based system. A group of key regulators of these QS systems have been identified, such as qteE, vqsM, vqsR, and vfr. However, the underlying regulatory mechanisms of these QS systems are not yet fully understood. Here, using electrophoretic mobility shift assays, we demonstrated that VqsR indirectly regulates acyl-HSL systems but specifically binds to the qscR promoter region, which indicates that VqsR influences QS-controlled pathways through QscR. Through a dye-based DNase I footprint assay, we showed that VqsR interacts with an inverted repeat (IR) motif (TCGCCN8GGCGA, where N is any nucleotide) in the promoter region of qscR. A genome-wide search identified 50 other promoter regions carrying the same putative IR motif. The recombinant VqsR protein exists as a homodimer in solution. In addition, using a qscR-lux reporter assay and Northern blot hybridization, we found that the transcription level of qscR increased 4-fold in the vqsR deletion strain compared to the wild-type PAO1 strain, indicating vqsR as a negative regulator of qscR. Taken together, these findings provide new insights into the complex regulation network of QS systems in P. aeruginosa. PMID:22505688

Deng, Xin; Ji, Quanjiang; Sun, Fei; Shen, Tuo; He, Chuan

2012-01-01

369

Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxododecanoyl) homoserine lactone attenuates lipopolysaccharide-induced inflammation by activating the unfolded protein response  

PubMed Central

N-3-oxododecanoyl homoserine lactone (3-oxo-C12-HSL), a quorum-sensing signal molecule produced by Pseudomonas aeruginosa (P. aeruginosa), is involved in the expression of bacterial virulence factors and in the modulation of host immune responses by directly disrupting nuclear factor-?B (NF-?B) signaling and inducing cell apoptosis. The unfolded protein response (UPR) triggered by endoplasmic reticulum (ER) stress may suppress inflammatory responses in the later phase by blocking NF-?B activation. It was recently demonstrated that 3-oxo-C12-HSL may induce UPR in human aortic endothelial cells (HAECs). Therefore, 3-oxo-C12-HSL may also inhibit NF-?B activation and suppress inflammatory responses by activating UPR. However, the possible underlying mechanism has not been fully elucidated. Accordingly, we investigated the effects of 3-oxo-C12-HSL on cellular viability, UPR activation, lipopolysaccharide (LPS)-induced NF-?B activation and inflammatory response in the RAW264.7 mouse macrophage cell line. Treatment with 6.25 ?M 3-oxo-C12-HSL was not found to affect the viability of RAW264.7 cells. However, pretreating RAW264.7 cells with 6.25 ?M 3-oxo-C12-HSL effectively triggered UPR and increased the expression of UPR target genes, such as CCAAT/enhancer-binding protein ? (C/EBP ?) and CCAAT/enhancer-binding protein-homologous protein (CHOP). The expression of C/EBP ? and CHOP was found to be inversely correlated with LPS-induced NF-?B activation. 3-Oxo-C12-HSL pretreatment was also shown to inhibit LPS-stimulated proinflammatory cytokine production. Hence, 3-oxo-C12-HSL may attenuate LPS-induced inflammation via UPR-mediated NF-?B inhibition without affecting cell viability. This may be another mechanism through which P. aeruginosa evades the host immune system and maintains a persistent infection. PMID:24649102

ZHANG, JIANGGUO; GONG, FENGYUN; LI, LING; ZHAO, MANZHI; SONG, JIANXIN

2014-01-01

370

The length of glycine-rich linker in DNA-binding domain is critical for optimal functioning of quorum-sensing master regulatory protein HapR.  

PubMed

HapR is a quorum-sensing master regulatory protein in Vibrio cholerae. Though many facts are known regarding its structural and functional aspects, much still can be learnt from natural variants of this wild-type protein. While unraveling the underlying cause of functional inertness of a natural variant (HapRV2), the significance of a conserved glycine residue at position 39 in a glycine-rich linker in DNA-binding domain comes into light. This work aims at investigating how the length of glycine-rich linker (R(33)GIGRGG(39)) bridging helices ?1 and ?2 modulates the functionality of HapR. In pursuit of our interest, glycine residues were inserted after terminal glycine (G39) of the linker in a sequential manner. To evaluate functionality, all the glycine linker variants were subjected to a battery of performance tests under various conditions. Combined in vitro and in vivo results clearly demonstrated a gradual functional impairment of HapR linker variants coupled with increasing length of glycine-rich linker and finally, linker variant harboring four glycine residues resulted in a functionally compromised protein with significant loss of communication with cognate DNAs. Molecular dynamics studies of modeled HapR linker variants in complex with cognate promoter region show that residues namely Ser50, Thr53 and Asn56 are involved in varying degree of interactions with different nucleotides of HapR-DNA complex. The diminished functionality between variants and DNA appears to result from reduced or no interactions between Phe55 and nucleotides of cognate DNA as observed during simulations. PMID:24997084

Singh, Naorem Santa; Kachhap, Sangita; Singh, Richa; Mishra, Rahul Chandra; Singh, Balvinder; Raychaudhuri, Saumya

2014-12-01

371

Bacillus pumilus of Palk Bay origin inhibits quorum-sensing-mediated virulence factors in Gram-negative bacteria  

Microsoft Academic Search

The aim of the current study was to inhibit quoring-sensing(QS)-mediated virulence factors of representative Gram-negative bacteria by marine bacterial isolates. Bacteria isolated from Palk Bay sediments were screened for anti-QS activity. Eleven strains inhibited QS signals in Chromobacterium violaceum (ATCC 12472) and C. violaceum CV026. The marine bacterial strain S8-07 reduced the accumulation of N-acyl homoserine lactone (AHLs) and showed

Chari Nithya; Chairman Aravindraja; Shunmugiah Karutha Pandian

2010-01-01

372

Resistance to Quorum-Quenching Compounds  

PubMed Central

Bacteria have the remarkable ability to communicate as a group in what has become known as quorum sensing (QS), and this trait has been associated with important bacterial phenotypes, such as virulence and biofilm formation. Bacteria also have an incredible ability to evolve resistance to all known antimicrobials. Hence, although inhibition of QS has been hailed as a means to reduce virulence in a manner that is impervious to bacterial resistance mechanisms, this approach is unlikely to be a panacea. Here we review the evidence that bacteria can evolve resistance to quorum-quenching compounds. PMID:24014536

García-Contreras, Rodolfo; Maeda, Toshinari

2013-01-01

373

The Availability of Quorum Systems  

Microsoft Academic Search

A quorum system is a collection of sets (quorums) every two of which intersect. Quorum systems have been used for many applications in the area of distributed systems, including mutual exclusion, data replication, and dissemination of information. In this paper we study the failure probabilities of quorum systems and in particular of nondominated coteries (NDC). We characterize NDC?s in terms

David Peleg; Avishai Wool

1995-01-01

374

Quorum Quenching in Culturable Phyllosphere Bacteria from Tobacco  

PubMed Central

Many Gram-negative plant pathogenic bacteria employ a N-acylhomoserine lactone (AHL)-based quorum sensing (QS) system to regulate their virulence traits. A sustainable biocontrol strategy has been developed using quorum quenching (QQ) bacteria to interfere with QS and protect plants from pathogens. Here, the prevalence and the diversity of QQ strains inhabiting tobacco leaf surfaces were explored. A total of 1177 leaf-associated isolates were screened for their ability to disrupt AHL-mediated QS, using the biosensor Chromobacterium violaceum CV026. One hundred and sixty-eight strains (14%) are capable of interfering with AHL activity. Among these, 106 strains (63%) of the culturable quenchers can enzymatically degrade AHL molecules, while the remaining strains might use other QS inhibitors to interrupt the chemical communication. Moreover, almost 79% of the QQ strains capable of inactivating AHLs enzymatically have lactonase activity. Further phylogenetic analysis based on 16S rDNA revealed that the leaf-associated QQ bacteria can be classified as Bacillus sp., Acinetobacter sp., Lysinibacillus sp., Serratia sp., Pseudomonas sp., and Myroides sp. The naturally occurring diversity of bacterial quenchers might provide opportunities to use them as effective biocontrol reagents for suppressing plant pathogen in situ. PMID:23857057

Ma, Anzhou; Lv, Di; Zhuang, Xuliang; Zhuang, Guoqiang

2013-01-01

375

Dissection of Quorum-Sensing Genes in Burkholderia glumae Reveals Non-Canonical Regulation and the New Regulatory Gene tofM for Toxoflavin Production  

PubMed Central

Burkholderia glumae causes bacterial panicle blight of rice and produces major virulence factors, including toxoflavin, under the control of the quorum-sensing (QS) system mediated by the luxI homolog, tofI, and the luxR homolog, tofR. In this study, a series of markerless deletion mutants of B. glumae for tofI and tofR were generated using the suicide vector system, pKKSacB, for comprehensive characterization of the QS system of this pathogen. Consistent with the previous studies by other research groups, ?tofI and ?tofR strains of B. glumae did not produce toxoflavin in Luria-Bertani (LB) broth. However, these mutants produced high levels of toxoflavin when grown in a highly dense bacterial inoculum (? 1011 CFU/ml) on solid media, including LB agar and King’s B (KB) agar media. The ?tofI/?tofR strain of B. glumae, LSUPB201, also produced toxoflavin on LB agar medium. These results indicate the presence of previously unknown regulatory pathways for the production of toxoflavin that are independent of tofI and/or tofR. Notably, the conserved open reading frame (locus tag: bglu_2g14480) located in the intergenic region between tofI and tofR was found to be essential for the production of toxoflavin by tofI and tofR mutants on solid media. This novel regulatory factor of B. glumae was named tofM after its homolog, rsaM, which was recently identified as a novel negative regulatory gene for the QS system of another rice pathogenic bacterium, Pseudomonas fuscovaginae. The ?tofM strain of B. glumae, LSUPB286, produced a less amount of toxoflavin and showed attenuated virulence when compared with its wild type parental strain, 336gr-1, suggesting that tofM plays a positive role in toxoflavin production and virulence. In addition, the observed growth defect of the ?tofI strain, LSUPB145, was restored by 1 µM N-octanoyl homoserine lactone (C8-HSL). PMID:23284909

Chen, Ruoxi; Barphagha, Inderjit K.; Karki, Hari S.; Ham, Jong Hyun

2012-01-01

376

Dissection of quorum-sensing genes in Burkholderia glumae reveals non-canonical regulation and the new regulatory gene tofM for toxoflavin production.  

PubMed

Burkholderia glumae causes bacterial panicle blight of rice and produces major virulence factors, including toxoflavin, under the control of the quorum-sensing (QS) system mediated by the luxI homolog, tofI, and the luxR homolog, tofR. In this study, a series of markerless deletion mutants of B. glumae for tofI and tofR were generated using the suicide vector system, pKKSacB, for comprehensive characterization of the QS system of this pathogen. Consistent with the previous studies by other research groups, ?tofI and ?tofR strains of B. glumae did not produce toxoflavin in Luria-Bertani (LB) broth. However, these mutants produced high levels of toxoflavin when grown in a highly dense bacterial inoculum (? 10(11) CFU/ml) on solid media, including LB agar and King's B (KB) agar media. The ?tofI/?tofR strain of B. glumae, LSUPB201, also produced toxoflavin on LB agar medium. These results indicate the presence of previously unknown regulatory pathways for the production of toxoflavin that are independent of tofI and/or tofR. Notably, the conserved open reading frame (locus tag: bglu_2g14480) located in the intergenic region between tofI and tofR was found to be essential for the production of toxoflavin by tofI and tofR mutants on solid media. This novel regulatory factor of B. glumae was named tofM after its homolog, rsaM, which was recently identified as a novel negative regulatory gene for the QS system of another rice pathogenic bacterium, Pseudomonas fuscovaginae. The ?tofM strain of B. glumae, LSUPB286, produced a less amount of toxoflavin and showed attenuated virulence when compared with its wild type parental strain, 336gr-1, suggesting that tofM plays a positive role in toxoflavin production and virulence. In addition, the observed growth defect of the ?tofI strain, LSUPB145, was restored by 1 µM N-octanoyl homoserine lactone (C8-HSL). PMID:23284909

Chen, Ruoxi; Barphagha, Inderjit K; Karki, Hari S; Ham, Jong Hyun

2012-01-01

377

Impact of QseBC system in c-di-GMP-dependent quorum sensing regulatory network in a clinical isolate SSU of Aeromonas hydrophila  

PubMed Central

Our earlier studies showed that ahyRI (AI-1) and LuxS-based (AI-2) quorum sensing (QS) systems were positive and negative regulators of virulence, respectively, in a diarrheal isolate SSU of A. hydrophila. Recently, we demonstrated that deletion of the QseBC two-component signal transduction system (AI-3 QS in enterohemorrhagic E. coli) also led to an attenuation of A. hydrophila in a septicemic mouse model of infection, and that interplay exists between AI-1, AI-2, and the second messenger cyclic-di-guanosine monophosphate (c-di-GMP) in modulating bacterial virulence. To further explore a network connection between all of the three QS systems in A. hydrophila SSU and their cross-talk with c-di-GMP, we overproduced a protein with a GGDEF domain, which increases c-di-GMP levels in bacteria, and studied phenotypes and transcriptional profiling of genes involved in biofilm formation and motility of the wild-type (WT) A. hydrophila and its ?qseB mutant. Over-expression of the GGDEF domain-encoding gene (aha0701h) resulted in a significantly reduced motility of the WT A. hydrophila similar to that of the ?qseB mutant. While enhanced protease production was noted in WT A. hydrophila that had increased c-di-GMP, no enzymatic activity was detected in the ?qseB mutant overexpressing the aha0701h gene. Likewise, denser biofilm formation was noted for WT bacteria when c-di-GMP was overproduced compared to its respective control; however, overproduction of c-di-GMP in the ?qseB mutant led to reduced biofilm formation, a finding similar to that noted for the parental A. hydrophila strain. These effects on bacterial motility and biofilm formation in the ?qseB mutant or the mutant with increased c-di-GMP were correlated with altered levels of fleN and vpsT genes. While we noted transcript levels of qseB and qseC genes to be increased in the ahyRI mutant, down-regulation of the ahyR and ahyI genes was observed in the ?qseB mutant, which correlated with decreased protease activity. Finally, an enhanced virulence of WT A. hydrophila with increased c-di-GMP was noted in a mouse model when compared to findings in the parental strain with vector alone. Overall, we conclude that cross talk between AI-1- and QseBC-systems exist in A. hydrophila SSU, and c-di-GMP modulation on QseBC-system is dependent on the expression of the AI-1 system. PMID:22664750

Kozlova, Elena V.; Khajanchi, Bijay K.; Popov, Vsevolod. L.; Wen, Julie; Chopra, Ashok K.

2012-01-01

378

Reconfiguring the Quorum-Sensing Regulator SdiA of Escherichia coli To Control Biofilm Formation via Indole and N-Acylhomoserine Lactones? †  

PubMed Central

SdiA is a homolog of quorum-sensing regulators that detects N-acylhomoserine lactone (AHL) signals from other bacteria. Escherichia coli uses SdiA to reduce its biofilm formation in the presence of both AHLs and its own signal indole. Here we reconfigured SdiA (240 amino acids) to control biofilm formation using protein engineering. Four SdiA variants were obtained with altered biofilm formation, including truncation variants SdiA1E11 (F7L, F59L, Y70C, M94K, and K153X) and SdiA14C3 (W9R, P49T, N87T, frameshift at N96, and L123X), which reduced biofilm formation by 5- to 20-fold compared to wild-type SdiA in the presence of endogenous indole. Whole-transcriptome profiling revealed that wild-type SdiA reduced biofilm formation by repressing genes related to indole synthesis and curli synthesis compared to when no SdiA was expressed, while variant SdiA1E11 induced genes related to indole synthesis in comparison to wild-type SdiA. These results suggested altered indole metabolism, and corroborating the DNA microarray results in regard to indole synthesis, variant SdiA1E11 produced ninefold more indole, which led to reduced swimming motility and cell density. Also, wild-type SdiA decreased curli production and tnaA transcription, while SdiA1E11 increased tnaA transcription (tnaA encodes tryptophanase, which forms indole) compared to wild-type SdiA. Hence, wild-type SdiA decreased biofilm formation by reducing curli production and motility, and SdiA1E11 reduced biofilm formation via indole. Furthermore, an AHL-sensitive variant (SdiA2D10, having four mutations at E31G, Y42F, R116H, and L165Q) increased biofilm formation sevenfold in the presence of N-octanoyl-dl-homoserine lactone and N-(3-oxododecatanoyl)-l-homoserine lactone. Therefore, SdiA can be evolved to increase or decrease biofilm formation, and biofilm formation may be controlled by altering sensors rather than signals. PMID:19168658

Lee, Jintae; Maeda, Toshinari; Hong, Seok Hoon; Wood, Thomas K.

2009-01-01

379

Identification of potential genetic components involved in the deviant quorum-sensing signaling pathways of Burkholderia glumae through a functional genomics approach  

PubMed Central

Burkholderia glumae is the chief causal agent for bacterial panicle blight of rice. The acyl-homoserine lactone (AHL)-mediated quorum-sensing (QS) system dependent on a pair of luxI and luxR homologs, tofI and tofR, is the primary cell-to-cell signaling mechanism determining the virulence of this bacterium. Production of toxoflavin, a major virulence factor of B. glumae, is known to be dependent on the tofI/tofR QS system. In our previous study, however, it was observed that B. glumae mutants defective in tofI or tofR produced toxoflavin if they grew on the surface of a solid medium, suggesting that alternative signaling pathways independent of tofI or tofR are activated in that growth condition for the production of toxoflavin. In this study, potential genetic components involved in the tofI- and tofR-independent signaling pathways for toxoflavin production were sought through screening random mini-Tn5 mutants of B. glumae to better understand the intercellular signaling pathways of this pathogen. Fifteen and three genes were initially identified as the potential genetic elements of the tofI- and tofR-independent pathways, respectively. Especially, the ORF (bglu_2g06320) divergently transcribed from toxJ, which encodes an orphan LuxR protein and controls toxoflavin biosynthesis, was newly identified in this study as a gene required for the tofR-independent toxoflavin production and named as toxK. Among those genes, flhD, dgcB, and wzyB were further studied to validate their functions in the tofI-independent toxoflavin production, and similar studies were also conducted with qsmR and toxK for their functions in the tofR-independent toxoflavin production. This work provides a foundation for future comprehensive studies of the intercellular signaling systems of B. glumae and other related pathogenic bacteria. PMID:25806356

Chen, Ruoxi; Barphagha, Inderjit K.; Ham, Jong Hyun

2015-01-01

380

Effect of protease inhibitors on the sense of taste  

Microsoft Academic Search

The purpose of this study was to investigate the taste properties of protease inhibitors which are essential components of drug regimes used to treat human immunodeficiency virus (HIV) infection. In this study, the taste properties of four protease inhibitors (indinavir, ritonavir, saquinavir, and nelfinavir) were investigated in unmedicated HIV-infected patients and healthy controls. Three of the four protease inhibitors (indinavir,

Susan S Schiffman; Jennifer Zervakis; Sean Heffron; Alison E Heald

1999-01-01

381

Probabilistic Quorum Systems  

Microsoft Academic Search

this paper, we also explore relaxing the intersectionproperties of these quorums, to achieve (b; ")-dissemination and (b; ")-masking systems.Again, we show that these systems oer substantial improvements over theirstrict counterparts in the measures described above.1.1. ApplicationsDue to their relaxed intersection properties, our probabilistic quorums are mostsuitable for use when the consistency of replicated data may be relaxed to achievegreater availability

Dahlia Malkhi; Michael K. Reiter; Avishai Wool; Rebecca N. Wright

2001-01-01

382

Thin-film modelling of biofilm growth and quorum Mathematical Biology Group, Department of Mathematical Sciences, Loughborough University,  

E-print Network

Thin-film modelling of biofilm growth and quorum sensing J.P. Ward , Mathematical Biology Group. Abstract Biofilms are slimy films of bacteria that typically grow on solid surfaces with a fluid interface. Two mathematical models for nutrient dependent, early-stage biofilm growth and quorum sensing

383

Application of molecular docking and ONIOM methods for the description of interactions between anti-quorum sensing active (AHL) analogues and the Pseudomonas aeruginosa LasR binding site.  

PubMed

Molecular docking methods were applied to simulate the coupling of a set of nineteen acyl homoserine lactone analogs into the binding site of the transcriptional receptor LasR. The best pose of each ligand was explored and a qualitative analysis of the possible interactions present in the complex was performed. From the results of the protein-ligand complex analysis, it was found that residues Tyr-64 and Tyr-47 are involved in important interactions, which mainly determine the antagonistic activity of the AHL analogues considered for this study. The effect of different substituents on the aromatic ring, the common structure to all ligands, was also evaluated focusing on how the interaction with the two previously mentioned tyrosine residues was affected. Electrostatic potential map calculations based on the electron density and the van der Waals radii were performed on all ligands to graphically aid in the explanation of the variation of charge density on their structures when the substituent on the aromatic ring is changed through the elements of the halogen group series. A quantitative approach was also considered and for that purpose the ONIOM method was performed to estimate the energy change in the different ligand-receptor complex regions. Those energy values were tested for their relationship with the corresponding IC50 in order to establish if there is any correlation between energy changes in the selected regions and the biological activity. The results obtained using the two approaches may contribute to the field of quorum sensing active molecules; the docking analysis revealed the role of some binding site residues involved in the formation of a halogen bridge with ligands. These interactions have been demonstrated to be responsible for the interruption of the signal propagation needed for the quorum sensing circuit. Using the other approach, the structure-activity relationship (SAR) analysis, it was possible to establish which structural characteristics and chemical requirements are necessary to classify a compound as a possible agonist or antagonist against the LasR binding site. PMID:24626770

Ahumedo, Maicol; Drosos, Juan Carlos; Vivas-Reyes, Ricardo

2014-05-01

384

Modulation of Quorum Sensing in Acylhomoserine Lactone-Producing or -Degrading Tobacco Plants Leads to Alteration of Induced Systemic Resistance Elicited by the Rhizobacterium Serratia marcescens 90-166  

PubMed Central

Numerous root-associated bacteria (rhizobacteria) are known to elicit induced systemic resistance (ISR) in plants. Bacterial cell-density-dependent quorum sensing (QS) is thought to be important for ISR. Here, we investigated the role of QS in the ISR elicited by the rhizobacterium, Serratia marcescens strain 90–166, in tobacco. Since S. marcescens 90–166 produces at least three QS signals, QS-mediated ISR in strain 90–166 has been difficult to understand. Therefore, we investigated the ISR capacity of two transgenic tobacco (Nicotiana tabacum) plants that contained either bacterial acylhomoserine lactone-producing (AHL) or -degrading (AiiA) genes in conjunction with S. marcescens 90–166 to induce resistance against bacterial and viral pathogens. Root application of S. marcescens 90–166 increased ISR to the bacterial pathogens, Pectobacterium carotovorum subsp. carotovorum and Pseudomonas syringae pv. tabaci, in AHL plants and decreased ISR in AiiA plants. In contrast, ISR to Cucumber mosaic virus was reduced in AHL plants treated with S. marcescens 90–166 but enhanced in AiiA plants. Taken together, these data indicate that QS-dependent ISR is elicited by S. marcescens 90–166 in a pathogen-dependent manner. This study provides insight into QS-dependent ISR in tobacco elicited by S. marcescens 90–166. PMID:25288945

Ryu, Choong-Min; Choi, Hye Kyung; Lee, Chi-Ho; Murphy, John F.; Lee, Jung-Kee; Kloepper, Joseph W.

2013-01-01

385

Sensing bacteria, without bitterness?  

PubMed Central

In addition to their recognized roles in intra- and inter-species signaling, bacterial quorum-sensing molecules have been implicated in inter-kingdom signaling. A new study in Pseudomonas aeruginosa suggests that mammalian bitter taste receptors may recognize bacterial quorum sensing molecules, and widens the scope of such inter-kingdom communication. Intestinal cells also harbor these receptors, but whether they eavesdrop on bacterial conversations remains an open question. PMID:23380647

Viswanathan, V.K.

2013-01-01

386

Intracellular protein-responsive supramolecules: protein sensing and in-cell construction of inhibitor assay system.  

PubMed

Supramolecular nanomaterials responsive to specific intracellular proteins should be greatly promising for protein sensing and imaging, controlled drug release or dynamic regulation of cellular processes. However, valid design strategies to create useful probes are poorly developed, particularly for proteins inside living cells as targets. We recently reported a unique supramolecular strategy for specific protein detection using self-assembling fluorescent probes consisting of a protein ligand and a fluorophore on the live cell surface, as well as in test tube settings. Herein, we discovered that our self-assembled supramolecular probes having a rhodamine derivative (tetramethylrhodamine or rhodamine-green) can incorporate and stay as less-fluorescent aggregates inside the living cells, so as to sense the protein activity in a reversible manner. Using the overexpressed model protein (dihydrofolate reductase), we demonstrated that this turn-on/off mode is controlled by selective ligand-protein recognition inside the live cells. Not only such a model protein, but also endogenous human carbonic anhydrase and heat shock protein 90 were specifically visualized in living mammalian cells, by use of the similar ligand-tethered supramolecular probes. Furthermore, such reversibility allowed us to intracellularly construct a unique system to evaluate the inhibitors affinity toward specific endogenous proteins in live cells, highlighting the potential of dynamic supramolecules as novel intelligent biomaterials. PMID:25361466

Yoshii, Tatsuyuki; Mizusawa, Keigo; Takaoka, Yousuke; Hamachi, Itaru

2014-11-26

387

A stochastic model of Escherichia coli AI-2 quorum signal circuit reveals alternative synthesis pathways  

E-print Network

.9.06 Quorum sensing (QS) is an important determinant of bacterial phenotype. Many cell functions are regulated investigated the synthesis, uptake, and regulation of AI-2, developed testable hypotheses, and made several steps are involved in AI-2 synthesis; and (3) experimental results validate this hypothesis. This work

Wood, Thomas K.

388

Quorum Quenching Mediated Approaches for Control of Membrane Biofouling  

PubMed Central

Membrane biofouling is widely acknowledged as the most frequent adverse event in wastewater treatment systems resulting in significant loss of treatment efficiency and economy. Different strategies including physical cleaning and use of antimicrobial chemicals or antibiotics have been tried for reducing membrane biofouling. Such traditional practices are aimed to eradicate biofilms or kill the bacteria involved, but the greater efficacy in membrane performance would be achieved by inhibiting biofouling without interfering with bacterial growth. As a result, the search for environmental friendly non-antibiotic antifouling strategies has received much greater attention among scientific community. The use of quorum quenching natural compounds and enzymes will be a potential approach for control of membrane biofouling. This approach has previously proven useful in diseases and membrane biofouling control by triggering the expression of desired phenotypes. In view of this, the present review is provided to give the updated information on quorum quenching compounds and elucidate the significance of quorum sensing inhibition in control of membrane biofouling. PMID:24910534

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

2014-01-01

389

Disruption of Biofilm Formation by the Human Pathogen Acinetobacter baumannii Using Engineered Quorum-Quenching Lactonases  

PubMed Central

Acinetobacter baumannii is a major human pathogen associated with multidrug-resistant nosocomial infections; its virulence is attributed to quorum-sensing-mediated biofilm formation, and disruption of biofilm formation is an attractive antivirulence strategy. Here, we report the first successful demonstrat