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1

Caffeine as a potential quorum sensing inhibitor.  

PubMed

Quorum sensing enables bacteria to control the gene expression in response to the cell density. It regulates a variety of bacterial physiological functions such as biofilm formation, bioluminescence, virulence factors and swarming which has been shown contribute to bacterial pathogenesis. The use of quorum sensing inhibitor would be of particular interest in treating bacterial pathogenicity and infections. In this work, we have tested caffeine as quorum sensing inhibitor by using Chromobacterium violaceum CV026 as a biosensor. We verified that caffeine did not degrade the N-acyl homoserine lactones tested. In this work, it is shown that caffeine could inhibit N-acyl homoserine lactone production and swarming of a human opportunistic pathogen, namely Pseudomonas aeruginosa PA01. To the best of our knowledge, this is the first documentation providing evidence on the presence of anti-quorum sensing activity in caffeine. Our work will allow caffeine to be explored as anti-infective drugs. PMID:23598500

Norizan, Siti Nur Maisarah; Yin, Wai-Fong; Chan, Kok-Gan

2013-04-18

2

Dietary phytochemicals as quorum sensing inhibitors  

Microsoft Academic Search

Quorum sensing (QS) is a cell density dependent expression of species in bacteria mediated by hormone like compounds called autoinducers (AI). Several processes responsible for successful establishment of bacterial infection are mediated by QS. Inhibition of QS is therefore being considered as a new target for antimicrobial chemotherapy. Dietary phytochemicals are secondary metabolites in plants known to have several health

D. A. Vattem; K. Mihalik; S. H. Crixell; R. J. C. McLean

2007-01-01

3

Novel AI-2 quorum sensing inhibitors in Vibrio harveyi identified through structure-based virtual screening.  

PubMed

In this letter, a high-throughput virtual screening was accomplished to identify potent inhibitors against AI-2 quorum sensing on the basis of Vibrio harveyi LuxPQ crystal structure. Seven compounds were found to inhibit AI-2 quorum sensing with IC(50) values in the micromolar range, and presented low cytotoxicity or no cytotoxicity in V. harveyi. PMID:22963763

Zhu, Peng; Peng, Hanjing; Ni, Nanting; Wang, Binghe; Li, Minyong

2012-08-24

4

Inhibition of marine biofouling by bacterial quorum sensing inhibitors  

Microsoft Academic Search

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

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

2011-01-01

5

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

PubMed Central

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

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

2012-01-01

6

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.

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

2010-01-01

7

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

2010-07-19

8

Structural understanding of quorum-sensing inhibitors by molecular modeling study in Pseudomonas aeruginosa  

Microsoft Academic Search

Inhibitors of 3OC12, an initial signal molecule of the quorum sensing (QS) signaling cascade in Pseudomonas aeruginosa have been developed. Eight inhibitor candidates were synthesized by substituting the head part of 3-oxododecanoyl-homoserine\\u000a lactone (3OC12) with different aromatic rings, and their docking poses and scores (binding energies) were predicted by in\\u000a silico modeling study. All compounds gave better docking scores than

Cheoljin Kim; Jaeeun Kim; Hyung-Yeon Park; Joon-Hee Lee; Hee-Jin Park; Chan Kyung Kim; Jeyong Yoon

2009-01-01

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.

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

2012-01-01

10

Screening for novel quorum-sensing inhibitors to interfere with the formation of Pseudomonas aeruginosa biofilm.  

PubMed

The objective of this study was to screen for novel quorum-sensing inhibitors (QSIs) from traditional Chinese medicines (TCMs) that inhibit bacterial biofilm formation. Six of 46 active components found in TCMs were identified as putative QSIs based on molecular docking studies. Of these, three compounds inhibited biofilm formation by Pseudomonas aeruginosa and Stenotrophomonas maltophilia at a concentration of 200 µM. A fourth compound (emodin) significantly inhibited biofilm formation at 20 µM and induced proteolysis of the quorum-sensing signal receptor TraR in Escherichia coli at a concentration of 3-30 mM. Emodin also increased the activity of ampicillin against P. aeruginosa. Therefore, emodin might be suitable for development into an antivirulence and antibacterial agent. PMID:21852522

Ding, Xian; Yin, Bo; Qian, Li; Zeng, Zhirui; Yang, Zeliang; Li, Huixian; Lu, Yongjun; Zhou, Shining

2011-08-18

11

Gram-positive marine bacteria as a potential resource for the discovery of quorum sensing inhibitors.  

PubMed

Inhibitors of bacterial quorum sensing have been proposed as potentially novel therapeutics for the treatment of certain bacterial diseases. We recently reported a marine Halobacillus salinus isolate that secretes secondary metabolites capable of quenching quorum sensing phenotypes in several Gram-negative reporter strains. To investigate how widespread the production of such compounds may be in the marine bacterial environment, 332 Gram-positive isolates from diverse habitats were tested for their ability to interfere with Vibrio harveyi bioluminescence, a cell signaling-regulated phenotype. Rapid assay methods were employed where environmental isolates were propagated alongside the reporter strain. "Actives" were defined as bacteria that interfered with bioluminescence without visible cell-killing effects (antibiotic activity). A total of 49 bacterial isolates interfered with bioluminescence production in the assays. Metabolite extracts were generated from cultures of the active isolates, and 28 reproduced the bioluminescence inhibition against V. harveyi. Of those 28, five extracts additionally inhibited violacein production by Chromobacterium violaceum. Chemical investigations revealed that phenethylamides and a cyclic dipeptide are two types of secondary metabolites responsible for the observed activities. The active bacterial isolates belonged primarily to either the genus Bacillus or Halobacillus. The results suggest that Gram-positive marine bacteria are worthy of further investigation for the discovery of quorum sensing antagonists. PMID:21152942

Teasdale, Margaret E; Donovan, Kellye A; Forschner-Dancause, Stephanie R; Rowley, David C

2010-12-09

12

Novel Pseudomonas aeruginosa quorum-sensing inhibitors identified in an ultra-high-throughput screen.  

PubMed

The opportunistic pathogen Pseudomonas aeruginosa has two complete acyl-homoserine lactone (acyl-HSL) signaling systems, LasR-LasI and RhlR-RhlI. LasI catalyzes the synthesis of N-3-oxododecanoyl homoserine lactone (3OC12-HSL), and LasR is a transcription factor that requires 3OC12-HSL as a ligand. RhlI catalyzes the synthesis of N-butanoyl homoserine lactone (C4), and RhlR is a transcription factor that responds to C4. LasR and RhlR control the transcription of hundreds of P. aeruginosa genes, many of which are critical virulence determinants, and LasR is required for RhlR function. We developed an ultra-high-throughput cell-based assay to screen a library of approximately 200,000 compounds for inhibitors of LasR-dependent gene expression. Although the library contained a large variety of chemical structures, the two best inhibitors resembled the acyl-homoserine lactone molecule that normally binds to LasR. One compound, a tetrazole with a 12-carbon alkyl tail designated PD12, had a 50% inhibitory concentration (IC50) of 30 nM. The second compound, V-06-018, had an IC50 of 10 microM and is a phenyl ring with a 12-carbon alkyl tail. A microarray analysis showed that both compounds were general inhibitors of quorum sensing, i.e., the expression levels of most LasR-dependent genes were affected. Both compounds also inhibited the production of two quorum-sensing-dependent virulence factors, elastase and pyocyanin. These compounds should be useful for studies of LasR-dependent gene regulation and might serve as scaffolds for the identification of new quorum-sensing modulators. PMID:16966394

Müh, Ute; Schuster, Martin; Heim, Roger; Singh, Ashvani; Olson, Eric R; Greenberg, E Peter

2006-09-11

13

Animal Models Commonly Used to Study Quorum-Sensing Inhibitors  

Microsoft Academic Search

\\u000a Multiple animal models exist for the study of biofilm infections and\\u000a their inhibitors in vivo. The infection models described in this chapter range\\u000a from the simple nematode-killing and amoeba-plate-killing assays, to models\\u000a with more relevance to human disease like the pulmonary and cellulitis\\u000a infection models in mice, the graft prosthesis, and the central venous\\u000a catheter infection models in rats, and

Naomi Balaban; Michael Givskov; Thomas Bovbjerg Rasmussen; Andrea Giacometti; Oscar Cirioni

14

Production of Quorum Sensing Inhibitors in Growing Onion Bulbs Infected with Pseudomonas aeruginosa E (HQ324110)  

PubMed Central

Eighteen organic compounds were present in growing onion bulbs cultivar Giza 6 infected with P. aeruginosa, but only fourteen of them are present in dry infected onion bulbs; however, four compounds were missing in dry onion. The missing compounds in dry infected onion bulbs are pantolactone, 4,5-dihydro-4,5-dimethylfuran-2(3H)-one, myristic acid, and linoleic acid. All of them were detected in growing onion (living cell) during Pseudomonas aeruginosa infection, and it is hypothesized that it may be produced by plants and act as defence system. Pantolactone and myristic acid were selected to explore their effects on growth and virulence factors of Pseudomonas aeruginosa. Exogenous application of pantolactone and myristic acid significantly inhibited pyocyanin production, protease, and lipase and polygalacturonase activity but did not have any significant effects on bacterial growth. The inhibition of virulence factors without reduction in bacterial growth may be providing strong support that these chemical molecules are general quorum sensing inhibitors than an antibacterial effect. Disruption of quorum sensing of pathogen indicates that this new approach has potential in fighting bacterial infections in human and plants.

Abd-Alla, Mohamed H.; Bashandy, Shymaa R.

2012-01-01

15

Synthesis of cembranoid analogues and evaluation of their potential as quorum sensing inhibitors.  

PubMed

Natural cembranoids have shown Quorum Sensing Inhibitory (QSI) activity, but their structure-function interactions are not well understood. Thirty-four cembranoid analogues were synthesized using six natural cembranoids (1-6) previously isolated from the Colombian Caribbean octocorals Eunicea knighti and Pseudoplexaura flagellosa as lead compounds. The analogues (7-40) obtained through the selected chemical transformations were tested in vitro against the QS systems of a Chromobacterium violaceum biosensor. Half of the cembranoid analogues assayed showed superior QSI activity to the lead compounds; three (8, 13, and 18) displayed remarkable potency up to three times higher than the natural compounds. Thereby, we have synthesized a pool of cembranoid QS inhibitors that can be used in concert with natural compounds to develop antipathogenic drugs and antifouling agents. PMID:23177728

Tello, Edisson; Castellanos, Leonardo; Duque, Carmenza

2012-10-31

16

A new quorum-sensing inhibitor attenuates virulence and decreases antibiotic resistance in Pseudomonas aeruginosa.  

PubMed

Quorum sensing (QS) has been a novel target for the treatment of infectious diseases. Here structural analogs of Pseudomonas aeruginosa autoinducer N-acyl homoserine lactone (AHL) were investigated for QS inhibitor (QSI) activity and a novel QSI was discovered, N-decanoyl-L-homoserine benzyl ester (C2). Virulence assays showed that C2 down-regulated total protease and elastase activities, as well as the production of rhamnolipid, that are controlled by QS in P. aeruginosa wild-type strain PAO1 without affecting growth. C2 was also shown to inhibit swarming motility of PAO1. Using a microdilution checkerboard method, we identified synergistic interactions between C2 and several antibiotics, tobramycin, gentamycin, cefepime, and meropenem. Data from real-time RT-PCR suggested that C2 inhibited the expression of lasR (29.67%), lasI (21.57%), rhlR (28.20%), and rhlI (29.03%). PMID:23274985

Yang, Yu-Xiang; Xu, Zhen-Hua; Zhang, Yu-Qian; Tian, Jing; Weng, Li-Xing; Wang, Lian-Hui

2012-12-30

17

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

PubMed

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; Yang, Liang; Givskov, Michael

2013-09-03

18

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

PubMed Central

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

Ng, Wai-Leung; Perez, Lark; Cong, Jianping; Semmelhack, Martin F.; Bassler, Bonnie L.

2012-01-01

19

Structural understanding of quorum-sensing inhibitors by molecular modeling study in Pseudomonas aeruginosa.  

PubMed

Inhibitors of 3OC12, an initial signal molecule of the quorum sensing (QS) signaling cascade in Pseudomonas aeruginosa have been developed. Eight inhibitor candidates were synthesized by substituting the head part of 3-oxododecanoyl-homoserine lactone (3OC12) with different aromatic rings, and their docking poses and scores (binding energies) were predicted by in silico modeling study. All compounds gave better docking scores than 3OC12 and good inhibition effects on LasR activity in the in vivo bioassay. Like the modifications in the tail part of 3OC12 in our previous study Kim et al. (2008), the head-part modifications also showed inhibition activity in a fairly good proportion to the docking scores from the modeling analysis. This implies that the head part of 3OC12 also contributes significantly to forming the active conformation of the LasR-3OC12 complex, and its modification could effectively induce the inactive conformation of the complex. We suggest that the head part of 3OC12 is also a good target moiety to develop the structure-based Pseudomonas QS inhibitors. PMID:19330325

Kim, Cheoljin; Kim, Jaeeun; Park, Hyung-Yeon; Lee, Joon-Hee; Park, Hee-Jin; Kim, Chan Kyung; Yoon, Jeyong

2009-03-28

20

Screening of traditional Chinese medicinal plants for quorum-sensing inhibitors activity.  

PubMed

The misuse of antibiotics has contributed to widespread development of antimicrobial resistance among clinically significant bacterial species. Alternative approaches other than those using antibiotics are needed in the fight against infectious diseases. Quorum sensing (QS) is an intercellular signaling and gene regulatory mechanism, which is used by a number of opportunistic pathogenic bacteria in determining virulence gene expression. The study of QS may yield another strategy for disease control by interference with QS signals. Scientific research on complementary therapies such as traditional Chinese medicine (TCM) has focused mainly on its antibacterial properties. To test for anti-QS activity, 10 TCM herbs were screened using two biomonitor strains, Chromobacterium violaceum CV026 and Pseudomonas aeruginosa PA01. Interference with violacein (purple pigment) production in CV026 (exogenously supplied with homoserine lactone signals), and swarming in PA01, both QS-regulated phenomena, was used as indication of anti-QS activity. Eight of the selected TCM (80%) yielded QS inhibitors: Prunus armeniaca, Prunella vulgaris, Nelumbo nucifera, Panax notoginseng (root and flower), Punica granatum, Areca catechu, and Imperata cylindrica. Compounds that interfere with QS are present in TCM herbs and these medicines may be a rich source of compounds to combat pathogenic bacteria and reduce the development of antibiotic resistance. PMID:21439518

Koh, Khee Hoon; Tham, Foong-Yee

2011-01-14

21

Cyanobacterial mats from hot springs produce antimicrobial compounds and quorum-sensing inhibitors under natural conditions  

Microsoft Academic Search

Polar (water) and non-polar (ethyl acetate) extracts from the cyanobacterial layer (top 1–3 mm) of four hot spring microbial\\u000a mats in the Sultanate of Oman were tested for their antibacterial, antidiatom and quorum-sensing inhibitory activities under\\u000a natural conditions. The chemical composition of the active extracts was analysed using gas chromatography–mass spectrometry\\u000a (GC-MS). Cyanobacteria within these mats were identified by direct microscopy

Sergey Dobretsov; Raeid M. M. Abed; Sultan M. S. Al Maskari; Jamal N. Al Sabahi; Reginald Victor

22

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

PubMed

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

2012-01-25

23

Insights into the role of quorum sensing in food spoilage.  

PubMed

Food spoilage is a consequence of the degrading enzymatic activity of some food-associated bacteria. Several proteolytic, lipolytic, chitinolytic, and pectinolytic activities associated with the deterioration of goods are regulated by quorum sensing, suggesting a potential role of such cell-to-cell communication in food spoilage. Here we review quorum sensing signaling molecules and methods of their detection and quantification, and we provide insights into the role of quorum sensing in food spoilage and address potential quorum sensing inhibitors that might be used as biopreservatives. PMID:18680957

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

2008-07-01

24

High-throughput screening of inhibitors targeting Agr/Fsr quorum sensing in Staphylococcus aureus and Enterococcus faecalis.  

PubMed

Staphylococcus aureus and Enterococcus faecalis employ cyclic peptide-mediated quorum sensing (QS) systems, termed agr and fsr respectively, to regulate the expression of a series of virulence genes. To identify quorum sensing inhibitors (QSIs) that target agr/fsr systems, an efficient screening system was established. In addition to the gelatinase-induction assay to examine E. faecalis fsr QS, the use of an S. aureus agr reporter strain that carries luciferase and green fluorescence protein genes under the agr P3 promoter facilitated the development of a high-throughput screen (HTS) for QSIs. As a result of screening of 906 actinomycetes culture extracts, four showed QSI activity against the agr and fsr systems without growth inhibitory activity. The extracts were purified on a small scale, and three HPLC peaks were obtained with obvious QSI activity. In sum, the established HTS system is a promising strategy for the discovery of anti-pathogenic agents targeting cyclic peptide-mediated QS in Gram-positive pathogens. PMID:23649251

Desouky, Said E; Nishiguchi, Kenzo; Zendo, Takeshi; Igarashi, Yasuhiro; Williams, Paul; Sonomoto, Kenji; Nakayama, Jiro

2013-05-07

25

Bacterial quorum sensing and biofilm formation  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

26

Screening of SdiA inhibitors from Melia dubia seeds extracts towards the hold back of uropathogenic E.coli quorum sensing-regulated factors.  

PubMed

Plants have always been a supreme source of drugs and India is endowed with a wide variety of them with high medicinal values. The Quorum Sensing (QS) quenching efficiency of various solvent extracts of Melia dubia seeds was investigated against uropathogenic Escherichia coli (UPEC) to screen the competitive inhibitor of SdiA, a transcriptional activator of quorum sensing in E. coli. In this study, potentiality of five different extracts of Melia dubia seeds for quorum sensing inhibitory activity was investigated against uropathogenic Escherichia coli (UPEC). Assays such as cell density, swarming motility, protein, protease, hemolysis, hemagglutination, hydrophobicity and biofilm inhibition were performed. Biofilm, hemolysis and swarming motility were found to be inhibited by 92.1%, 20.9 % and 48.52% respectively, when the medium was supplemented with 30 mg/ml of the ethanolic extract. GC-MS spectrum of the ethanolic extract showed an array of 27 structurally unlinked compounds with natural ligand C8HSL. The docking against QS transcriptional regulator SdiA was predicted by in silico studies and the ligand C6 showed significant activity with -10.8 GScore. In vitro and in silico docking analysis showed fairly a good correlation, suggesting that the ethanolic extract showed potency to attenuate quorum sensing of uropathogenic E. coli. Further studies by in vitro and in vivo strategies are necessary to foresee the quorum quenching effect of the ligands. PMID:23210902

Ravichandiran, Vinothkannan; Shanmugam, Karthi; Solomon, Adline Princy

2013-09-01

27

QUORUM SENSING AND FOOD SAFETY  

Technology Transfer Automated Retrieval System (TEKTRAN)

Bacteria use various cell-to-cell signaling mechanisms to control the expression of characteristic survival traits in a density dependent manner, which is designated 'quorum sensing'. It is generally recognized that regulating such extracellular communication in microorganisms including those that c...

28

Synthesis and evaluation of thiazolidinedione and dioxazaborocane analogues as inhibitors of AI-2 quorum sensing in Vibrio harveyi.  

PubMed

Two focused libraries based on two types of compounds, that is, thiazolidinediones and dioxazaborocanes were designed. Structural resemblances can be found between thiazolidinediones and well-known furanone type quorum sensing (QS) inhibitors such as N-acylaminofuranones, and/or acyl-homoserine lactone signaling molecules, while dioxazaborocanes structurally resemble previously reported oxazaborolidine derivatives which antagonized autoinducer 2 (AI-2) binding to its receptor. Because of this, we hypothesized that these compounds could affect AI-2 QS in Vibrio harveyi. Although all compounds blocked QS, the thiazolidinediones were the most active AI-2 QS inhibitors, with EC(50) values in the low micromolar range. Their mechanism of inhibition was elucidated by measuring the effect on bioluminescence in a series of V. harveyi QS mutants and by DNA-binding assays with purified LuxR protein. The active compounds neither affected bioluminescence as such nor the production of AI-2. Instead, our results indicate that the thiazolidinediones blocked AI-2 QS in V. harveyi by decreasing the DNA-binding ability of LuxR. In addition, several dioxazaborocanes were found to block AI-2 QS by targeting LuxPQ. PMID:23286963

Brackman, Gilles; Al Quntar, Abed Al Aziz; Enk, Claes D; Karalic, Izet; Nelis, Hans J; Van Calenbergh, Serge; Srebnik, Morris; Coenye, Tom

2012-12-11

29

Revisiting AI-2 quorum sensing inhibitors: Direct comparison of alkyl-DPD analogs and a natural product fimbrolide  

PubMed Central

Quorum sensing (QS) systems have been proposed in a wide variety of bacteria. The AI-2-based QS system represents the most studied of these proposed interspecies systems, and has been shown to regulate diverse functions such as bioluminescence, expression of virulence factors, and biofilm formation. As such, the development of modulatory compounds, both agonists and antagonists, is of great interest for the study of unknown AI-2 based QS systems and the potential treatment of bacterial infections. The fimbrolide class of natural products has exhibited excellent inhibitory activity against AI-2-based QS, and as such may be considered the “gold-standard” of AI-2 inhibitors. Thus, we sought to include a fimbrolide as a control compound for our recently developed alkyl-DPD panel of AI-2 modulators. Herein, we present a revised synthesis of a commonly studied fimbrolide, as well as a direct comparison between the fimbrolide and alkyl-DPD analogs. We demonstrate that our alkyl-DPD analogs are more potent inhibitors of QS in both Vibrio harveyi and Salmonella typhimurium, the two organisms with defined AI-2 systems, and in doing so, call into question the widely accepted use of fimbrolide-derived compounds as the “gold standard” of AI-2 inhibition.

Lowery, Colin A.; Abe, Takumi; Park, Junguk; Eubanks, Lisa M.; Sawada, Daisuke; Kaufmann, Gunnar F.; Janda, Kim D.

2009-01-01

30

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

31

Vfr Controls Quorum Sensing in Pseudomonas aeruginosa  

Microsoft Academic Search

Pseudomonas aeruginosa controls several genes in a cell density-dependent manner through a phenomenon termed quorum sensing. The transcriptional activator protein of the las quorum-sensing system is encoded for by the lasR gene, which is at the top of a quorum-sensing hierarchy. The activation of LasR as a transcriptional activator induces the expression of multiple genes that code for factors important

ANNE M. ALBUS; EVERETT C. PESCI; LAURA J. RUNYEN-JANECKY; SUSAN E. H. WEST; BARBARA H. IGLEWSKI

1997-01-01

32

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.

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

33

QUORUM SENSING: A PRIMER FOR FOOD MICROBIOLOGISTS  

Technology Transfer Automated Retrieval System (TEKTRAN)

Quorum sensing is a signaling mechanism through which bacteria modulate a number of cellular functions (genes) including sporulation, biofilm formation, bacteriocin production, and virulence responses. Quorum sensing is a mechanism of cell-to-cell communication and is mediated by extracellular chem...

34

Quorum-Sensing Inhibitory Compounds  

Microsoft Academic Search

\\u000a Biofilm\\u000a formation plays an important role in antimicrobial resistance, posing\\u000a a global threat to the economy and public health. Hence, discovery of\\u000a novel antagonists is critical. In this chapter, we introduce a class of\\u000a compounds, brominated furanones, which have a broad spectrum of\\u000a activities against bacterial multicellular behaviors, such as biofilm\\u000a formation and quorum sensing. The application of these compounds and the\\u000a mechanisms

Dacheng Ren; Michael Givskov; Thomas Bovbjerg Rasmussen; Naomi Balaban

35

GENE EXPRESSION IN SALMONELLA ENTERICA SEROTYPE TYPHIMURIUM LUXS MUTANT IN RESPONSE TO QUORUM SENSING SIGNALS AND A POULTRY MEAT-DERIVED QUORUM SENSING INHIBITOR USING MICROARRAY-BASED STUDIES  

Technology Transfer Automated Retrieval System (TEKTRAN)

Quorum sensing describes the processes in which bacteria cells produce, secrete, and communicate using chemical signal molecules. There is evidence that these sensing signals, especially AI-2, can influence bacterial gene expression. We have previously shown that food matrices, such as poultry wash ...

36

Method for Modulating Microbial Quorum Sensing.  

National Technical Information Service (NTIS)

The present invention provides compositions and methods for modulating bacterial quorum sensing using antagonist or agonist compounds. Further, the present invention provides methods of treating or preventing microbial damages and diseases, in particular ...

B. R. Borlee J. E. Handelsman

2005-01-01

37

Quorum sensing in Escherichia coli and Salmonella  

Microsoft Academic Search

Quorum sensing in Escherichia coli and Salmonella has been an elusive topic for a long time. However, in the past 8 years, several research groups have demonstrated that these bacteria use several quorum-sensing systems, such as: the luxS\\/AI-2, AI-3\\/epinephrine\\/norepinephrine, indole, and the LuxR homolog SdiA to achieve intercellular signaling. The majority of these signaling systems are involved in interspecies communication,

Matthew Walters; Vanessa Sperandio

2006-01-01

38

Garlic as an inhibitor of Pseudomonas aeruginosa quorum sensing in cystic fibrosis--a pilot randomized controlled trial.  

PubMed

Pseudomonas aeruginosa forms biofilms in the cystic fibrosis lung. Quorum sensing (QS) controls biofilm maturation, immune evasion, antibiotic tolerance and virulence factor production. Garlic shows QS inhibitory activity in vitro and in animal models. We report the first clinical trial in man of a QS inhibitor.We randomized 34 patients to garlic or olive oil capsules (both 656 mg daily). Clinical outcomes and safety bloods were measured at baseline and after 8 weeks treatment. In this exploratory study, analysis was per protocol.Eight patients withdrew, leaving 26 for analysis (13 garlic). With placebo, there was a greater decline in mean (SD) percentage change from baseline FEV(1) [-3.6% (11.3)] than with garlic [-2.0% (12.3)]. This was not significant (mean difference = 1.6, 95% CI -12.7 to 15.9, P = 0.8). The mean (SD) increase in weight was greater with garlic [1.0% (2.0)] than with placebo [0.6% (2.0)]--non-significant (mean difference = 0.4%, 95% CI -1.3 to 2.0, P = 0.6). The median (range) change in clinical score with garlic was -1 (-3 to 5) and 1 (-1 to 4) with placebo (negative score means improvement). This was non-significant [median difference = -1 (-3 to 0), P = 0.16]. In the garlic group, seven patients had IV antibiotics versus five placebo. There was a highly significant correlation between plasma and sputum measurements of the QS molecule 3-oxo-C12-HSL (Pearson correlation coefficient = 0.914, P = 0.004). At the end of treatment five patients in each group had abnormal liver function or triglycerides and five garlic patients (one placebo) reported minor adverse effects.Garlic capsules were well tolerated. Although there was no significant effect of garlic compared to placebo in this pilot study, there was a suggestion of improvement with garlic which should be investigated in a larger trial. PMID:20306535

Smyth, Alan R; Cifelli, Paramita M; Ortori, Catharine A; Righetti, Karima; Lewis, Sarah; Erskine, Penny; Holland, Elaine D; Givskov, Michael; Williams, Paul; Cámara, Miguel; Barrett, David A; Knox, Alan

2010-04-01

39

Construction of an effective screening system for detection of Pseudomonas aeruginosa quorum sensing inhibitors and its application in bioautographic thin-layer chromatography.  

PubMed

In Pseudomonas aeruginosa, quorum sensing (QS) regulates dozens of genes and proteins, many of which contribute to the virulence of this pathogen. QS inhibitory (QSI) compounds have been proposed as potential agents for treatment of bacterial infections. To search for Ps. aeruginosa QS inhibitors, we constructed an effective screening system, QSIS-lasI selector, based on the PlasI-sacB reporter, in which QS could be induced with 20 nM 3-oxo-N-[(3S)-tetrahydro-2-oxo-3-furanyl]-dodecanamide (3-oxo-C(12)-HSL). During screening of the crude extracts from 65 marine fungi, an isolate of Penicillium atramentosum was found to have QSI activity. Thin-layer chromatography assay of the fungal extracts for bioautographic identification of QSIS-lasI indicated that this fungus produced several QSI compounds, including QS inhibitors other than penicillic acid or patulin. PMID:21344206

Wang, Linna; Zou, Shanshan; Yin, Shouliang; Liu, Hongbing; Yu, Wengong; Gong, Qianhong

2011-02-23

40

Quorum-sensing quenching by rhizobacterial volatiles.  

PubMed

We show that volatile organic compounds (VOCs) produced by rhizospheric strains Pseudomonas fluorescens B-4117 and Serratia plymuthica IC1270 may act as inhibitors of the cell-cell communication quorum-sensing (QS) network mediated by N-acyl homoserine lactone (AHL) signal molecules produced by various bacteria, including strains of Agrobacterium, Chromobacterium, Pectobacterium and Pseudomonas. This quorum-quenching effect was observed when AHL-producing bacteria were treated with VOCs emitted by strains B-4117 and IC1270 or with dimethyl disulfide (DMDS), the major volatile produced by strain IC1270. LC-MS/MS analysis revealed that treatment of strains Pseudomonas chlororaphis 449, Pseudomonas aeruginosa PAO1 or Ps.?fluorescens 2-79 with VOCs emitted by strain IC1270 or DMDS drastically decreases the amount of AHLs produced by these bacteria. Volatile organic compounds produced by Ps.?chlororaphis 449 were able to suppress its own QS-induction activity, suggesting a negative interaction between VOCs and AHL molecules in the same strain. Quantitative RT-PCR analysis showed that treatment of Ps.?chlororaphis 449 with VOCs emitted by cells of IC1270, B-4117 or 449 itself, or with DMDS, leads to significant suppression of transcription of AHL synthase genes phzI and csaI. Thus, along with AHLs, bacterial volatiles might be considered another type of signal molecule involved in microbial communication in the rhizosphere. PMID:23761359

Chernin, Leonid; Toklikishvili, Natela; Ovadis, Marianna; Kim, Sofia; Ben-Ari, Julius; Khmel, Inessa; Vainstein, Alexander

2011-10-26

41

566. Inactivation of a Bacterial Quorum-Sensing Signal by Expression of Bacterial Autoinducer Inhibitor, aiiA, in Mammalian Cells  

Microsoft Academic Search

Many bacteria regulate production of extracellular virulence factors and biofilm formation through the cell-cell communication system, quorum-sensing. Quorum-sensing molecules frequently take the form of acylated homoserine lactones (HSLs). A gene recently isolated from Bacillus sp. 240B1 encodes an enzyme, AiiA, that inactivates HSLs through cleavage of the lactone ring. We asked whether expression of aiiA in mammalian cells would be

Egon A. Ozer; Joseph Zabner

2004-01-01

42

Quorum sensing regulates denitrification in Pseudomonas aeruginosa PAO1.  

PubMed

Anaerobic growth of Pseudomonas aeruginosa PAO1 was affected by quorum sensing. Deletion of genes that produce N-acyl-l-homoserine lactone signals resulted in an increase in denitrification activity, which was repressed by exogenous signal molecules. The effect of the las quorum-sensing system was dependent on the rhl quorum-sensing system in regulating denitrification. PMID:17449629

Toyofuku, Masanori; Nomura, Nobuhiko; Fujii, Tatsuya; Takaya, Naoki; Maseda, Hideaki; Sawada, Isao; Nakajima, Toshiaki; Uchiyama, Hiroo

2007-04-20

43

Quorum Sensing Regulates Denitrification in Pseudomonas aeruginosa PAO1?  

PubMed Central

Anaerobic growth of Pseudomonas aeruginosa PAO1 was affected by quorum sensing. Deletion of genes that produce N-acyl-l-homoserine lactone signals resulted in an increase in denitrification activity, which was repressed by exogenous signal molecules. The effect of the las quorum-sensing system was dependent on the rhl quorum-sensing system in regulating denitrification.

Toyofuku, Masanori; Nomura, Nobuhiko; Fujii, Tatsuya; Takaya, Naoki; Maseda, Hideaki; Sawada, Isao; Nakajima, Toshiaki; Uchiyama, Hiroo

2007-01-01

44

Identification of Genes Controlled by Quorum Sensing in Pseudomonas aeruginosa  

Microsoft Academic Search

Bacteria communicate with each other to coordinate expression of specific genes in a cell density-dependent fashion, a phenomenon called quorum sensing and response. Although we know that quorum sensing via acyl-homoserine lactone (HSL) signals controls expression of several virulence genes in the human pathogen Pseudomonas aeruginosa, the number and types of genes controlled by quorum sensing have not been studied

Marvin Whiteley; Kimberly M. Lee; E. P. Greenberg

1999-01-01

45

Attenuation of bacterial virulence by quorum sensing-regulated lysis  

Microsoft Academic Search

Genetically attenuated pathogenic bacteria have been extensively considered as vaccine candidates. However, insufficient attenuation has been a frequent limitation of this approach. Many pathogens use quorum sensing to escape host defense mechanism. Here, we hypothesized that quorum sensing can be manipulated to diminish pathogenesis. To test this hypothesis, we modified the quorum sensing circuitry of a live cholera vaccine strain

Anisia J. Silva; Jorge A. Benitez; Jian-He Wu

2010-01-01

46

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

PubMed

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 µM 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

2013-10-08

47

Streptomycin Inhibits Quorum Sensing in Acinetobacter baumannii  

PubMed Central

Streptomycin at subinhibitory concentrations was found to inhibit quorum sensing in Acinetobacter baumannii. Conditioned medium prepared by growth of A. baumannii in the presence of subinhibitory concentrations of streptomycin exhibited reduced activation of two quorum-sensing-regulated genes, abaI, encoding an autoinducer synthase, and A1S_0112. The reduced expression of AbaI resulted in greatly decreased levels of 3-OH-C12-HSL as confirmed by direct analysis using thin-layer chromatography. The effect on acyl-homoserine lactone (AHL) signal production was specific to streptomycin, as gentamicin and myomycin had no significant effect at subinhibitory levels.

Saroj, Sunil D.

2013-01-01

48

Streptomycin inhibits quorum sensing in Acinetobacter baumannii.  

PubMed

Streptomycin at subinhibitory concentrations was found to inhibit quorum sensing in Acinetobacter baumannii. Conditioned medium prepared by growth of A. baumannii in the presence of subinhibitory concentrations of streptomycin exhibited reduced activation of two quorum-sensing-regulated genes, abaI, encoding an autoinducer synthase, and A1S_0112. The reduced expression of AbaI resulted in greatly decreased levels of 3-OH-C(12)-HSL as confirmed by direct analysis using thin-layer chromatography. The effect on acyl-homoserine lactone (AHL) signal production was specific to streptomycin, as gentamicin and myomycin had no significant effect at subinhibitory levels. PMID:23318804

Saroj, Sunil D; Rather, Philip N

2013-01-14

49

Development and validation of a UHPLC-MS/MS procedure for quantification of the Pseudomonas Quinolone Signal in bacterial culture after acetylation for characterization of new quorum sensing inhibitors.  

PubMed

The appearance of antibiotic resistance requires novel therapeutic strategies. One approach is to selectively attenuate bacterial pathogenicity by interfering with bacterial cell-to-cell communication known as quorum sensing. The PQS quorum sensing system of Pseudomonas aeruginosa employs as signal molecule the Pseudomonas Quinolone Signal (PQS; 2-heptyl-3-hydroxy-4-(1H)-quinolone), a key contributor to virulence and biofilm formation. Thus, interference with PQS production is considered as promising approach for the development of novel anti-infectives. Therefore, in this study, we developed and validated an ultra-high performance liquid chromatographic-tandem mass spectrometric approach for reliable quantification of PQS in P. aeruginosa cultures for activity determination of new quorum sensing inhibitors. The poor chromatographic properties of PQS reported by others could be overcome by fast microwave-assisted acetylation. The validation procedure including matrix effects, recovery, process efficiency, selectivity, carry-over, accuracy and precision, stability of the processed sample, and limit of quantification demonstrated that the method fulfilled all requirements of common validation guidelines. Its applicability was successfully proven in routine testing. In addition, two-point calibration was shown to be applicable for fast and reliable PQS quantification saving time and resources. In summary, the described method provides a powerful tool for the discovery of new quorum sensing inhibitors as potential anti-infectives and illustrated the usefulness of chemical derivatization, acetylation, in liquid chromatography-mass spectrometry analysis. PMID:24001903

Maurer, Christine K; Steinbach, Anke; Hartmann, Rolf W

2013-08-14

50

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

51

A strategy for antagonizing quorum sensing  

PubMed Central

SUMMARY 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 ~60 Å, twice the ~30 Å separation required for operator binding. This approach may represent a general strategy for the inhibition of multi-domain proteins.

Chen, Guozhou; Swem, Lee R.; Swem, Danielle L.; Stauff, Devin L.; O'Loughlin, Colleen T.; Jeffrey, Philip D.; Bassler, Bonnie L.; Hughson, Frederick M.

2011-01-01

52

AI-2 Quorum Sensing in Campylobacter jejuni  

Technology Transfer Automated Retrieval System (TEKTRAN)

Quorum sensing response modulates many physiological attributes, such as bacterial virulence/pathogenesis, competence, and biofilm formation, when the bacterial population has reached a certain threshold. Among the various signaling compounds, autoinducer-2 (AI-2) is produced by most bacterial spec...

53

Regulation of virulence factors by quorum sensing in Vibrio harveyi.  

PubMed

Vibrio harveyi is an important aquatic pathogen that produces several virulence factors. In this study, the effect of quorum sensing, bacterial cell-to-cell communication, on the production of the virulence factors caseinase, gelatinase, lipase, hemolysin, and phospholipase, was investigated. The activity of virulence factors was studied through enzymatic plate assays using V. harveyi wild type and mutants with constitutively maximal or minimal quorum sensing activity. The results showed that quorum sensing negatively regulates phospholipase activity as higher activity was observed in mutants with minimal quorum sensing activity than in the mutant with maximal quorum sensing activity.Reverse transcriptase real-time PCR with specific primers revealed that the expression level of three phospholipase genes was 2-fold higher [corrected] in the mutant with minimal quorum sensing activity than in the mutant with maximal quorum sensingactivity. As far as we know, this is the first report of quorum sensing regulation of phospholipase. Finally, caseinase and gelatinase activity were positively regulated by quorum sensing, which is consistent with previous reports, and lipase and hemolysin activity were found to be independent of quorum sensing. Hence, the regulation is different for different virulence factors, with some being either positively or negatively regulated, and others being independent of quorum sensing. This might reflect the need to produce the different virulence factors at different stages during infection. PMID:21775075

Natrah, F M I; Ruwandeepika, H A Darshanee; Pawar, Sushant; Karunasagar, Indrani; Sorgeloos, Patrick; Bossier, Peter; Defoirdt, Tom

2011-07-01

54

Quorum sensing and quorum quenching in Vibrio harveyi: lessons learned from in vivo work.  

PubMed

Luminescent vibrios, bacteria belonging to the species Vibrio harveyi and closely related species, are important pathogens in aquaculture that can affect almost all types of cultured animals. Due to large-scale use of antibiotics, many luminescent vibrios have acquired (multiple) resistance, which render antibiotic treatments ineffective. One of the alternative strategies that has recently been developed to control infections caused by antibiotic-resistant bacteria is the disruption of quorum sensing, bacterial cell-to-cell communication. The quorum sensing system of V. harveyi has been studied quite intensively in vitro. Recent studies have been directed towards understanding the impact of quorum sensing and quorum sensing disruption on the virulence of luminescent vibrios towards different host organisms in vivo. This mini-review aims at discussing the current knowledge of quorum sensing in luminescent vibrios in vivo. Subsequently, quorum quenching by halogenated furanones is discussed and finally, some directions for further research are presented. PMID:18180744

Defoirdt, Tom; Boon, Nico; Sorgeloos, Patrick; Verstraete, Willy; Bossier, Peter

2007-10-25

55

Is quorum sensing a side effect of diffusion sensing?  

Microsoft Academic Search

Many bacteria appear to communicate by releasing and sensing autoinducer molecules, which are believed to function primarily as sensors of population density. However, this quorum-sensing hypothesis rests on very weak foundations, as neither the need for group action nor the selective conditions required for its evolution have been demonstrated. Here, I argue for a more direct function of autoinducer secretion

Rosemary J. Redfield

2002-01-01

56

Cross-species induction of antimicrobial compounds, biosurfactants and quorum-sensing inhibitors in tropical marine epibiotic bacteria by pathogens and biofouling microorganisms.  

PubMed

Enhancement or induction of antimicrobial, biosurfactant, and quorum-sensing inhibition property in marine bacteria due to cross-species and cross-genera interactions was investigated. Four marine epibiotic bacteria (Bacillus sp. S3, B. pumilus S8, B. licheniformis D1, and Serratia marcescens V1) displaying antimicrobial activity against pathogenic or biofouling fungi (Candida albicans CA and Yarrowia lipolytica YL), and bacteria (Pseudomonas aeruginosa PA and Bacillus pumilus BP) were chosen for this study. The marine epibiotic bacteria when co-cultivated with the aforementioned fungi or bacteria showed induction or enhancement in antimicrobial activity, biosurfactant production, and quorum-sensing inhibition. Antifungal activity against Y. lipolytica YL was induced by co-cultivation of the pathogens or biofouling strains with the marine Bacillus sp. S3, B. pumilus S8, or B. licheniformis D1. Antibacterial activity against Ps. aeruginosa PA or B. pumilus BP was enhanced in most of the marine isolates after co-cultivation. Biosurfactant activity was significantly increased when cells of B. pumilus BP were co-cultivated with S. marcescens V1, B. pumilus S8, or B. licheniformis D1. Pigment reduction in the quorum-sensing inhibition indicator strain Chromobacterium violaceum 12472 was evident when the marine strain of Bacillus sp. S3 was grown in the presence of the inducer strain Ps. aeruginosa PA, suggesting quorum-sensing inhibition. The study has important ecological and biotechnological implications in terms of microbial competition in natural environments and enhancement of secondary metabolite production. PMID:21086131

Dusane, Devendra H; Matkar, Pratiek; Venugopalan, Valayam P; Kumar, Ameeta Ravi; Zinjarde, Smita S

2010-11-18

57

P. aeruginosa quorum-sensing systems and virulence  

Microsoft Academic Search

Quorum sensing is an important mechanism for the regulation of genes in many Gram-negative and Gram-positive bacteria. In the opportunistic pathogen Pseudomonas aeruginosa, the absence of one or more components of the quorum-sensing system results in a significant reduction in virulence. Recent advances in the past year have demonstrated that the quorum-sensing signal molecule 3O-C12-HSL is also a potent stimulator

Roger S Smith; Barbara H Iglewski

2003-01-01

58

Azithromycin Inhibits Quorum Sensing in Pseudomonas aeruginosa  

Microsoft Academic Search

We report that 2 mg of azithromycin\\/ml inhibits the quorum-sensing circuitry of Pseudomonas aeruginosa strain PAO1. Addition of synthetic autoinducers partially restored the expression of the trancriptional acti- vator-encoding genes lasR and rhlR but not that of the autoinducer synthase-encoding gene lasI. We propose that azithromycin interferes with the synthesis of autoinducers, by an unknown mechanism, leading to a reduction

KAZUHIRO TATEDA; RACHEL COMTE; JEAN-CLAUDE PECHERE; THILO KOHLER; KEIZO YAMAGUCHI; CHRISTIAN VAN DELDEN

2001-01-01

59

Quorum Sensing Antagonism from Marine Organisms  

Microsoft Academic Search

With the global emergence of multiresistant bacteria there is an increasing demand for development of new treatments to combat\\u000a pathogens. Bacterial cell–cell communication [quorum sensing (QS)] regulates expression of virulence factors in a number of\\u000a bacterial pathogens and is a new promising target for the control of infectious bacteria. We present the results of screening\\u000a of 284 extracts of marine

Mette Elena Skindersoe; Piers Ettinger-Epstein; Thomas Bovbjerg Rasmussen; Thomas Bjarnsholt; Rocky de Nys; Michael Givskov

2008-01-01

60

Drimendiol, a drimane sesquiterpene with quorum sensing inhibition activity.  

PubMed

Quorum sensing (QS) is a regulatory mechanism that enables bacteria to make collective decisions such as an increase in virulence factors and biofilm production. Inhibitors of QS are important research tools in the discovery of new potential anti-bacterial agents. Polygodial, drimenol and drimendiol are drimane sesquiterpenoids isolated from Drimys winteri, a Chilean native tree. Their QS activity, when tested on Chromobacterium violaceum ATCC 12472, showed that drimendiol is an inhibitor of QS, decreasing violaceine production in C violaceum and decreasing biofilm formation of Pseudomonas syringae strains. Consequently it increased the biocide effects of CuSO4 on biofilms of P. syringae. PMID:23513712

Paza, Cristian; Cárcamo, Gerardo; Silva, Mario; Becerra, José; Urrutia, Homero; Sossa, Katherine

2013-02-01

61

Identification of Quorum-Sensing-Regulated Genes of Burkholderia cepacia  

PubMed Central

Quorum sensing is a regulatory mechanism (operating in response to cell density) which in gram-negative bacteria usually involves the production of N-acyl homoserine lactones (HSL). Quorum sensing in Burkholderia cepacia has been associated with the regulation of expression of extracellular proteins and siderophores and also with the regulation of swarming and biofilm formation. In the present study, several quorum-sensing-controlled gene promoters of B. cepacia ATCC 25416 were identified and characterized. A total of 28 putative gene promoters show CepR-C8-HSL-dependent expression, suggesting that quorum sensing in B. cepacia is a global regulatory system.

Aguilar, Claudio; Friscina, Arianna; Devescovi, Giulia; Kojic, Milan; Venturi, Vittorio

2003-01-01

62

Global convergence of quorum-sensing networks  

NASA Astrophysics Data System (ADS)

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

Russo, Giovanni; Slotine, Jean Jacques E.

2010-10-01

63

Quorum signaling and sensing by nontypeable Haemophilus influenzae  

PubMed Central

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

Swords, W. Edward

2012-01-01

64

Transition state analogues in quorum sensing and SAM recycling.  

PubMed

Transition state structures can be derived from kinetic isotope effects and computational chemistry. Molecular electrostatic potential maps of transition states serve as blueprints to guide synthesis of transition state analogue inhibitors of target enzymes. 5'- Methylthioadenosine phosphorylase (MTAP) functions in the polyamine pathway by recycling methylthioadenosine (MTA) and maintaining cellular S-adenosylmethionine (SAM). Its transition state structure was used to guide synthesis of MT-DADMe-ImmA, a picomolar inhibitor that shows anticancer effects against solid tumors. Biochemical and genomic analysis suggests that MTAP inhibition acts by altered DNA methylation and gene expression patterns. A related bacterial enzyme, 5'-methylthioadenosine nucleosidase (MTAN), functions in pathways of quorum sensing involving AI-1 and AI-2 molecules. Transition states have been solved for several bacterial MTANs and used to guide synthesis of powerful inhibitors with dissociation constants in the femtomolar to picomolar range. BuT-DADMe-ImmA blocks quorum sensing in Vibrio cholerae without changing bacterial growth rates. Transition state analogue inhibitors show promise as anticancer and antibacterial agents. PMID:18776260

Schramm, Vern L; Gutierrez, Jemy A; Cordovano, Grace; Basu, Indranil; Guha, Chandan; Belbin, Thomas J; Evans, Gary B; Tyler, Peter C; Furneaux, Richard H

2008-01-01

65

Transition state analogues in quorum sensing and SAM recycling  

PubMed Central

Transition state structures can be derived from kinetic isotope effects and computational chemistry. Molecular electrostatic potential maps of transition states serve as blueprints to guide synthesis of transition state analogue inhibitors of target enzymes. 5’-Methylthioadenosine phosphorylase (MTAP) functions in the polyamine pathway by recycling methylthioadenosine (MTA) and maintaining cellular S-adenosylmethionine (SAM). Its transition state structure was used to guide synthesis of MT-DADMe-ImmA, a picomolar inhibitor that shows anticancer effects against solid tumors. Biochemical and genomic analysis suggests that MTAP inhibition acts by altered DNA methylation and gene expression patterns. A related bacterial enzyme, 5’-methylthioadcnosine nucleosidase (MTAN), functions in pathways of quorum sensing involving AI-1 and AI-2 molecules. Transition states have been solved for several bacterial MTANs and used to guide synthesis of powerful inhibitors with dissociation constants in the femtomolar to picomolar range. BuT-DADMe-ImmA blocks quorum sensing in Vibrio cholerae without changing bacterial growth rates. Transition state analogue inhibitors show promise as anticancer and antibacterial agents.

Schramm, Vern L.; Gutierrez, Jemy A.; Cordovano, Grace; Basu, Indranil; Guha, Chandan; Belbin, Thomas J.; Evans, Gary B.; Tyler, Peter C.; Furneaux, Richard H.

2009-01-01

66

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

PubMed

In this study, the link between quorum sensing in Aeromonas spp. and its virulence towards burbot (Lota lota) was investigated. High mortality occurred in burbot juveniles challenged with Aeromonas salmonicida HN-00, but not in juveniles challenged with Aeromonas hydrophila AH-1N. Meanwhile, both A. hydrophila AH-1N and A. salmonicida HN-00 were virulent towards larvae. The effect of quorum sensing on the virulence of A. hydrophila AH-1N towards burbot larvae was further investigated using quorum sensing mutants (N-(butyryl)-L-homoserine lactone production and receptor mutants). Challenge with these mutants resulted in higher survival of burbot larvae when compared to challenge with the wild type, and the addition of the signal molecule N-butyryl-L-homoserine lactone restored the virulence of the quorum sensing production mutant. Moreover, quorum sensing inhibitors protected the burbot larvae from both Aeromonas strains. Finally, the freshwater micro-algae Chlorella saccharophila and Chlamydomonas reinhardtii, which are able to interfere with quorum sensing, also protected burbot from the pathogens. However, QS interference was unlikely to be the only mechanism. This study revealed that the virulence of Aeromonas spp. towards burbot is regulated by quorum sensing and that quorum sensing inhibitors and micro-algae are promising biocontrol agents. PMID:22465799

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

2012-03-14

67

Quorum sensing controls biofilm formation in Vibrio cholerae  

Microsoft Academic Search

Summary Multiple quorum-sensing circuits function in parallel to control virulence and biofilm formation in Vibrio cholerae . In contrast to other bacterial pathogens that induce virulence factor production and\\/or biofilm for- mation at high cell density in the presence of quorum- sensing autoinducers, V. cholerae represses these behaviours at high cell density. Consistent with this, we show here that V.

Brian K. Hammer; Bonnie L. Bassler

2003-01-01

68

Bacterial Quorum Sensing and Metabolic Incentives to Cooperate  

PubMed Central

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

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

2013-01-01

69

Bacterial quorum sensing and metabolic incentives to cooperate.  

PubMed

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

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

2012-10-12

70

[Quorum sensing in bacteria and yeast].  

PubMed

Bacterial sets are complex dynamic systems, which interact with each other and through the interaction, bacteria coexist, collaborate, compete and share information in a coordinated manner. A way of bacterial communication is quorum sensing. Through this mechanism the bacteria can recognize its concentration in a given environment and they can decide the time at which the expression of a particular set of genes should be started for developing a specific and simultaneous response. The result of these interconnections raises properties that cannot be explained from a single isolated bacterial cell. PMID:23622893

March Rosselló, Gabriel Alberto; Eiros Bouza, José María

2013-04-23

71

AI-2 quorum-sensing inhibitors affect the starvation response and reduce virulence in several Vibrio species, most likely by interfering with LuxPQ.  

PubMed

The increase of disease outbreaks caused by Vibrio species in aquatic organisms as well as in humans, together with the emergence of antibiotic resistance in Vibrio species, has led to a growing interest in alternative disease control measures. Quorum sensing (QS) is a mechanism for regulating microbial gene expression in a cell density-dependent way. While there is good evidence for the involvement of auto-inducer 2 (AI-2)-based interspecies QS in the control of virulence in multiple Vibrio species, only few inhibitors of this system are known. From the screening of a small panel of nucleoside analogues for their ability to disturb AI-2-based QS, an adenosine derivative with a p-methoxyphenylpropionamide moiety at C-3' emerged as a promising hit. Its mechanism of inhibition was elucidated by measuring the effect on bioluminescence in a series of Vibrio harveyi AI-2 QS mutants. Our results indicate that this compound, as well as a truncated analogue lacking the adenine base, block AI-2-based QS without interfering with bacterial growth. The active compounds affected neither the bioluminescence system as such nor the production of AI-2, but most likely interfered with the signal transduction pathway at the level of LuxPQ in V. harveyi. The most active nucleoside analogue (designated LMC-21) was found to reduce the Vibrio species starvation response, to affect biofilm formation in Vibrio anguillarum, Vibrio vulnificus and Vibrio cholerae, to reduce pigment and protease production in V. anguillarum, and to protect gnotobiotic Artemia from V. harveyi-induced mortality. PMID:19778962

Brackman, Gilles; Celen, Shari; Baruah, Kartik; Bossier, Peter; Van Calenbergh, Serge; Nelis, Hans J; Coenye, Tom

2009-09-24

72

Engineered biological nanofactories trigger quorum sensing response in targeted bacteria  

NASA Astrophysics Data System (ADS)

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

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

2010-03-01

73

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

PubMed

With the emergence of antibiotic-resistant strains of bacteria, the available options for treating bacterial infections have become very limited, and the search for a novel general antibacterial therapy has received much greater attention. Quorum quenching can be used to control disease in a quorum sensing system by triggering the pathogenic phenotype. The interference with the quorum sensing system by the quorum quenching enzyme is a potential strategy for replacing traditional antibiotics because the quorum quenching strategy does not aim to kill the pathogen or limit cell growth but to shut down the expression of the pathogenic gene. Quorum quenching enzymes have been identified in quorum sensing and non-quorum sensing microbes, including lactonase, acylase, oxidoreductase and paraoxonase. Lactonase is widely conserved in a range of bacterial species and has variable substrate spectra. The existence of quorum quenching enzymes in the quorum sensing microbes can attenuate their quorum sensing, leading to blocking unnecessary gene expression and pathogenic phenotypes. In this review, we discuss the physiological function of quorum quenching enzymes in bacterial infection and elucidate the enzymatic protection in quorum sensing systems for host diseases and their application in resistance against microbial diseases. PMID:24065091

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

2013-08-26

74

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

PubMed Central

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

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

2013-01-01

75

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

PubMed

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 IC(50) 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(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. PMID:19270684

Gutierrez, Jemy A; Crowder, Tamara; Rinaldo-Matthis, Agnes; Ho, Meng-Chiao; Almo, Steven C; Schramm, Vern L

2009-03-08

76

Transition state analogues of 5?-methylthioadenosine nucleosidase disrupt quorum sensing  

PubMed Central

SUMMARY 5?-Methylthioadenosine nucleosidase (MTAN) is a bacterial enzyme involved in S-adenosylmethionine-related quorum sensing pathways that induce bacterial pathogenesis factors. Transition state analogues 5?-methylthio- (MT-), 5?-ethylthio- (EtT-) and 5?-butylthio- (BuT-) DADMe-ImmucillinAs are slow-onset, tight-binding inhibitors of Vibrio cholerae MTAN (VcMTAN), with dissociation constants of 73, 70, and 208 pM, respectively. Structural analysis of VcMTAN with BuT-DADMe-ImmucillinA reveals interactions contributing to the high affinity. 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-ImmucillinA, disrupting autoinducer production in a dose-dependent manner without affecting growth. MT- and BuT-DADMe-ImmucillinA also inhibit autoinducer-2 production in enterohemorrhagic Escherichia coli O157:H7 with IC50 values of 600, and 125 nM, respectively. BuT-DADMe-ImmucillinA inhibition of autoinducer-2 production in both strains persists for several generations, and causes reduction in biofilm formation. These results support MTAN’s role in quorum sensing, and its potential as target for bacterial anti-infective drug design.

Gutierrez, Jemy A.; Crowder, Tamara; Rinaldo-Matthis, Agnes; Ho, Meng-Chiao; Almo, Steven C.; Schramm, Vern L.

2009-01-01

77

A multivalent probe for AI-2 quorum-sensing receptors.  

PubMed

Multivalency is a common principle in the recognition of cellular receptors, and multivalent agonists and antagonists have played a major role in understanding mammalian cell receptor biology. The study of bacterial cell receptors using similar approaches, however, has lagged behind. Herein we describe our efforts toward the development of a dendrimer-based multivalent probe for studying AI-2 quorum-sensing receptors. From these studies, we have discovered a chemical probe specific for Lsr-type AI-2 quorum-sensing receptors with the potential for enabling the identification of new bacterial species that utilize AI-2 as a quorum-sensing signaling molecule. PMID:21913711

Garner, Amanda L; Park, Junguk; Zakhari, Joseph S; Lowery, Colin A; Struss, Anjali Kumari; Sawada, Daisuke; Kaufmann, Gunnar F; Janda, Kim D

2011-09-15

78

A Multivalent Probe for AI-2 Quorum Sensing Receptors  

PubMed Central

Multivalency is a common principle in the recognition of cellular receptors, and multivalent agonists and antagonists have played a major role in understanding mammalian cell receptor biology. The study of bacterial cell receptors using similar approaches, however, has lagged behind. Herein we describe our efforts toward the development of a dendrimer-based multivalent probe for studying AI-2 quorum sensing receptors. From these studies, we have discovered a chemical probe specific for Lsr-type AI-2 quorum sensing receptors with the potential for enabling the identification of new bacterial species that utilize AI-2 as a quorum sensing signaling molecule.

Garner, Amanda L.; Park, Junguk; Zakhari, Joseph S.; Lowery, Colin A.; Struss, Anjali Kumari; Sawada, Daisuke; Kaufmann, Gunnar F.; Janda, Kim D.

2011-01-01

79

A Mobile Quorum-Sensing System in Serratia marcescens  

PubMed Central

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

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

2006-01-01

80

Electronic implementation of a repressilator with quorum sensing feedback.  

PubMed

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

2013-05-02

81

Pseudomonas aeruginosa quorum sensing as a potential antimicrobial target  

PubMed Central

Pseudomonas aeruginosa has two complete quorum-sensing systems. Both of these systems have been shown to be important for Pseudomonas virulence in multiple models of infection. Thus, these systems provide unique targets for novel antimicrobial drugs.

Smith, Roger S.; Iglewski, Barbara H.

2003-01-01

82

Early development and quorum sensing in bacterial biofilms  

Microsoft Academic Search

.  ?We develop mathematical models to examine the formation, growth and quorum sensing activity of bacterial biofilms. The growth\\u000a aspects of the model are based on the assumption of a continuum of bacterial cells whose growth generates movement, within\\u000a the developing biofilm, described by a velocity field. A model proposed in Ward et al. (2001) to describe quorum sensing, a process

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

2003-01-01

83

Detection of quorum-sensing-related molecules in Vibrio scophthalmi  

Microsoft Academic Search

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

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

2008-01-01

84

Temporal Quorum-Sensing Induction Regulates Vibrio cholerae Biofilm Architecture  

Microsoft Academic Search

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 expres- sion 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.

Zhi Liu; Fiona R. Stirling; Jun Zhu

2007-01-01

85

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

PubMed Central

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

Li, Zhi; Nair, Satish K

2012-01-01

86

Use of quorum sensing antagonists to deter the formation of crystalline Proteus mirabilis biofilms.  

PubMed

Proteus mirabilis biofilms are a major cause of urinary catheter blockage. Antibiotic-impregnated catheters used to prevent catheter blockage have achieved limited success. Research has examined the efficacy of quorum sensing inhibitors against Pseudomonas aeruginosa biofilms, but there are few reports of the effects of these compounds against crystalline P. mirabilis biofilms. This study examined the effect of two quorum sensing antagonists, p-nitrophenyl glycerol (PNPG) and tannic acid, against crystalline P. mirabilis biofilms. Tannic acid and PNPG were observed to inhibit the quorum sensing system and the formation of P. mirabilis biofilms grown in artificial urine. The success of these compounds provides a possible means of preventing urinary catheter encrustation. PMID:19619987

Jones, Steven M; Dang, Tammy T; Martinuzzi, Robert

2009-07-19

87

Quo vadis quorum quenching?  

PubMed

With the emergence of microbial pathogens increasingly resistant against commonly used antibiotics, new treatment strategies are desperately needed. Bacterial quorum sensing has attracted a lot of attention over the last decade as a potential new target for antimicrobial therapy. Interference with quorum sensing signaling, or quorum quenching, might offer new avenues to prevent and/or treat bacterial infections via inhibition of virulence factor expression and biofilm formation. While many inhibitors of quorum sensing signaling have been described, only few have been evaluated in vivo and none has been clinically developed. This review will highlight recent findings and discuss interesting future areas where quorum quenching might be a promising strategy. PMID:23876839

Zhu, Jie; Kaufmann, Gunnar F

2013-07-19

88

Computational modeling of the quorum-sensing network in bacteria  

NASA Astrophysics Data System (ADS)

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

Fenley, Andrew; Banik, Suman; Kulkarni, Rahul

2007-03-01

89

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.

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

2013-01-01

90

Choosing an appropriate infection model to study quorum sensing inhibition in pseudomonas infections.  

PubMed

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

2013-09-23

91

Quorum sensing in the squid-Vibrio symbiosis.  

PubMed

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

Verma, Subhash C; Miyashiro, Tim

2013-08-07

92

Quorum sensing negatively regulates chitinase in Vibrio harveyi.  

PubMed

Quorum sensing, bacterial cell-to-cell communication, regulates the virulence of Vibrio harveyi towards different hosts. Chitinase can be considered as a virulence factor because it helps pathogenic bacteria to attach to the host and to penetrate its tissues (e.g. in case of shrimp). Here, we show that quorum sensing negatively regulates chitinase in V. harveyi. Chitinolytic activity towards natural chitin from crab shells, the synthetic chitin derivative chitin azure, and fluorogenic chitin oligomers was significantly higher in a mutant in which the quorum-sensing system is completely inactivated when compared with a mutant in which the system is maximally active. Furthermore, the addition of signal molecule containing cell-free culture fluids decreased chitinase activity in a Harveyi Autoinducer 1 and Autoinducer 2-deficient double mutant. Finally, chitinase A mRNA levels were fivefold lower in the mutant in which the quorum-sensing system is maximally active when compared with the mutant in which the system is completely inactivated. [Correction added on 25 September 2009, after first online publication: the preceding sentence was corrected from 'Finally, chitinase A mRNA levels were fivefold lower in the mutant in which the quorum-sensing system is completely inactivated when compared with the mutant in which the system is maximally active.'] We argue that this regulation might help the vibrios to switch between host-associated and free-living life styles. PMID:23765997

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

2009-07-01

93

Integrated analysis of bacterial quorum-sensing networks  

NASA Astrophysics Data System (ADS)

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

Kulkarni, Rahul

2005-11-01

94

Inhibition of quorum sensing in Pseudomonas aeruginosa by N-acyl cyclopentylamides.  

PubMed

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

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

2007-03-16

95

LuxS quorum sensing: more than just a numbers game  

Microsoft Academic Search

Quorum sensing is a process of bacterial cell-to-cell communication involving the production and detection of extracellular signaling molecules called autoinducers. Quorum sensing allows populations of bacteria to collectively control gene expression, and thus synchronize group behavior. Processes controlled by quorum sensing are typically ones that are unproductive unless many bacteria act together. Most autoinducers enable intraspecies communication; however, a recently

Karina B Xavier; Bonnie L Bassler

2003-01-01

96

Quorum sensing and the population-dependent control of virulence.  

PubMed Central

One crucial feature of almost all bacterial infections is the need for the invading pathogen to reach a critical cell population density sufficient to overcome host defences and establish the infection. Controlling the expression of virulence determinants in concert with cell population density may therefore confer a significant survival advantage on the pathogen such that the host is overwhelmed before a defence response can be fully initiated. Many different bacterial pathogens are now known to regulate diverse physiological processes including virulence in a cell-density-dependent manner through cell-cell communication. This phenomenon, which relies on the interaction of a diffusible signal molecule (e.g. an N-acylhomoserine lactone) with a sensor or transcriptional activator to couple gene expression with cell population density, has become known as 'quorum sensing'. Although the size of the 'quorum' is likely to be highly variable and influenced by the diffusibility of the signal molecule within infected tissues, nevertheless quorum-sensing signal molecules can be detected in vivo in both experimental animal model and human infections. Furthermore, certain quorum-sensing molecules have been shown to possess pharmacological and immunomodulatory activity such that they may function as virulence determinants per se. As a consequence, quorum sensing constitutes a novel therapeutic target for the design of small molecular antagonists capable of attenuating virulence through the blockade of bacterial cell-cell communication.

Williams, P; Camara, M; Hardman, A; Swift, S; Milton, D; Hope, V J; Winzer, K; Middleton, B; Pritchard, D I; Bycroft, B W

2000-01-01

97

Silencing Quorum Sensing through Extracts of Melicope lunu-ankenda  

PubMed Central

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

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

2012-01-01

98

Modeling of signal transduction in bacterial quorum-sensing  

NASA Astrophysics Data System (ADS)

Several species of bacteria are able to coordinate gene regulation in response to population density, a process known as ``quorum-sensing''. Quorum-sensing bacteria produce, secrete, and detect signal molecules called autoinducers. For several species of bacteria in the Vibrio genus, recent results have shown that the external autoinducer concentrations control the expression of regulatory small RNA(s) which are critical to the process of quorum-sensing. We present a theoretical analysis of the network which relates the rate of small RNA expression to the external autoinducer concentrations. We relate the results from our modeling to previous experimental observations and suggest new experiments based on testable predictions of the model.

Fenley, Andrew; Banik, Suman; Kulkarni, Rahul

2006-03-01

99

Mathematical Modeling of Quorum-Sensing Control in Biofilms  

Microsoft Academic Search

\\u000a This chapter begins with an overview of the relevant\\u000a \\u0009 literature on theoretical approaches to modeling biofilms, quorum\\u000a \\u0009 sensing in bacteria, and anti-quorum-sensing treatment. Following\\u000a \\u0009 this, new mathematical models are proposed to investigate\\u000a \\u0009 anti-quorum-sensing treatment in batch cultures and in biofilm\\u000a \\u0009 environments. Details for the models' derivation are aimed so that\\u000a \\u0009 readers with a nonmathematical background will have a good idea of\\u000a \\u0009 how

John Ward

100

[Quorum-sensing regulation in soil pseudomonads].  

PubMed

228 strains of soil and rhizosphere pseudomonads isolated in different geographic zones were screened, with the use of two tester systems, for the capacity to produce N-acetyl-homoserine lactones (AHLs), which are autoinducers involved in quorum-sensing (QS) regulation. AHL production was found in 11.4% of the strains investigated. In five Pseudomonas chlororaphis strains shown to be active AHL producers and chosen for further study, PCR identified two QS systems that involved the phzI, phzR, csaI, and csaR genes; this finding suggests the conservative nature of these regulation systems in P. chlororaphis. Strain P. chlororaphis 449, chosen as a model object and studied in greater detail, produced three AHL species including N-butanoyl-homoserine lactone and N-hexanoyl-homoserine lactone. This strain produced three types of phenazine antibiotics, as well as siderophores and cyanide; it also exhibited antagonistic properties toward a wide spectrum of phytopathogenic fungi. The phzI and csaI genes, coding for synthases of AHLs of two types, were cloned and sequenced; mutants with knocked-out phzI and csal genes were obtained. With the use of transposon mutagenesis and the gene substitution method, mutations were obtained in the global expression regulator genes gacS, coding for the GacA-GacS regulation system kinase, and rpoS, coding for the sigma S subunit of RNA polymerase. The effect of these mutations on the AHL synthesis and on the regulation of various metabolic processes in P. chlororaphis was studied. PMID:17025170

Veselova, M A; Lipasova, V A; Astaurova, O B; Atamova, E E; Protsenko, M A; Buza, L N; Metlitskaia, A Z; Danilova, N N; Chernin, L S; Khmel', I A

101

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.

2013-01-01

102

Quorum-sensing regulates biofilm formation in Vibrio scophthalmi  

PubMed Central

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

2012-01-01

103

Information processing and signal integration in bacterial quorum sensing  

NASA Astrophysics Data System (ADS)

Bacteria communicate with each other using secreted chemical signaling molecules called autoinducers (AIs) in a process known as quorum sensing. Quorum sensing enables bacteria to collectively regulate their behavior depending on the number and/or species of bacteria present. The quorum-sensing network of the marine-bacteria Vibrio harveyi consists of three AIs encoding distinct ecological information, each detected by its own histidine-kinase sensor protein. The sensor proteins all phosphorylate a common response regulator and transmit sensory information through a shared phosphorelay that regulates expression of downstream quorum-sensing genes. Despite detailed knowledge of the Vibrio quorum-sensing circuit, it is still unclear how and why bacteria integrate information from multiple input signals to coordinate collective behaviors. Here we develop a mathematical framework for analyzing signal integration based on Information Theory and use it to show that bacteria must tune the kinase activities of sensor proteins in order to transmit information from multiple inputs. This is demonstrated within a quantitative model that allows us to quantify how much Vibrio's learn about individual inputs and explains experimentally measured input-output relations. Furthermore, we predicted and experimentally verified that bacteria manipulate the production rates of AIs in order to increase information transmission and argue that the quorum-sensing circuit is designed to coordinate a multi-cellular developmental program. Our results show that bacteria can successfully learn about multiple signals even when they are transmitted through a shared pathway and suggest that Information Theory may be a powerful tool for analyzing biological signaling networks.

Mehta, Pankaj

2009-03-01

104

Structure-Activity Relationship of Cinnamaldehyde Analogs as Inhibitors of AI-2 Based Quorum Sensing and Their Effect on Virulence of Vibrio spp  

PubMed Central

Background Many bacteria, including Vibrio spp., regulate virulence gene expression in a cell-density dependent way through a communication process termed quorum sensing (QS). Hence, interfering with QS could be a valuable novel antipathogenic strategy. Cinnamaldehyde has previously been shown to inhibit QS-regulated virulence by decreasing the DNA-binding ability of the QS response regulator LuxR. However, little is known about the structure-activity relationship of cinnamaldehyde analogs. Methodology/Principal Findings By evaluating the QS inhibitory activity of a series of cinnamaldehyde analogs, structural elements critical for autoinducer-2 QS inhibition were identified. These include an ?,? unsaturated acyl group capable of reacting as Michael acceptor connected to a hydrophobic moiety and a partially negative charge. The most active cinnamaldehyde analogs were found to affect the starvation response, biofilm formation, pigment production and protease production in Vibrio spp in vitro, while exhibiting low cytotoxicity. In addition, these compounds significantly increased the survival of the nematode Caenorhabditis elegans infected with Vibrio anguillarum, Vibrio harveyi and Vibrio vulnificus. Conclusions/Significance Several new and more active cinnamaldehyde analogs were discovered and they were shown to affect Vibrio spp. virulence factor production in vitro and in vivo. Although ligands for LuxR have not been identified so far, the nature of different cinnamaldehyde analogs and their effect on the DNA binding ability of LuxR suggest that these compounds act as LuxR-ligands.

Brackman, Gilles; Celen, Shari; Hillaert, Ulrik; Van Calenbergh, Serge; Cos, Paul; Maes, Louis; Nelis, Hans J.; Coenye, Tom

2011-01-01

105

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

PubMed Central

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

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

2004-01-01

106

A Variant Quorum Sensing System in Aeromonas veronii MTCC 3249  

PubMed Central

We have investigated the quorum sensing control in Aeromonas veronii MTCC 3249, originally isolated as A. culicicola from the midgut of Culex quinquefasciatus. Based on biosensor assays, the bacterium showed constant production of multiple acyl-homoserine lactones (AHLs) with increasing cell-density. The luxRI gene homologs, acuR (A. culicicola transcriptional Regulator) and acuI (A. culicicola autoInducer) were successfully amplified by inverse-PCR. Sequence analysis indicated acuRI were divergent from all known quorum sensing gene homologs in Aeromonas. Two localized regions in the C-terminal autoinducer binding domain of acuR showed indels suggesting variations in autoinducer specificity. Further, only a single copy of the quorum sensing genes was detected, suggesting a tight regulation of mechanisms under its control. Chromatography and further chemical analysis identified two AHLs in the culture supernatant: 6-carboxy-HHL (homoadipyl homoserine lactone), a novel AHL, and N-tetradecanoylhomoserine lactone. The existence of a potentially variant quorum sensing system might therefore, reflect in some way the ecological strategies adopted by this bacterium in the mosquito midgut.

Jangid, Kamlesh; Parameswaran, Perunninakulath S.; Shouche, Yogesh S.

2012-01-01

107

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

PubMed

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

2013-10-18

108

The interplay of two Quorum sensing regulation systems of  

Microsoft Academic Search

Many bacteria developed a possibility to recognise aspects of their environment or to communicate with each other by chemical signals. One important case is the so-called Quorum sensing (QS), a regulatory mechanism for the gene expression, where the bacteria measure their own cell density by means of this signalling pathway. One of the best-studied species using QS is the marine

Christina Kuttler; Burkhard A. Hense

109

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

110

Effects of Antibiotics on Quorum Sensing in Pseudomonas aeruginosa?  

PubMed Central

During infection, Pseudomonas aeruginosa employs bacterial communication (quorum sensing [QS]) to coordinate the expression of tissue-damaging factors. QS-controlled gene expression plays a pivotal role in the virulence of P. aeruginosa, and QS-deficient mutants cause less severe infections in animal infection models. Treatment of cystic fibrosis (CF) patients chronically infected with P. aeruginosa with the macrolide antibiotic azithromycin (AZM) has been demonstrated to improve the clinical outcome. Several studies indicate that AZM may accomplish its beneficial action in CF patients by impeding QS, thereby reducing the pathogenicity of P. aeruginosa. This led us to investigate whether QS inhibition is a common feature of antibiotics. We present the results of a screening of 12 antibiotics for their QS-inhibitory activities using a previously described QS inhibitor selector 1 strain. Three of the antibiotics tested, AZM, ceftazidime (CFT), and ciprofloxacin (CPR), were very active in the assay and were further examined for their effects on QS-regulated virulence factor production in P. aeruginosa. The effects of the three antibiotics administered at subinhibitory concentrations were investigated by use of DNA microarrays. Consistent results from the virulence factor assays, reverse transcription-PCR, and the DNA microarrays support the finding that AZM, CFT, and CPR decrease the expression of a range of QS-regulated virulence factors. The data suggest that the underlying mechanism may be mediated by changes in membrane permeability, thereby influencing the flux of N-3-oxo-dodecanoyl-l-homoserine lactone.

Skindersoe, Mette E.; Alhede, Morten; Phipps, Richard; Yang, Liang; Jensen, Peter O.; Rasmussen, Thomas B.; Bjarnsholt, Thomas; Tolker-Nielsen, Tim; H?iby, Niels; Givskov, Michael

2008-01-01

111

Substituted lactam and cyclic azahemiacetals modulate Pseudomonas aeruginosa quorum sensing.  

PubMed

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

2011-07-28

112

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.

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

2011-01-01

113

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.

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

2013-01-01

114

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

115

Analysis of Autoinducer-2 Quorum Sensing in Yersinia pestis.  

PubMed

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; Minion, F Chris

2013-08-19

116

Screening for Antibacterial, Antifungal, and Anti quorum Sensing Activity.  

PubMed

The plate-hole diffusion assay is an invaluable screening tool to evaluate the antibacterial potential of natural products. It relies on the diffusion of test material from pre-cut wells through agar seeded with bacteria. Samples that are capable of inhibiting bacterial growth will produce a clear zone surrounding their well. For the evaluation of antifungal activity of natural products, we describe the broth microdilution method. This assay is performed using a 96 well microtiter tray containing fungal inoculum, test medium and natural product material. Samples demonstrating antifungal activity will prevent any discernible growth as detected visually. A disk diffusion assay, utilizing the pigmented indicator strain Chromobacterium violaceum, is described here for the screening of natural products for anti quorum sensing activity. Inhibition of quorum sensing results in growth of non-pigmented bacteria. PMID:23963914

Hayhoe, Elisa J; Palombo, Enzo A

2013-01-01

117

Contribution of Quorum Sensing to the Virulence of Pseudomonas aeruginosa in Burn Wound Infections  

Microsoft Academic Search

The Pseudomonas aeruginosa quorum-sensing systems, las and rhl, control the production of numerous virulence factors. In this study, we have used the burned-mouse model to examine the contribution of quorum-sensing systems to the pathogenesis of P. aeruginosa infections in burn wounds. Different quorum- sensing mutants of P. aeruginosa PAO1 that were defective in the lasR, lasI ,o rrhlI gene or

KENDRA P. RUMBAUGH; JOHN A. GRISWOLD; BARBARA H. IGLEWSKI; ABDUL N. HAMOOD

1999-01-01

118

Quorum-Sensing Mutations Affect Attachment and Stability of Burkholderia cenocepacia Biofilms  

Microsoft Academic Search

Biofilm formation in Burkholderia cenocepacia has been shown to rely in part on acylhomoserine lactone- based quorum sensing. For many other bacterial species, it appears that both the initial adherence and the later stages of biofilm maturation are affected when quorum sensing pathways are inhibited. In this study, we examined the effects of mutations in the cepIR and cciIR quorum-sensing

Kerry L. Tomlin; Rebecca J. Malott; Gordon Ramage; Douglas G. Storey; Pamela A. Sokol; H. Ceri

2005-01-01

119

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

Microsoft Academic Search

Quorum-sensing is the mechanism by which bacteria communicate and synchronize group behaviors. Quantitative information on parameters such as the copy number of particular quorum-sensing proteins should contribute strongly to understanding how the quorum-sensing network functions. Here, we show that the copy number of the master regulator protein LuxR in Vibrio harveyi can be determined in vivo by exploiting small-number fluctuations of

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

2010-01-01

120

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

121

Role of quorum sensing in the pathogenicity of Burkholderia pseudomallei  

Microsoft Academic Search

Burkholderia pseudomallei is the causative agent of human and animal melioidosis. The role of quorum sensing (QS) in the in vivo pathogenicity of B. pseudomallei via inhalational exposure of BALB\\/c mice and intraperitoneal challenge of Syrian hamsters has not been reported. This investigation demonstrates that B. pseudomallei encodes a minimum of three luxI and five luxR homologues that are involved

Ricky L. Ulrich; David DeShazer; Ernst E. Brueggemann; Harry B. Hines; Petra C. Oyston; Jeffrey A. Jeddeloh

2004-01-01

122

Simple models for quorum sensing: Nonlinear dynamical analysis  

NASA Astrophysics Data System (ADS)

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

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

2011-10-01

123

Quorum Sensing-Dependent Biofilms Enhance Colonization in Vibrio cholerae  

Microsoft Academic Search

Vibrio cholerae is the causative agent of the diarrheal disease cholera. By an incompletely understood developmental process, V. cholerae forms complex surface-associated communities called biofilms. Here we show that quorum sensing-deficient mutants of V. cholerae produce thicker biofilms than those formed by wild-type bacteria. Microarray analysis of biofilm-associated bacteria shows that expression of the Vibrio polysaccharide synthesis (vps) operons is

Jun Zhu; John J. Mekalanos

2003-01-01

124

QUORUM SENSING: Cell-to-Cell Communication in Bacteria  

Microsoft Academic Search

Abstract Bacteria communicate,with,one,another,using,chemical,signal molecules. As in higher organisms, the information supplied by these molecules is critical for synchronizing,the activities of large groups of cells. In bacteria, chemical communication involves producing, re- leasing, detecting, and responding to small hormone-like molecules termed autoinducers. This process, termed quorum sensing, allows bacteria to monitor,the environment,for other bacteria and to al- ter behavior,on a population-wide,scale

Christopher M. Waters; Bonnie L. Bassler

2005-01-01

125

Characterization of Quorum Sensing Signals in Coral-Associated Bacteria  

Microsoft Academic Search

Marine environment habitats, such as the coral mucus layer, are abundant in nutrients and rich with diverse populations of\\u000a microorganisms. Since interactions among microorganisms found in coral mucus can be either mutualistic or competitive, understanding\\u000a quorum sensing-based acyl homoserine lactone (AHL) language may shed light on the interaction between coral-associated microbial\\u000a communities in the native host. More than 100 bacterial

Karina Golberg; Evgeni Eltzov; Maya Shnit-Orland; Robert S. Marks; Ariel Kushmaro

2011-01-01

126

RETRACTED ARTICLE: Quorum-sensing of bacteria and its application  

Microsoft Academic Search

Quorum sensing, or auto induction, as a cell density dependent signaling mechanism in many microorganisms, is triggered via\\u000a auto inducers which passively diffuse across the bacterial envelope and therefore intracellulaly accumulate only at higher\\u000a bacterial densities to regulate specialized processes such as genetic competence, bioluminescence, virulence and sporulation.\\u000a N-acyl homoserine lactones are the most common type of signal molecules. Aquaculture

Guoliang Jiang; Mingxia Su

2009-01-01

127

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

128

Dynorphin Activates Quorum Sensing Quinolone Signaling in Pseudomonas aeruginosa  

PubMed Central

There is now substantial evidence that compounds released during host stress directly activate the virulence of certain opportunistic pathogens. Here, we considered that endogenous opioids might function as such compounds, given that they are among the first signals to be released at multiple tissue sites during host stress. We tested the ability of various opioid compounds to enhance the virulence of Pseudomonas aeruginosa using pyocyanin production as a biological readout, and demonstrated enhanced virulence when P. aeruginosa was exposed to synthetic (U-50,488) and endogenous (dynorphin) ?-agonists. Using various mutants and reporter strains of P. aeruginosa, we identified involvement of key elements of the quorum sensing circuitry such as the global transcriptional regulator MvfR and the quorum sensing-related quinolone signaling molecules PQS, HHQ, and HQNO that respond to ?-opioids. The in vivo significance of ?-opioid signaling of P. aeruginosa was demonstrated in mice by showing that dynorphin is released from the intestinal mucosa following ischemia/reperfusion injury, activates quinolone signaling in P. aeruginosa, and enhances the virulence of P. aeruginosa against Lactobacillus spp. and Caenorhabditis elegans. Taken together, these data demonstrate that P. aeruginosa can intercept opioid compounds released during host stress and integrate them into core elements of quorum sensing circuitry leading to enhanced virulence.

Zaborina, Olga; Lepine, Francois; Xiao, Gaoping; Valuckaite, Vesta; Chen, Yimei; Li, Terry; Ciancio, Mae; Zaborin, Alex; Petroff, Elaine; Turner, Jerrold R; Rahme, Laurence G; Chang, Eugene; Alverdy, John C

2007-01-01

129

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.

H?yland-Kroghsbo, Nina Molin; Maerkedahl, Rasmus Baadsgaard; Svenningsen, Sine Lo

2013-01-01

130

Negative Feedback in the Vibrio harveyi Quorum-Sensing Circuit  

NASA Astrophysics Data System (ADS)

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

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

2010-03-01

131

A structurally unrelated mimic of a Pseudomonas aeruginosa acyl-homoserine lactone quorum-sensing signal.  

PubMed

The pathogenic bacterium Pseudomonas aeruginosa uses acyl-homoserine lactone quorum-sensing signals to coordinate the expression of a battery of virulence genes in a cascade of regulatory events. The quorum-sensing signal that triggers the cascade is N-3-oxo-dodecanoyl homoserine lactone (3OC12-HSL), which interacts with two signal receptor-transcription factors, LasR and QscR. This signal is base labile, and it is degraded by mammalian PON lactonases. We have identified a structurally unrelated triphenyl mimic of 3OC12-HSL that is base-insensitive and PON-resistant. The triphenyl mimic seems to interact specifically with LasR but not with QscR. In silico analysis suggests that the mimic fits into the 3OC12-HSL-binding site of LasR and makes key contacts with LasR. The triphenyl mimic is an excellent scaffold for developing quorum-sensing inhibitors, and its stability and potency make it ideal for biotechnology uses such as heterologous gene expression. PMID:17075036

Müh, Ute; Hare, Brian J; Duerkop, Breck A; Schuster, Martin; Hanzelka, Brian L; Heim, Roger; Olson, Eric R; Greenberg, E Peter

2006-10-30

132

Quorum sensing in the context of food microbiology.  

PubMed

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; Nychas, George-John E

2012-06-15

133

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.

Skandamis, Panagiotis N.

2012-01-01

134

Quorum sensing and butanediol fermentation affect colonization and spoilage of carrot slices by Serratia plymuthica  

Microsoft Academic Search

In this work we investigated the role of quorum sensing and specific quorum-sensing dependent properties in the colonization and spoilage of carrot slices by Serratia plymuthica RVH1, a strain isolated previously from a vegetable washing and cutting machine in an industrial kitchen. Disinfected carrot slices were inoculated by immersion in a bacterial suspension and then placed in a Petri dish

Eva Wevers; Pieter Moons; Rob Van Houdt; Ine Lurquin; Abram Aertsen; Chris W. Michiels

2009-01-01

135

How bacteria talk to each other: regulation of gene expression by quorum sensing  

Microsoft Academic Search

Quorum sensing, or the control of gene expression in response to cell density, is used by both Gram-negative and Gram-positive bacteria to regulate a variety of physiological functions. In all cases, quorum sensing involves the production and detection of extracellular signalling molecules called autoinducers. While universal signalling themes exist, variations in the design of the extracellular signals, the signal detection

Bonnie L Bassler

1999-01-01

136

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.

2011-01-01

137

A Model of the Quorum Sensing System in Vibrio fischeri Using P Systems  

Microsoft Academic Search

Quorum sensing is a cell density dependent gene regulation system that allows an entire population of bacterial cells to communi- cate in order to regulate the expression of certain or specific genes in a coordinated way depending on the size of the population. In this paper we present a model of the Quorum Sensing System in Vibrio fischeri us- ing

Francisco José Romero-campero; Mario J. Pérez-jiménez

2008-01-01

138

Transient interference with staphylococcal quorum sensing blocks abscess formation  

PubMed Central

The staphylococcal virulon is controlled largely by the agr locus, a global accessory gene regulator that is autoinduced by a self-coded peptide (AIP) and is therefore a quorum sensor. The agr locus has diverged within and between species, giving rise to AIP variants that inhibit heterologous agr activation, an effect with therapeutic potential against Staphylococcus aureus: a single dose of an inhibitory AIP blocks the formation of an experimental murine abscess. As the AIP is unstable at physiological pH, owing to its essential thiolactone bond, its single-dose efficacy seems paradoxical, which has led us to analyze the in vivo kinetics of agr activation and the consequences of its blockage by a heterologous AIP. Initially, the infecting bacteria grow rapidly, achieving sufficient population density within the first 3 h to activate agr, and then enter a neutrophil-induced metabolic eclipse lasting for 2–3 d, followed by agr reactivation concomitantly with the development of the abscess. The inhibitory AIP prevents agr expression only during its short in vivo lifetime, suggesting that the agr-induced and therefore quorum-dependent synthesis of virulence factors shortly after infection is necessary for the subsequent development of the abscess lesion and bacterial survival. We confirm this finding by showing that a sterile agr+ supernatant causes a sterile abscess similar to the septic abscess caused by live bacteria. These results may provide a biological rationale for regulation of virulence factor expression by quorum sensing rather than by response to specific host signals.

Wright, Jesse S.; Jin, Rhuzong; Novick, Richard P.

2005-01-01

139

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

NASA Astrophysics Data System (ADS)

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

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

2011-03-01

140

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

PubMed

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

2012-11-01

141

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

142

Immune modulation by Pseudomonas aeruginosa quorum-sensing signal molecules.  

PubMed

There is burgeoning recent interest in the potential of bacterial quorum-sensing signal molecules (QSSMs) such as the long chain N-acylhomoserine lactones (AHLs) and 4-quinolones produced by Pseudomonas aeruginosa for modulating immune function. While it is clear that QSSMs have well defined immune modulatory potential in vitro, and are detectable in body fluids (such as sputum from cystic fibrosis patients infected with P. aeruginosa) at levels which might be expected to modify immune competence, the true impact of bacterial QSSMs on host physiology in vivo has yet to be fully determined. PMID:16503197

Pritchard, David Idris

2006-02-28

143

Quorum Sensing and Expression of Virulence in Pectobacteria  

PubMed Central

Quorum sensing (QS) is a population density-dependent regulatory mechanism in which gene expression is coupled to the accumulation of a chemical signaling molecule. QS systems are widespread among the plant soft-rotting bacteria. In Pectobacterium carotovorum, at least two QS systems exist being specified by the nature of chemical signals involved. QS in Pectobacterium carotovorum uses N-acylhomoserine lactone (AHL) based, as well as autoinducer-2 (AI-2) dependent signaling systems. This review will address the importance of the QS in production of virulence factors and interaction of QS with other regulatory systems in Pectobacterium carotovorum.

Pollumaa, Lee; Alamae, Tiina; Mae, Andres

2012-01-01

144

Prediction by promoter logic in bacterial quorum sensing.  

PubMed

Quorum-sensing systems mediate chemical communication between bacterial cells, coordinating cell-density-dependent processes like biofilm formation and virulence-factor expression. In the proteobacterial LuxI/LuxR quorum sensing paradigm, a signaling molecule generated by an enzyme (LuxI) diffuses between cells and allosterically stimulates a transcriptional regulator (LuxR) to activate its cognate promoter (pR). By expressing either LuxI or LuxR in positive feedback from pR, these versatile systems can generate smooth (monostable) or abrupt (bistable) density-dependent responses to suit the ecological context. Here we combine theory and experiment to demonstrate that the promoter logic of pR - its measured activity as a function of LuxI and LuxR levels - contains all the biochemical information required to quantitatively predict the responses of such feedback loops. The interplay of promoter logic with feedback topology underlies the versatility of the LuxI/LuxR paradigm: LuxR and LuxI positive-feedback systems show dramatically different responses, while a dual positive/negative-feedback system displays synchronized oscillations. These results highlight the dual utility of promoter logic: to probe microscopic parameters and predict macroscopic phenotype. PMID:22275861

Rai, Navneet; Anand, Rajat; Ramkumar, Krishna; Sreenivasan, Varun; Dabholkar, Sugat; Venkatesh, K V; Thattai, Mukund

2012-01-19

145

LuxS and quorum-sensing in Campylobacter  

PubMed Central

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

Plummer, Paul J.

2012-01-01

146

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.

Praneenararat, Thanit; Palmer, Andrew G.

2012-01-01

147

Quorum Sensing Activity of Enterobacter asburiae Isolated from Lettuce Leaves.  

PubMed

Bacterial communication or quorum sensing (QS) is achieved via sensing of QS signaling molecules consisting of oligopeptides in Gram-positive bacteria and N-acyl homoserine lactones (AHL) in most Gram-negative bacteria. In this study, Enterobacteriaceae isolates from Batavia lettuce were screened for AHL production. Enterobacter asburiae, identified by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) was found to produce short chain AHLs. High resolution triple quadrupole liquid chromatography mass spectrometry (LC/MS) analysis of the E. asburiae spent supernatant confirmed the production of N-butanoyl homoserine lactone (C4-HSL) and N-hexanoyl homoserine lactone (C6-HSL). To the best of our knowledge, this is the first report of AHL production by E. asburiae. PMID:24152877

Lau, Yin Yin; Sulaiman, Joanita; Chen, Jian Woon; Yin, Wai-Fong; Chan, Kok-Gan

2013-10-22

148

Quenching quorum-sensing-dependent bacterial infection by an N-acyl homoserine lactonase  

Microsoft Academic Search

Bacterial cells sense their population density through a sophisticated cell-cell communication system and trigger expression of particular genes when the density reaches a threshold. This type of gene regulation, which controls diverse biological functions including virulence, is known as quorum sensing. Quorum-sensing signals, such as acyl-homoserine lactones (AHLs), are the essential components of the communication system. AHLs regulate virulence gene

Yi-Hu Dong; Lian-Hui Wang; Jin-Ling Xu; Hai-Bao Zhang; Xi-Fen Zhang; Lian-Hui Zhang

2001-01-01

149

Cell-Cell Communication by Quorum Sensing and Dimension-Reduction  

Microsoft Academic Search

Abstract: The bioluminescence of the bacterium Vibrio fischeri depends strongly on the density of the cells. Thisphenomenon can be interpreted as the consequence of a communication system between the bacteria andis called quorum sensing. We introduce a modeling approach for the description of this quorum sensingsystem, including a detailed discussion of the regulatory network and its bistable behavior. Based on

Johannes Muller; Christina Kuttler; Burkhard A. Hense

2005-01-01

150

Modeling the quorum sensing regulatory network of human-pathogenic Pseudomonas aeruginosa.  

PubMed

The biochemical network underlying quorum sensing in human-pathogenic Pseudomonas aeruginosa is one of the best characterized. Mathematical modeling is required to untangle the complexity of its architecture and dynamics. We present a qualitative model of the P. aeruginosa quorum-sensing network including interactions between the las and rhl modules, the signaling molecule PQS and the regulatory proteins Mvfr and VfR. Simulations exemplify the model to reproduce natural network behavior and suggest quorum-sensing responses to pharmacological interference. PMID:15176867

Viretta, Alessandro Usseglio; Fussenegger, Martin

151

Novel quorum-sensing peptides mediating interspecies bacterial cell death.  

PubMed

ABSTRACT Escherichia coli mazEF is a toxin-antitoxin stress-induced module mediating cell death. It requires the quorum-sensing signal (QS) "extracellular death factor" (EDF), the penta-peptide NNWNN (EcEDF), enhancing the endoribonucleolytic activity of E. coli toxin MazF. Here we discovered that E. coli mazEF-mediated cell death could be triggered by QS peptides from the supernatants (SN) of the Gram-positive bacterium Bacillus subtilis and the Gram-negative bacterium Pseudomonas aeruginosa. In the SN of B. subtilis, we found one EDF, the hexapeptide RGQQNE, called BsEDF. In the SN of P. aeruginosa, we found three EDFs: the nonapeptide INEQTVVTK, called PaEDF-1, and two hexadecapeptides, VEVSDDGSGGNTSLSQ, called PaEDF-2, and APKLSDGAAAGYVTKA, called PaEDF-3. When added to a diluted E. coli cultures, each of these peptides acted as an interspecies EDF that triggered mazEF-mediated death. Furthermore, though their sequences are very different, each of these EDFs amplified the endoribonucleolytic activity of E. coli MazF, probably by interacting with different sites on E. coli MazF. Finally, we suggest that EDFs may become the basis for a new class of antibiotics that trigger death from outside the bacterial cells. IMPORTANCE Bacteria communicate with one another via quorum-sensing signal (QS) molecules. QS provides a mechanism for bacteria to monitor each other's presence and to modulate gene expression in response to population density. Previously, we added E. coli EDF (EcEDF), the peptide NNWNN, to this list of QS molecules. Here we extended the group of QS peptides to several additional different peptides. The new EDFs are produced by two other bacteria, Bacillus subtilis and Pseudomonas aeruginosa. Thus, in this study we established a "new family of EDFs." This family provides the first example of quorum-sensing molecules participating in interspecies bacterial cell death. Furthermore, each of these peptides provides the basis of a new class of antibiotics triggering death by acting from outside the cell. PMID:23736285

Kumar, Sathish; Kolodkin-Gal, Ilana; Engelberg-Kulka, Hanna

2013-06-04

152

Attenuation of Vibrio fischeri quorum sensing using rationally designed polymers.  

PubMed

A first attempt to attenuate the quorum sensing (QS) of a marine heterotroph microorganism, Vibrio fischeri , using signal molecule-sequestering polymers (SSPs) is presented. A set of rationally designed polymers with affinity toward a signal molecule of V. fischeri , N-(beta-ketocaproyl)-l-homoserine lactone (3-oxo-C6-AHL) was produced. It is reported that computationally designed polymers could sequester a signal molecule of V. fischeri and prevent QS-controlled phenotypes (in this case, bioluminescence) from being up-regulated. It was proven that the attenuation of bioluminescence of V. fischeri was due to sequestration of the signal molecule by specific polymers and not due to the toxicity of polymer or nonspecific depletion of nutrients. The ability to disrupt the bacterial communication using easy to synthesize and chemically inert polymers could provide a new concept for the development of pharmaceuticals and susceptible device coatings such as catheters. PMID:20230030

Piletska, Elena V; Stavroulakis, Georgios; Karim, Kal; Whitcombe, Michael J; Chianella, Iva; Sharma, Anant; Eboigbodin, Kevin E; Robinson, Gary K; Piletsky, Sergey A

2010-04-12

153

Modeling a synthetic multicellular clock: Repressilators coupled by quorum sensing  

NASA Astrophysics Data System (ADS)

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

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

2004-07-01

154

Crowd Synchrony and Quorum Sensing in Delay-Coupled Lasers  

NASA Astrophysics Data System (ADS)

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

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

2010-12-01

155

Studying bacterial quorum-sensing at the single cell level  

NASA Astrophysics Data System (ADS)

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

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

2010-03-01

156

Infection control by antibody disruption of bacterial quorum sensing signaling  

PubMed Central

Summary Quorum sensing (QS) is the process through which bacteria communicate utilizing small diffusible molecules termed autoinducers. It has been demonstrated that QS controls a plethora of microbial processes including the expression of virulence factors. Here, we report an immunopharmacotherapeutic approach for the attenuation of QS in the Gram-positive human pathogen Staphylococcus aureus. An anti-autoinducer monoclonal antibody, AP4-24 H11, was elicited against a rationally-designed hapten, and efficiently inhibited QS in vitro through the sequestration of the autoinducing peptide (AIP)-4 produced by S. aureus RN4850. Importantly, AP4-24H11 suppressed S. aureus pathogenicity in an abscess formation mouse model in vivo and provided complete protection against a lethal S. aureus challenge. These findings provide a strong foundation for further investigations of using immunopharmacotherapy for the treatment of bacterial infections in which QS controls the expression of virulence factors.

Park, Junguk; Jagasia, Reshma; Kaufmann, Gunnar F.; Mathison, John C.; Ruiz, Diana I.; Moss, Jason A.; Meijler, Michael M.; Ulevitch, Richard J.; Janda, Kim D.

2007-01-01

157

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.

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

2013-01-01

158

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

PubMed

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

2013-08-29

159

Microarray Analysis of Quorum-Sensing-Regulated Genes in Porphyromonas gingivalis  

Microsoft Academic Search

Quorum sensing is a phenomenon defined as gene regulation in response to cell density that regulates various functions in bacteria. The periodontopathogen Porphyromonas gingivalis possesses a luxS gene homo- logue that may encode a quorum-sensing system. In order to identify genes of P. gingivalis that are regulated by luxS, gene expression analysis was done using microarrays and RNA samples from

Lihui Yuan; Jeffrey D. Hillman; Ann Progulske-Fox

2005-01-01

160

Quorum Sensing Primes the Oxidative Stress Response in the Insect Endosymbiont, Sodalis glossinidius  

Microsoft Academic Search

BackgroundSodalis glossinidius, a maternally transmitted bacterial endosymbiont of tsetse flies (Glossina spp.), uses an acylated homoserine lactone (AHL)-based quorum sensing system to modulate gene expression in accordance with bacterial cell density. The S. glossinidius quorum sensing system relies on the function of two regulatory proteins; SogI (a LuxI homolog) synthesizes a signaling molecule, characterized as N-(3-oxohexanoyl) homoserine lactone (OHHL), and

Mauricio H. Pontes; Markus Babst; Robert Lochhead; Kelly Oakeson; Kari Smith; Colin Dale; Raphael H. Valdivia

2008-01-01

161

The RNPP family of quorum-sensing proteins in Gram-positive bacteria  

Microsoft Academic Search

Quorum sensing is one of several mechanisms that bacterial cells use to interact with each other and coordinate certain physiological\\u000a processes in response to cell density. This mechanism is mediated by extracellular signaling molecules; once a critical threshold\\u000a concentration has been reached, a target sensor kinase or response regulator is activated (or repressed), facilitating the\\u000a expression of quorum sensing-dependent genes.

Jorge Rocha-Estrada; Angel E. Aceves-Diez; Gabriel Guarneros; Mayra de la Torre

2010-01-01

162

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

Microsoft Academic Search

Novel molecular tools have been constructed which allow for in situ detection of N-acyl homoserine lactone (AHL)-mediated quorum sensing in Pseudomonas aeruginosa biofilms. The reporter responds to AHL activation of LasR by expression of an unstable version of the green-fluorescent protein (Gfp). Gfp- based reporter technology has been applied for non-destructive, single-cell- level detection of quorum sensing in laboratory-based P.

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

2002-01-01

163

N -Phenylacetanoyl- l Homoserine Lactones Can Strongly Antagonize or Superagonize Quorum Sensing in Vibrio fischeri  

Microsoft Academic Search

Bacteria monitor their population densities using low-molecular-weight ligands in a process known as quorum sensing. At sufficient cell densities, bacteria can change their mode of growth and behave as multicellular communities that play critical roles in both beneficial symbio- ses and the pathogenesis of infectious disease. The development of non-native ligands that can block quorum-sensing signals has emerged as a

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

2007-01-01

164

Extracellular noise-induced stochastic synchronization in heterogeneous quorum sensing network.  

PubMed

Quorum sensing is a bacterial mechanism used to synchronize the coordinated response of a microbial population. Because quorum sensing in Gram-negative bacteria depends on release and detection of a diffusible signaling molecule (autoinducer) among a multicellular group, it is considered a simple form of cell-cell communication for the purposes of mathematical analysis. Stochastic equation systems have provided a common approach to model biochemical or biophysical processes. Recently, the effect of noise to synchronize a specific homogeneous quorum sensing network was successfully modeled using a stochastic equation system with fixed parameters. The question remains of how to model quorum sensing networks in a general setting. To address this question, we first set a stochastic equation system as a general model for a heterogeneous quorum sensing network. Then, using two relevant biophysical characteristics of Gram-negative bacteria (the permeability of the cell membrane to the autoinducer and the symmetry of autoinducer diffusion) we construct the solution of the stochastic equation system at an abstract level. The solution indicates that stable synchronization of a quorum sensing network is robustly induced by an environment with a heterogenous distribution of extracellular and intracellular noise. The synchronization is independent of the initial state of the system and is solely the result of the connectivity of the cell network established through the effects of extracellular noise. PMID:17239902

Hong, Dawei; Saidel, William M; Man, Shushuang; Martin, Joseph V

2006-12-12

165

Mini-review: quorum sensing in the marine environment and its relationship to biofouling.  

PubMed

Bacterial quorum sensing (QS) is a cell-cell communication and gene regulatory mechanism that allows bacteria to coordinate swarming, biofilm formation, stress resistance, and production of toxins and secondary metabolites in response to threshold concentrations of QS signals that accumulate within a diffusion-limited environment. This review focuses on the role of QS signaling and QS inhibition in marine bacteria by compounds derived from marine organisms. Since the formation of a biofilm is considered to be an initial step in the development of fouling, direct and indirect effects of QS signals and inhibitors on the process of marine biofouling are discussed. Directions for future investigations and QS-related biotechnological applications are highlighted. PMID:19306145

Dobretsov, Sergey; Teplitski, Max; Paul, Valerie

2009-01-01

166

Significant immunomodulatory effects of Pseudomonas aeruginosa quorum-sensing signal molecules: possible link in human sepsis.  

PubMed

Pathogenic bacteria use quorum-sensing signal molecules to co-ordinate the expression of virulence genes. Animal-based studies have demonstrated the immunomodulatory effects of quorum-sensing signal molecules. In the present study, we have examined the impact of these molecules on normal human immune function in vitro and compared this with immune changes in patients with sepsis where quorum-sensing signal molecules were detected in the sera of patients. Quorum-sensing signal molecules inhibited normal dendritic cell and T-cell activation and proliferation, and down-regulated the expression of co-stimulatory molecules on dendritic cells; in MLDCRs (mixed lymphocyte dendritic cell reactions), secretion of IL (interleukin)-4 and IL-10 was enhanced, but TNF-alpha (tumour necrosis factor-alpha), IFN-gamma (interferon-gamma) and IL-6 was reduced. Quorum-sensing signal molecules induced apoptosis in dendritic cells and CD4(+) cells, but not CD8(+) cells. Dendritic cells from patients with sepsis were depleted and ex vivo showed defective expression of co-stimulatory molecules and dysfunctional stimulation of allogeneic T-lymphocytes. Enhanced apoptosis of dendritic cells and differential CD4(+) Th1/Th2 (T-helper 1/2) cell apoptotic rate, and modified Th1/Th2 cell cytokine profiles in MLDCRs were also demonstrated in patients with sepsis. The pattern of immunological changes in patients with sepsis mirrors the effects of quorum-sensing signal molecules on responses of immune cells from normal individuals in vitro, suggesting that quorum-sensing signal molecules should be investigated further as a cause of immune dysfunction in sepsis. PMID:18363571

Boontham, Pisake; Robins, Adrian; Chandran, Palanichamy; Pritchard, David; Cámara, Miguel; Williams, Paul; Chuthapisith, Suebwong; McKechnie, Alasdair; Rowlands, Brian J; Eremin, Oleg

2008-12-01

167

Inhibition of quorum sensing in the opportunistic pathogenic bacterium Chromobacterium violaceum by an extract from fruiting bodies of Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum (W.Curt.:Fr.) P. Karst. (higher Basidiomycetes).  

PubMed

Extracts of Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum, inhibited quorum sensing in Chromobacterium violaceum CV026. G. lucidum fruiting bodies were milled and extracted with ethyl acetate. The crude extract was dissolved in an appropriate concentration of methanol, sterilized by filtration through a 0.22-?m membrane filter, and added to Ch. Violaceum CV026 cultures, which were used as an indicator to monitor quorum sensing inhibition. Inhibitory activity was measured by quantifying violacein production using a microplate reader. Methanol-soluble compounds extracted from G. lucidum significantly inhibited quorum sensing-controlled behavior in Ch. Violaceum in a concentration-dependent manner. The results suggest that compounds in G. lucidum might be useful to control and handle detrimental infections caused by human, animal, and plant pathogens. Further studies are in progress in our lab to isolate the specific compounds from G. lucidum extract, evaluate them as quorum sensing inhibitors, and analyze their mechanism of action. PMID:22181844

Zhu, Hu; Liu, Wei; Tian, Baozhen; Liu, Huijun; Ning, Shoujiao

2011-01-01

168

Characterization of quorum sensing signals in coral-associated bacteria.  

PubMed

Marine environment habitats, such as the coral mucus layer, are abundant in nutrients and rich with diverse populations of microorganisms. Since interactions among microorganisms found in coral mucus can be either mutualistic or competitive, understanding quorum sensing-based acyl homoserine lactone (AHL) language may shed light on the interaction between coral-associated microbial communities in the native host. More than 100 bacterial isolates obtained from different coral species were screened for their ability to produce AHL. When screening the isolated coral bacteria for AHL induction activity using the reporter strains Escherichia coli K802NR-pSB1075 and Agrobacterium tumefaciens KYC55, we found that approximately 30% of the isolates tested positive. Thin layer chromatography separation of supernatant extracts revealed different AHL profiles, with detection of at least one active compound in the supernatant of those bacterial extracts being able to induce AHL activity in the two different bioreporter strains. The active extract of bacterial isolate 3AT 1-10-4 was subjected to further analysis by preparative thin layer chromatography and liquid chromatography tandem mass spectrometry. One of the compounds was found to correspond with N-(3-hydroxydecanoyl)-L-homoserine lactone. 16S rRNA gene sequencing of the isolates with positive AHL activity affiliated them with the Vibrio genus. Understanding the ecological role of AHL in the coral environment and its regulatory circuits in the coral holobiont-associated microbial community will further expand our knowledge of such interactions. PMID:21523464

Golberg, Karina; Eltzov, Evgeni; Shnit-Orland, Maya; Marks, Robert S; Kushmaro, Ariel

2011-04-27

169

Identification of quorum sensing-controlled genes in Burkholderia ambifaria  

PubMed Central

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.

Chapalain, Annelise; Vial, Ludovic; Laprade, Natacha; Dekimpe, Valerie; Perreault, Jonathan; Deziel, Eric

2013-01-01

170

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

2013-02-05

171

Novel Quorum-Sensing Peptides Mediating Interspecies Bacterial Cell Death  

PubMed Central

ABSTRACT Escherichia coli mazEF is a toxin-antitoxin stress-induced module mediating cell death. It requires the quorum-sensing signal (QS) “extracellular death factor” (EDF), the penta-peptide NNWNN (EcEDF), enhancing the endoribonucleolytic activity of E. coli toxin MazF. Here we discovered that E. coli mazEF-mediated cell death could be triggered by QS peptides from the supernatants (SN) of the Gram-positive bacterium Bacillus subtilis and the Gram-negative bacterium Pseudomonas aeruginosa. In the SN of B. subtilis, we found one EDF, the hexapeptide RGQQNE, called BsEDF. In the SN of P. aeruginosa, we found three EDFs: the nonapeptide INEQTVVTK, called PaEDF-1, and two hexadecapeptides, VEVSDDGSGGNTSLSQ, called PaEDF-2, and APKLSDGAAAGYVTKA, called PaEDF-3. When added to a diluted E. coli cultures, each of these peptides acted as an interspecies EDF that triggered mazEF-mediated death. Furthermore, though their sequences are very different, each of these EDFs amplified the endoribonucleolytic activity of E. coli MazF, probably by interacting with different sites on E. coli MazF. Finally, we suggest that EDFs may become the basis for a new class of antibiotics that trigger death from outside the bacterial cells.

Kumar, Sathish; Kolodkin-Gal, Ilana; Engelberg-Kulka, Hanna

2013-01-01

172

Social conflict drives the evolutionary divergence of quorum sensing  

PubMed Central

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

Eldar, Avigdor

2011-01-01

173

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

174

Virulence of Burkholderia mallei Quorum-Sensing Mutants  

PubMed Central

Many Proteobacteria use acyl-homoserine lactone-mediated quorum-sensing (QS) to activate specific sets of genes as a function of cell density. QS often controls the virulence of pathogenic species, and in fact a previous study indicated that QS was important for Burkholderia mallei mouse lung infections. To gain in-depth information on the role of QS in B. mallei virulence, we constructed and characterized a mutant of B. mallei strain GB8 that was unable to make acyl-homoserine lactones. The QS mutant showed virulence equal to that of its wild-type parent in an aerosol mouse infection model, and growth in macrophages was indistinguishable from that of the parent strain. Furthermore, we assessed the role of QS in B. mallei ATCC 23344 by constructing and characterizing a mutant strain producing AiiA, a lactonase enzyme that degrades acyl-homoserine lactones. Although acyl-homoserine lactone levels in cultures of this strain are very low, it showed full virulence. Contrary to the previous report, we conclude that QS is not required for acute B. mallei infections of mice. QS may be involved in some stage of chronic infections in the natural host of horses, or the QS genes may be remnants of the QS network in B. pseudomallei from which this host-adapted pathogen evolved.

Majerczyk, Charlotte; Kinman, Loren; Han, Tony; Bunt, Richard

2013-01-01

175

luxS Mutant Regulation: Quorum Sensing Impairment or Methylation Disorder?  

PubMed Central

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

Wang, Qian; He, Zhiyan; Hu, Yuejian; Jiang, Yuntao; Ma, Rui; Tang, Zisheng; Liang, Jingping; Liu, Zheng; Huang, Zhengwei

2012-01-01

176

Quorum-sensing antagonistic activities of azithromycin in Pseudomonas aeruginosa PAO1: a global approach.  

PubMed

The administration of macrolides such as azithromycin for chronic pulmonary infection of cystic fibrosis patients has been reported to be of benefit. Although the mechanisms of action remain obscure, anti-inflammatory effects as well as interference of the macrolide with Pseudomonas aeruginosa virulence factor production have been suggested to contribute to an improved clinical outcome. In this study we used a systematic approach and analyzed the impact of azithromycin on the global transcriptional pattern and the protein expression profile of P. aeruginosa PAO1 cultures versus those in untreated controls. The most remarkable result of this study is the finding that azithromycin exhibited extensive quorum-sensing antagonistic activities. In accordance with the inhibition of the quorum-sensing systems, virulence factor production was diminished and the oxidative stress response was impaired, whereas the type III secretion system was strongly induced. Moreover, P. aeruginosa motility was reduced, which probably accounts for the previously observed impaired biofilm formation capabilities of azithromycin-treated cultures. The interference of azithromycin with quorum-sensing-dependent virulence factor production, biofilm formation, and oxidative stress resistance in P. aeruginosa holds great promise for macrolide therapy in cystic fibrosis. Clearly quorum-sensing antagonist macrolides should be paid more attention in the management of chronic P. aeruginosa infections, and as quorum-sensing antagonists, macrolides might gain vital importance for more general application against chronic infections. PMID:16641435

Nalca, Yusuf; Jänsch, Lothar; Bredenbruch, Florian; Geffers, Robert; Buer, Jan; Häussler, Susanne

2006-05-01

177

Quorum-Sensing Antagonistic Activities of Azithromycin in Pseudomonas aeruginosa PAO1: a Global Approach  

PubMed Central

The administration of macrolides such as azithromycin for chronic pulmonary infection of cystic fibrosis patients has been reported to be of benefit. Although the mechanisms of action remain obscure, anti-inflammatory effects as well as interference of the macrolide with Pseudomonas aeruginosa virulence factor production have been suggested to contribute to an improved clinical outcome. In this study we used a systematic approach and analyzed the impact of azithromycin on the global transcriptional pattern and the protein expression profile of P. aeruginosa PAO1 cultures versus those in untreated controls. The most remarkable result of this study is the finding that azithromycin exhibited extensive quorum-sensing antagonistic activities. In accordance with the inhibition of the quorum-sensing systems, virulence factor production was diminished and the oxidative stress response was impaired, whereas the type III secretion system was strongly induced. Moreover, P. aeruginosa motility was reduced, which probably accounts for the previously observed impaired biofilm formation capabilities of azithromycin-treated cultures. The interference of azithromycin with quorum-sensing-dependent virulence factor production, biofilm formation, and oxidative stress resistance in P. aeruginosa holds great promise for macrolide therapy in cystic fibrosis. Clearly quorum-sensing antagonist macrolides should be paid more attention in the management of chronic P. aeruginosa infections, and as quorum-sensing antagonists, macrolides might gain vital importance for more general application against chronic infections.

Nalca, Yusuf; Jansch, Lothar; Bredenbruch, Florian; Geffers, Robert; Buer, Jan; Haussler, Susanne

2006-01-01

178

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

PubMed

Novel molecular tools have been constructed which allow for in situ detection of N-acyl homoserine lactone (AHL)-mediated quorum sensing in Pseudomonas aeruginosa biofilms. The reporter responds to AHL activation of LasR by expression of an unstable version of the green-fluorescent protein (Gfp). Gfp-based reporter technology has been applied for non-destructive, single-cell-level detection of quorum sensing in laboratory-based P. aeruginosa biofilms. It is reported that a synthetic halogenated furanone compound, which is a derivative of the secondary metabolites produced by the Australian macroalga Delisea pulchra, is capable of interfering with AHL-mediated quorum sensing in P. aeruginosa. It is demonstrated that the furanone compound specifically represses expression of a PlasB-gfp reporter fusion without affecting growth or protein synthesis. In addition, it reduces the production of important virulence factors, indicating a general effect on target genes of the las quorum sensing circuit. The furanone was applied to P. aeruginosa biofilms established in biofilm flow chambers. The Gfp-based analysis reveals that the compound penetrates microcolonies and blocks cell signalling and quorum sensing in most biofilm cells. The compound did not affect initial attachment to the abiotic substratum. It does, however, affect the architecture of the biofilm and enhances the process of bacterial detachment, leading to a loss of bacterial biomass from the substratum. PMID:11782502

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

2002-01-01

179

The Transcriptional Regulator VqmA Increases Expression of the Quorum-Sensing Activator HapR in Vibrio cholerae  

Microsoft Academic Search

Vibrio cholerae is the causative agent of the severe diarrheal disease cholera. A number of environmental stimuli regulate virulence gene expression in V. cholerae, including quorum-sensing signals. At high cell densities, quorum sensing in V. cholerae invokes a series of signal transduction pathways in order to activate the expression of the master regulator HapR, which then represses the virulence regulon

Zhi Liu; Ansel Hsiao; Adam Joelsson; Jun Zhu

2006-01-01

180

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

PubMed

Quorum sensing is a mechanism of cell-to-cell communication that allows bacteria to coordinately regulate gene expression in response to changes in cell-population density. At the core of the Vibrio cholerae quorum-sensing signal transduction pathway reside four homologous small RNAs (sRNAs), named the quorum regulatory RNAs 1-4 (Qrr1-4). The four Qrr sRNAs are functionally redundant. That is, expression of any one of them is sufficient for wild-type quorum-sensing behaviour. Here, we show that the combined action of two feedback loops, one involving the sRNA-activator LuxO and one involving the sRNA-target HapR, promotes gene dosage compensation between the four qrr genes. Gene dosage compensation adjusts the total Qrr1-4 sRNA pool and provides the molecular mechanism underlying sRNA redundancy. The dosage compensation mechanism is exquisitely sensitive to small perturbations in Qrr levels. Precisely maintained Qrr levels are required to direct the proper timing and correct patterns of expression of quorum-sensing-regulated target genes. PMID:19165149

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

2009-01-22

181

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

PubMed

The bacterium Brenneria salicis is the causal agent of watermark disease in willow. This work shows the importance of in situ studies and high-resolution separation of biological samples with ultrahigh performance liquid chromatography combined with ion trap mass spectrometry to unambiguously identify molecular compounds associated with this disease. Approximately 40 oligolignols accumulated in wood sap of watermark diseased willow, and are indicative for degradation of the xylem cell wall, of which 15 were structurally assigned based on an earlier study. Many bacteria are known to produce and release quorum sensing signal molecules that switch on the expression of specific, sometimes pathogenic functions. Two quorum sensing signal molecules, N-(3-oxohexanoyl)-l-homoserine lactone and N-(hexanoyl)-l-homoserine lactone, were present in 4/1 ratios in diseased wood and in high-density in vitro cultures of B. salicis at 0.13-1.2 microM concentrations, and absent in healthy wood and in low-density in vitro cultures of B. salicis. Although it is not a proof, it can be an indication for involvement of quorum sensing in B. salicis pathogenesis. Cyclic dipeptides were present at high concentrations in high-density in vitro cultures of B. salicis, but not in situ, and were found not to be involved in quorum sensing signaling, therefore, the attribution of quorum signal properties to cyclic dipeptides isolated from in vitro cultures of pathogenic bacteria should be reconsidered. PMID:18675599

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

2008-07-17

182

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

183

Mathematical modelling of therapies targeted at bacterial quorum sensing.  

PubMed

Bacteria commonly use diffusible signal molecules to synchronise their behaviour by facilitating population dependent co-ordination. This cell-to-cell signalling mechanism is known as quorum sensing (QS) and provides a way of ensuring that certain genes are 'switched on' only when a certain signal concentration (typically corresponding to a large population density) has been reached. In this paper we focus on the QS system of the human pathogen Pseudomonas aeruginosa, which employs a complex hierarchy of QS signalling systems, which regulate the formation of multiple exoproducts, swarming and biofilm differentiation. In P. aeruginosa, the signal molecules are N-acylated homoserine lactones (AHLs; e.g., N-(3-oxododecanoyl)-homoserine lactone [3-oxo-C12-HSL]), which bind to transcriptional regulator proteins (LasR in the case of 3-oxo-C12-HSL) to activate the expression of target genes including lasI, which codes for the 3-oxo-C12-HSL synthase. Since the virulence of P. aeruginosa is controlled by QS, agents (QSBs) designed to block this cell-to-cell communication have potential as novel antibacterials. By drawing on existing models for the reaction kinetics of this system, we model a growing population subject to treatment with two kinds of QSB, together with a conventional antibiotic. The first kind of QSB is assumed to act by diffusing through the cell membrane and then destabilising/sequestering LasR, while the second kind remains outside the cell and degrades the AHL signal molecule itself. Numerical and mathematical analysis of the resulting systems of ordinary differential equations reveals in particular that, while a sufficiently high dose of QSB is, in all cases considered, able to reduce the AHL concentration (and hence virulence) to a negligible level, the qualitative response to treatment is sensitive to parameter values. PMID:15494175

Anguige, K; King, J R; Ward, J P; Williams, P

2004-11-01

184

Negative regulation of bacterial quorum sensing tunes public goods cooperation.  

PubMed

Bacterial quorum sensing (QS) often coordinates the expression of other, generally more costly public goods involved in virulence and nutrient acquisition. In many Proteobacteria, the basic QS circuitry consists of a synthase that produces a diffusible acyl-homoserine lactone and a cognate receptor that activates public goods expression. In some species, the circuitry also contains negative regulators that have the potential to modulate the timing and magnitude of activation. In this study, we experimentally investigated the contribution of this regulatory function to the evolutionary stability of public goods cooperation in the opportunistic pathogen Pseudomonas aeruginosa. We compared fitness and public goods expression rates of strains lacking either qteE or qscR, each encoding a distinct negative regulator, with those of the wild-type parent and a signal-blind receptor mutant under defined growth conditions. We found that (1) qteE and qscR mutations behave virtually identically and have a stronger effect on the magnitude than on the timing of expression, (2) high expression in qteE and qscR mutants imposes a metabolic burden under nutrient conditions that advance induction and (3) high expression in qteE and qscR mutants increases population growth when QS is required, but also permits invasion by both wild-type and receptor mutant strains. Our data indicate that negative regulation of QS balances the costs and benefits of public goods by attenuating expression after transition to the induced state. As the cells cannot accurately assess the amount of cooperation needed, such bet-hedging would be advantageous in changing parasitic and nonparasitic environments. PMID:23823496

Gupta, Rashmi; Schuster, Martin

2013-07-04

185

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.

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

2013-01-01

186

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

2012-11-05

187

A model for signal transduction during quorum sensing in Vibrio harveyi  

NASA Astrophysics Data System (ADS)

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

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

2009-12-01

188

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

NASA Astrophysics Data System (ADS)

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

Sakaguchi, Hidetsugu; Maeyama, Satomi

2013-02-01

189

Malyngolide from the cyanobacterium Lyngbya majuscula interferes with quorum sensing circuitry.  

PubMed

Extracts of several cyanobacterial species collected from different marine and estuarine locations predominately in Florida (USA), with one sample each from Belize and Oman, were screened for their ability to disrupt quorum sensing (QS) in the reporter strain Chromobacterium violaceum CV017. Inhibitory activities were detected in the ethyl acetate?:?methanol (1:1) extracts of several Lyngbya spp., and extracts of Lyngbya majuscula contained the strongest QS inhibitory activities. Extracts of L. majuscula from the Indian River Lagoon, FL, USA, were further purified by bioassay-guided fractionation. The antibiotic malyngolide (MAL) was identified as a QS inhibitor. Activity of MAL was investigated using N-acyl homoserine lactone (AHL) reporters based on the LasR receptor of Pseudomonas aeruginosa. MAL at concentrations ranging from 3.57?µM to 57?µM (EC50 ?=?12.2?±?1.6?µM) inhibited responses of the LasR reporters without affecting bacterial growth. MAL inhibited (EC50 ?=? 10.6?±?1.8?µM) Las QS-dependent production of elastase by P. aeruginosa PAO1. We propose that this QS inhibitor plays a role in controlling interactions of heterotrophic bacteria associated with the cyanobacterium L. majuscula. PMID:23766278

Dobretsov, Sergey; Teplitski, Max; Alagely, Ali; Gunasekera, Sarath P; Paul, Valerie J

2010-12-01

190

Methylthioinosine Phosphorylase from Pseudomonas aeruginosa. Structure and Annotation of a Novel Enzyme in Quorum Sensing  

PubMed Central

The PA3004 gene of Pseudomonas aeruginosa PAO1 was originally annotated as a 5’-methylthioadenosine phosphorylase (MTAP). However, the PA3004 encoded protein uses 5’-methylthioinosine (MTI) as a preferred substrate and represents the only known example of a specific MTI phosphorylase (MTIP). MTIP does not utilize 5’-methylthioadenosine (MTA). Inosine is a weak substrate with a kcat/Km value 290-fold less than MTI and is the second best substrate identified. The crystal structure of P. aeruginosa MTIP (PaMTIP) in complex with hypoxanthine was determined to 2.8 Å resolution and revealed a three-fold symmetric homotrimer. The methylthioribose and phosphate binding regions of PaMTIP are similar to MTAPs, and the purine binding region is similar to that of purine nucleoside phosphorylases (PNPs). The catabolism of MTA in P. aeruginosa involves deamination to MTI and phosphorolysis to hypoxanthine (MTA ? MTI ? hypoxanthine). This pathway also exists in Plasmodium falciparum, where the purine nucleoside phosphorylase (PfPNP) acts on both inosine and MTI. Three tight-binding transition state analogue inhibitors of PaMTIP are identified with dissociation constants in the picomolar range. Inhibitor specificity suggests an early dissociative transition state for PaMTIP. Quorum sensing molecules are associated with MTA metabolism in bacterial pathogens suggesting PaMTIP as a potential therapeutic target.

Guan, Rong; Ho, Meng-Chiao; Almo, Steven C.; Schramm, Vern L.

2011-01-01

191

Iron-Depletion prevents biofilm formation in Pseudomonas Aeruginosa through twitching mobility and quorum sensing  

PubMed Central

Influence of iron-depletion on twitching motility and quorum sensing (QS) system in P. aeruginosa was evaluated. The results demonstrated iron-depletion can retard biofilm formation and increase the twitching motility and expression of QS-related genes, suggesting a potential interaction between twitching motility and QS system in P. aeruginosa biofilm formation.

Cai, Yun; Wang, Rui; An, Mao-Mao; Liang, Bei-Bei

2010-01-01

192

Genome Sequence of the Quorum-Sensing-Signal-Producing Nonpathogen Agrobacterium tumefaciens Strain P4  

PubMed Central

Agrobacterium tumefaciens P4 is a quorum-sensing-signal-producing bacterium that has been isolated from the tobacco rhizosphere. This strain belongs to genomospecies 1 of the A. tumefaciens complex; it is avirulent on various putative host plants, devoid of the Ti plasmid, and contains a luxI homolog on the At plasmid.

Mondy, Samuel; Lalouche, Ouaghlis; Dessaux, Yves

2013-01-01

193

Chitinolytic Activity in Chromobacterium violaceum: Substrate Analysis and Regulation by Quorum Sensing  

Microsoft Academic Search

Quorum sensing control mediated by N-acyl homoserine lactone (AHL) signaling molecules has been es- tablished as a key feature of the regulation of exoenzyme production in many gram-negative bacteria. In Chromobacterium violaceum ATCC 31532 a number of phenotypic characteristics, including production of the purple pigment violacein, hydrogen cyanide, antibiotics, and exoproteases are known to be regulated by the endogenous AHL

LEONID S. CHERNIN; MICHAEL K. WINSON; JACQUELYN M. THOMPSON; SHOSHAN HARAN; BARRIE W. BYCROFT; ILAN CHET; PAUL WILLIAMS; GORDON S. A. B. STEWART; Otto Warburg

1998-01-01

194

Biofilm Formation and Sloughing in Serratia marcescens Are Controlled by Quorum Sensing and Nutrient Cues  

Microsoft Academic Search

We describe here a role for quorum sensing in the detachment, or sloughing, of Serratia marcescens filamentous biofilms, and we show that nutrient conditions affect the biofilm morphotype. Under reduced carbon or nitrogen conditions, S. marcescens formed a classical biofilm consisting of microcolonies. The filamentous biofilm could be converted to a microcolony-type biofilm by switching the medium after estab- lishment

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

2005-01-01

195

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

196

Testing the Efficacy of Panax ginseng Extract as a Novel Anti-Quorum Sensing Agent  

Microsoft Academic Search

Quorum sensing (QS) is the phenomenon by which microorganisms regulate gene expression in response to cell-population density. These microorganisms synthesize and secrete small molecules known as autoinducers that increase in concentration as a function of cell density. Once the cell detects the minimal threshold concentration of an autoinducer, the gene expression is altered accordingly. Although the cellular circuitry responding to

Christian Villaseca

2009-01-01

197

Control of Gram-Negative Bacterial Quorum Sensing with CyclodextrinImmobilized Cellulose Ether Gel  

Microsoft Academic Search

Inclusion complex between cyclodextrins (CDs) and bacterial signal molecules is responsible for inhibitory effects on quorum sensing (QS). Since many bacteria have QS system for controlling gene expression in response to cell population density by means of signal molecules, an intercept of the QS signal onto the CDs can be a general method to control transcription of the QS-regulated genes.

Norihiro Kato; Tomohiro Morohoshi; Tomoyo Nozawa; Hitomi Matsumoto; Tsukasa Ikeda

2006-01-01

198

Genome Sequence of the Quorum-Sensing-Signal-Producing Nonpathogen Agrobacterium tumefaciens Strain P4.  

PubMed

Agrobacterium tumefaciens P4 is a quorum-sensing-signal-producing bacterium that has been isolated from the tobacco rhizosphere. This strain belongs to genomospecies 1 of the A. tumefaciens complex; it is avirulent on various putative host plants, devoid of the Ti plasmid, and contains a luxI homolog on the At plasmid. PMID:24092790

Mondy, Samuel; Lalouche, Ouaghlis; Dessaux, Yves; Faure, Denis

2013-10-03

199

Microarray Analysis of Pseudomonas aeruginosa Quorum-Sensing Regulons: Effects of Growth Phase and Environment  

Microsoft Academic Search

Bacterial communication via quorum sensing (QS) has been reported to be important in the production of virulence factors, antibiotic sensitivity, and biofilm development. Two QS systems, known as the las and rhl systems, have been identified previously in the opportunistic pathogen Pseudomonas aeruginosa. High-density oligonucleotide microarrays for the P. aeruginosa PAO1 genome were used to investigate global gene expression patterns

Victoria E. Wagner; Daniel Bushnell; Luciano Passador; Andrew I. Brooks; Barbara H. Iglewski

2003-01-01

200

Individuals in the crowd: studying bacterial quorum-sensing at the single-cell level  

Microsoft Academic Search

Like many bacterial species, the marine bacterium Vibrio fischeri can detect its own population density through a quorum sensing (QS) mechanism. The bacterium releases a small molecule signal -- the autoinducer (AI) -- into its environment: high AI concentration indicates high population density and triggers a genetic switch that, in V.fischeri, leads to bioluminescence. Although the QS behavior of bulk

Pablo Delfino Perez; Jonathan Young; Elaine L. Johnson; Stephen J. Hagen

2009-01-01

201

Quorum-sensing signals in the microbial community of the cabbage white butterfly larval midgut  

Microsoft Academic Search

The overall goal of this study was to examine the role of quorum-sensing (QS) signals in a multispecies microbial community. Toward this aim, we studied QS signals produced by an indigenous member and an invading pathogen of the microbial community of the cabbage white butterfly (CWB) larval midgut (Pieris rapae). As an initial step, we characterized the QS system in

Bradley R Borlee; Grant D Geske; Courtney J Robinson; Helen E Blackwell; Jo Handelsman

2008-01-01

202

Quorum-sensing-directed protein expression in Serratia proteamaculans B5a  

Microsoft Academic Search

N-Acyl-L-homoserine-lactone-producing Serratia species are frequently encountered in spoiling foods of vegetable and protein origin. The role of quorum sensing in the food spoiling properties of these bacteria is currently being investigated. A set of luxR luxI homologous genes encoding a putative quorum sensor was identified in the N-(3-oxo-hexanoyl)-L-homoserine lactone (3-oxo-C6- HSL)-producing Serratia proteamaculans strain B5a. The 3-oxo-C6-HSL synthase SprI showed

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

2003-01-01

203

Heterologous overexpression of quorum-sensing regulators to study cell-density-dependent phenotypes in a symbiotic plant bacterium Mesorhizobium huakuii  

Microsoft Academic Search

Quorum-sensing is widespread among many prokaryotic lineages. In order to investigate quorum regulation in the plant bacterium Mesorhizobium huakuii which produces an N-acyl homoserine lactone (AHL) quorum signal, the Agrobacterium quorum-sensing regulator TraR was heterologously expressed in this bacterium. The resulting strains showed reduced AHL production in the supernatant compared to wild-type, but similar intracellular levels of AHLs were detected,

Hui Wang; Zengtao Zhong; Tao Cai; Shunpeng Li; Jun Zhu

2004-01-01

204

Quorum-sensing regulators control virulence gene expression in Vibrio cholerae  

Microsoft Academic Search

The production of virulence factors including cholera toxin and the toxin-coregulated pilus in the human pathogen Vibrio cholerae is strongly influenced by environmental conditions. The well-characterized ToxR signal transduction cascade is responsible for sensing and integrating the environmental information and controlling the virulence regulon. We show here that, in addition to the known components of the ToxR signaling circuit, quorum-sensing

Jun Zhu; Melissa B. Miller; Russell E. Vance; Michelle Dziejman; John J. Mekalanos

2002-01-01

205

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

PubMed

In enteric bacteria, the kinase LsrK catalyzes the phosphorylation of the C5-hydroxyl group in the linear form of 4,5-dihydroxy-2,3-pentanedione (DPD), the precursor of the type II bacterial quorum sensing molecule (AI-2). This phosphorylation is required for AI-2 sequestration in the cytoplasm and subsequent derepression of AI-2-related genes necessary for quorum development. While LsrK is a critical enzyme within the DPD quorum sensing relay system, kinetic details of this kinase have yet to be reported. A continuous UV-vis spectrophotometric assay was developed that allowed steady-state kinetic analysis of LsrK to be undertaken with the substrates ATP and DPD. The data was most consistent with a rapid equilibrium ordered mechanism with ATP binding first: kcat (7.4 ± 0.6 s(-1)), Km,ATP (150 ± 30 ?M) and Km(app),DPD (1.0 ± 0.2 mM). The assay also allowed a DPD substrate profile to be conducted, which provided an unexpected biochemical disconnect between the previous agonist/antagonist cell-based reporter assay and the LsrK assay presented herein. Together these findings raise the importance of LsrK and lay the foundation not only for further understanding of this enzyme and its critical biological role but also for the rational design of regulatory molecules targeting AI-2 quorum sensing in pathogenic bacteria. PMID:23672516

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

2013-05-16

206

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

PubMed Central

SUMMARY 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, Matthew B.; Federle, Michael J.; Pompeani, Audra J.; Kelly, Robert C.; Swem, Danielle L.; Jeffrey, Philip D.; Bassler, Bonnie L.; Hughson, Frederick M.

2012-01-01

207

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

208

A Nitric Oxide-Responsive Quorum Sensing Circuit in Vibrio harveyi Regulates Flagella Production and Biofilm Formation  

PubMed Central

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

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

2013-01-01

209

Ajoene, a sulfur-rich molecule from garlic, inhibits genes controlled by quorum sensing.  

PubMed

In relation to emerging multiresistant bacteria, development of antimicrobials and new treatment strategies of infections should be expected to become a high-priority research area. Quorum sensing (QS), a communication system used by pathogenic bacteria like Pseudomonas aeruginosa to synchronize the expression of specific genes involved in pathogenicity, is a possible drug target. Previous in vitro and in vivo studies revealed a significant inhibition of P. aeruginosa QS by crude garlic extract. By bioassay-guided fractionation of garlic extracts, we determined the primary QS inhibitor present in garlic to be ajoene, a sulfur-containing compound with potential as an antipathogenic drug. By comprehensive in vitro and in vivo studies, the effect of synthetic ajoene toward P. aeruginosa was elucidated. DNA microarray studies of ajoene-treated P. aeruginosa cultures revealed a concentration-dependent attenuation of a few but central QS-controlled virulence factors, including rhamnolipid. Furthermore, ajoene treatment of in vitro biofilms demonstrated a clear synergistic, antimicrobial effect with tobramycin on biofilm killing and a cease in lytic necrosis of polymorphonuclear leukocytes. Furthermore, in a mouse model of pulmonary infection, a significant clearing of infecting P. aeruginosa was detected in ajoene-treated mice compared to a nontreated control group. This study adds to the list of examples demonstrating the potential of QS-interfering compounds in the treatment of bacterial infections. PMID:22314537

Jakobsen, Tim Holm; van Gennip, Maria; Phipps, Richard Kerry; Shanmugham, Meenakshi Sundaram; Christensen, Louise Dahl; Alhede, Morten; Skindersoe, Mette Eline; Rasmussen, Thomas Bovbjerg; Friedrich, Karlheinz; Uthe, Friedrich; Jensen, Peter Østrup; Moser, Claus; Nielsen, Kristian Fog; Eberl, Leo; Larsen, Thomas Ostenfeld; Tanner, David; Høiby, Niels; Bjarnsholt, Thomas; Givskov, Michael

2012-02-06

210

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.

McInnis, Christine E.; Blackwell, Helen E.

2011-01-01

211

Ajoene, a Sulfur-Rich Molecule from Garlic, Inhibits Genes Controlled by Quorum Sensing  

PubMed Central

In relation to emerging multiresistant bacteria, development of antimicrobials and new treatment strategies of infections should be expected to become a high-priority research area. Quorum sensing (QS), a communication system used by pathogenic bacteria like Pseudomonas aeruginosa to synchronize the expression of specific genes involved in pathogenicity, is a possible drug target. Previous in vitro and in vivo studies revealed a significant inhibition of P. aeruginosa QS by crude garlic extract. By bioassay-guided fractionation of garlic extracts, we determined the primary QS inhibitor present in garlic to be ajoene, a sulfur-containing compound with potential as an antipathogenic drug. By comprehensive in vitro and in vivo studies, the effect of synthetic ajoene toward P. aeruginosa was elucidated. DNA microarray studies of ajoene-treated P. aeruginosa cultures revealed a concentration-dependent attenuation of a few but central QS-controlled virulence factors, including rhamnolipid. Furthermore, ajoene treatment of in vitro biofilms demonstrated a clear synergistic, antimicrobial effect with tobramycin on biofilm killing and a cease in lytic necrosis of polymorphonuclear leukocytes. Furthermore, in a mouse model of pulmonary infection, a significant clearing of infecting P. aeruginosa was detected in ajoene-treated mice compared to a nontreated control group. This study adds to the list of examples demonstrating the potential of QS-interfering compounds in the treatment of bacterial infections.

Jakobsen, Tim Holm; van Gennip, Maria; Phipps, Richard Kerry; Shanmugham, Meenakshi Sundaram; Christensen, Louise Dahl; Alhede, Morten; Skindersoe, Mette Eline; Rasmussen, Thomas Bovbjerg; Friedrich, Karlheinz; Uthe, Friedrich; Jensen, Peter ?strup; Moser, Claus; Nielsen, Kristian Fog; Eberl, Leo; Larsen, Thomas Ostenfeld; Tanner, David; H?iby, Niels; Bjarnsholt, Thomas

2012-01-01

212

Inhibition of bacterial quorum sensing-regulated behaviors by Tremella fuciformis extract.  

PubMed

Quorum sensing (QS), or the control of gene expression in response to cell density, is used by both gram-negative and gram-positive bacteria to regulate a variety of physiological functions. Increasing evidence implies that certain eukaryotes produce QS-inhibitory compounds. In this work, we tested Tremella fuciformis for their ability to inhibit QS-regulated behaviors. T. fuciformis fruiting bodies were dried and extracted using 75% (v/v) aqueous methanol. The crude extract was redissolved in appropriate concentrations of dimethyl sulfoxide (DMSO), sterilized by filtration through a 0.45-microm membrane filter and added to Chromobacterium violaceum CV026 cultures, which was used to monitor QS inhibition. Inhibitory activity was measured by quantifying violacein production using a microplate reader. The results have revealed that the DMSO-soluble compounds extracted from T. fuciformis could inhibit violacein production, a QS-regulated behavior in C. violaceum. The results suggest an attractive tool to control and handle detrimental infections caused by human, animal, and plant pathogens. Further studies are required to isolate specific substances from T. fuciformis extract acting as QS inhibitors. PMID:18661179

Zhu, H; Sun, S J

2008-07-26

213

AiiA quorum-sensing quenching controls proteolytic activity and biofilm formation by Enterobacter cloacae.  

PubMed

The aim of this work was to evaluate a quorum-quenching approach to identify functions regulated by quorum sensing in Enterobacter cloacae. We employed an aiiA transconjugant strain of E. cloacae that synthesizes a lactonase enzyme that hydrolyzes N-acyl homoserine lactone signaling molecules to compare bacterial phenotypes in the presence and absence of quorum signals. The aiiA-expressing strain displayed increased proteolytic activity and intensity of a milk-clotting reaction when compared to the wild-type strain. Although both strains growing on polystyrene plates in rich media and a minimal medium of salts formed biofilms, the wild-type strain exhibited a higher number of adhered cells. On the surface of stainless steel coupons that were submerged in culture media, the number of adhered cells of the wild type contained up to one log more cells compared with the aiiA transconjugant. However, after 48 h of incubation, there was no significant difference between the strains. The results demonstrated that the quorum-sensing system negatively regulates proteolytic activity and is likely involved in the early steps of biofilm formation by E. cloacae 067. PMID:22986817

dos Reis Ponce, Adriana; Martins, Maurilio Lopes; de Araujo, Elza Fernandes; Mantovani, Hilário Cuquetto; Vanetti, Maria Cristina Dantas

2012-09-18

214

The quorum-sensing system in a plant bacterium Mesorhizobium huakuii affects growth rate and symbiotic nodulation  

Microsoft Academic Search

Mesorhizobium huakuii is a free-living bacterium which is capable of establishing a specific symbiotic relationship with Astragalus sinicus, an important winter green manure widely used in Eastern Asia, allowing for nitrogen fixing during this process. Previous studies demonstrate that M.?huakuii produces quorum-sensing molecules at high cell density and quorum sensing plays a role in biofilm formations. In this study, we

Yijing Gao; Zengtao Zhong; Kejing Sun; Hui Wang; Jun Zhu

2006-01-01

215

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

Microsoft Academic Search

BACKGROUND: Burkholderia cenocepacia belongs to a group of closely related organisms called the B. cepacia complex (Bcc) which are important opportunistic human pathogens. B. cenocepacia utilizes a mechanism of cell-cell communication called quorum sensing to control gene expression including genes involved in virulence. The B. cenocepacia quorum sensing network includes the CepIR and CciIR regulatory systems. RESULTS: Global gene expression

Eoin P O'Grady; Duber F Viteri; Rebecca J Malott; Pamela A Sokol

2009-01-01

216

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

Microsoft Academic Search

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

Hong Wu; Zhijun Song; Michael Givskov; Gerd Doring; Dieter Worlitzsch; Kalai Mathee; Jørgen Rygaard; Niels Høiby

2001-01-01

217

The Small RNA Chaperone Hfq and Multiple Small RNAs Control Quorum Sensing in Vibrio harveyi and Vibrio cholerae  

Microsoft Academic Search

Quorum-sensing bacteria communicate with extracellular signal molecules called autoinducers. This process allows community-wide synchronization of gene expression. A screen for additional components of the Vibrio harveyi and Vibrio cholerae quorum-sensing circuits revealed the protein Hfq. Hfq mediates interactions between small, regulatory RNAs (sRNAs) and specific messenger RNA (mRNA) targets. These interactions typically alter the stability of the target transcripts. We

Derrick H. Lenz; Kenny C. Mok; Brendan N. Lilley; Rahul V. Kulkarni; Ned S. Wingreen; Bonnie L. Bassler

2004-01-01

218

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

PubMed

Constructing robust gene circuits is a fundamental work for synthetic biology. Bacteria with suicide gene circuit based on quorum-sensing will kill themselves in a controllable pattern upon certain cell density. In the media of different IPTG inducer concentration, we observed the growth and suicidal behavior of the Escherichia coli. Top10F' with such gene circuit, screened the mutants and determined their mutated loci. The results show that, with higher IPTG concentration, the more wild type bacteria were killed; as well the mutants emerged earlier and spread over the population more quickly. The sequence of plasmids in those mutants revealed that a transposon inserted into the luxR gene and therefore disrupted Quorum-Sensing of these individuals. Furthermore, the insertion sequence of the plasmid can solely result in the mutants escaping from suicide. PMID:24063233

Gao, Qi; Zheng, Xuesong

2013-06-01

219

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.

Gelencser, Zsolt; Galbats, Borisz; Gonzalez, Juan F.; Choudhary, K. Sonal; Hudaiberdiev, Sanjarbek; Venturi, Vittorio; Pongor, Sandor

2012-01-01

220

Dynamical quorum-sensing in oscillators coupled through an external medium  

NASA Astrophysics Data System (ADS)

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

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

2012-11-01

221

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

PubMed

p-Nitrophenylglycerol (PNPG) effectively inhibits swarming of the enterobacterium Proteus mirabilis. The underlying mechanism of inhibition is unclear. We have now found that both PNPG also inhibits motility and swarming in another enterobacterium, Serratia marcescens. While the peak promoter activities of the flagellar master operon (flhDCSm), the flagellin structural gene (hagSm) and the nuclease gene (nucASm) in S. marcescens increased with increasing PNPG concentration, the expression of these genes was delayed in accordance with the reduced growth rate. As the quorum-sensing system is involved in the regulation of swarming in S. marcescens, we also examined the effect of PNPG on the production of quorum-sensing signal molecules and found that their expression was delayed with a reduced level. PNPG, therefore, had a pleiotropic effect on all aspects of S. marcescens physiology relating to swarming. The underlying molecular mechanism remains to be elucidated. PMID:15060680

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

2004-02-01

222

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

PubMed Central

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

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

2009-01-01

223

A negative feedback loop involving small RNAs accelerates Vibrio cholerae's transition out of quorum-sensing mode  

PubMed Central

Quorum sensing is a cell-to-cell communication process that allows bacteria to measure their population numbers and to synchronously alter gene expression in response to changes in cell population density. At the core of the Vibrio cholerae quorum-sensing signal transduction pathway lie four redundant small RNAs (sRNAs), named the Quorum Regulatory RNAs (Qrr1–4). Expression of qrr1–4 is cell population density-dependent due to a requirement for the quorum-sensing controlled phosphorylated response regulator LuxO-P, which is abundant only at low cell population density. When expressed, Qrr1–4 repress translation of HapR, the “master” quorum-sensing transcription factor. Here we show a negative feedback loop in which HapR activates transcription of the qrr genes, which indirectly leads to hapR repression. Efficient feedback activation of the qrr genes requires the simultaneous presence of LuxO-P (present only at low cell population density) and HapR (present only at high cell population density). For this reason, the feedback loop does not influence quorum sensing at steady-state low or high cell population density. However, LuxO-P and HapR are simultaneously present immediately following the switch from high to low cell density conditions. In this state, the HapR feedback loop dramatically accelerates V. cholerae’s transition from the high to the low cell density mode.

Svenningsen, Sine L.; Waters, Christopher M.; Bassler, Bonnie L.

2008-01-01

224

Role of Quorum Sensing and Antimicrobial Component Production by Serratia plymuthica in Formation of Biofilms, Including Mixed Biofilms with Escherichia coli  

Microsoft Academic Search

We have previously characterized the N-acyl-L-homoserine lactone-based quorum-sensing system of the biofilm isolate Serratia plymuthica RVH1. Here we investigated the role of quorum sensing and of quorum- sensing-dependent production of an antimicrobial compound (AC) on biofilm formation by RVH1 and on the cocultivation of RVH1 and Escherichia coli in planktonic cultures or in biofilms. Biofilm formation of S. plymuthica was

Pieter Moons; Rob Van Houdt; Abram Aertsen; Kristof Vanoirbeek; Yves Engelborghs; Chris W. Michiels

2006-01-01

225

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

226

Quenching of acyl-homoserine lactone-dependent quorum sensing by enzymatic disruption of signal molecules  

Microsoft Academic Search

Many Gram-positive and Gram-negative bacteria communicate using small diffusible signal mol - ecules called autoinducers. This process, known as quorum sensing (QS), links cell density to the expression of genes as diverse as those associated with virulence factors production of plant and animal pathogens, bioluminescence, antibiotic production, sporulation or biofilm formation. In Gram-negative bacteria, this communication is mainly mediated by

Robert Czajkowski; Sylwia Jafra

2009-01-01

227

StructureActivity Analysis of Quorum-Sensing Signaling Peptides from Streptococcus mutans  

Microsoft Academic Search

Streptococcus mutans secretes and utilizes a 21-amino-acid signaling peptide pheromone to initiate quorum sensing for genetic competence, biofilm formation, stress responses, and bacteriocin production. In this study, we designed and synthesized a series of truncated peptides and peptides with amino acid substitutions to investigate their structure-activity relationships based on the three-dimensional structures of S. mutans wild-type signaling peptide UA159sp and

Raymond T. Syvitski; Xiao-Lin Tian; Kamal Sampara; Alan Salman; Song F. Lee; David L. Jakeman; Yung-Hua Li

2007-01-01

228

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

Microsoft Academic Search

To utilize biofilms for chemical transformations in biorefineries they need to be controlled and replaced. Previously, we engineered the global regulator Hha and cyclic diguanylate-binding BdcA to create proteins that enable biofilm dispersal. Here we report a biofilm circuit that utilizes these two dispersal proteins along with a population-driven quorum-sensing switch. With this synthetic circuit, in a novel microfluidic device,

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

2012-01-01

229

Starvation Selection Restores Elastase and Rhamnolipid Production in a Pseudomonas aeruginosa Quorum-Sensing Mutant  

Microsoft Academic Search

The las quorum-sensing system of Pseudomonas aeruginosa controls the expression of elastase and rhamno- lipid. We report that starvation can select a mutant producing these virulence factors in spite of a lasR deletion. Expression of the autoinducer synthase gene rhlI was increased in this suppressor mutant, suggesting com- pensation by the rhl system. These data show that P. aeruginosa can

CHRISTIAN VAN DELDEN; EVERETT C. PESCI; JAMES P. PEARSON; BARBARA H. IGLEWSKI

1998-01-01

230

Mutational Analysis of Burkholderia thailandensis Quorum Sensing and Self-Aggregation ? †  

PubMed Central

Acyl-homoserine lactone (acyl-HSL) quorum-sensing signaling is common to many Proteobacteria. Acyl-HSLs are synthesized by the LuxI family of synthases, and the signal response is mediated by members of the LuxR family of transcriptional regulators. Burkholderia thailandensis is a member of a closely related cluster of three species, including the animal pathogens Burkholderia mallei and Burkholderia pseudomallei. Members of this group have similar luxI and luxR homologs, and these genes contribute to B. pseudomallei and B. mallei virulence. B. thailandensis possesses three pairs of luxI-luxR homologs. One of these pairs, BtaI2-BtaR2, has been shown to produce and respond to 3OHC10-HSL and to control the synthesis of an antibiotic. By using a markerless-exhange method, we constructed an assortment of B. thailandensis quorum-sensing mutants, and we used these mutants to show that BtaI1 is responsible for C8-HSL production and BtaI3 is responsible for 3OHC8-HSL production. We also show that a strain incapable of acyl-HSL production is capable of growth on the same assortment of carbon and nitrogen sources as the wild type. Furthermore, this mutant shows no loss of virulence compared to the wild type in mice. However, the wild type self-aggregates in minimal medium, whereas the quorum-sensing mutant does not. The wild-type aggregation phenotype is recovered by addition of the BtaI1-R1 HSL signal C8-HSL. We propose that the key function of the BtaR1-BtaI1 quorum-sensing system is to cause cells to gather into aggregates once a sufficient population has been established.

Chandler, Josephine R.; Duerkop, Breck A.; Hinz, Aaron; West, T. Eoin; Herman, Jake P.; Churchill, Mair E. A.; Skerrett, Shawn J.; Greenberg, E. Peter

2009-01-01

231

Antioxidant and anti-quorum sensing activities of green pod of Acacia nilotica L  

Microsoft Academic Search

The antioxidant and anti-quorum sensing activities of eight extracts were studied in green pods of Acacia nilotica. The specific phenolic compositions and their quantifications were performed by HPLC and MS\\/MS, which showed that the HEF (pH 4) was higher in gallic acid, ellagic acid, epicatechin, rutin, and GTs. In order to find antioxidant potential of various extracts, their activities were

Brahma N. Singh; B. R. Singh; R. L. Singh; D. Prakash; B. K. Sarma; H. B. Singh

2009-01-01

232

Salmonella typhimurium Recognizes a Chemically Distinct Form of the Bacterial Quorum-Sensing Signal AI2  

Microsoft Academic Search

Bacterial populations use cell-cell communication to coordinate community-wide regulation of processes such as biofilm formation, virulence, and bioluminescence. This phenomenon, termed quorum sensing, is mediated by small molecule signals known as autoinducers. While most autoinducers are species specific, autoinducer-2 (AI-2), first identified in the marine bacterium Vibrio harveyi, is produced and detected by many Gram-negative and Gram-positive bacteria. The crystal

Stephen T. Miller; Karina B. Xavier; Shawn R. Campagna; Michiko E. Taga; Martin F. Semmelhack; Bonnie L. Bassler; Frederick M. Hughson

2004-01-01

233

Quorum sensing as a population-density-dependent determinant of bacterial physiology  

Microsoft Academic Search

The discovery that bacterial cells can communicate with each other has led to the realization that bacteria are capable of exhibiting much more complex patterns of co-operative behaviour than would be expected for simple unicellular microorganisms. Now generically termed ‘quorum sensing’, bacterial cell-to-cell communication enables a bacterial population to mount a unified response that is advantageous to its survival by

Simon Swift; J. Allan Downie; Neil A. Whitehead; Anne M. L. Barnard; George P. C. Salmond; Paul Williams

2001-01-01

234

The Pseudomonas Quinolone Signal Regulates rhl Quorum Sensing in Pseudomonas aeruginosa  

Microsoft Academic Search

The opportunistic pathogen Pseudomonas aeruginosa uses intercellular signals to control the density-depen- dent expression of many virulence factors. The las and rhl quorum-sensing systems function, respectively, through the autoinducers N-(3-oxododecanoyl)-L-homoserine lactone and N-butyryl-L-homoserine lactone (C4- HSL), which are known to positively regulate the transcription of the elastase-encoding gene, lasB. Recently, we reported that a second type of intercellular signal is

SUSAN L. MCKNIGHT; BARBARA H. IGLEWSKI; EVERETT C. PESCI

2000-01-01

235

Quorum-Sensing Genes in Pseudomonas aeruginosa Biofilms: Their Role and Expression Patterns  

Microsoft Academic Search

Acylated homoserine lactone molecules are used by a number of gram-negative bacteria to regulate cell density-dependent gene expression by a mechanism known as quorum sensing (QS). In Pseudomonas aerugi- nosa, QS or cell-to-cell signaling controls expression of a number of virulence factors, as well as biofilm differentiation. In this study, we investigated the role played by the las and rhl

TERESA R. DE KIEVIT; RICHARD GILLIS; STEVE MARX; CHRIS BROWN; BARBARA H. IGLEWSKI

2001-01-01

236

Quorum Sensing in Burkholderia cepacia: Identification of the LuxRI Homologs CepRI  

Microsoft Academic Search

Burkholderia cepacia has emerged as an important pathogen in patients with cystic fibrosis. Many gram- negative pathogens regulate the production of extracellular virulence factors by a cell density-dependent mech- anism termed quorum sensing, which involves production of diffusible N-acylated homoserine lactone signal molecules, called autoinducers. Transposon insertion mutants of B. cepacia K56-2 which hyperproduced sidero- phores on chrome azurol S

SHAWN LEWENZA; BARBARA CONWAY; E. P. GREENBERG; PAMELA A. SOKOL

1999-01-01

237

Quorum sensing signaling molecules involved in the production of violacein by Pseudoalteromonas.  

PubMed

The production of violacein by Pseudoalteromonas sp. 520P1 has many features of quorum sensing. Signaling molecules were extracted from bacterial culture and subsequently identified as N-(3-oxooctanoyl)-homoserine lactone and N-tetradecanoyl-homoserine lactone. The former but not the latter induced the production of violacein in strain 520P1. We conclude that N-(3-oxooctanoyl)-homoserine lactone is a signaling molecule involved in the production of violacein. PMID:18603795

Wang, Yi; Ikawa, Atsushi; Okaue, Satoka; Taniguchi, Seishin; Osaka, Issey; Yoshimoto, Arihumi; Kishida, Yoshie; Arakawa, Ryuichi; Enomoto, Keiichi

2008-07-07

238

Expression of Pseudomonas aeruginosa exoS is controlled by quorum sensing and RpoS  

Microsoft Academic Search

In Pseudomonas aeruginosa, virulence determinants and biofilm formation are coordinated via a hierarchical quorum sensing cascade, which involves the transcriptional regulators LasR and RhlR and their cognate homoserine lactone activators C12-HSL (N-(3-oxododecanoyl)-L-homoserine lactone) and C4-HSL (N-butanoyl-L-homoserine lactone), which are produced by LasI and RhlI, respectively. The exoenzyme S regulon of P. aeruginosa, comprises genes for a type III secretion system

Michael Hogardt; Maximilian Roeder; Anna Maria Schreff; Leo Eberl; Jurgen Heesemann

2004-01-01

239

How Delisea pulchra furanones affect quorum sensing and swarming motility in Serratia liquefaciens MG1  

Microsoft Academic Search

Halogenated furanones produced by the benthic marine macroalga Delisea pulchra inhibit swarming motility of Serratia liquefaciens MG1. This study demonstrates that exogenously added furanones control transcription of the quorum sensing regulated gene swrA in competition with the cognate signal molecule N-butanoyl-L-homoserine lactone. This in turn results in reduced production of the surface-active compound serrawettin W2, which is crucial for surface

Thomas Bovbjerg Rasmussen; Michael Manefield; Jens Bo Andersen; Leo Eberl; Uffe Anthoni; Carsten Christophersen; Peter Steinberg; Staffan Kjelleberg; Michael Givskov

2000-01-01

240

A negative regulator mediates quorum-sensing control of exopolysaccharide production in Pantoea stewartii subsp. stewartii  

Microsoft Academic Search

Classical quorum-sensing (autoinduction) regulation, as exemplified by the lux system of Vibrio fischeri, requires N-acyl homoserine lactone (AHL) signals to stimulate cognate transcriptional activators for the cell density-dependent expression of specific target gene systems. For Pantoea stewartii subsp. stewartii, a bacterial pathogen of sweet corn and maize, the extracellular polysaccharide (EPS) stewartan is a major virulence factor, and its production

S. B. von Bodman; D R Majerczak; D L Coplin

1998-01-01

241

A Negative Regulator Mediates Quorum-Sensing Control of Exopolysaccharide Production in Pantoea stewartii Subsp. stewartii  

Microsoft Academic Search

Classical quorum-sensing (autoinduction) regulation, as exemplified by the lux system of Vibrio fischeri, requires N-acyl homoserine lactone (AHL) signals to stimulate cognate transcriptional activators for the cell density-dependent expression of specific target gene systems. For Pantoea stewartii subsp. stewartii, a bacterial pathogen of sweet corn and maize, the extracellular polysaccharide (EPS) stewartan is a major virulence factor, and its production

Susanne Beck von Bodman; Doris R. Majerczak; David L. Coplin

1998-01-01

242

Detection of quorum sensing signal molecules and mutation of luxS gene in Vibrio ichthyoenteri  

Microsoft Academic Search

Some pathogenic species belonging to the Vibrionaceae family have been shown to regulate virulence through a complicated network of quorum sensing systems. In this study, three kinds of N-acylhomoserine lactone (AHL) signal molecules were detected in Vibrio ichthyoenteri DA3, a pathogen of cultured turbot (Scophthalmus maximus), with the Agrobacterium tumefaciens reporter strain KYC55 (pJZ372)(pJZ384)(pJZ410). DA3 produced AHLs during the entire

Xuan Li; Yin Han; Qian Yang; Xiao-Hua Zhang

2010-01-01

243

Characterization of N -acylhomoserine lactone-degrading bacteria associated with the Zingiber officinale (ginger) rhizosphere: Co-existence of quorum quenching and quorum sensing in Acinetobacter and Burkholderia  

Microsoft Academic Search

Background  Cell-to-cell communication (quorum sensing (QS)) co-ordinates bacterial behaviour at a population level. Consequently the\\u000a behaviour of a natural multi-species community is likely to depend at least in part on co-existing QS and quorum quenching\\u000a (QQ) activities. Here we sought to discover novel N -acylhomoserine lactone (AHL)-dependent QS and QQ strains by investigating a bacterial community associated with the rhizosphere\\u000a of

Kok-Gan Chan; Steve Atkinson; Kalai Mathee; Choon-Kook Sam; Siri Ram Chhabra; Miguel Cámara; Chong-Lek Koh; Paul Williams

2011-01-01

244

Inactivation of a Pseudomonas aeruginosa quorum-sensing signal by human airway epithelia.  

PubMed

Mammalian airways protect themselves from bacterial infection by using multiple defense mechanisms including antimicrobial peptides, mucociliary clearance, and phagocytic cells. We asked whether airways might also target a key bacterial cell-cell communication system, quorum-sensing. The opportunistic pathogen Pseudomonas aeruginosa uses two quorum-sensing molecules, N-(3-oxododecanoyl)-l-homoserine lactone (3OC12-HSL) and N-butanoyl-l-homoserine lactone (C4-HSL), to control production of extracellular virulence factors and biofilm formation. We found that differentiated human airway epithelia inactivated 3OC12-HSL. Inactivation was selective for acyl-HSLs with certain acyl side chains, and C4-HSL was not inactivated. In addition, the capacity for inactivation varied widely in different cell types. 3OC12-HSL was inactivated by a cell-associated activity rather than a secreted factor. These data suggest that the ability of human airway epithelia to inactivate quorum-sensing signal molecules could play a role in the innate defense against bacterial infection. PMID:14970327

Chun, Carlene K; Ozer, Egon A; Welsh, Michael J; Zabner, Joseph; Greenberg, E P

2004-02-17

245

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

PubMed Central

In a process called quorum sensing, bacteria communicate using extracellular signal molecules termed autoinducers. 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 human pathogen, possesses System 2 (LuxS, AI-2, and LuxPQ) but does not have obvious homologues of V. harveyi System 1. Rather, System 1 of V. cholerae is made up of the CqsA-dependent autoinducer CAI-1 and a sensor called CqsS. Using a V. cholerae CAI-1 reporter strain we show that many other marine bacteria, including V. harveyi, produce CAI-1 activity. Genetic analysis of V. harveyi reveals cqsA and cqsS, and phenotypic analysis of V. harveyi cqsA and cqsS mutants shows that these functions comprise a third V. harveyi quorum-sensing system that acts in parallel to Systems 1 and 2. Together these communication systems act as a three-way coincidence detector in the regulation of a variety of genes, including those responsible for bioluminescence, type III secretion, and metalloprotease production.

Henke, Jennifer M.; Bassler, Bonnie L.

2004-01-01

246

Quorum sensing in Chromobacterium violaceum: DNA recognition and gene regulation by the CviR receptor.  

PubMed

The bacterial pathogen Chromobacterium violaceum uses a LuxIR-type quorum-sensing system to detect and respond to changes in cell population density. CviI synthesizes the autoinducer C(10)-homoserine lactone (C(10)-HSL), and CviR is a cytoplasmic DNA binding transcription factor that activates gene expression following binding to C(10)-HSL. A number of behaviors are controlled by quorum sensing in C. violaceum. However, few genes have been shown to be directly controlled by CviR, in part because the DNA motif bound by CviR is not well characterized. Here, we define the DNA sequence required for promoter recognition by CviR. Using in vivo data generated from a library of point mutations in a CviR-regulated promoter, we find that CviR binds to a palindrome with the ideal sequence CTGNCCNNNNGGNCAG. We constructed a position weight matrix using these in vivo data and scanned the C. violaceum genome to predict CviR binding sites. We measured direct activation of the identified promoters by CviR and found that CviR controls the expression of the promoter for a chitinase, a type VI secretion-related gene, a transcriptional regulator gene, a guanine deaminase gene, and cviI. Indeed, regulation of cviI expression by CviR generates a canonical quorum-sensing positive-feedback loop. PMID:21622734

Stauff, Devin L; Bassler, Bonnie L

2011-05-27

247

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

NASA Astrophysics Data System (ADS)

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

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

2010-05-01

248

Stereochemical diversity of AI-2 analogs modulates quorum sensing in Vibrio harveyi and Escherichia coli.  

PubMed

Bacteria coordinate population-dependent behaviors such as virulence by intra- and inter-species communication (quorum sensing). Autoinducer-2 (AI-2) regulates inter-species quorum sensing. AI-2 derives from the spontaneous cyclisation of linear (S)-4,5-dihydroxypentanedione (DPD) into two isomeric forms in dynamic equilibrium. Different species of bacteria have different classes of AI-2 receptors (LsrB and LuxP) which bind to different cyclic forms. In the present work, DPD analogs with a new stereocenter at C-5 (4,5-dihydroxyhexanediones (DHDs)) have been synthesized and their biological activity tested in two bacteria. (4S,5R)-DHD is a synergistic agonist in Escherichia coli (which contains the LsrB receptor), while it is an agonist in Vibrio harveyi (LuxP), displaying the strongest agonistic activity reported so far (EC(50)=0.65?M) in this organism. Thus, modification at C-5 opens the way to novel methods to manipulate quorum sensing as a method for controlling bacteria. PMID:22137598

Rui, Fabio; Marques, João C; Miller, Stephen T; Maycock, Christopher D; Xavier, Karina B; Ventura, M Rita

2011-11-12

249

Quorum Sensing in Chromobacterium violaceum: DNA Recognition and Gene Regulation by the CviR Receptor ? †  

PubMed Central

The bacterial pathogen Chromobacterium violaceum uses a LuxIR-type quorum-sensing system to detect and respond to changes in cell population density. CviI synthesizes the autoinducer C10-homoserine lactone (C10-HSL), and CviR is a cytoplasmic DNA binding transcription factor that activates gene expression following binding to C10-HSL. A number of behaviors are controlled by quorum sensing in C. violaceum. However, few genes have been shown to be directly controlled by CviR, in part because the DNA motif bound by CviR is not well characterized. Here, we define the DNA sequence required for promoter recognition by CviR. Using in vivo data generated from a library of point mutations in a CviR-regulated promoter, we find that CviR binds to a palindrome with the ideal sequence CTGNCCNNNNGGNCAG. We constructed a position weight matrix using these in vivo data and scanned the C. violaceum genome to predict CviR binding sites. We measured direct activation of the identified promoters by CviR and found that CviR controls the expression of the promoter for a chitinase, a type VI secretion-related gene, a transcriptional regulator gene, a guanine deaminase gene, and cviI. Indeed, regulation of cviI expression by CviR generates a canonical quorum-sensing positive-feedback loop.

Stauff, Devin L.; Bassler, Bonnie L.

2011-01-01

250

Garlic blocks quorum sensing and attenuates the virulence of Pseudomonas aeruginosa.  

PubMed

Pseudomonas aeruginosa is an opportunistic pathogen that colonizes urinary catheters, forms biofilms, and is responsible for causing persistent and recurrent nosocomial catheter-associated urinary tract infections (UTIs). These infections show increased morbidity and mortality in immunocompromised patients. Quorum sensing in P. aeruginosa plays a key role in biofilm formation, virulence factor production 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. In the present study, garlic was evaluated as a prophylactic agent in vivo in a mouse UTI model. Oral treatment with garlic significantly lowered renal bacterial counts and protected mouse kidney from tissue destruction. In vitro data showed decreased elaboration of virulence factors and reduced production of quorum-sensing signals by P. aeruginosa in the presence of fresh garlic extract. The results suggest that decreased virulence of P. aeruginosa in garlic-fed mice can be attributed to the quorum-sensing inhibitory property of garlic. This might have contributed towards reduced production of virulence factors, as seen in vitro. PMID:19878318

Harjai, Kusum; Kumar, Ravi; Singh, Sukhvinder

2009-09-18

251

Periodontal pathogens interfere with quorum-sensing-dependent virulence properties in Streptococcus mutans  

PubMed Central

Background and objective The mechanism by which periodontal pathogens dominate at disease sites is not yet understood. One possibility is that these late colonizers antagonize quorum-sensing systems of early colonizers and render those early colonizers less resistant to environmental factors. In this study, we utilized Streptococcus mutans, a well-documented oral Streptococcus with many quorum-sensing dependent properties, as an example of targeted earlier colonizers that are antagonized by periodontal pathogens. Material and Methods S. mutans NG8, LT11, and BM71 were used in this study for assessment of transformation and bacteriocin production, respectively. The effects of Porphyromonas gingivalis and Treponema denticola on these competence-stimulating peptide (CSP)-dependent properties were evaluated in mixed broth assays. Results Both P. gingivalis (either live bacteria or membrane vesicles) and T. denticola antagonized transformation in S. mutans NG8 and LT11. S. mutans BM71 bacteriocin production was also inhibited by P. gingivalis and T. denticola. Boiling of these late colonizers before mixing the broth cultures abolished their ability to inhibit S. mutans transformation and bacteriocin production. P. gingivalis and T. denticola inactivated S. mutans exogenous CSP, whereas the boiled bacteria did not. Conclusions This study demonstrated that periodontal pathogens antagonized S. mutans quorum-sensing properties. This may render S. mutans less virulent and less resistant to environmental antibacterial factors.

Wang, B.Y.; Alvarez, P.; Hong, J.; Kuramitsu, H.K.

2010-01-01

252

New Life for an Old Drug: the Anthelmintic Drug Niclosamide Inhibits Pseudomonas aeruginosa Quorum Sensing  

PubMed Central

The need for novel antibacterial strategies and the awareness of the importance of quorum sensing (QS) in bacterial infections have stimulated research aimed at identifying QS inhibitors (QSIs). However, clinical application of QSIs identified so far is still distant, likely due to their unsuitability for use in humans. A promising way to overcome this problem is searching for anti-QS side activity among the thousands of drugs approved for clinical use in the treatment of different diseases. Here, we applied this strategy to the search for QSIs, by screening a library of FDA-approved compounds for their ability to inhibit the QS response in the Gram-negative pathogen Pseudomonas aeruginosa. We found that the anthelmintic drug niclosamide strongly inhibits the P. aeruginosa QS response and production of acyl-homoserine lactone QS signal molecules. Microarray analysis showed that niclosamide affects the transcription of about 250 genes, with a high degree of target specificity toward the QS-dependent regulon. Phenotypic assays demonstrated that niclosamide suppresses surface motility and production of the secreted virulence factors elastase, pyocyanin, and rhamnolipids, and it reduces biofilm formation. In accordance with the strong antivirulence activity disclosed in vitro, niclosamide prevented P. aeruginosa pathogenicity in an insect model of acute infection. Besides the finding that an FDA-approved drug has a promising antivirulence activity against one of the most antibiotic-resistant bacterial pathogens, this work provides a proof of concept that a lateral anti-QS activity can be detected among drugs already used in humans, validating a new approach to identify QSIs that could easily move into clinical applications.

Imperi, Francesco; Massai, Francesco; Ramachandran Pillai, Cejoice; Longo, Francesca; Zennaro, Elisabetta; Rampioni, Giordano; Visca, Paolo

2013-01-01

253

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

PubMed Central

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

O'Grady, Eoin P; Viteri, Duber F; Malott, Rebecca J; Sokol, Pamela A

2009-01-01

254

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

PubMed

Quorum sensing is a chemical communication process that bacteria use to control collective behaviours including bioluminescence, biofilm formation, and virulence factor production. In Vibrio harveyi, five homologous small RNAs (sRNAs) called Qrr1-5, control quorum-sensing transitions. Here, we identify 16 new targets of the Qrr sRNAs. Mutagenesis reveals that particular sequence differences among the Qrr sRNAs determine their target specificities. Modelling coupled with biochemical and genetic analyses show that all five of the Qrr sRNAs possess four stem-loops: the first stem-loop is crucial for base pairing with a subset of targets. This stem-loop also protects the Qrr sRNAs from RNase E-mediated degradation. The second stem-loop contains conserved sequences required for base pairing with the majority of the target mRNAs. The third stem-loop plays an accessory role in base pairing and stability. The fourth stem-loop functions as a rho-independent terminator. In the quorum-sensing regulon, Qrr sRNAs-controlled genes are the most rapid to respond to quorum-sensing autoinducers. The Qrr sRNAs are conserved throughout vibrios, thus insights from this work could apply generally to Vibrio quorum sensing. PMID:23838640

Shao, Yi; Feng, Lihui; Rutherford, Steven T; Papenfort, Kai; Bassler, Bonnie L

2013-07-09

255

Allele-Dependent Differences in Quorum-Sensing Dynamics Result in Variant Expression of Virulence Genes in Staphylococcus aureus  

PubMed Central

Agr is an autoinducing, quorum-sensing system that functions in many Gram-positive species and is best characterized in the pathogen Staphylococcus aureus, in which it is a global regulator of virulence gene expression. Allelic variations in the agr genes have resulted in the emergence of four quorum-sensing specificity groups in S. aureus, which correlate with different strain pathotypes. The basis for these predilections is unclear but is hypothesized to involve the phenomenon of quorum-sensing interference between strains of different agr groups, which may drive S. aureus strain isolation and divergence. Whether properties intrinsic to each agr allele directly influence virulence phenotypes within S. aureus is unknown. In this study, we examined group-specific differences in agr autoinduction and virulence gene regulation by utilizing congenic strains, each harboring a unique S. aureus agr allele, enabling a dissection of agr locus-dependent versus genotype-dependent effects on quorum-sensing dynamics and virulence factor production. Employing a reporter fusion to the principal agr promoter, P3, we observed allele-dependent differences in the timing and magnitude of agr activation. These differences were mediated by polymorphisms within the agrBDCA genes and translated to significant variations in the expression of a key transcriptional regulator, Rot, and of several important exoproteins and surface factors involved in pathogenesis. This work uncovers the contribution of divergent quorum-sensing alleles to variant expression of virulence determinants within a bacterial species.

Geisinger, Edward; Chen, John

2012-01-01

256

A Quorum-Quenching Approach To Investigate the Conservation of Quorum-Sensing-Regulated Functions within the Burkholderia cepacia Complex  

PubMed Central

Taxonomic studies of the past few years have shown that the Burkholderia cepacia complex, a heterogeneous group of B. cepacia-like organisms, consists of at least nine species. B. cepacia complex strains are ubiquitously distributed in nature and have been used for biocontrol, bioremediation, and plant growth promotion purposes. At the same time, B. cepacia complex strains have emerged as important opportunistic pathogens of humans, particularly those with cystic fibrosis. All B. cepacia complex species investigated thus far use quorum-sensing (QS) systems that rely on N-acylhomoserine lactone (AHL) signal molecules to express certain functions, including the production of extracellular proteases, swarming motility, biofilm formation, and pathogenicity, in a population-density-dependent manner. In this study we constructed a broad-host-range plasmid that allowed the heterologous expression of the Bacillus sp. strain 240B1 AiiA lactonase, which hydrolyzes the lactone ring of various AHL signal molecules, in all described B. cepacia complex species. We show that expression of AiiA abolished or greatly reduced the accumulation of AHL molecules in the culture supernatants of all tested B. cepacia complex strains. Phenotypic characterization of wild-type and transgenic strains revealed that protease production, swarming motility, biofilm formation, and Caenorhabditis elegans killing efficiency was regulated by AHL in the large majority of strains investigated.

Wopperer, Julia; Cardona, Silvia T.; Huber, Birgit; Jacobi, Christoph A.; Valvano, Miguel A.; Eberl, Leo

2006-01-01

257

Quorum sensing regulation of virulence gene expression in Vibrio harveyi in vitro and in vivo during infection of gnotobiotic brine shrimp larvae.  

PubMed

In this study, we investigated quorum sensing regulation of virulence genes in Vibrio harveyi by determining their expression levels, both in vitro and in vivo during infection of gnotobiotic brine shrimp. The quorum sensing master regulator luxR and the vhp metalloprotease showed around threefold and fivefold higher expression levels in a luxO mutant with maximum quorum sensing activity than in a luxO mutant with minimum quorum sensing activity. There was no difference in expression of the vhh haemolysin gene between the two mutants. There was however more than 2.5-fold lower expression in an AI-2-negative mutant, suggesting that this gene is specifically regulated by AI-2 quorum sensing through a yet unknown signal transduction cascade. The in vivo expression data showed a peak in expression of the quorum sensing master regulator luxR and the vhp metalloprotease after 24?h of incubation in wild-type V. harveyi and the luxO mutant mimicking a maximally activated quorum sensing system, whereas the expression remained low in the luxO mutant mimicking a completely inactivated quorum sensing system. The vhh haemolysin gene showed a peak in expression after 24?h in the wild type and a constantly low expression in an AI-2-negative mutant. PMID:23761340

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

2011-06-08

258

Characterization of the Staphylococcus epidermidis Accessory-Gene Regulator Response: Quorum-Sensing Regulation of Resistance to Human Innate Host Defense  

Microsoft Academic Search

Staphylococci are important opportunistic pathogens. However, there is a lack of information on how these bacteria survive inside the human body during infection. This study demonstrates that quorum-sensing regulation in Staphylococcus epidermidis protects it from key mechanisms of human innate host defense. To gain a better understanding of the basis of the observed phenotype, the agr quorum-sensing regulon of S.

Yufeng Yao; Cuong Vuong; Stanislava Kocianova; Yuping Lai; Michael Otto

2006-01-01

259

The LuxR Homolog ExpR, in Combination with the Sin Quorum Sensing System, Plays a Central Role in Sinorhizobium meliloti Gene Expression  

Microsoft Academic Search

Quorum sensing, a population density-dependent mechanism for bacterial communication and gene regu- lation, plays a crucial role in the symbiosis between alfalfa and its symbiont Sinorhizobium meliloti. The Sin system, one of three quorum sensing systems present in S. meliloti, controls the production of the symbiotically active exopolysaccharide EPS II. Based on DNA microarray data, the Sin system also seems

Hanh H. Hoang; Anke Becker; Juan E. Gonzalez

2004-01-01

260

Quorum-sensing non-coding small RNAs use unique pairing regions to differentially control mRNA targets  

PubMed Central

Summary Quorum sensing is a mechanism of cell–cell communication that bacteria use to control collective behaviours including bioluminescence, biofilm formation and virulence factor production. In the Vibrio harveyi and Vibrio cholerae quorum-sensing circuits, multiple non-coding small regulatory RNAs called the quorum-regulated small RNAs (Qrr sRNAs) function to establish the global quorum-sensing gene expression pattern by modulating translation of multiple mRNAs encoding quorum-sensing regulatory factors. Here we show that the Qrr sRNAs post-transcriptionally activate production of the low cell density master regulator AphA through base pairing to aphA mRNA, and this is crucial for the accumulation of appropriate levels of AphA protein at low cell density. We find that the Qrr sRNAs use unique pairing regions to discriminate between their different targets. Qrr1 is not as effective as Qrr2–5 in activating aphA because Qrr1 lacks one of two required pairing regions. However, Qrr1 is equally effective as the other Qrr sRNAs at controlling targets like luxR and luxO because it harbours all of the required pairing regions for these targets. Sequence comparisons reveal that Vibrionaceae species possessing only qrr1 do not have the aphA gene under Qrr sRNA control. Our findings suggest co-evolving relationships between particular Qrr sRNAs and particular mRNA targets.

Shao, Yi; Bassler, Bonnie L

2012-01-01

261

The regulation of virulence in phytopathogenic Erwinia species: quorum sensing, antibiotics and ecological considerations.  

PubMed

Erwinia carotovora is a Gram-negative bacterial phytopathogen that causes soft-rot disease and potato blackleg. The organism is environmentally widespread and exhibits an opportunistic plant pathogenesis. The ability to secrete multiple plant cell wall-degrading enzymes is a key virulence trait and exoenzyme production is responsive to multiple environmental and physiological cues. One important cue is the cell population density of the pathogen. Cell density is monitored via an acylated homoserine lactone (acyl HSL) signalling molecule, which is thought to diffuse between Erwinia cells in a process now commonly known as 'quorum sensing'. This molecule also acts as the chemical communication signal controlling production of a broad-spectrum beta-lactam antibiotic (1-carbapen-2-em-3-carboxylic acid; carbapenem) synthesised in concert with exoenzyme elaboration, possibly for niche defence. In antibiotic production control, quorum sensing acts at the level of transcriptional activation of the antibiotic biosynthetic cluster. This is achieved via a dedicated LuxR-type protein, CarR that is bound to the signalling molecule. The molecular relay connecting acyl HSL production and exoenzyme induction is not clear, despite the identification of a multitude of global regulatory genes, including those of the RsmA/rsmB system, impinging on enzyme synthesis. Quorum sensing control mediated by acyl HSLs is widespread in Gram-negative bacteria and is responsible for the regulation of diverse phenotypes. Although there is still a paucity of meaningful information on acyl HSL availability and in-situ biological function, there is growing evidence that such molecules play significant roles in microbial ecology. PMID:12448721

Whitehead, Neil A; Byers, Joseph T; Commander, Paul; Corbett, Mark J; Coulthurst, Sarah J; Everson, Lee; Harris, Abigail K P; Pemberton, Clare L; Simpson, Natalie J L; Slater, Holly; Smith, Debra S; Welch, Martin; Williamson, Neil; Salmond, George P C

2002-08-01

262

Paraoxonase-2 deficiency enhances Pseudomonas aeruginosa quorum sensing in murine tracheal epithelia.  

PubMed

Pseudomonas aeruginosa is an important cause of nosocomial infections and is frequently present in the airways of cystic fibrosis patients. Quorum sensing mediates P. aeruginosa's virulence and biofilm formation through density-dependent interbacterial signaling with autoinducers. N-3-oxododecanoyl homoserine lactone (3OC12-HSL) is the major autoinducer in P. aeruginosa. We have previously shown that human airway epithelia and paraoxonases (PONs) degrade 3OC12-HSL. This study investigated the role of PON1, PON2, and PON3 in airway epithelial cell inactivation of 3OC12-HSL. All three PONs were present in murine tracheal epithelial cells, with PON2 and PON3 expressed at the highest levels. Lysates of tracheal epithelial cells from PON2, but not PON1 or PON3, knockout mice had impaired 3OC12-HSL inactivation compared with wild-type mice. In contrast, PON1-, PON2-, or PON3-targeted deletions did not affect 3OC12-HSL degradation by intact epithelia. Overexpression of PON2 enhanced 3OC12-HSL degradation by human airway epithelial cell lysates but not by intact epithelia. Finally, using a quorum-sensing reporter strain of P. aeruginosa, we found that quorum sensing was enhanced in PON2-deficient airway epithelia. In summary, these results show that loss of PON2 impairs 3OC12-HSL degradation by airway epithelial cells and suggests that diffusion of 3OC12-HSL into the airway cells can be the rate-limiting step for degradation of the molecule. PMID:17122353

Stoltz, David A; Ozer, Egon A; Ng, Carey J; Yu, Janet M; Reddy, Srinivasa T; Lusis, Aldons J; Bourquard, Noam; Parsek, Matthew R; Zabner, Joseph; Shih, Diana M

2006-11-22

263

Bis-(3?-5?)-cyclic dimeric GMP-linked quorum sensing controls swarming in Vibrio parahaemolyticus  

PubMed Central

Movement over and colonization of surfaces are important survival strategies for bacteria, and many find it advantageous to perform these activities as a group, using quorum sensing to sample population size and synchronize behavior. It is puzzling however, that swarming-proficient and virulent strains of Vibrio parahaemolyticus are silenced for the vibrio archetypal pathway of quorum sensing. Here we describe the S-signal, a pheromone that can be communicated between cells in coculture to regulate surface colonization. This signal was harvested in cell-free supernatants and demonstrated to stimulate swarming gene expression at low cell density. The S-signal was generated by the pyridoxal phosphate-dependent aminotransferase ScrA; signal reception required the periplasmic binding protein ScrB and the membrane-bound GGDEF-EAL domain-containing protein ScrC. ScrC is a bifunctional enzyme that has the ability to form and degrade the second messenger bis-(3?-5?) cyclic dimeric GMP (c-di-GMP). ScrA in neighboring cells was able to alter the activity of ScrC in a ScrB-dependent manner, transforming ScrC’s repressing ability to inducing activity with respect to swarming. Conversely, cell–cell signaling repressed capsule gene expression. In summary, we report that quorum sensing can stimulate swarming in V. parahaemolyticus; it does so via an alternative pathway capable of generating an autoinducing signal that influences c-di-GMP, thereby expanding the lexicon and language of cell–cell communication.

Trimble, Michael J.; McCarter, Linda L.

2011-01-01

264

Iron and Quorum Sensing Coordinately Regulate the Expression of Vulnibactin Biosynthesis in Vibrio vulnificus*  

PubMed Central

Vibrio vulnificus is a halophilic marine pathogen associated with human diseases such as septicemia and serious wound infections. Genes vvsA and vvsB, which are co-transcribed and encode a member of the nonribosomal peptide synthase family, are required for vulnibactin biosynthesis in V. vulnificus. In this study, we found that quorum sensing represses the transcription of a vvsAB-lux reporter fusion. Gel shift assay and DNaseI footprinting experiments show that the main regulator of quorum sensing, SmcR, binds to a 22-bp region located between ?40 and ?19 with respect to the vvsA transcription start site. Mutation of the SmcR binding site abolishes the repression of vvsA::luxAB by SmcR. Fur represses vvsAB transcription in the presence of iron by binding to a 47-bp region located between ?45 and +2 with respect to the vvsA transcription start site. A competition gel shift assay and footprinting experiment using Fur and SmcR showed that Fur binds to the vvsA promoter region with higher affinity than SmcR. Studies with the vvsAB::luxAB transcriptional fusion demonstrate that in the presence of iron, Fur is the key repressor of vvsAB transcription, whereas in iron-limited conditions, SmcR is the key regulator repressing vvsAB transcription. This study demonstrates that the Fe-Fur complex and quorum sensing cooperate to repress the transcription of vvsAB in response to iron conditions, suggesting that fine tuning of the intracellular iron level is important for the survival and pathogenicity of V. vulnificus.

Wen, Yancheng; Kim, In Hwang; Son, Jee-Soo; Lee, Byeong-Ha; Kim, Kun-Soo

2012-01-01

265

Quorum sensing inhibition by Asparagopsis taxiformis, a marine macro alga: separation of the compound that interrupts bacterial communication.  

PubMed

The majority of the marine algal species, though completing their life cycle in seawater, are rarely susceptible to fouling, making them an important source of quorum sensing (QS) inhibitory substances. The separation and characterization of QS inhibitors are crucial for any potential application. Thirty marine macroalgae were tested for QS inhibition activity by using Chromobacterium violaceum CV026 as the reporter strain, and among them, Asparagopsis taxiformis showed antibacterial, as well as antiquorum, sensing activities. Cinnamaldehyde (75 mM) and methanol were used as positive and negative controls, respectively. The antiquorum sensing activity of A. taxiformis was further confirmed using the sensor strain, Serratia liquefaciens MG44, having green fluorescent protein (gfp). Methanolic extract of the alga was fractionated by solid phase extraction (SPE), and each fraction was tested for QS inhibition. Two types of activities were observed-zone of clearance (antibacterial activity) and zone of inhibition with or without finger-like projections (QS inhibition). Out of five SPE cartridges, Bond Elut PH showed clear separation of these two fractions. The Ion Cyclotron Resonance Fourier Transformation Mass Spectrometer (ICR-FT/MS) analysis of the fractions further supported the bioassay results. The presence of strong QS inhibitory compound in A. taxiformis indicates its potential use in antifouling preparations. PMID:23344114

Jha, Bhavanath; Kavita, Kumari; Westphal, Jenny; Hartmann, Anton; Schmitt-Kopplin, Philippe

2013-01-23

266

Structure and inhibition of a quorum sensing target from Streptococcus pneumoniae.  

PubMed

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(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., Núñez, 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(N)1 transition state. It is a weak inhibitor of S. pneumoniae MTAN with a K(i) of 1.0 microM. 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(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(i) value of 24 nM, and replacing the 5'-methyl group with p-Cl-phenyl (p-Cl-PhT-DADMe-ImmA) gave a K(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(3)-10(4)-fold more tightly to the E. coli enzyme. Catalytic site efficiency is primarily responsible for this difference since k(cat)/K(m) for S. pneumoniae MTAN is decreased 845-fold relative to that of E. coli MTAN. PMID:17059210

Singh, Vipender; Shi, Wuxian; Almo, Steven C; Evans, Gary B; Furneaux, Richard H; Tyler, Peter C; Painter, Gavin F; Lenz, Dirk H; Mee, Simon; Zheng, Renjian; Schramm, Vern L

2006-10-31

267

Structure and Inhibition of a Quorum Sensing Target from Streptococcus pneumoniae  

PubMed Central

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 growth and pathogenicity of bacteria, making it a target for antibiotic design. Kinetic isotope effects and computational studies have established a dissociative SN1 transition state for E. coli MTAN and transition state analogues resembling the transition state are powerful inhibitors of the enzyme (Singh, V., Lee, J. L., Núñez, S., Howell, P. L. and Schramm, V. L. (2005) Biochemistry 44, 11647-11659). The MTAN from S. pneumoniae has 40% sequence identity to E. coli MTAN, but exhibits remarkably distinct kinetic and inhibitory properties. 5?-Methylthio-Immucillin-A (MT-ImmA) is a transition state analogue resembling an early SN1 transition state. It is a weak inhibitor of S. pneumoniae MTAN with a Ki of 1.0 ?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 Ki values of 335 nM, 60 nM 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 Ki value of 24 nM and replacing the 5?-methyl group with p-Cl-phenyl (p-Cl-PhT-DADMe-ImmA) gave a Ki* 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 103 to 104 fold more tightly to the E. coli enzyme. Catalytic site efficiency is primarily responsible for this difference since kcat/Km for S. pneumoniae MTAN is <10-2 that of E. coli MTAN.

Singh, Vipender; Shi, Wuxian; Almo, Steven C.; Evans, Gary B.; Furneaux, Richard H.; Tyler, Peter C.; Zheng, Renjian; Schramm, Vern L.

2008-01-01

268

N-acylhomoserine lactones antagonize virulence gene expression and quorum sensing in Staphylococcus aureus.  

PubMed

Many gram-negative bacteria employ N-acylhomoserine lactone (AHL)-mediated quorum sensing to control virulence. To determine whether gram-positive bacteria such as Staphylococcus aureus respond to AHLs, we used a growth-dependent lux reporter fusion. Exposure of S. aureus to different AHLs revealed that 3-oxo-substituted AHLs with C10 to C14 acyl chains inhibited light output and growth in a concentration-dependent manner, while short-chain AHLs had no effect. N-(3-Oxododecanoyl)-L-homoserine lactone (3-oxo-C12-HSL) inhibited the production of exotoxins and cell wall fibronectin-binding proteins but enhanced protein A expression. Since these processes are reciprocally regulated via the S. aureus agr quorum-sensing system, which in turn, is regulated via sar, we examined the effect of AHLs on sarA and agr. At sub-growth-inhibitory concentrations of 3-oxo-C12-HSL, both sarA expression and agr expression were inhibited, indicating that the action of 3-oxo-C12-HSL is mediated at least in part through antagonism of quorum sensing in S. aureus. Spent culture supernatants from Pseudomonas aeruginosa, which produces both 3-oxo-C12-HSL and N-butanoyl-homoserine lactone (C4-HSL), also inhibited agr expression, although C4-HSL itself was inactive in this assay. Since quorum sensing in S. aureus depends on the activities of membrane-associated proteins, such as AgrB, AgrC, and AgrD, we investigated whether AHLs perturbed S. aureus membrane functionality by determining their influence on the membrane dipole potential. From the binding curves obtained, a dissociation constant of 7 muM was obtained for 3-oxo-C12-HSL, indicating the presence of a specific saturable receptor, whereas no binding was observed for C4-HSL. These data demonstrate that long-chain 3-oxo-substituted AHLs, such as 3-oxo-C12-HSL, are capable of interacting with the S. aureus cytoplasmic membrane in a saturable, specific manner and at sub-growth-inhibitory concentrations, down-regulating exotoxin production and both sarA and agr expression. PMID:16428734

Qazi, Saara; Middleton, Barry; Muharram, Siti Hanna; Cockayne, Alan; Hill, Philip; O'Shea, Paul; Chhabra, Siri Ram; Cámara, Miguel; Williams, Paul

2006-02-01

269

Analysis of a bacteria-immunity model with delay quorum sensing  

NASA Astrophysics Data System (ADS)

A bacteria-immunity model with bacterial quorum sensing is formulated, which describes the competition between bacteria and immune cells. A distributed delay is introduced to characterize the time in which bacteria receive signal molecules and then combat with immune cells. In this paper, we focus on a subsystem of the bacteria-immunity model, analyze the stability of the equilibrium points, discuss the existence and stability of periodic solutions bifurcated from the positive equilibrium point, and finally investigate the stability of the nonhyperbolic equilibrium point by the center manifold theorem.

Zhang, Zhonghua; Peng, Jigen; Zhang, Juan

2008-04-01

270

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

NASA Astrophysics Data System (ADS)

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

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

2010-06-01

271

Identification of a New Regulator in Streptococcus pneumoniae Linking Quorum Sensing to Competence for Genetic Transformation  

Microsoft Academic Search

Competence for genetic transformation in Streptococcus pneumoniae is regulated by a quorum-sensing system encoded by two genetic loci, comCDE and comAB. Additional competence-specific operons, cilA, cilB, cilC, cilD, cilE, cinA-recA, coiA, and cfl, involved in the DNA uptake process and recombination, share an unusual consensus sequence at 210 and 225 in the promoter, which is absent from the promoters of

MYEONG S. LEE; DONALD A. MORRISON

1999-01-01

272

Quorumpeps database: chemical space, microbial origin and functionality of quorum sensing peptides  

PubMed Central

Quorum-sensing (QS) peptides are biologically attractive molecules, with a wide diversity of structures and prone to modifications altering or presenting new functionalities. Therefore, the Quorumpeps database (http://quorumpeps.ugent.be) is developed to give a structured overview of the QS oligopeptides, describing their microbial origin (species), functionality (method, result and receptor), peptide links and chemical characteristics (3D-structure-derived physicochemical properties). The chemical diversity observed within this group of QS signalling molecules can be used to develop new synthetic bio-active compounds.

Wynendaele, Evelien; Bronselaer, Antoon; Nielandt, Joachim; D'Hondt, Matthias; Stalmans, Sofie; Bracke, Nathalie; Verbeke, Frederick; Van De Wiele, Christophe; De Tre, Guy; De Spiegeleer, Bart

2013-01-01

273

Quorum-Sensing Mutations Affect Attachment and Stability of Burkholderia cenocepacia Biofilms  

PubMed Central

Biofilm formation in Burkholderia cenocepacia has been shown to rely in part on acylhomoserine lactone-based quorum sensing. For many other bacterial species, it appears that both the initial adherence and the later stages of biofilm maturation are affected when quorum sensing pathways are inhibited. In this study, we examined the effects of mutations in the cepIR and cciIR quorum-sensing systems of Burkholderia cenocepacia K56-2 with respect to biofilm attachment and antibiotic resistance. We also examined the role of the cepIR system in biofilm stability and structural development. Using the high-throughput MBEC assay system to produce multiple equivalent biofilms, the biomasses of both the cepI and cepR mutant biofilms, measured by crystal violet staining, were less than half of the value observed for the wild-type strain. Attachment was partially restored upon providing functional gene copies via multicopy expression vectors. Surprisingly, neither the cciI mutant nor the double cciI cepI mutant was deficient in attachment, and restoration of the cciI gene resulted in less attachment than for the mutants. Meanwhile, the cciR mutant did show a significant reduction in attachment, as did the cciR cepIR mutant. While there was no change in antibiotic susceptibility with the individual cepIR and cciIR mutants, the cepI cciI mutant biofilms were more sensitive to ciprofloxacin. A significant increase in sensitivity to removal by sodium dodecyl sulfate was seen for the cepI and cepR mutants. Flow cell analysis of the individual cepIR mutant biofilms indicated that they were both structurally and temporally impaired in attachment and development. These results suggest that biofilm structural defects might be present in quorum-sensing mutants of B. cenocepacia that affect the stability and resistance of the adherent cell mass, providing a basis for future studies to design preventative measures against biofilm formation in this species, an important lung pathogen of cystic fibrosis patients.

Tomlin, Kerry L.; Malott, Rebecca J.; Ramage, Gordon; Storey, Douglas G.; Sokol, Pamela A.; Ceri, H.

2005-01-01

274

Regulation of Quorum Sensing by RpoS in Pseudomonas aeruginosa  

Microsoft Academic Search

The LasR-LasI and RhlR-RhlI quorum-sensing systems are global regulators of gene expression in the opportunistic pathogen Pseudomonas aeruginosa. Previous studies suggest that the RhlR-RhlI system activates expression of rpoS. We constructed merodiploid strains of P. aeruginosa containing the native rpoS gene and an rpoS-lacZ fusion. Studies of lacZ transcription in these strains indicated that rpoS was not regulated by RhlR-RhlI.

MARVIN WHITELEY; MATTHEW R. PARSEK; E. P. Greenberg

2000-01-01

275

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

Microsoft Academic Search

Background  Biofilms are microbial communities encased in a layer of extracellular polymeric substances (EPS). The EPS matrix provides\\u000a several functional purposes for the biofilm, such as protecting bacteria from environmental stresses, and providing mechanical\\u000a stability. Quorum sensing is a cell-cell communication mechanism used by several bacterial taxa to coordinate gene expression\\u000a and behaviour in groups, based on population densities.\\u000a \\u000a \\u000a \\u000a \\u000a Model  We mathematically

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

2011-01-01

276

Influence of quorum sensing signal molecules on biofilm formation in Proteus mirabilis O18.  

PubMed

The influence of basis of quorum sensing molecules on Proteus strains is much less known as compared to Pseudomonas or Escherichia. We have previously shown that a series of acylated homoserine lactones (acyl-HSL) does not influence the ureolytic, proteolytic, or hemolytic abilities, and that the swarming motility of Proteus mirabilis rods is strain specific. The aim of the presented study was to find out if the presence of a series of acyl-HSL influences biofilm formation of P. mirabilis laboratory strain belonging to O18 serogroup. This serogroup is characterized by the presence of a unique non-carbohydrate component, namely phosphocholine. Escherichia coli and P. mirabilis O18 strains used in this work contains cloned plasmids encoding fluorescent protein genes with constitutive gene expression. In mixed biofilms in stationary and continuous flow conditions, P. mirabilis O18 overgrow whole culture. P. mirabilis O18 strain has genetically proved a presence of AI-2 quorum sensing system. Differences in biofilm structure were observed depending on the biofilm type and culture methods. From tested acylated homoserine lactones (BHL, HHL, OHL, DHL, dDHL, tDHL), a significant influence had BHL on thickness, structure, and the amount of exopolysaccharides produced by biofilms formed by P. mirabilis O18 pDsRed(2). PMID:22198843

Stankowska, Dorota; Czerwonka, Grzegorz; Rozalska, Sylwia; Grosicka, Michalina; Dziadek, Jaroslaw; Kaca, Wieslaw

2011-12-24

277

Influence of Pseudomonas aeruginosa quorum sensing signal molecule N-(3-oxododecanoyl) homoserine lactone on mast cells.  

PubMed

Quorum sensing system is a cell-to-cell communication system that plays a pivotal role in virulence expression in bacteria. Recent advances have demonstrated that the Pseudomonas aeruginosa quorum sensing molecule, N-3-oxododecanoyl homoserine lactone (3OC(12)-HSL), exerts effects on mammalian cells and modulates host immune response. Mast cells (MCs) are strategically located in the tissues that are constantly exposed to external stimulus. Therefore, it is very much possible that 3OC(12)-HSL may interact with MCs. Little is known, however, about specific effects of 3OC(12)-HSL on MCs. To address this, we investigated the influence of 3OC(12)-HSL on cell viability, apoptosis, intracellular calcium and cytokine release in MCs. We found that at high concentrations (100 microM), 3OC(12)-HSL inhibited proliferation and induced apoptosis in P815. The 3OC(12)-HSL treatment significantly increased intracellular calcium release in both P815 and HMC-1. We also observed that 3OC(12)-HSL-induced histamine release and degranulation in HMC-1 cells. Furthermore, 3OC(12)-HSL-induced IL-6 production at lower concentrations (6.25-12.5 microM) but steadily reduced IL-6 production at high concentration (50-100 muM). These data demonstrate that P. aeruginosa 3OC(12)-HSL affects MCs function. PMID:19337750

Li, Hongtao; Wang, Lili; Ye, Lu; Mao, Yan; Xie, Xuhua; Xia, Chao; Chen, Jia; Lu, Zimin; Song, Jianxin

2009-04-01

278

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

NASA Astrophysics Data System (ADS)

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

Long, Tao; Bassler, Bonnie; Wingreen, Ned

2007-03-01

279

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

NASA Astrophysics Data System (ADS)

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.

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

2012-10-01

280

Quorum-Sensing Regulation of the Production of Blp Bacteriocins in Streptococcus thermophilus? †  

PubMed Central

The blp gene cluster identified in the genome sequences of Streptococcus thermophilus (blpSt) LMG18311, CNRZ1066, and LMD-9 displays all the characteristics of a class II bacteriocin locus. In the present study, we showed that the blpSt locus is only fully functional in strain LMD-9 and regulates the production of antimicrobial peptides that inhibit strains LMG18311 and CNRZ1066. The blpSt cluster of LMD-9 contains 23 genes that are transcriptionally organized in six operons: blpABCSt (peptide transporter genes and pheromone gene); blpRHSt (two-component regulatory system genes); blpDSt-orf1, blpUSt-orf3, and blpE-FSt (bacteriocin precursors and immunity genes); and blpG-XSt (unknown function). All the operons, except the regulatory unit blpRHSt, were shown to be coregulated at the transcriptional level by a quorum-sensing mechanism involving the mature S. thermophilus pheromone BlpC* (BlpC*St), which was extracellularly detected as two active forms (30 and 19 amino acids). These operons are differentially transcribed depending on growth phase and pheromone concentration. They all contain a motif with two imperfect direct repeats in their mapped promoter regions that could serve as binding sites of the response regulator BlpRSt. Through the construction of deletion mutants, the blpSt locus of strain LMD-9 was shown to encode all the essential functions associated with bacteriocin production, quorum-sensing regulation, and immunity.

Fontaine, Laetitia; Boutry, Celine; Guedon, Eric; Guillot, Alain; Ibrahim, Mariam; Grossiord, Benoit; Hols, Pascal

2007-01-01

281

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

282

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

NASA Astrophysics Data System (ADS)

We model the dynamics of the synthetic genetic oscillator Repressilator equipped with quorum sensing. In addition to a circuit of 3 genes repressing each other in a unidirectional manner, the model includes a phase-repulsive type of the coupling module implemented as the production of a small diffusive molecule--autoinducer (AI). We show that the autoinducer (which stimulates the transcription of a target gene) is responsible for the disappearance of the limit cycle (LC) through the infinite period bifurcation and the formation of a stable steady state (SSS) for sufficiently large values of the transcription rate. We found conditions for hysteresis between the limit cycle and the stable steady state. The parameters' region of the hysteresis is determined by the mRNA to protein lifetime ratio and by the level of transcription-stimulating activity of the AI. In addition to hysteresis, increasing AI-dependent stimulation of transcription may lead to the complex dynamic behavior which is characterized by the appearance of several branches on the bifurcation continuation, containing different regular limit cycles, as well as a chaotic regime. The multistability which is manifested as the coexistence between the stable steady state, limit cycles, and chaos seems to be a novel type of the dynamics for the ring oscillator with the added quorum sensing positive feedback.

Potapov, I.; Zhurov, B.; Volkov, E.

2012-06-01

283

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

284

Coral-associated bacteria, quorum sensing disrupters, and the regulation of biofouling.  

PubMed

Marine biofouling, the settlement of microorganisms and macroorganisms on structures submerged in seawater, although economically detrimental, is a successful strategy for survival in hostile environments, where coordinated bacterial communities establish biofilms via the regulation of quorum sensing (QS) communication systems. The inhibition of QS activity among bacteria isolated from different coral species was investigated to gain further insight into its potency in the attenuation, or even the prevention, of undesirable biofouling on marine organisms. It is hypothesized that coral mucus/microorganism interactions are competitive, suggesting that the dominant communities secrete QS disruptive compounds. One hundred and twenty bacterial isolates were collected from healthy coral species and screened for their ability to inhibit QS using three bioreporter strains. Approximately 12, 11, and 24% of the isolates exhibited anti-QS activity against Escherichia coli pSB1075, Chromobacterium violaceum CV026, and Agrobacterium tumefaciens KYC55 indicator strains, respectively. Isolates with positive activity against the bioluminescent monitor strains were scanned via a cytotoxic/genotoxic, E. coli TV1061 and DPD2794 antimicrobial panel. Isolates detected by C. violaceum CV026 and A. tumefaciens KYC55 reporter strains were tested for their ability to inhibit the growth of these reporter strains, which were found to be unaffected. Tests of the Favia sp. coral isolate Fav 2-50-7 (>98% similarity to Vibrio harveyi) for its ability to attenuate the formation of biofilm showed extensive inhibitory activity against biofilms of Pseudomonas aeruginosa and Acinetobacter baumannii. To ascertain the stability and general structure of the active compound, cell-free culture supernatants exposed to an increasing temperature gradient or to digestion by proteinase K, were shown to maintain potent QS attenuation and the ability to inhibit the growth of biofilms. Mass spectrometry confirmed the presence of a low molecular mass compound. The anti-QS strategy exemplified in the coral mucus is a model with potentially wide applications, including countering the ecological threat posed by biofilms. Manipulating synchronized bacterial behavior by detecting new QS inhibitors will facilitate the discovery of new antifouling compounds. PMID:23777289

Golberg, Karina; Pavlov, Valentina; Marks, Robert S; Kushmaro, Ariel

2013-06-18

285

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

Microsoft Academic Search

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

Zvia Agur; Yuri Kogan; Liora Levi; Hannah Harrison; Rebecca Lamb; Oleg U Kirnasovsky; Robert B Clarke

2010-01-01

286

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

287

AN EVALUATION OF ASCORBIC ACID AS A QUORUM SENSING ANALOGUE TO CONTROL GROWTH, SPORULATION, AND ENTEROTOXIN PRODUCTION IN CLOSTRIDIUM PERFRINGENS  

Technology Transfer Automated Retrieval System (TEKTRAN)

Inhibition of quorum sensing by enterotoxin-producing strains of Clostridium perfringens was investigated. Autoinducer-2 (AI-2) activity was measured in the presence and absence of ascorbic acid (vitamin C; concentrations ranging from 10 to 300 mM), an AI-2 analogue. Subsequent effects on AI-2 pro...

288

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

National Technical Information Service (NTIS)

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, t...

C. Wu J. J. Valdes L. Wang M. P. DeLisa W. E. Bentley

2001-01-01

289

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

Microsoft Academic Search

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

Allison Adonizio; Kok-Fai Kong; Kalai Mathee

2008-01-01

290

The Quorum-Sensing Molecules Farnesol/Homoserine Lactone and Dodecanol Operate via Distinct Modes of Action in Candida albicans?  

PubMed Central

Living as a commensal, Candida albicans must adapt and respond to environmental cues generated by the mammalian host and by microbes comprising the natural flora. These signals have opposing effects on C. albicans, with host cues promoting the yeast-to-hyphal transition and bacteria-derived quorum-sensing molecules inhibiting hyphal development. Hyphal development is regulated through modulation of the cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway, and it has been postulated that quorum-sensing molecules can affect filamentation by inhibiting the cAMP pathway. Here, we show that both farnesol and 3-oxo-C12-homoserine lactone, a quorum-sensing molecule secreted by Pseudomonas aeruginosa, block hyphal development by affecting cAMP signaling; they both directly inhibited the activity of the Candida adenylyl cyclase, Cyr1p. In contrast, the 12-carbon alcohol dodecanol appeared to modulate hyphal development and the cAMP signaling pathway without directly affecting the activity of Cyr1p. Instead, we show that dodecanol exerted its effects through a mechanism involving the C. albicans hyphal repressor, Sfl1p. Deletion of SFL1 did not affect the response to farnesol but did interfere with the response to dodecanol. Therefore, quorum sensing in C. albicans is mediated via multiple mechanisms of action. Interestingly, our experiments raise the possibility that the Burkholderia cenocepacia diffusible signal factor, BDSF, also mediates its effects via Sfl1p, suggesting that dodecanol's mode of action, but not farnesol or 3-oxo-C12-homoserine lactone, may be used by other quorum-sensing molecules.

Hall, Rebecca A.; Turner, Kara J.; Chaloupka, James; Cottier, Fabien; De Sordi, Luisa; Sanglard, Dominique; Levin, Lonny R.; Buck, Jochen; Muhlschlegel, Fritz A.

2011-01-01

291

Quorum sensing of bacteria and trans-kingdom interactions of N-acyl homoserine lactones with eukaryotes.  

PubMed

Many environmental and interactive important traits of bacteria, such as antibiotic, siderophore or exoenzyme (like cellulose, pectinase) production, virulence factors of pathogens, as well as symbiotic interactions, are regulated in a population density-dependent manner by using small signaling molecules. This phenomenon, called quorum sensing (QS), is widespread among bacteria. Many different bacterial species are communicating or "speaking" through diffusible small molecules. The production often is sophisticatedly regulated via an autoinducing mechanism. A good example is the production of N-acyl homoserine lactones (AHL), which occur in many variations of molecular structure in a wide variety of Gram-negative bacteria. In Gram-positive bacteria, other compounds, such as peptides, regulate cellular activity and behavior by sensing the cell density. The degradation of the signaling molecule--called quorum quenching--is probably another important integral part in the complex quorum sensing circuit. Most interestingly, bacterial quorum sensing molecules also are recognized by eukaryotes that are colonized by QS-active bacteria. In this case, the cross-kingdom interaction can lead to specific adjustment and physiological adaptations in the colonized eukaryote. The responses are manifold, such as modifications of the defense system, modulation of the immune response, or changes in the hormonal status and growth responses. Thus, the interaction with the quorum sensing signaling molecules of bacteria can profoundly change the physiology of higher organisms too. Higher organisms are obligatorily associated with microbial communities, and these truly multi-organismic consortia, which are also called holobionts, can actually be steered via multiple interlinked signaling substances that originate not only from the host but also from the associated bacteria. PMID:22648507

Hartmann, Anton; Schikora, Adam

2012-05-31

292

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

PubMed Central

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

Steiner, Elisabeth; Scott, Jamie

2012-01-01

293

Label-Free Critical Micelle Concentration Determination of Bacterial Quorum Sensing Molecules  

PubMed Central

A practical label-free method for the rapid determination of small-molecule critical micelle concentration (CMC) using a fixed-angle light-scattering technique is described. Change in 90° light scattering at a fixed wavelength of incident radiation with increasing bacterial quorum molecule concentration and the observation of a break point is used to determine CMC. In our study, this technique is utilized to investigate the aqueous CMC of previously uncharacterized Pseudomonas aeruginosa quorum sensing signaling molecules (QSSM) belonging to the n-acylhomoserine lactone and 2-alkyl-4-quinolone classes. Several were found to form micelles within a physiologically relevant concentration range and potential roles of these micelles as QSSM transporters are discussed. The influence of temperature and the presence of biological membranes or serum proteins on QSSM CMC are also investigated and evidence is obtained to suggest the QSSMs studied are capable of both membrane and serum protein interaction. This demonstrates that the fixed-angle light-scattering technique outlined can be used simply and rapidly to determine small-molecule CMC under a variety of conditions.

Davis, B.M.; Richens, J.L.; O'Shea, P.

2011-01-01

294

Conformational Change-Induced Repeat Domain Expansion Regulates Rap Phosphatase Quorum-Sensing Signal Receptors  

PubMed Central

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

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

2013-01-01

295

Small RNA-mediated switch-like regulation in bacterial quorum sensing.  

PubMed

Quorum sensing (QS) is a signalling mechanism by which bacteria produce, release and then detect and respond to changes in their density and biosignals called autoinducers (AIs). There are multiple feedback loops in the QS system of Vibrio harveyi. However, how these feedback loops function to control signal processing remains unclear. In this study, the authors present a computational model for the switch-like regulation of signal transduction by small regulatory RNA-mediated QS based on intertwined network involving AIs, LuxO, LuxU, Qrr sRNAs and LuxR. In agreement with experimental observations, the model suggests that different feedbacks play critical roles in the switch-like regulation. The authors results reveal that V. harveyi uses multiple feedbacks to precisely control signal transduction. PMID:24067418

Liu, Xi; Zhou, Peipei; Wang, Ruiqi

2013-10-01

296

Small Protein-Mediated Quorum Sensing in a Gram-Negative Bacterium  

PubMed Central

The rice XA21 pattern recognition receptor binds a type I secreted sulfated peptide, called axYS22, derived from the Ax21 (activator of XA21-mediated immunity) protein. The conservation of Ax21 in all sequenced Xanthomonas spp. and closely related genera suggests that Ax21 serves a key biological function. Here we show that the predicted N-terminal sequence of Ax21 is cleaved prior to secretion outside the cell and that mature Ax21 serves as a quorum sensing (QS) factor in Xanthomonas oryzae pv. oryzae. Ax21-mediated QS controls motility, biofilm formation and virulence. We provide genetic evidence that the Xoo RaxH histidine kinase serves as the bacterial receptor for Ax21. This work establishes a critical role for small protein-mediated QS in a Gram-negative bacterium.

Sharma, Manoj; Bahar, Ofir; Bower, Zachary; Ronald, Pamela C.

2011-01-01

297

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

PubMed

Streptococci are among the predominant bacterial species living in the human body. They are normally harmless bacteria, but have the ability to cause diverse infections, ranging from mild (e.g., tooth decay and sore throat) to life-threatening (e.g., endocarditis and meningitis). Streptococci have evolved various means of coping with the deleterious effects of environmental stressors and avoiding the host immune system. Recently, several studies have shown that streptococci colonizing the mouth and upper respiratory tract are able to mount complex stress responses in order to persist and successfully survive competition in their ecological niche. Using a small quorum-sensing peptide pheromone acting as a stress-inducible 'alarmone', oral streptococci synchronize the gene expression of a specific group of cells to coordinate important biological activities. PMID:23642115

Dufour, Delphine; Lévesque, Céline M

2013-05-01

298

Tailor-made LasR agonists modulate quorum sensing in Pseudomonas aeruginosa.  

PubMed

The primary quorum sensing system in the opportunistic pathogen Pseudomonas aeruginosa is regulated through the synthesis and secretion of N-3-oxo-dodecanoyl-l-homoserine lactone (C12) which binds the transcriptional activator LasR. In this study we report the design, synthesis and biological evaluation of new analogs of C12. Analysis of the autoinducer binding site cavity of LasR revealed a positively charged cavity near the center of bound C12. Accordingly, we synthesized two piperidine-C12 diastereoisomers and tested their biological activity. Both analogs proved to be strong LasR agonists that showed a synergistic effect when presented together with the natural ligand. Moreover, binding of the analogs resulted in phenotypic changes characteristic of QS controlled receptor activation. PMID:24057196

Rabin, Nira; Delago, Antonia; Inbal, Boaz; Krief, Pnina; Meijler, Michael M

2013-10-01

299

A cell-cell communication signal integrates quorum sensing and stress response.  

PubMed

Pseudomonas aeruginosa uses a hierarchical quorum sensing (QS) network consisting of las, pqs and rhl regulatory elements to coordinate the expression of bacterial virulence genes. However, clinical isolates frequently contain loss-of-function mutations in the central las system. This motivated us to search for a mechanism that may functionally substitute las. Here we report identification of a new QS signal, IQS. Disruption of IQS biosynthesis paralyzes the pqs and rhl QS systems and attenuates bacterial virulence. Production of IQS is tightly controlled by las under normal culture conditions but is also activated by phosphate limitation, a common stressor that bacteria encounter during infections. Thus, these results have established an integrated QS system that connects the central las system and phosphate-stress response mechanism to the downstream pqs and rhl regulatory systems. Our discovery highlights the complexity of QS signaling systems and extends the gamut of QS and stress-response mechanisms. PMID:23542643

Lee, Jasmine; Wu, Jien; Deng, Yinyue; Wang, Jing; Wang, Chao; Wang, Jianhe; Chang, Changqing; Dong, Yihu; Williams, Paul; Zhang, Lian-Hui

2013-03-31

300

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

PubMed Central

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

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

2012-01-01

301

Reverse engineering gene regulatory networks related to quorum sensing in the plant pathogen Pectobacterium atrosepticum.  

PubMed

The objective of the project reported in the present chapter was the reverse engineering of gene regulatory networks related to quorum sensing in the plant pathogen Pectobacterium atrosepticum from micorarray gene expression profiles, obtained from the wild-type and eight knockout strains. To this end, we have applied various recent methods from multivariate statistics and machine learning: graphical Gaussian models, sparse Bayesian regression, LASSO (least absolute shrinkage and selection operator), Bayesian networks, and nested effects models. We have investigated the degree of similarity between the predictions obtained with the different approaches, and we have assessed the consistency of the reconstructed networks in terms of global topological network properties, based on the node degree distribution. The chapter concludes with a biological evaluation of the predicted network structures. PMID:20835805

Lin, Kuang; Husmeier, Dirk; Dondelinger, Frank; Mayer, Claus D; Liu, Hui; Prichard, Leighton; Salmond, George P C; Toth, Ian K; Birch, Paul R J

2010-01-01

302

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

2006-01-06

303

Detection of quorum sensing signals in the haloalkaliphilic archaeon Natronococcus occultus.  

PubMed

Bacteria communicate at high cell density through quorum sensing, however, there are no reports about this mechanism in archaea. The archaeon Natronococcus occultus produces an extracellular protease at the end of growth. Early production of protease activity was observed when a low density culture was incubated with late exponential conditioned medium suggesting the presence of factor(s) inducing this activity. Conditioned medium and ethyl acetate extracts corresponding to the transition from exponential to stationary phase showed a positive signal in Agrobacterium biosensor. We report the detection of potential autoinducer molecules of the acylated homoserine lactone type in the archaeon N. occultus. These molecules may be responsible for the production/activation of extracellular protease. PMID:12694909

Paggi, Roberto A; Martone, Celina B; Fuqua, Clay; De Castro, Rosana E

2003-04-11

304

Modelling antibiotic- and anti-quorum sensing treatment of a spatially-structured Pseudomonas aeruginosa population.  

PubMed

The bacterial cell to cell signalling system known as quorum sensing (QS) is essential for the regulation of virulence in many pathogens and offers a specific biochemical target for novel antibacterial therapies. Expanding on earlier work, in which consideration was given to the primary QS system (lasR system) in a homogeneous population of the common human pathogen Pseudomonas aeruginosa, we build a simple spatial model of an early-stage P. aeruginosa biofilm subject to treatment with topically applied anti-QS drugs (of two specific kinds) and conventional antibiotics. In the case of a slowly growing biofilm we show that both kinds of anti-quorum sensing drug are effective in reducing the level of the relevant signal molecule (3-oxo-C12-homoserine lactone; henceforth AHL), in each case obtaining an explicit bound on the steady-state AHL profile in terms of a prescribed surface drug concentration. Using numerical methods, we are also able to reproduce the hysteretic phenomena exhibited by the homogeneous model, in particular showing that for each kind of anti-QS drug there is a parameter regime in which a catastrophic collapse occurs in the steady-state AHL concentration as the surface drug concentration passes some critical value; an alternative way of interpreting this result is to say that, for a prescribed surface drug concentration, there is a critical biofilm depth such that treatment is successful until this depth is reached, but fails thereafter. In the thick-biofilm limit we show that the critical concentration of each drug increases exponentially with the biofilm thickness (or, conversely, that the critical depth increases logarithmically with surface drug concentration); this is dramatically different to the behaviour observed in the corresponding homogeneous model, where the critical concentrations grow linearly with bacterial carrying capacity, and thus highlights the relative difficulty of treating a large, spatially-structured population with diffusing antibacterials. PMID:16012802

Anguige, K; King, J R; Ward, J P

2005-07-13

305

Differential immune modulatory activity of Pseudomonas aeruginosa quorum-sensing signal molecules.  

PubMed

Pseudomonas aeruginosa releases a spectrum of well-regulated virulence factors, controlled by intercellular communication (quorum sensing) and mediated through the production of small diffusible quorum-sensing signal molecules (QSSM). We hypothesize that QSSM may in fact serve a dual purpose, also allowing bacterial colonization via their intrinsic immune-modulatory capacity. One class of signal molecule, the N-acylhomoserine lactones, has pleiotropic effects on eukaryotic cells, particularly those involved in host immunity. In the present study, we have determined the comparative effects of two chemically distinct and endobronchially detectable QSSM, N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12-HSL) and 2-heptyl-3-hydroxy-4 (1H)-quinolone or the Pseudomonas quinolone signal (PQS), on human leukocytes exposed to a series of stimuli designed to detect differential immunological activity in vitro. 3-Oxo-C12-HSL and PQS displayed differential effects on the release of interleukin-2 (IL-2) when human T cells were activated via the T-cell receptor and CD28 (a costimulatory molecule). 3-Oxo-C12-HSL inhibited cell proliferation and IL-2 release; PQS inhibited cell proliferation without affecting IL-2 release. Both molecules inhibited cell proliferation and the release of IL-2 following mitogen stimulation. Furthermore, in the presence of Escherichia coli lipopolysaccharide, 3-oxo-C12-HSL inhibited tumor necrosis factor alpha release from human monocytes, as reported previously (K. Tateda et al., Infect. Immun. 64:37-43, 1996), whereas PQS did not inhibit in this assay. These data highlight the presence of two differentially active immune modulatory QSSM from P. aeruginosa, which are detectable endobronchially and may be active at the host/pathogen interface during infection with P. aeruginosa, should the bronchial airway lymphoid tissues prove to be accessible to QSSM. PMID:15501777

Hooi, Doreen S W; Bycroft, Barrie W; Chhabra, Siri Ram; Williams, Paul; Pritchard, David I

2004-11-01

306

Involvement of Bacterial Quorum-Sensing Signals in Spoilage of Bean Sprouts  

PubMed Central

Bacterial communication signals, acylated homoserine lactones (AHLs), were extracted from samples of commercial bean sprouts undergoing soft-rot spoilage. Bean sprouts produced in the laboratory did not undergo soft-rot spoilage and did not contain AHLs or AHL-producing bacteria, although the bacterial population reached levels similar to those in the commercial sprouts, 108 to 109 CFU/g. AHL-producing bacteria (Enterobacteriaceae and pseudomonads) were isolated from commercial sprouts, and strains that were both proteolytic and pectinolytic were capable of causing soft-rot spoilage in bean sprouts. Thin-layer chromatography and liquid chromatography-high-resolution mass spectrometry revealed the presence of N-3-oxo-hexanoyl-l-homoserine lactone in spoiled bean sprouts and in extracts from pure cultures of bacteria. During normal spoilage, the pH of the sprouts increased due to proteolytic activity, and the higher pH probably facilitated the activity of pectate lyase. The AHL synthetase gene (I gene) from a spoilage Pectobacterium was cloned, sequenced, and inactivated in the parent strain. The predicted amino acid sequence showed 97% homology to HslI and CarI in Erwinia carotovora. Spoilage of laboratory bean sprouts inoculated with the AHL-negative mutant was delayed compared to sprouts inoculated with the wild type, and the AHL-negative mutant did not cause the pH to rise. Compared to the wild-type strain, the AHL-negative mutant had significantly reduced protease and pectinase activities and was negative in an iron chelation (siderophore) assay. This is the first study demonstrating AHL regulation of iron chelation in Enterobacteriaceae. The present study clearly demonstrates that the bacterial spoilage of some food products is influenced by quorum-sensing-regulated phenotypes, and understanding these processes may be useful in the development of novel food preservation additives that specifically block the quorum-sensing systems.

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

2005-01-01

307

Chitinolytic Activity in Chromobacterium violaceum: Substrate Analysis and Regulation by Quorum Sensing  

PubMed Central

Quorum sensing control mediated by N-acyl homoserine lactone (AHL) signaling molecules has been established as a key feature of the regulation of exoenzyme production in many gram-negative bacteria. In Chromobacterium violaceum ATCC 31532 a number of phenotypic characteristics, including production of the purple pigment violacein, hydrogen cyanide, antibiotics, and exoproteases are known to be regulated by the endogenous AHL N-hexanoyl-l-homoserine lactone (HHL). In this study we show that C. violaceum produces a set of chitinolytic enzymes whose production is regulated by HHL. The chitinolytic activity was induced in strains grown in the presence of chitin as the sole carbon source and quantitated in the secreted proteins by using p-nitrophenol analogs of disaccharide, trisaccharide, and tetrasaccharide oligomers of N-acetylglucosamine. By using 4-methylumbelliferyl analogs of the same oligomers of N-acetylglucosamine as substrates for proteins separated and renatured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, at least six enzymes were detected: a chitobiase with high specificity to a dimeric substrate of 87 kDa, two N-acetylglucosaminidases with apparent molecular masses of 162 and 133 kDa, two endochitinases of 108 and 67 kDa, and a chitobiosidase of 56 kDa. In addition, two unidentified bands of >205 kDa were found where a tetrameric chitin derivative was used as a substrate. A pleiotropic mini-Tn5 mutant of C. violaceum (CV026) that is defective in HHL production and other quorum-sensing-regulated factors was also found to be completely deficient in chitinolytic activity. Growth of this mutant on minimal medium with chitin supplemented with culture supernatant from the C. violaceum wild-type strain or 10 ?M synthetic HHL restored chitinase production to the level shown by the parental strain. These results constitute the most complete evidence so far for regulation of chitinolytic activity by AHL signaling in a gram-negative bacterium.

Chernin, Leonid S.; Winson, Michael K.; Thompson, Jacquelyn M.; Haran, Shoshan; Bycroft, Barrie W.; Chet, Ilan; Williams, Paul; Stewart, Gordon S. A. B.

1998-01-01

308

Interference of quorum sensing in Pseudomonas syringae by bacterial epiphytes that limit iron availability.  

PubMed

Leaf surfaces harbour bacterial epiphytes that are capable of influencing the quorum sensing (QS) system, density determination through detection of diffusible signal molecules, of the plant-pathogen Pseudomonas syringae pv. syringae (Pss) which controls expression of extracellular polysaccharide production, motility and other factors contributing to virulence to plants. Approximately 11% of the bacterial epiphytes recovered from a variety of plants produced a diffusible factor capable of inhibiting the QS system of Pss as indicated by suppression of ahlI. Blockage of QS by these interfering strains correlated strongly with their ability to limit iron availability to Pss. A direct relationship between the ability of isogenic Escherichia coli strains to sequester iron via their production of different siderophores and their ability to suppress QS in Pss was also observed. Quorum sensing induction was inversely related to iron availability in culture media supplemented with iron chelators or with FeCl(3). Co-inoculation of interfering strains with Pss onto leaves increased the number of resultant disease lesions over twofold compared with that on plants inoculated with Pss alone. Transposon-generated mutants of interfering strains in which QS inhibition was blocked did not increase disease when co-inoculated with Pss. Increased disease incidence was also not observed when a non-motile mutant of Pss was co-inoculated onto plants with QS interfering bacteria suggesting that these strains enhanced the motility of Pss in an iron-dependent manner, leading to an apparent increase in virulence of this pathogen. Considerable cross-talk mediated by iron scavenging apparently occurs on plants, thereby altering the behaviour of bacteria such as Pss that exhibit important QS-dependent traits in this habitat. PMID:20553555

Dulla, Glenn F J; Krasileva, Ksenia V; Lindow, Steven E

2010-06-01

309

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.

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

2012-01-01

310

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

311

Quorum Sensing-Disrupting Brominated Furanones Protect the Gnotobiotic Brine Shrimp Artemia franciscana from Pathogenic Vibrio harveyi, Vibrio campbellii, and Vibrio parahaemolyticus Isolates†  

PubMed Central

Autoinducer 2 (AI-2) quorum sensing was shown before to regulate the virulence of Vibrio harveyi towards the brine shrimp Artemia franciscana. In this study, several different pathogenic V. harveyi, Vibrio campbellii, and Vibrio parahaemolyticus isolates were shown to produce AI-2. Furthermore, disruption of AI-2 quorum sensing by a natural and a synthetic brominated furanone protected gnotobiotic Artemia from the pathogenic isolates in in vivo challenge tests.

Defoirdt, Tom; Crab, Roselien; Wood, Thomas K.; Sorgeloos, Patrick; Verstraete, Willy; Bossier, Peter

2006-01-01

312

Quorum sensing-disrupting brominated furanones protect the gnotobiotic brine shrimp Artemia franciscana from pathogenic Vibrio harveyi, Vibrio campbellii, and Vibrio parahaemolyticus isolates.  

PubMed

Autoinducer 2 (AI-2) quorum sensing was shown before to regulate the virulence of Vibrio harveyi towards the brine shrimp Artemia franciscana. In this study, several different pathogenic V. harveyi, Vibrio campbellii, and Vibrio parahaemolyticus isolates were shown to produce AI-2. Furthermore, disruption of AI-2 quorum sensing by a natural and a synthetic brominated furanone protected gnotobiotic Artemia from the pathogenic isolates in in vivo challenge tests. PMID:16957276

Defoirdt, Tom; Crab, Roselien; Wood, Thomas K; Sorgeloos, Patrick; Verstraete, Willy; Bossier, Peter

2006-09-01

313

The impact of mutations in the quorum sensing systems of Aeromonas hydrophila, Vibrio anguillarum and Vibrio harveyi on their virulence towards gnotobiotically cultured Artemia franciscana.  

PubMed

Disruption of quorum sensing, bacterial cell-to-cell communication by means of small signal molecules, has been suggested as a new anti-infective strategy for aquaculture. However, data about the impact of quorum sensing on the virulence of aquatic pathogens are scarce. In this study, a model system using gnotobiotically cultured Artemia franciscana was developed in order to determine the impact of mutations in the quorum sensing systems of Aeromonas hydrophila, Vibrio anguillarum and V. harveyi on their virulence. Mutations in the autoinducer 2 (AI-2) synthase gene luxS, the AI-2 receptor gene luxP or the response regulator gene luxO of the dual channel quorum sensing system of V. harveyi abolished virulence of the strain towards Artemia. Moreover, the addition of an exogenous source of AI-2 could restore the virulence of an AI-2 non-producing mutant. In contrast, none of the mutations in either the acylated homoserine lactone (AHL)-mediated component of the V. harveyi system or the quorum sensing systems of Ae. hydrophila and V. anguillarum had an impact on virulence of these bacteria towards Artemia. Our results indicate that disruption of quorum sensing could be a good alternative strategy to combat infections caused by V. harveyi. PMID:16011761

Defoirdt, Tom; Bossier, Peter; Sorgeloos, Patrick; Verstraete, Willy

2005-08-01

314

A case study on chemical defense based on quorum sensing: antibacterial activity of sponge-associated bacterium Pseudoalteromonas sp. NJ6-3-1 induced by quorum sensing mechanisms  

Microsoft Academic Search

A case study to investigate the relationship between antibacterial activity and quorum sensing mechanisms was carried out\\u000a on a sponge-associated bacterium with remarkable biological activities: Pseudoalteromonas sp. NJ6-3-1. The dependence of active substance production on cell density was studied under various growth conditions. Bacteria\\u000a NJ6-3-1 was found to start producing antibacterial compounds only when cell density reached the threshold value

Xiuchun Guo; Li Zheng; Wenhui Zhou; Zhisong Cui; Ping Han; Li Tian; Xiaoru Wang

2011-01-01

315

The junctional integrity of epithelial cells is modulated by Pseudomonas aeruginosa quorum sensing molecule through phosphorylation-dependent mechanisms.  

PubMed

In Pseudomonas aeruginosa, cell-cell communication based on acyl-homoserine lactone (HSL) quorum sensing molecules is known to coordinate the production of virulence factors and biofilms by the bacterium. Incidentally, these bacterial signals can also modulate mammalian cell behaviour. We report that 3O-C(12)-HSL can disrupt adherens junctions in human epithelial Caco-2 cells as evidenced by a reduction of the expression and distribution of E-cadherin and beta-catenin. Using co-immunoprecipitation we also found that P. aeruginosa 3O-C(12)-HSL-treatment resulted in tyrosine hyperphosphorylation of E-cadherin, beta-catenin, occludin and ZO-1. Similarly, serine and threonine residues of E-cadherin and ZO-1 became more phosphorylated after 3O-C(12)-HSL treatment. On the contrary, occludin and beta-catenin underwent dephosphorylation on serine and threonine residues after exposition of 3O-C(12)-HSL. These changes in the phosphorylation state were paralleled by alteration in the structure of junction complexes and increased paracellular permeability. Moreover, pre-treatment of the Caco-2 cells with protein phosphatase and kinase inhibitors prevented 3O-C(12)-HSL-induced changes in paracellular permeability and interactions between occludin-ZO-1 and the E-cadherin-beta-catenin. These findings clearly suggest that an alteration in the phosphorylation status of junction proteins are involved in the changes in cell junction associations and enhanced paracellular permeability, and that bacterial signals are indeed sensed by the host cells. PMID:19038248

Vikström, Elena; Bui, Lan; Konradsson, Peter; Magnusson, Karl-Eric

2008-11-12

316

The quorum quenching antibody RS2-1G9 protects macrophages from the cytotoxic effects of the Pseudomonas aeruginosa quorum sensing signalling molecule N-3-oxo-dodecanoyl-homoserine lactone.  

PubMed

The Gram-negative bacterium Pseudomonas aeruginosa, an opportunistic human pathogen, uses acyl-homoserine lactone-based quorum sensing systems to control its pathogenicity. One of its quorum sensing factors, N-3-oxo-dodecanoyl-homoserine lactone, has been shown not only to mediate bacterial quorum sensing but also to exert cytotoxic effects on mammalian cells. The monoclonal antibody RS2-1G9 generated against a 3-oxo-dodecanoyl-homoserine lactone analogue hapten was able to protect murine bone marrow-derived macrophages from the cytotoxic effects and also prevented the activation of the mitogen-activated protein kinase p38. These data demonstrate that an immunopharmacotherapeutic approach to combat P. aeruginosa infections might be a viable therapeutic option as the monoclonal antibody RS2-1G9 can readily sequester bacterial N-3-oxo-dodecanoyl-homoserine lactone molecules, thus interfering with their biological effects in prokaryotic and eukaryotic systems. PMID:18304641

Kaufmann, Gunnar F; Park, Junguk; Mee, Jenny M; Ulevitch, Richard J; Janda, Kim D

2008-03-04

317

A multitask biosensor for micro-volumetric detection of N-3-oxo-dodecanoyl-homoserine lactone quorum sensing signal.  

PubMed

N-3-oxo-dodecanoyl-homoserine lactone (3OC(12)-HSL) is the main quorum sensing (QS) signal produced by the human pathogen Pseudomonas aeruginosa, a major cause of hard-to-treat nosocomial infections and years-lasting chronic biofilm infections in the lungs of cystic fibrosis (CF) patients. 3OC(12)-HSL-dependent QS is considered a promising target for novel anti-pseudomonads drugs. However, the screening systems employed to date for the identification of QS inhibitors (QSI) were aimed at the identification of inhibitors of 3OC(12)-HSL signaling rather than of the synthesis or the export of this molecule. Moreover, the low concentration of 3OC(12)-HSL in CF sputum has hampered large scale studies aimed at addressing the role of this molecule in the CF lung infection. Here we describe the construction and characterization of PA14-R3, a new whole-cell biosensor for the quantitative detection of 3OC(12)-HSL. PA14-R3 provides fast and direct quantification of 3OC(12)-HSL over a wide range of concentrations (from pM to ?M), and proved to be an easy-to-handle, cost-effective and reliable biosensor for high-throughput screening of 3OC(12)-HSL levels in samples of different origin, including CF sputum. Moreover, the specific features of PA14-R3 made it possible to develop and validate a novel high-throughput screening system for QSI based on the co-cultivation of PA14-R3 with the PA14 wild-type strain. With respect to previous screening systems for QSI, this approach has the advantage of being cost-effective and allowing the identification of compounds targeting, besides 3OC(12)-HSL signaling, any cellular process critical for QS response, including 3OC(12)-HSL synthesis and secretion. PMID:21324665

Massai, Francesco; Imperi, Francesco; Quattrucci, Serena; Zennaro, Elisabetta; Visca, Paolo; Leoni, Livia

2011-01-25

318

Individual and Combined Roles of the Master Regulators AphA and LuxR in Control of the Vibrio harveyi Quorum-Sensing Regulon  

PubMed Central

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

van Kessel, Julia C.; Rutherford, Steven T.; Shao, Yi; Utria, Alan F.

2013-01-01

319

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

Microsoft Academic Search

Quorum sensing (QS) is a specific type of regulation of gene expression in bacteria; it is dependent on the population density.\\u000a QS systems include two obligate components: a low-molecular-weight regulator (autoinducer), readily diffusible through the\\u000a cytoplasmic membrane, and a regulatory receptor protein, which interacts with the regulator. As the bacterial population reaches\\u000a a critical level of density, autoinducers accumulate to

I. A. Khmel

2006-01-01

320

Evidence for a Functional Quorum-Sensing Type AI-1 System in the Extremophilic Bacterium Acidithiobacillus ferrooxidans†  

PubMed Central

Acidithiobacillus ferrooxidans is one of the main acidophilic chemolithotrophic bacteria involved in the bioleaching of metal sulfide ores. The bacterium-mineral interaction requires the development of biofilms, whose formation is regulated in many microorganisms by type AI-1 quorum sensing. Here, we report the existence and characterization of a functional type AI-1 quorum-sensing system in A. ferrooxidans. This microorganism produced mainly acyl-homoserine lactones (AHL) with medium and large acyl chains and different C-3 substitutions, including 3-hydroxy-C8-AHL, 3-hydroxy-C10-AHL, C12-AHL, 3-oxo-C12-AHL, 3-hydroxy-C12-AHL, C14-AHL, 3-oxo-C14-AHL, 3-hydroxy-C14-AHL, and 3-hydroxy-C16-AHL. A quorum-sensing genetic locus that includes two open reading frames, afeI and afeR, which have opposite orientations and code for proteins with high levels of similarity to members of the acyl synthase (I) and transcriptional regulator (R) protein families, respectively, was identified. Overexpression of AfeI in Escherichia coli and the associated synthesis of AHLs confirmed that AfeI is an AHL synthase. As determined by reverse transcription-PCR, the afeI and afeR genes were transcribed in A. ferrooxidans. The transcription levels of the afeI gene were higher in cells grown in sulfur and thiosulfate media than in iron-grown cells. Phosphate starvation induced an increase in the transcription levels of afeI which correlated with an increase in AHL levels. Two afe boxes which could correspond to the AfeR binding sites were identified upstream of the afeI gene. This is the first report of a functional type AI-1 quorum-sensing system in an acidophilic chemolithotrophic microorganism, and our results provide a very interesting opportunity to explore the control and regulation of biofilm formation during the bioleaching process.

Farah, Carolina; Vera, Mario; Morin, Daniele; Haras, Dominique; Jerez, Carlos A.; Guiliani, Nicolas

2005-01-01

321

Regulatory targets of quorum sensing in Vibrio cholerae: evidence for two distinct HapR-binding motifs  

Microsoft Academic Search

The quorum-sensing pathway in Vibrio cholerae controls the expression of the master regulator HapR, which in turn regulates several important pro- cesses such as virulence factor production and bio- film formation. While HapR is known to control several important phenotypes, there are only a few target genes known to be transcriptionally regulated by HapR. In this work, we combine bioinformatic

Amy M. Tsou; Tao Cai; Zhi Liu; Jun Zhu; Rahul V. Kulkarni

2009-01-01

322

Response of Arabidopsis thaliana to N -hexanoyl- dl -homoserine-lactone, a bacterial quorum sensing molecule produced in the rhizosphere  

Microsoft Academic Search

The bacterial quorum sensing signals N-acyl-l-homoserine lactones enable bacterial cells to regulate gene expression depending on population density, in order to undertake\\u000a collective actions such as the infection of host cells. Only little is known about the molecular ways of plants reacting to\\u000a these bacterial signals. In this study we show that the contact of Arabidopsis thaliana roots with N-hexanoyl-dl-homoserine-lactone

Uta von Rad; Ilona Klein; Petre I. Dobrev; Jana Kottova; Eva Zazimalova; Agnes Fekete; Anton Hartmann; Philippe Schmitt-Kopplin; Jörg Durner

2008-01-01

323

Virulence Effect of Enterococcus faecalis Protease Genes and the Quorum-Sensing Locus fsr in Caenorhabditis elegans and Mice  

Microsoft Academic Search

The expression of two Enterococcus faecalis extracellular virulence-related proteins, gelatinase (GelE) and serine protease (SprE), has been shown to be positively regulated by the fsr quorum-sensing system. We recently developed a novel system for studying E. faecalis pathogenicity that involves killing of the nematode worm Caenorhabditis elegans and showed that an E. faecalis fsrB mutant (strain TX5266) exhibited attenuated killing.

Costi D. Sifri; Eleftherios Mylonakis; Kavindra V. Singh; Xiang Qin; Danielle A. Garsin; Barbara E. Murray; Frederick M. Ausubel; Stephen B. Calderwood

2002-01-01

324

Salmonella Typhimurium invasion of HEp2 epithelial cells in vitro is increased by N -acylhomoserine lactone quorum sensing signals  

Microsoft Academic Search

Background  In Gram-negative bacteria, the most commonly studied quorum sensing signals are the N-acylhomoserine lactones (AHLs). In Salmonella, AHLs are recognized by SdiA, which is believed to be a sensor of AHLs produced by other bacteria, since Salmonella does not produce AHLs itself. It has been speculated that AHLs produced by the gastrointestinal flora may influence the regulation\\u000a of virulence traits

Live L Nesse; Kristin Berg; Lene K Vestby; Ingrid Olsaker; Berit Djønne

2011-01-01

325

Quorum sensing in halophilic bacteria: detection of N -acyl-homoserine lactones in the exopolysaccharide-producing species of Halomonas  

Microsoft Academic Search

Some members of the moderately halophilic genus Halomonas, such as H. eurihalina, H. maura, H. ventosae and H. anticariensis, produce exopolysaccharides with applications in many industrial fields. We report here that these four species also produce autoinducer molecules that are involved in the cell-to-cell signaling process known as quorum sensing. By using the N-acyl homoserine lactone (AHL) indicator strains Agrobacterium

Inmaculada Llamas; Emilia Quesada; Maria José Martínez-Cánovas; Matthew Gronquist; Anatol Eberhard; Juan E. González

2005-01-01

326

Mucoidy, Quorum Sensing, Mismatch Repair and Antibiotic Resistance in Pseudomonas aeruginosa from Cystic Fibrosis Chronic Airways Infections  

Microsoft Academic Search

Survival of Pseudomonas aeruginosa in cystic fibrosis (CF) chronic infections is based on a genetic adaptation process consisting of mutations in specific genes, which can produce advantageous phenotypic switches and ensure its persistence in the lung. Among these, mutations inactivating the regulators MucA (alginate biosynthesis), LasR (quorum sensing) and MexZ (multidrug-efflux pump MexXY) are the most frequently observed, with those

Sofía Feliziani; Adela M. Luján; Alejandro J. Moyano; Claudia Sola; José L. Bocco; Patricia Montanaro; Liliana Fernández Canigia; Carlos E. Argaraña; Andrea M. Smania

2010-01-01

327

Regulation of the violacein biosynthetic gene cluster by acylhomoserine lactone-mediated quorum sensing in Chromobacterium violaceum ATCC 12472.  

PubMed

Chromobacterium violaceum produces the purple pigment violacein by quorum-sensing regulation. 20-bp of the lux box-like sequence was found upstream of vioA in C. violaceum ATCC 12472. CviR received C10-HSL and C6-HSL and activated the transcription of vioA in Escherichia coli. However, in strain ATCC 12472, C6-HSL inhibited both C10-HSL-mediated violacein production and the transcription of vioA. PMID:20944413

Morohoshi, Tomohiro; Fukamachi, Katsumasa; Kato, Masashi; Kato, Norihiro; Ikeda, Tsukasa

2010-10-07

328

Quorum Sensing and Phenazines are Involved in Biofilm Formation by Pseudomonas chlororaphis (aureofaciens) Strain 30-84  

Microsoft Academic Search

The biological control bacterium Pseudomonas chlororaphis (aureofaciens) strain 30-84 employs two quorum sensing (QS) systems: PhzR\\/PhzI regulates the production of the antibiotics phenazine-1-carboxylic acid, 2-hydroxy-phenazine-1-carboxylic acid, and 2-hydroxy-phenazine, whereas CsaR\\/CsaI regulates currently unknown aspects of the cell surface. Previously characterized derivatives of strain 30-84 with mutations in each QS system and in the phenazine biosynthetic genes were screened for their

V. S. R. K. Maddula; Z. Zhang; E. A. Pierson; L. S. Pierson

2006-01-01

329

The cep quorum-sensing system of Burkholderia cepacia H111 controls biofilm formation and swarming motility.  

PubMed

Burkholderia cepacia and Pseudomonas aeruginosa often co-exist as mixed biofilms in the lungs of patients suffering from cystic fibrosis (CF). Here, the isolation of random mini-Tn5 insertion mutants of B. cepacia H111 defective in biofilm formation on an abiotic surface is reported. It is demonstrated that one of these mutants no longer produces N-acylhomoserine lactones (AHLs) due to an inactivation of the cepR gene. cepR and the cepI AHL synthase gene together constitute the cep quorum-sensing system of B. cepacia. By using a gene replacement method, two defined mutants, H111-I and H111-R, were constructed in which cepI and cepR, respectively, had been inactivated. These mutants were used to demonstrate that biofilm formation by B. cepacia H111 requires a functional cep quorum-sensing system. A detailed quantitative analysis of the biofilm structures formed by wild-type and mutant strains suggested that the quorum-sensing system is not involved in the regulation of initial cell attachment, but rather controls the maturation of the biofilm. Furthermore, it is shown that B. cepacia is capable of swarming motility, a form of surface translocation utilized by various bacteria to rapidly colonize appropriate substrata. Evidence is provided that swarming motility of B. cepacia is quorum-sensing-regulated, possibly through the control of biosurfactant production. Complementation of the cepR mutant H111-R with different biosurfactants restored swarming motility while biofilm formation was not significantly increased. This result suggests that swarming motility per se is not essential for biofilm formation on abiotic surfaces. PMID:11535791

Huber, B; Riedel, K; Hentzer, M; Heydorn, A; Gotschlich, A; Givskov, M; Molin, S; Eberl, L

2001-09-01

330

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

Microsoft Academic Search

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

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

2005-01-01

331

Possible Quorum Sensing in Marine Snow Bacteria: Production of Acylated Homoserine Lactones by Roseobacter Strains Isolated from Marine Snow  

Microsoft Academic Search

We report here, for the first time, that bacteria associated with marine snow produce communication signals involved in quorum sensing in gram-negative bacteria. Four of 43 marine microorganisms isolated from marine snow were found to produce acylated homoserine lactones (AHLs) in well diffusion and thin-layer chromatographic assays based on the Agrobacterium tumefaciens reporter system. Three of the AHL-producing strains were

Lone Gram; Hans-Peter Grossart; Andrea Schlingloff; T. Kiorboe

2002-01-01

332

LuxS-dependent quorum sensing in Porphyromonas gingivalis modulates protease and haemagglutinin activities but is not essential for virulence  

Microsoft Academic Search

Porphyromonas gingivalis is a Gram-negative black-pigmented obligate anaerobe implicated in the aetiology of human periodontal disease. The virulence of P. gingivalis is associated with the elaboration of the cysteine proteases Arg-gingipain (Rgp) and Lys-gingipain (Kgp), which are produced at high bacterial cell densities. To determine whether quorum sensing plays a role in the regulation of Rgp and Kgp, biosensors capable

Nicola A. Burgess; David F. Kirke; Paul Williams; Klaus Winzer; Kim R. Hardie; Nicholas L. Meyers; Joseph Aduse-Opoku; Michael A. Curtis; SmithKline Beecham

333

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

Microsoft Academic Search

Received 22 November 2005\\/Accepted 7 December 2005 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

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

2006-01-01

334

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

Microsoft Academic Search

Quorum sensing (QS) is a bacterial cell-cell communication process by which bacteria communicate using extracellular signals called autoinducers. Two QS systems have been identified in Escherichia coli K-12, including an intact QS system 2 that is stimulated by the cyclic AMP (cAMP)-cAMP receptor protein (CRP) complex and a partial QS system 1 that consists of SdiA (suppressor of cell division

Xianxuan Zhou; Xiaoming Meng; Baolin Sun

2008-01-01

335

Quorum Sensing in Escherichia coli Is Signaled by AI2\\/LsrR: Effects on Small RNA and Biofilm Architecture  

Microsoft Academic Search

The regulatory network for the uptake of Escherichia coli autoinducer 2 (AI-2) is comprised of a transporter complex, LsrABCD; its repressor, LsrR; and a cognate signal kinase, LsrK. This network is an integral part of the AI-2 quorum-sensing (QS) system. Because LsrR and LsrK directly regulate AI-2 uptake, we hypothe- sized that they might play a wider role in regulating

Jun Li; Liang Wang; Thomas K. Wood; James J. Valdes; William E. Bentley

2007-01-01

336

Encapsulated fusion protein confers "sense and respond" activity to chitosan-alginate capsules to manipulate bacterial quorum sensing.  

PubMed

We demonstrate that "nanofactory"-loaded biopolymer capsules placed in the midst of a bacterial population can direct bacterial communication. Quorum sensing (QS) is a process by which bacteria communicate through small-molecules, such as autoinducer-2 (AI-2), leading to collective behaviors such as virulence and biofilm formation. In our approach, a "nanofactory" construct is created, which comprises an antibody complexed with a fusion protein that produces AI-2. These nanofactories are entrapped within capsules formed by electrostatic complexation of cationic (chitosan) and anionic (sodium alginate) biopolymers. The chitosan capsule shell is crosslinked by tripolyphosphate (TPP) to confer structural integrity. The capsule shell is impermeable to the encapsulated nanofactories, but freely permeable to small molecules. In turn, the capsules are able to take in substrates from the external medium via diffusion, and convert these via the nanofactories into AI-2, which then diffuses out. The exported AI-2 is shown to stimulate QS responses in vicinal Escherichia coli. Directing bacterial population behavior has potential applications in next-generation antimicrobial therapy and pathogen detection. We also envision such capsules to be akin to artificial "cells" that can participate in native biological signaling and communicate in real-time with the human microbiome. Through such interaction capabilities, these "cells" may sense the health of the microbiome, and direct its function in a desired, host-friendly manner. PMID:22903626

Gupta, Apoorv; Terrell, Jessica L; Fernandes, Rohan; Dowling, Matthew B; Payne, Gregory F; Raghavan, Srinivasa R; Bentley, William E

2012-09-18

337

Pseudomonas aeruginosa quorum-sensing signal molecules interfere with dendritic cell-induced T-cell proliferation.  

PubMed

Pseudomonas aeruginosa releases a wide array of toxins and tissue-degrading enzymes. Production of these malicious virulence factors is controlled by interbacterial communication in a process known as quorum sensing. An increasing body of evidence reveals that the bacterial signal molecule N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL) exhibits both quorum-sensing signalling and immune-modulating properties. Recently, yet another quorum-sensing signal molecule, the Pseudomonas quinolone signal (PQS), has been shown to affect cytokine release by mitogen-stimulated human T cells. In the present article we demonstrate that both OdDHL and PQS decrease the production of interleukin-12 (IL-12) by Escherichia coli lipopolysaccharide-stimulated bone marrow-derived dendritic cells (BM-DCs) without altering their IL-10 release. Moreover, BM-DCs exposed to PQS and OdDHL during antigen stimulation exhibit a decreased ability to induce T-cell proliferation in vitro. Collectively, this suggests that OdDHL and PQS change the maturation pattern of stimulated DCs away from a proinflammatory T-helper type I directing response, thereby decreasing the antibacterial activity of the adaptive immune defence. OdDHL and PQS thus seem to possess dual activities in the infection process: as inducers of virulence factors as well as immune-modulators facilitating the infective properties of this pathogen. PMID:19187218

Skindersoe, Mette E; Zeuthen, Louise H; Brix, Susanne; Fink, Lisbeth N; Lazenby, James; Whittall, Christine; Williams, Paul; Diggle, Stephen P; Froekiaer, Hanne; Cooley, Margaret; Givskov, Michael

2009-01-28

338

Detection of Pseudomonas aeruginosa quorum sensing signals in an infected ischemic wound: an experimental study in rats.  

PubMed

Quorum sensing is a cell-to-cell communication that occurs via autoinducers, regulating a number of bacterial virulence factors including the opportunistic wound pathogen Pseudomonas aeruginosa, which uses the N-(3-oxododecanoyl)-homoserine lactone as one of the two main autoinducers; however, little is known about its role in chronic wound infection. This study was designed to quantify this autoinducer from P. aeruginosa-infected wounds with the aim of examining the possible use of autoinducers as an indicator of chronic wound infection. Pressure-induced ischemic wounds were infected with P. aeruginosa (N=12) or uninfected as a control (N=12). The autoinducer was quantified by bioassay method employing Escherichia coli DH5 alpha (pJN105L, pSC11) or Agrobacterium tumefaciens NTL4 (pZLR4) reporter, which expresses beta-galactosidase when exposed to P. aeruginosa quorum sensing signals. The average concentration of autoinducer was 0.33 pmol/g at day 3 and 0.49 pmol/g at day 7 in the infected wounds, as detected from tissue samples. A linear correlation between autoinducer concentration and bacterial counts was observed. No autoinducer was detected in tissue samples from the uninfected control group. Our findings indicate that the quantification of autoinducers is possible and quorum sensing system could play a role in in vivo wound infection models, and also suggest possible clinical implications of autoinducer signal quantification in diagnosis of chronic wound infection. PMID:18211577

Nakagami, Gojiro; Sanada, Hiromi; Sugama, Junko; Morohoshi, Tomohiro; Ikeda, Tsukasa; Ohta, Yasunori

339

Degradation of Bacterial Quorum Sensing Signaling Molecules by the Microscopic Yeast Trichosporon loubieri Isolated from Tropical Wetland Waters.  

PubMed

Proteobacteria produce N-acylhomoserine lactones as signaling molecules, which will bind to their cognate receptor and activate quorum sensing-mediated phenotypes in a population-dependent manner. Although quorum sensing signaling molecules can be degraded by bacteria or fungi, there is no reported work on the degradation of such molecules by basidiomycetous yeast. By using a minimal growth medium containing N-3-oxohexanoylhomoserine lactone as the sole source of carbon, a wetland water sample from Malaysia was enriched for microbial strains that can degrade N-acylhomoserine lactones, and consequently, a basidiomycetous yeast strain WW1C was isolated. Morphological phenotype and molecular analyses confirmed that WW1C was a strain of Trichosporon loubieri. We showed that WW1C degraded AHLs with N-acyl side chains ranging from 4 to 10 carbons in length, with or without oxo group substitutions at the C3 position. Re-lactonisation bioassays revealed that WW1C degraded AHLs via a lactonase activity. To the best of our knowledge, this is the first report of degradation of N-acyl-homoserine lactones and utilization of N-3-oxohexanoylhomoserine as carbon and nitrogen source for growth by basidiomycetous yeast from tropical wetland water; and the degradation of bacterial quorum sensing molecules by an eukaryotic yeast. PMID:24072030

Wong, Cheng-Siang; Koh, Chong-Lek; Sam, Choon-Kook; Chen, Jian Woon; Chong, Yee Meng; Yin, Wai-Fong; Chan, Kok-Gan

2013-09-25

340

A Quorum-Sensing Antagonist Targets Both Membrane-Bound and Cytoplasmic Receptors And Controls Bacterial Pathogenicity  

PubMed Central

Summary Quorum sensing is a process of bacterial communication involving production and detection of secreted molecules called autoinducers. Gram-negative bacteria use acyl-homoserine lactone (AHL) autoinducers, which are detected by one of two receptor types. First, cytoplasmic LuxR-type receptors bind accumulated intracellular AHLs. AHL-LuxR complexes bind DNA and alter gene expression. Second, membrane-bound LuxN-type receptors bind accumulated extracellular AHLs. AHL-LuxN complexes relay information internally by phosphorylation cascades that direct gene-expression changes. Here we show that a small molecule, previously identified as an antagonist of LuxN-type receptors, is also a potent antagonist of the LuxR family, despite differences in receptor structure, localization, AHL specificity, and signaling mechanism. Derivatives were synthesized and optimized for potency, and in each case, we characterized the mode of action of antagonism. The most potent antagonist protects Caenorhabditis elegans from quorum-sensing-mediated killing by Chromobacterium violaceum, validating the notion that targeting quorum sensing has potential for antimicrobial drug development.

Swem, Lee R.; Swem, Danielle L.; O'Loughlin, Colleen T.; Gatmaitan, Raleene; Zhao, Bixiao; Ulrich, Scott M.; Bassler, Bonnie L.

2009-01-01

341

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

Microsoft Academic Search

In Pseudomonas aeruginosa, many exoproduct virulence determinants are regulated via a hierarchical quo- rum-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

KLAUS WINZER; COLIN FALCONER; NACHMAN C. GARBER; STEPHEN P. DIGGLE; MIGUEL CAMARA; PAUL WILLIAMS

2000-01-01

342

Characterization of a Phosphotriesterase-Like Lactonase from Sulfolobus solfataricus and Its Immobilization for Disruption of Quorum Sensing? †  

PubMed Central

SsoPox, a bifunctional enzyme with organophosphate hydrolase and N-acyl homoserine lactonase activities from the hyperthermophilic archaeon Sulfolobus solfataricus, was overexpressed and purified from recombinant Pseudomonas putida KT2440 with a yield of 9.4 mg of protein per liter of culture. The enzyme has a preference for N-acyl homoserine lactones (AHLs) with acyl chain lengths of at least 8 carbon atoms, mainly due to lower Km values for these substrates. The highest specificity constant obtained was for N-3-oxo-decanoyl homoserine lactone (kcat/Km = 5.5 × 103 M?1·s?1), but SsoPox can also degrade N-butyryl homoserine lactone (C4-HSL) and N-oxo-dodecanoyl homoserine lactone (oxo-C12-HSL), which are important for quorum sensing in our Pseudomonas aeruginosa model system. When P. aeruginosa PAO1 cultures were grown in the presence of SsoPox-immobilized membranes, the production of C4-HSL- and oxo-C12-HSL-regulated virulence factors, elastase, protease, and pyocyanin were significantly reduced. This is the first demonstration that immobilized quorum-quenching enzymes can be used to attenuate the production of virulence factors controlled by quorum-sensing signals.

Ng, Filomena S. W.; Wright, Daniel M.; Seah, Stephen Y. K.

2011-01-01

343

Regulated proteolysis of Candida albicans Ras1 is involved in morphogenesis and quorum sensing regulation  

PubMed Central

Summary In Candida albicans, a fungal pathogen, the small G-protein Ras1 regulates many important behaviors including white-opaque switching, biofilm formation, and the induction and maintenance of hyphal growth. Like other Ras proteins, Ras1 is activated upon guanine triphosphate binding, and its activity is further modulated by post-translational lipid modifications. Here, we report that the levels of membrane-associated, full-length Ras1 were higher in hyphae than in yeast, and that yeast contained a shorter, soluble Ras1 species that resulted from cleavage. Deletion of the putative cleavage site led to more rapid induction of hyphal growth and delayed hypha-to-yeast transitions. The cleaved Ras1 species was less able to activate its effector, adenylate cyclase (Cyr1), unless tethered to the membrane by a heterologous membrane-targeting domain. Ras1 cleavage was repressed by cAMP-signaling, indicating the presence of a positive feedback loop in which Cyr1 and cAMP influence Ras1. The C. albicans quorum sensing molecule farnesol, which inhibits Cyr1 and represses filamentation, caused an increase in the fraction of Ras1 in the cleaved form, particularly in nascent yeast formed from hyphae. This newly recognized mode of Ras regulation may control C. albicans Ras1 activity in important ways.

Piispanen, Amy; Grahl, Nora; Hollomon, Jeffrey M.; Hogan, Deborah A.

2013-01-01

344

Electrochemical detection of quorum sensing signaling molecules by dual signal confirmation at microelectrode arrays.  

PubMed

n-Acyl homoserine lactones (AHLs) are produced by gram-negative bacteria to regulate gene expression in a cell density dependent manner. For instance, expression of virulence factors by pathogens such as Pseudomonas aeruginosa is induced only when a threshold concentration of AHLs is reached, which indicates that the bacterial population is big enough to promote infection. In this study, the indicator strain Agrobacterium tumefaciens NTL4 (pZLR4), which carries a ?-galactosidase (?-gal) reporter gene under the control of a quorum sensing promoter, was used to develop an electrochemical biosensor to detect AHLs using the model n-(3-oxo)-dodecanoyl-L-homoserine lactone (oxo-C12-HSL), an AHL previously detected in cystic fibrosis patients infected with P. aeruginosa. The substrate 4-aminophenyl ?-D-galactopyranoside was used to detect ?-gal activity by cyclic voltammetry. Furthermore, simultaneous monitoring of substrate consumption and p-aminophenol production by ?-gal allowed on-chip result verification by dual-signal confirmation. The sensor exhibited high reproducibility and accurately detected oxo-C12-HSL in a low picomolar to low nanomolar range in spiked liquid cultures and artificial saliva, as well as AHLs naturally released by P. aeruginosa in culture supernatants. Moreover, detection took just 2 h, required no sample pretreatment or preconcentration steps, and was easier and faster than traditional methods. PMID:21323339

Baldrich, Eva; Muñoz, Francesc Xavier; García-Aljaro, Cristina

2011-02-16

345

Synthesis and stability of small molecule probes for Pseudomonas aeruginosa quorum sensing modulation.  

PubMed

The human pathogen Pseudomonas aeruginosa uses N-butyryl-L-homoserine lactone (BHL) and N-(3-oxododecanyl)-L-homoserine lactone (OdDHL) as small molecule intercellular signals in a phenomenon known as quorum sensing (QS). QS modulators are effective at attenuating P. aeruginosa virulence; therefore, they are a potential new class of antibacterial agent. The lactone in BHL and OdDHL is hydrolysed under physiological conditions. The hydrolysis proceeds at a rate faster than racemisation of the alpha-chiral centre. Non-hydrolysable, non-racemic analogues (small molecule probes) were designed and synthesised, replacing the lactone with a ketone. OdDHL analogues were found to be relatively unstable to decomposition unless they were difluorinated between the beta-keto amide. Stability studies on a non-hydrolysable, cyclohexanone analogue indicated that racemisation of the alpha-chiral centre was relatively slow. This analogue was assayed to show that the L-isomer is likely to be responsible for the QS autoinducing activity in P. aeruginosa and Serratia strain ATCC39006. PMID:15534711

Glansdorp, Freija G; Thomas, Gemma L; Lee, Jungjoon K; Dutton, Jenny M; Salmond, George P C; Welch, Martin; Spring, David R

2004-10-13

346

Microbial quorum-sensing molecules induce acrosome loss and cell death in human spermatozoa.  

PubMed

Infertility in men and women is frequently associated with genital contamination by various commensal or uropathogenic microbes. Since many microorganisms are known to release quorum-sensing signals in substantial amounts, we raised the question whether such molecules can directly affect human spermatozoa. Here we show that farnesol and 3-oxododecanoyl-l-homoserine lactone, employed by the opportunistic pathogenic yeast Candida albicans and the gram-negative bacterium Pseudomonas aeruginosa, respectively, induce multiple damage in spermatozoa. A reduction in the motility of spermatozoa coincided in a dose-dependent manner with apoptosis and necrosis at concentrations which were nondeleterious for dendritic cell-like immune cells. Moreover, sublethal doses of both signaling molecules induced premature loss of the acrosome, a cap-like structure of the sperm head which is essential for fertilization. Addressing their mechanism of action, we found that the bacterial molecule, but not the fungal molecule, actively induced the acrosome reaction via a calcium-dependent mechanism. This work uncovers a new facet in the interaction of microorganisms with human gametes and suggests a putative link between microbial communication systems and host infertility. PMID:19687207

Rennemeier, Claudia; Frambach, Torsten; Hennicke, Florian; Dietl, Johannes; Staib, Peter

2009-08-17

347

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.

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

2010-01-01

348

LsrR-binding site recognition and regulatory characteristics in Escherichia coli AI-2 quorum sensing.  

PubMed

In quorum sensing (QS) process, bacteria regulate gene expression by utilizing small signaling molecules called autoinducers in response to a variety of environmental cues. Autoinducer 2 (AI-2), a QS signaling molecule proposed to be involved in interspecies communication, is produced by many species of gram-negative and gram-positive bacteria. In Escherichia coli and Salmonella typhimurium, the extracellular AI-2 is imported into the cell by a transporter encoded by the lsr operon. Upstream of the lsr operon, there is a divergently transcribed gene encoding LsrR, which was reported previously to repress the transcription of the lsr operon and itself. Here, we have demonstrated for the first time that LsrR represses the transcription of the lsr operon and itself by directly binding to their promoters using gel shift and DNase I footprinting assays. The beta-galactosidase reporter assays further suggest that two motifs in both the lsrR and lsrA promoter regions are crucial for the LsrR binding. Furthermore, in agreement with the conclusion that phosphorylated AI-2 can relieve the repression of LsrR in previous studies, our data show that phospho-AI-2 renders LsrR unable to bind to its own promoter in vitro. PMID:19636340

Xue, Ting; Zhao, Liping; Sun, Haipeng; Zhou, Xianxuan; Sun, Baolin

2009-07-28

349

Aspergillus oxylipin signaling and quorum sensing pathways depend on g protein-coupled receptors.  

PubMed

Oxylipins regulate Aspergillus development and mycotoxin production and are also involved in Aspergillus quorum sensing mechanisms. Despite extensive knowledge of how these oxylipins are synthesized and what processes they regulate, nothing is known about how these signals are detected and transmitted by the fungus. G protein-coupled receptors (GPCR) have been speculated to be involved as they are known oxylipin receptors in mammals, and many putative GPCRs have been identified in the Aspergilli. Here, we present evidence that oxylipins stimulate a burst in cAMP in A. nidulans, and that loss of an A. nidulans GPCR, gprD, prevents this cAMP accumulation. A. flavus undergoes an oxylipin-mediated developmental shift when grown at different densities, and this regulates spore, sclerotial and aflatoxin production. A. flavus encodes two putative GprD homologs, GprC and GprD, and we demonstrate here that they are required to transition to a high-density development state, as well as to respond to spent medium of a high-density culture. The finding of GPCRs that regulate production of survival structures (sclerotia), inoculum (spores) and aflatoxin holds promise for future development of anti-fungal therapeutics. PMID:23105976

Affeldt, Katharyn J; Brodhagen, Marion; Keller, Nancy P

2012-09-18

350

Quorum-Sensing Genes in Pseudomonas aeruginosa Biofilms: Their Role and Expression Patterns  

PubMed Central

Acylated homoserine lactone molecules are used by a number of gram-negative bacteria to regulate cell density-dependent gene expression by a mechanism known as quorum sensing (QS). In Pseudomonas aeruginosa, QS or cell-to-cell signaling controls expression of a number of virulence factors, as well as biofilm differentiation. In this study, we investigated the role played by the las and rhl QS systems during the early stages of static biofilm formation when cells are adhering to a surface and forming microcolonies. These studies revealed a marked difference in biofilm formation between the PAO1 parent and the QS mutants when glucose, but not citrate, was used as the sole carbon source. To further elucidate the contribution of lasI and rhlI to biofilm maturation, we utilized fusions to unstable green fluorescent protein in concert with confocal microscopy to perform real-time temporal and spatial studies of these genes in a flowing environment. During the course of 8-day biofilm development, lasI expression was found to progressively decrease over time. Conversely, rhlI expression remained steady throughout biofilm development but occurred in a lower percentage of cells. Spatial analysis revealed that lasI and rhlI were maximally expressed in cells located at the substratum and that expression decreased with increasing biofilm height. Because QS was shown previously to be involved in biofilm differentiation, these findings have important implications for the design of biofilm prevention and eradication strategies.

De Kievit, Teresa R.; Gillis, Richard; Marx, Steve; Brown, Chris; Iglewski, Barbara H.

2001-01-01

351

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

PubMed

Plant cell wall-degrading enzymes (PCWDE) are key virulence determinants in the pathogenesis of the potato pathogen Pectobacterium atrosepticum. In this study, we report the impact on virulence of a transposon insertion mutation in the metJ gene that codes for the repressor of the methionine biosynthesis regulon. In a mutant strain defective for the small regulatory RNA rsmB, PCWDE are not produced and virulence in potato tubers is almost totally abolished. However, when the metJ gene is disrupted in this background, the rsmB(-) phenotype is suppressed and virulence and PCWDE production are restored. Additionally, when metJ is disrupted, production of the quorum-sensing signal, N-(3-oxohexanoyl)-homoserine lactone, is increased. The metJ mutant strains showed pleiotropic transcriptional impacts affecting approximately a quarter of the genome. Genes involved in methionine biosynthesis were most highly upregulated but many virulence-associated transcripts were also upregulated. This is the first report of the impact of the MetJ repressor on virulence in bacteria. PMID:23113713

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

2013-03-01

352

Proline antagonizes GABA-induced quenching of quorum-sensing in Agrobacterium tumefaciens.  

PubMed

Plants accumulate free L-proline (Pro) in response to abiotic stresses (drought and salinity) and presence of bacterial pathogens, including the tumor-inducing bacterium Agrobacterium tumefaciens. However, the function of Pro accumulation in host-pathogen interaction is still unclear. Here, we demonstrated that Pro antagonizes plant GABA-defense in the A. tumefaciens C58-induced tumor by interfering with the import of GABA and consequently the GABA-induced degradation of the bacterial quorum-sensing signal, 3-oxo-octanoylhomoserine lactone. We identified a bacterial receptor Atu2422, which is implicated in the uptake of GABA and Pro, suggesting that Pro acts as a natural antagonist of GABA-signaling. The Atu2422 amino acid sequence contains a Venus flytrap domain that is required for trapping GABA in human GABA(B) receptors. A constructed atu2422 mutant was more virulent than the wild type bacterium; moreover, transgenic plants with a low level of Pro exhibited less severe tumor symptoms than did their wild-type parents, revealing a crucial role for Venus flytrap GABA-receptor and relative abundance of GABA and Pro in host-pathogen interaction. PMID:19706545

Haudecoeur, E; Planamente, S; Cirou, A; Tannières, M; Shelp, B J; Moréra, S; Faure, D

2009-08-13

353

Antioxidant and anti-quorum sensing activities of green pod of Acacia nilotica L.  

PubMed

The antioxidant and anti-quorum sensing activities of eight extracts were studied in green pods of Acacia nilotica. The specific phenolic compositions and their quantifications were performed by HPLC and MS/MS, which showed that the HEF (pH 4) was higher in gallic acid, ellagic acid, epicatechin, rutin, and GTs. In order to find antioxidant potential of various extracts, their activities were studied for TPC, AOA, FRSA, RP, inhibition of LPO, FIC activity, HO* and O(2)(-) scavenging activities. Among them HEF (pH 4) has shown potent antioxidant activity. HEF (pH 4) was also found effective in protecting plasmid DNA and HAS protein oxidation induced by HO*. Pre-treatment of HEF (pH 4) at 75 and 150 mg/kg body weight for 6 days caused a significant increase in the levels of CAT and SOD and decrease in the level of MDA content in liver, lungs, kidneys and blood when compared to CCl(4)-intoxicated rats. Eventually, the extracts were also screened for anti-QS activity. Of these extracts two showed QS inhibition: HEF (pH 4) and HCE. The results obtained strongly indicate that green pod of A. nilotica are important source of natural antioxidants. PMID:19168114

Singh, Brahma N; Singh, B R; Singh, R L; Prakash, D; Sarma, B K; Singh, H B

2009-01-09

354

Collective behavior and quorum sensing in a system of communicating microcapsules  

NASA Astrophysics Data System (ADS)

We report the results on collective motion of polymeric microcapsules in a fluid-filled microchannel. We consider the case where motion of the nanoparticle-filled microcapsules is controlled by adhesion at the channel's wall and hydrodynamic coupling between the capsules. Using the hybrid Lattice Boltzmann method for fluid dynamics and Lattice spring model for the micromechanics of elastic solid, we determined how the characteristics of the substrate, the polymeric shell, encapsulated fluid and the surrounding solution affect the capsule's velocity and ``gait'' of the capsule within the system. In numerical computations we find the conditions under which microcapsules communicating through modification of the microchannel surface by released nanoparticles exhibit collective motion, thereby mimicking behavior of the colony of living cells. In particular, we show that this system demonstrates a quorum sensing. That is, the capsules motion depends on population and behavior of neighboring groups of capsules. Finally, the design of a repair-and-go system is presented, in which we show that deposition of nanoparticles from moving microcapsules onto a damaged substrate can be used as an effective tool for selective repair of defects or cracks on the substrate.

Kolmakov, German; Bhattacharya, Amitabh; Balazs, Anna

2009-11-01

355

Linking molecular and population processes in mathematical models of quorum sensing.  

PubMed

Many bacteria alter their behaviors as a function of population density, via a process known as quorum sensing (QS). QS is achieved by the synthesis and detection of diffusible signal molecules, often involving complex signal transduction pathways and regulatory networks. Mathematical models have been developed to investigate a number of aspects of QS, resulting in a wide range of model structures; many have focused on either the molecular or the population scale. In this paper, I show that many published models fail to satisfy physical constraints (such as conservation of matter) or rely on a priori assumptions that may not be valid. I present new, simple models of canonical Gram-negative and Gram-positive QS systems, in both well-mixed and biofilm populations, focusing on the interaction between molecular and population processes. I show that this interaction may be crucial for several important features of QS, including bistability and the localization of QS in space. The results highlight the need to link molecular and population processes carefully in QS models, provide a general framework for understanding the behavior of complex system-specific models, and suggest new directions for both theoretical and experimental work. PMID:23892934

Brown, David

2013-07-27

356

Identification of an rsh Gene from a Novosphingobium sp. Necessary for Quorum-Sensing Signal Accumulation? †  

PubMed Central

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 (rshNsp) 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 rshNsp gene restored these phenotypes. This is the first discovery of a functional rsh gene in a member of the Novosphingobium genus.

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

2009-01-01

357

A transcriptional regulator linking quorum sensing and chitin induction to render Vibrio cholerae naturally transformable  

PubMed Central

The human pathogen Vibrio cholerae is an aquatic bacterium associated with zooplankton and their chitinous exoskeletons. On chitinous surfaces, V. cholerae initiates a developmental programme, known as natural competence, to mediate transformation, which is a mode of horizontal gene transfer. Competence facilitates the uptake of free DNA and recombination into the bacterial genome. Recent studies have indicated that chitin surfaces are required, but not sufficient to induce competence. Two additional regulatory pathways, i.e. catabolite repression and quorum sensing (QS), are components of the regulatory network that controls natural competence in V. cholerae. In this study, we investigated the link between chitin induction and QS. We show that the major regulators of these two pathways, TfoX and HapR, are both involved in the activation of a gene encoding a transcriptional regulator of the LuxR-type family, which we named QS and TfoX-dependent regulator (QstR). We demonstrate that HapR binds the promoter of qstR in a site-specific manner, indicating a role for HapR as an activator of qstR. In addition, epistasis experiments indicate that QstR compensates for the absence of HapR. We also provide evidence that QstR is required for the proper expression of a small but essential subset of competence genes and propose a new regulatory model in which QstR links chitin-induced TfoX activity with QS.

Lo Scrudato, Mirella; Blokesch, Melanie

2013-01-01

358

Bacterial quorum sensing, cooperativity, and anticipation of stationary-phase stress  

PubMed Central

Acyl-homoserine lactone–mediated quorum sensing (QS) regulates diverse activities in many species of Proteobacteria. QS-controlled genes commonly code for production of secreted or excreted public goods. The acyl-homoserine lactones are synthesized by members of the LuxI signal synthase family and are detected by cognate members of the LuxR family of transcriptional regulators. QS affords a means of population density-dependent gene regulation. Control of public goods via QS provides a fitness benefit. Another potential role for QS is to anticipate overcrowding. As population density increases and stationary phase approaches, QS might induce functions important for existence in stationary phase. Here we provide evidence that in three related species of the genus Burkholderia QS allows individuals to anticipate and survive stationary-phase stress. Survival requires QS-dependent activation of cellular enzymes required for production of excreted oxalate, which serves to counteract ammonia-mediated alkaline toxicity during stationary phase. Our findings provide an example of QS serving as a means to anticipate stationary phase or life at the carrying capacity of a population by activating the expression of cytoplasmic enzymes, altering cellular metabolism, and producing a shared resource or public good, oxalate.

Goo, Eunhye; Majerczyk, Charlotte D.; An, Jae Hyung; Chandler, Josephine R.; Seo, Young-Su; Ham, Hyeonheui; Lim, Jae Yun; Kim, Hongsup; Lee, Bongsoo; Jang, Moon Sun; Greenberg, E. Peter; Hwang, Ingyu

2012-01-01

359

Vibrio vulnificus produces quorum sensing signals of the AHL-class.  

PubMed

Vibrio vulnificus is an aquatic pathogenic bacterium that can cause vibriosis in humans and fish. The species is subdivided into three biotypes with the fish-virulent strains belonging to biotype 2. The quorum sensing (QS) phenomenon mediated by furanosyl borate diester or autoinducer 2 (AI-2) has been described in human strains of biotype 1, and here we show that the luxS gene which encodes AI-2 is present in all strains of V. vulnificus regardless of origin, biotype or serovar. In this study, we also demonstrate that V. vulnificus produces QS signals of the acylated homoserine lactone (AHL) class (AI-1). AHLs were detected in strains of biotype 1 and 2 from water, fish and human wound infections but not in strains isolated from human septicaemic cases. The AHL compound was identified as N-butanoyl-homoserine-lactone (C(4)-HL) by both reporter strains and by HPLC-high-resolution MS. C(4)-HL was detected when AHL-positive strains were grown in low-nutrient medium [modified sea water yeast extract (MSWYE)] but not in rich media (tryptic soy broth or brain-heart infusion) and its production was enhanced when blood factors were added to MSWYE. C(4)-HL was detected in vivo, in eels infected with AHL-positive biotype 2 strains. No known AHL-related gene was detected by PCR or Southern blot suggesting that AHL-related genes in V. vulnificus are different from those found in other Gram-negative bacteria. PMID:19453744

Valiente, Esmeralda; Bruhn, Jesper Bartholin; Nielsen, Kristian Fog; Larsen, Jens Laurits; Roig, Francisco J; Gram, Lone; Amaro, Carmen

2009-04-25

360

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

2012-05-07

361

Regulation of Vibrio alginolyticus virulence by the LuxS quorum-sensing system.  

PubMed

Quorum sensing (QS) is a bacterial intercommunication system that controls the expression of multiple genes in response to population density. The LuxS QS system regulates the expression of several virulence factors in a wide variety of pathogenic bacteria. LuxS has been characterized to be responsible for producing a type of autoinducer, AI-2, which stimulates the expression of the luciferase operon in Vibrio harveyi. Vibrio alginolyticus is established as an opportunistic pathogen of several marine animals, and its LuxS QS system remains undefined. To investigate the pathogenic role of luxS in V. alginolyticus, the luxS mutants of both the standard strain ATCC 33787 and a fish-clinical isolate MVP01, named MYJS and MYJM, respectively, were constructed. The mutation resulted in reduced lethality to Pagrus major. Intraperitoneal LD(50) of MYJS and MYJM increased by 15- and 93-fold, respectively. The two luxS mutants exhibited a lower growth rate and defective flagellar biosynthesis. They also showed a significant decrease in protease production and an increase in both extracellular polysaccharide production and biofilm development. The results suggest that the LuxS QS system plays an important role in regulating the expression of virulence factors in V. alginolyticus. PMID:18261029

Ye, J; Ma, Y; Liu, Q; Zhao, D L; Wang, Q Y; Zhang, Y X

2008-03-01

362

Quorum sensing modulation of a putative glycosyltransferase gene cluster essential for Xanthomonas campestris biofilm formation.  

PubMed

Findings from previous studies suggest that the quorum sensing signal DSF (diffusible signal factor) negatively regulates biofilm formation in Xanthomonas campestris pv. campestris (Xcc) by affecting the expression of manA encoding biofilm dispersion and an unknown factor(s). In this study, by analysing the double deletion mutant ?rpfF?manA, in which DSF biosynthesis gene rpfF and biofilm dispersal gene manA were deleted, we found that DSF modulated biofilm development by suppression of a mechanism essential for biofilm formation. Transposon mutagenesis of ?rpfF?manA and subsequent analyses led to the identification of a novel gene locus xagABC encoding a putative glycosyl transferase system. Genetic analysis revealed that the transcriptional expression of xagABC was negatively regulated by DSF through the RpfC/RpfG two-component regulatory system. Deletion of the xag genes resulted in decreased extracellular polysaccharide production, abolished Xcc biofilm formation and attenuated the bacterial resistance to oxidative stress. Furthermore, we provide evidence that xagABC and manA were differentially expressed in Xcc and the biofilm formed by overexpression of xagABC in wild-type Xcc could be dispersed by ManA. These results provide new insight into the molecular mechanisms by which Xcc switches between planktonic growth and biofilm lifestyle. PMID:20636376

Tao, Fei; Swarup, Sanjay; Zhang, Lian-Hui

2010-12-01

363

Pseudomonas aeruginosa Las quorum sensing autoinducer suppresses growth and biofilm production in Legionella species.  

PubMed

Bacteria commonly communicate with each other by a cell-to-cell signalling mechanism known as quorum sensing (QS). Recent studies have shown that the Las QS autoinducer N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C(12)-HSL) of Pseudomonas aeruginosa performs a variety of functions not only in intraspecies communication, but also in interspecies and interkingdom interactions. In this study, we report the effects of Pseudomonas 3-oxo-C(12)-HSL on the growth and suppression of virulence factors in other bacterial species that frequently co-exist with Ps. aeruginosa in nature. It was found that 3-oxo-C(12)-HSL, but not its analogues, suppressed the growth of Legionella pneumophila in a dose-dependent manner. However, 3-oxo-C(12)-HSL did not exhibit a growth-suppressive effect on Serratia marcescens, Proteus mirabilis, Escherichia coli, Alcaligenes faecalis and Stenotrophomonas maltophilia. A concentration of 50 microM 3-oxo-C(12)-HSL completely inhibited the growth of L. pneumophila. Additionally, a significant suppression of biofilm formation was demonstrated in L. pneumophila exposed to 3-oxo-C(12)-HSL. Our results suggest that the Pseudomonas QS autoinducer 3-oxo-C(12)-HSL exerts both bacteriostatic and virulence factor-suppressive activities on L. pneumophila alone. PMID:19383702

Kimura, Soichiro; Tateda, Kazuhiro; Ishii, Yoshikazu; Horikawa, Manabu; Miyairi, Shinichi; Gotoh, Naomasa; Ishiguro, Masaji; Yamaguchi, Keizo

2009-04-21

364

The Pseudomonas aeruginosa quinolone quorum sensing signal alters the multicellular behaviour of Pseudomonas putida KT2440.  

PubMed

The molecule 2-heptyl-3-hydroxy-4-quinolone (referred to as the Pseudomonas quinolone signal, or PQS) is produced by Pseudomonas aeruginosa as part of its quorum sensing circuit, and has been shown to influence a variety of processes in this bacterium, including the production of siderophores and secondary metabolites, virulence determinants and biofilm development. In this report we present evidence of the effect of PQS as an interspecies signal with a negative impact on the multicellular behaviour of Pseudomonas putida KT2440. PQS reduces biofilm formation and swarming motility, and interferes with iron uptake by this bacterium. Addition of PQS also causes changes in the transcription of several P. putida genes, indicating a specific response to the signal molecule, which is not produced by strain KT2440. Among the genes with increased expression in response to PQS is PP1563, which forms part of a large prophage cluster (PP1532-PP1584); consistently, phage-mediated lysis of some cells in the population was observed in the presence of PQS. Overall, these data indicate that PQS may be used by P. aeruginosa as a chemical weapon against potential competitors. PMID:21742029

Fernández-Piñar, Regina; Cámara, Miguel; Dubern, Jean-Frédéric; Ramos, Juan L; Espinosa-Urgel, Manuel

2011-06-26

365

Screening of certain medicinal plants from India for their anti-quorum sensing activity.  

PubMed

Discovery of quorum sensing (QS) system to coordinate virulence and biofilm formation in bacterial pathogens has triggered search for safe, stable and non-toxic anti-QS compounds from natural products. Ethanolic extracts of 24 Indian medicinal plants were tested by agar well and disc diffusion assay for anti-QS activity using Chromobacterium violaceum (CV12472 and CVO26) reporter strains. AHL from C. violaceum CV31532 was isolated and partially purified for its use in CVO26 based bioassay. Effect on swarming-motility of Pseudomonas aeruginosa (PAO1) was also recorded at sub-MIC concentrations of extracts. Of the 24 medicinal plants screened Hemidesmus indicus (L.) Schult (root), Holarrhena antidysenterica (Roth) A.DC. (bark), Mangifera indica L. (seed) Punica granatum L. (pericarp) and Psoralea corylifolia L. (seed) demonstrated varying level of inhibition of violacein production in the reporter strains. Moreover, a significant reduction in swarms was recorded over control. The inhibition of violacein production and swarming motility may be due to direct or indirect interference on QS by active constituents or the interactive effect of different phytocompounds present in the extracts. These plant extracts may be selected for activity guided fractionation to identify and characterize the active principle. PMID:21250604

Zahin, Maryam; Hasan, Sameena; Aqil, Farrukh; Khan, Mohd Sajjad Ahmad; Husain, Fohad Mabood; Ahmad, Iqbal

2010-12-01

366

Antibiotics at subinhibitory concentrations improve the quorum sensing behavior of Chromobacterium violaceum.  

PubMed

Increasing evidence has shown that antibiotics function as intermicrobial signaling molecules instead of killing weapons. However, mechanisms and key factors that are involved in such functions remain poorly understood. Earlier findings have associated antibiotic signaling with quorum sensing (QS); however, results varied among experiments, antibiotics, and bacterial strains. In this study, we found that antibiotics at subinhibitory concentrations improved the violacein-producing ability of Chromobacterium violaceum ATCC 12472. Quantitative real-time polymerase chain reaction of QS-associated gene transcripts and bioassay of violacein production in a QS mutant strain demonstrated that antibiotics enhanced the production of N-acyl-L-homoserine lactones (AHLs; QS signaling molecules) and increased AHL-inducing QS-mediated virulence, including chitinase production and biofilm formation. Moreover, a positive flagellar activity and an increased bacterial clustering ability were found, which are related to the antibiotic-induced biofilm formation. Our findings suggested that antibiotic-mediated interspecific signaling also occurs in C. violaceum, thereby expanding the knowledge and language of cell-to-cell communication. PMID:23330731

Liu, Zhanjun; Wang, Weishan; Zhu, Ying; Gong, Qianhong; Yu, Wengong; Lu, Xinzhi

2013-02-06

367

Oxidative DNA damage protective activity, antioxidant and anti-quorum sensing potentials of Moringa oleifera.  

PubMed

The aqueous extract of leaf (LE), fruit (FE) and seed (SE) of Moringa oleifera was assessed to examine the ability to inhibit the oxidative DNA damage, antioxidant and anti-quorum sensing (QS) potentials. It was found that these extracts could significantly inhibit the OH-dependent damage of pUC18 plasmid DNA and also inhibit synergistically with trolox, with an activity sequence of LE > FE > SE. HPLC and MS/MS analysis was carried out, which showed the presence of gallic acid, chlorogenic acid, ellagic acid, ferulic acid, kaempferol, quercetin and vanillin. The LE was with comparatively higher total phenolics content (105.04 mg gallic acid equivalents (GAE)/g), total flavonoids content (31.28 mg quercetin equivalents (QE)/g), and ascorbic acid content (106.95 mg/100 g) and showed better antioxidant activity (85.77%), anti-radical power (74.3), reducing power (1.1 ascorbic acid equivalents (ASE)/ml), inhibition of lipid peroxidation, protein oxidation, OH-induced deoxyribose degradation, and scavenging power of superoxide anion and nitric oxide radicals than did the FE, SE and standard alpha-tocopherol. Eventually, LE and FE were found to inhibit violacein production, a QS-regulated behavior in Chromobacterium violaceum 12472. PMID:19425184

Singh, Brahma N; Singh, B R; Singh, R L; Prakash, D; Dhakarey, R; Upadhyay, G; Singh, H B

2009-06-01

368

Bioassays of quorum sensing compounds using Agrobacterium tumefaciens and Chromobacterium violaceum.  

PubMed

In most bacteria, a global level of regulation exists involving intercellular communication via the production and response to cell density-dependent signal molecules. This cell density-dependent regulation has been termed quorum sensing (QS). QS is a global regulator, which has been associated with a number of important features in bacteria including virulence regulation and biofilm formation. Consequently, there is considerable interest in understanding, detecting, and inhibiting QS. Acyl homoserine lactones (acyl HSLs) are used as extracellular QS signals by a variety of Gram-negative bacteria. Chromobacterium violaceum, a Gram-negative bacterium commonly found in soil and water, produces the characteristic purple pigment violacein, the production of which is regulated by acyl HSL-mediated QS. Based on this readily observed pigmentation phenotype, C. violaceum strains can be used to detect various aspects of acyl HSL-mediated QS activity. In another commonly used bioassay organism, Agrobacterium tumefaciens, QS can be detected by the use of a reporter gene such as lacZ. Here, we describe several commonly used approaches incorporating C. violaceum and A. tumefaciens that can be used to detect acyl HSLs and QS inhibition. PMID:21031300

Chu, Weihua; Vattem, Dhiraj A; Maitin, Vatsala; Barnes, Mary B; McLean, Robert J C

2011-01-01

369

Quorum sensing-controlled buoyancy through gas vesicles: Intracellular bacterial microcompartments for environmental adaptation  

PubMed Central

Gas vesicles are gas-filled microcompartments produced by many cyanobacteria and haloarchaea to regulate buoyancy and control positioning in the water column. Recently we identified the first case of gas vesicle production by a member of the Enterobacteriaceae, Serratia sp ATCC39006. Gas vesicle production enabled colonisation of the air-liquid interface and was positively regulated in low-oxygen conditions, suggesting development of these intracellular organelles is an adpative mechanism facilitating migration to the water surface. Vesicle production was also regulated by the intercellular communication molecule N?butanoyl-L?homoserine lactone (BHL) showing that gas vesicle production is controlled at the population level, through quorum sensing, with BHL acting as a morphogen. Gas vesicle production was also reciprocally regulated with flagella-driven swarming motility by the global regulatory protein RsmA, suggesting a fork in the regulatory pathway that controls induction of these distinct modes of mobility. Here we discuss these findings in the context of the interesting physiology of Serratia 39006 and highlight future prospects for gas vesicle research in this highly tractable strain.

Ramsay, Joshua P.

2012-01-01

370

Inhibition of quorum sensing regulated biofilm formation in Serratia marcescens causing nosocomial infections.  

PubMed

Serratia marcescens is an opportunistic pathogen causing severe urinary tract infections in hospitalized individuals. Infections of S. marcescens are of great concern because of its increasing resistance towards conventional antibiotics. Quorum sensing (QS)-a cell to cell communication-system of S. marcescens acts as a global regulator of almost all the virulence factors and majorly its biofilm formation. Since, the QS system of S. marcescens directly accords to its pathogenesis, targeting QS system will provide an improved strategy to combat drug resistant pathogens. In the present study, QS system of S. marcescens has been used as target and its inhibition has been studied upon exposure to bioactives from coral associated bacteria (CAB). This study also emphasises the potential of CAB in producing bioactive agents with anti-QS and antibiofilm properties. Two CAB isolates CAB 23 and 41 have shown to inhibit biofilm formation and the production of QS dependent virulence factors like prodigiosin, protease, lipase and swarming motility. The study, on the whole explicates the potential of QS system as a target to treat drug resistant bacterial infections. PMID:22487181

Bakkiyaraj, Dhamodharan; Sivasankar, Chandran; Pandian, Shunmugiah Karutha

2012-03-22

371

Dynamics of AHL mediated quorum sensing under flow and non-flow conditions  

NASA Astrophysics Data System (ADS)

Quorum sensing (QS) describes the capability of microbes to communicate with each other by the aid of small molecules. Here we investigate the dynamics of QS-regulated gene expression induced by acylhomoserine lactones (AHLs) in Pseudomonas putida IsoF containing a green fluorescent protein-based AHL reporter. The fluorescence time course of individual colonies is monitored following the external addition of a defined AHL concentration to cells which had previously reached the QS-inactive state in AHL-free medium. Using a microfluidic setup the experiment is performed both under flow and non-flow conditions. We find that without supplying external AHL gene expression is induced without flow while flow suppresses the induction. Both without and with flow, at a low AHL concentration the fluorescence onset is significantly delayed while fluorescence starts to increase directly upon the addition of AHL at a high concentration. The differences between no flow and flow can be accounted for using a two-compartment model. This indicates AHL accumulation in a volume which is not affected by the flow. The experiments furthermore show significant cell-to-cell and colony-to-colony variability which is discussed in the context of a compartmentalized QS mechanism.

Meyer, Andrea; Megerle, Judith A.; Kuttler, Christina; Müller, Johannes; Aguilar, Claudio; Eberl, Leo; Hense, Burkhard A.; Rädler, Joachim O.

2012-04-01

372

Quorum sensing : a novel target for the treatment of biofilm infections.  

PubMed

Present-day treatment of chronic infections is based on compounds that aim to kill or inhibit growth of bacteria. Two problems are recognised to be intrinsically associated with this approach: (i) the frequently observed development of resistance to antimicrobial compounds; and (ii) the fact that all therapeutics are considerably less effective on bacteria growing as biofilms when compared with planktonic cells. The latter point is of particular importance as evidence has accumulated over the past few years that most chronic bacterial infections involve biofilms. The discovery of bacterial communication systems (quorum sensing systems) in Gram-negative bacteria which are believed to orchestrate important temporal events during the infectious process, including the production of virulence factors and the formation of biofilms, has afforded a novel opportunity to control the activity of infecting bacteria by other means than interfering with growth. Compounds that interfere with communication systems are present in nature. Such compounds should not only specifically attenuate the production of virulence factors but should also affect biofilm formation in a manner that is unlikely to pose a selective pressure for the development of resistant mutants. PMID:12899641

Hentzer, Morten; Eberl, Leo; Nielsen, John; Givskov, Michael

2003-01-01

373

Identification of functions linking quorum sensing with biofilm formation in Burkholderia cenocepacia H111.  

PubMed

Burkholderia cenocepacia has emerged as an important pathogen for patients suffering from cystic fibrosis (CF). Previous work has shown that this organism employs the CepIR quorum-sensing (QS) system to control the expression of virulence factors as well as the formation of biofilms. To date, however, very little is known about the QS-regulated virulence factors and virtually nothing about the factors that link QS and biofilm formation. Here, we have employed a combined transcriptomic and proteomic approach to precisely define the QS regulon in our model strain B. cenocepacia H111, a CF isolate. Among the identified CepR-activated loci, three were analyzed in better detail for their roles in biofilm development: (i) a gene cluster coding for the BclACB lectins, (ii) the large surface protein BapA, and (iii) a type I pilus. The analysis of defined mutants revealed that BapA plays a major role in biofilm formation on abiotic surfaces while inactivation of the type I pilus showed little effect both in a static microtitre dish-based biofilm assay and in flow-through cells. Inactivation of the bclACB lectin genes resulted in biofilms containing hollow microcolonies, suggesting that the lectins are important for biofilm structural development. PMID:22950027

Inhülsen, Silja; Aguilar, Claudio; Schmid, Nadine; Suppiger, Angela; Riedel, Kathrin; Eberl, Leo

2012-06-01

374

Identification of functions linking quorum sensing with biofilm formation in Burkholderia cenocepacia H111  

PubMed Central

Burkholderia cenocepacia has emerged as an important pathogen for patients suffering from cystic fibrosis (CF). Previous work has shown that this organism employs the CepIR quorum-sensing (QS) system to control the expression of virulence factors as well as the formation of biofilms. To date, however, very little is known about the QS-regulated virulence factors and virtually nothing about the factors that link QS and biofilm formation. Here, we have employed a combined transcriptomic and proteomic approach to precisely define the QS regulon in our model strain B. cenocepacia H111, a CF isolate. Among the identified CepR-activated loci, three were analyzed in better detail for their roles in biofilm development: (i) a gene cluster coding for the BclACB lectins, (ii) the large surface protein BapA, and (iii) a type I pilus. The analysis of defined mutants revealed that BapA plays a major role in biofilm formation on abiotic surfaces while inactivation of the type I pilus showed little effect both in a static microtitre dish-based biofilm assay and in flow-through cells. Inactivation of the bclACB lectin genes resulted in biofilms containing hollow microcolonies, suggesting that the lectins are important for biofilm structural development.

Inhulsen, Silja; Aguilar, Claudio; Schmid, Nadine; Suppiger, Angela; Riedel, Kathrin; Eberl, Leo

2012-01-01

375

Quorum sensing in the dimorphic fungus Candida albicans is mediated by farnesol.  

PubMed

The inoculum size effect in the dimorphic fungus Candida albicans results from production of an extracellular quorum-sensing molecule (QSM). This molecule prevents mycelial development in both a growth morphology assay and a differentiation assay using three chemically distinct triggers for germ tube formation (GTF): L-proline, N-acetylglucosamine, and serum (either pig or fetal bovine). In all cases, the presence of QSM prevents the yeast-to-mycelium conversion, resulting in actively budding yeasts without influencing cellular growth rates. QSM exhibits general cross-reactivity within C. albicans in that supernatants from strain A72 are active on five other strains of C. albicans and vice versa. The QSM excreted by C. albicans is farnesol (C(15)H(26)O; molecular weight, 222.37). QSM is extracellular, and is produced continuously during growth and over a temperature range from 23 to 43 degrees C, in amounts roughly proportional to the CFU/milliliter. Production is not dependent on the type of carbon source nor nitrogen source or on the chemical nature of the growth medium. Both commercial mixed isomer and (E,E)-farnesol exhibited QSM activity (the ability to prevent GTF) at a level sufficient to account for all the QSM activity present in C. albicans supernatants, i.e., 50% GTF at ca. 30 to 35 microM. Nerolidol was ca. two times less active than farnesol. Neither geraniol (C(10)), geranylgeraniol (C(20)), nor farnesyl pyrophosphate had any QSM activity. PMID:11425711

Hornby, J M; Jensen, E C; Lisec, A D; Tasto, J J; Jahnke, B; Shoemaker, R; Dussault, P; Nickerson, K W

2001-07-01

376

Quorum Sensing in the Dimorphic Fungus Candida albicans Is Mediated by Farnesol  

PubMed Central

The inoculum size effect in the dimorphic fungus Candida albicans results from production of an extracellular quorum-sensing molecule (QSM). This molecule prevents mycelial development in both a growth morphology assay and a differentiation assay using three chemically distinct triggers for germ tube formation (GTF): l-proline, N-acetylglucosamine, and serum (either pig or fetal bovine). In all cases, the presence of QSM prevents the yeast-to-mycelium conversion, resulting in actively budding yeasts without influencing cellular growth rates. QSM exhibits general cross-reactivity within C. albicans in that supernatants from strain A72 are active on five other strains of C. albicans and vice versa. The QSM excreted by C. albicans is farnesol (C15H26O; molecular weight, 222.37). QSM is extracellular, and is produced continuously during growth and over a temperature range from 23 to 43°C, in amounts roughly proportional to the CFU/milliliter. Production is not dependent on the type of carbon source nor nitrogen source or on the chemical nature of the growth medium. Both commercial mixed isomer and (E,E)-farnesol exhibited QSM activity (the ability to prevent GTF) at a level sufficient to account for all the QSM activity present in C. albicans supernatants, i.e., 50% GTF at ca. 30 to 35 ?M. Nerolidol was ca. two times less active than farnesol. Neither geraniol (C10), geranylgeraniol (C20), nor farnesyl pyrophosphate had any QSM activity.

Hornby, Jacob M.; Jensen, Ellen C.; Lisec, Amber D.; Tasto, Joseph J.; Jahnke, Brandon; Shoemaker, Richard; Dussault, Patrick; Nickerson, Kenneth W.

2001-01-01

377

Proline antagonizes GABA-induced quenching of quorum-sensing in Agrobacterium tumefaciens  

PubMed Central

Plants accumulate free L-proline (Pro) in response to abiotic stresses (drought and salinity) and presence of bacterial pathogens, including the tumor-inducing bacterium Agrobacterium tumefaciens. However, the function of Pro accumulation in host-pathogen interaction is still unclear. Here, we demonstrated that Pro antagonizes plant GABA-defense in the A. tumefaciens C58-induced tumor by interfering with the import of GABA and consequently the GABA-induced degradation of the bacterial quorum-sensing signal, 3-oxo-octanoylhomoserine lactone. We identified a bacterial receptor Atu2422, which is implicated in the uptake of GABA and Pro, suggesting that Pro acts as a natural antagonist of GABA-signaling. The Atu2422 amino acid sequence contains a Venus flytrap domain that is required for trapping GABA in human GABAB receptors. A constructed atu2422 mutant was more virulent than the wild type bacterium; moreover, transgenic plants with a low level of Pro exhibited less severe tumor symptoms than did their wild-type parents, revealing a crucial role for Venus flytrap GABA-receptor and relative abundance of GABA and Pro in host-pathogen interaction.

Haudecoeur, E.; Planamente, S.; Cirou, A.; Tannieres, M.; Shelp, B. J.; Morera, S.; Faure, D.

2009-01-01

378

A fine control of quorum-sensing communication in Agrobacterium tumefaciens  

PubMed Central

The bacterial pathogen Agrobacterium tumefaciens produces the quorum-sensing (QS) signal 3-oxo-octanoylhomoserine lactone (OC8HSL) for controlling horizontal transfer of its tumor inducing (Ti) plasmid that carries both the T-DNA and the virulence genes. Over-accumulation of OC8HSL also increases severity of plant symptoms (number of emerging tumors at infection site) by an unknown mechanism. A. tumefaciens strain C58 expresses two lactonases, AttM (BlcC) and AiiB, that cleave OC8HSL and are potential modulators of QS. Recent data highlight the direct contribution of lactonases AttM and AiiB in the control of OC8HSL level and QS-regulated functions such as conjugation of Ti plasmid and seriousness of plant symptoms. Expression of the two lactonases is regulated by different plant signals. A working model of QS in the course of the A. tumefaciens-plant host interaction is proposed and discussed.

Haudecoeur, Elise

2010-01-01

379

Individuals in the crowd: studying bacterial quorum-sensing at the single-cell level  

NASA Astrophysics Data System (ADS)

Like many bacterial species, the marine bacterium Vibrio fischeri can detect its own population density through a quorum sensing (QS) mechanism. The bacterium releases a small molecule signal -- the autoinducer (AI) -- into its environment: high AI concentration indicates high population density and triggers a genetic switch that, in V.fischeri, leads to bioluminescence. Although the QS behavior of bulk cultures of V.fischeri has been extensively studied, little is known about either the response of individual cells to AI signal levels or the role of noise and local diffusion in QS signaling. We have used a photon-counting camera to record the luminescence of individual V.fischeri cells immobilized in a flow cell and subject to varying concentrations of AI. We observe that light output by individual cells varies not only with bulk AI concentration, but also over time, between cells, with local (micron-scale) population density, and even with the flow rate of the medium. Most of these variations would not be evident in a bulk culture. We will present an analysis of this heterogeneity at the cell level and its implications for the role of noise in QS signaling.

Delfino Perez, Pablo; Young, Jonathan; Johnson, Elaine L.; Hagen, Stephen J.

2009-03-01

380

Anti-Quorum Sensing Potential of Crude Kigelia africana Fruit Extracts  

PubMed Central

The increasing incidence of multidrug-resistant pathogens has stimulated the search for novel anti-virulence compounds. Although many phytochemicals show promising antimicrobial activity, their power lies in their anti-virulence properties. Thus the quorum sensing (QS) inhibitory activity of four crude Kigelia africana fruit extracts was assessed qualitatively and quantitatively using the Chromobacterium violaceum and Agrobacterium tumefaciens biosensor systems. Inhibition of QS-controlled violacein production in C. violaceum was assayed using the qualitative agar diffusion assay as well as by quantifying violacein inhibition using K. africana extracts ranging from 0.31–8.2 mg/mL. Qualitative modulation of QS activity was investigated using the agar diffusion double ring assay. All four extracts showed varying levels of anti-QS activity with zones of violacein inhibition ranging from 9–10 mm. The effect on violacein inhibition was significant in the following order: hexane > dichloromethane > ethyl acetate > methanol. Inhibition was concentration-dependent, with the ?90% inhibition being obtained with ?1.3 mg/mL of the hexane extract. Both LuxI and LuxR activity were affected by crude extracts suggesting that the phytochemicals target both QS signal and receptor. K. africana extracts with their anti-QS activity, have the potential to be novel therapeutic agents, which might be important in reducing virulence and pathogenicity of drug-resistant bacteria in vivo.

Chenia, Hafizah Y.

2013-01-01

381

Bioinformatic Prediction of Gene Functions Regulated by Quorum Sensing in the Bioleaching Bacterium Acidithiobacillus ferrooxidans  

PubMed Central

The biomining bacterium Acidithiobacillus ferrooxidans oxidizes sulfide ores and promotes metal solubilization. The efficiency of this process depends on the attachment of cells to surfaces, a process regulated by quorum sensing (QS) cell-to-cell signalling in many Gram-negative bacteria. At. ferrooxidans has a functional QS system and the presence of AHLs enhances its attachment to pyrite. However, direct targets of the QS transcription factor AfeR remain unknown. In this study, a bioinformatic approach was used to infer possible AfeR direct targets based on the particular palindromic features of the AfeR binding site. A set of Hidden Markov Models designed to maintain palindromic regions and vary non-palindromic regions was used to screen for putative binding sites. By annotating the context of each predicted binding site (PBS), we classified them according to their positional coherence relative to other putative genomic structures such as start codons, RNA polymerase promoter elements and intergenic regions. We further used the Multiple EM for Motif Elicitation algorithm (MEME) to further filter out low homology PBSs. In summary, 75 target-genes were identified, 34 of which have a higher confidence level. Among the identified genes, we found afeR itself, zwf, genes encoding glycosyltransferase activities, metallo-beta lactamases, and active transport-related proteins. Glycosyltransferases and Zwf (Glucose 6-phosphate-1-dehydrogenase) might be directly involved in polysaccharide biosynthesis and attachment to minerals by At. ferrooxidans cells during the bioleaching process.

Banderas, Alvaro; Guiliani, Nicolas

2013-01-01

382

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.

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

2008-01-01

383

Inhibition of quorum sensing-controlled virulence factor production in Pseudomonas aeruginosa by South Florida plant extracts.  

PubMed

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

2007-10-15

384

The flavanone naringenin reduces the production of quorum sensing-controlled virulence factors in Pseudomonas aeruginosa PAO1.  

PubMed

Preliminary screening of the Malagasy plant Combretum albiflorum for compounds attenuating the production of quorum sensing (QS)-controlled virulence factors in bacteria led to the identification of active fractions containing flavonoids. In the present study, several flavonoids belonging to the flavone, flavanone, flavonol and chalcone structural groups were screened for their capacity to reduce the production of QS-controlled factors in the opportunistic pathogen Pseudomonas aeruginosa (strain PAO1). Flavanones (i.e. naringenin, eriodictyol and taxifolin) significantly reduced the production of pyocyanin and elastase in P. aeruginosa without affecting bacterial growth. Consistently, naringenin and taxifolin reduced the expression of several QS-controlled genes (i.e. lasI, lasR, rhlI, rhlR, lasA, lasB, phzA1 and rhlA) in P. aeruginosa PAO1. Naringenin also dramatically reduced the production of the acylhomoserine lactones N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12-HSL) and N-butanoyl-L-homoserine lactone (C4-HSL), which is driven by the lasI and rhlI gene products, respectively. In addition, using mutant strains deficient for autoinduction (?lasI and ?rhlI) and LasR- and RhlR-based biosensors, it was shown that QS inhibition by naringenin not only is the consequence of a reduced production of autoinduction compounds but also results from a defect in the proper functioning of the RlhR-C4-HSL complex. Widely distributed in the plant kingdom, flavonoids are known for their numerous and determinant roles in plant physiology, plant development and in the success of plant-rhizobia interactions, but, as shown here, some of them also have a role as inhibitors of the virulence of pathogenic bacteria by interfering with QS mechanisms. PMID:21546585

Vandeputte, Olivier M; Kiendrebeogo, Martin; Rasamiravaka, Tsiry; Stévigny, Caroline; Duez, Pierre; Rajaonson, Sanda; Diallo, Billo; Mol, Adeline; Baucher, Marie; El Jaziri, Mondher

2011-05-05

385

Optimality and robustness in quorum sensing (QS)-mediated regulation of a costly public good enzyme  

PubMed Central

Bacteria secrete a variety of public good exoproducts into their environment. These exoproducts are typically produced under the control of quorum sensing (QS), a signaling mechanism by which bacteria sense and respond to changes in their density. QS seems to provide an advantageous strategy to regulate these costly but beneficial exoproducts: it delays production until sufficiently high cell density, when the overall benefit of exoproducts outweighs cost of their production. This notion raises several fundamental questions about QS as a general control strategy adopted by bacteria. How much delay is advantageous? Under what conditions does QS-mediated regulation become advantageous? How does this advantage depend on the kinetic properties of QS? How robust is a given QS system to the stochastic events that occur over bacterial lifecycles? To quantitatively address these questions, we engineered a gene circuit in Escherichia coli to control the synthesis and secretion of a costly but beneficial exoenzyme. We show that exoenzyme production is overall advantageous only if initiated at a sufficiently high density. This property sets the potential advantage for QS-mediated regulation when the initial density is low and the growth cycle is sufficiently long compared with the exoenzyme response time. This advantage of QS-mediated regulation is robust to varying initial cell densities and growth durations, and it is particularly striking when bacteria face uncertainty, such as from stochastic dispersal during their lifecycle. We show, however, that, for QS to be optimal, its kinetic properties must be appropriately tuned; this property has implications for antibacterial treatments that target QS.

Pai, Anand; Tanouchi, Yu; You, Lingchong

2012-01-01

386

The fur-iron complex modulates expression of the quorum-sensing master regulator, SmcR, to control expression of virulence factors in Vibrio vulnificus.  

PubMed

The gene vvpE, encoding the virulence factor elastase, is a member of the quorum-sensing regulon in Vibrio vulnificus and displays enhanced expression at high cell density. We observed that this gene was repressed under iron-rich conditions and that the repression was due to a Fur (ferric uptake regulator)-dependent repression of smcR, a gene encoding a quorum-sensing master regulator with similarity to luxR in Vibrio harveyi. A gel mobility shift assay and a footprinting experiment demonstrated that the Fur-iron complex binds directly to two regions upstream of smcR (-82 to -36 and -2 to +27, with respect to the transcription start site) with differing affinities. However, binding of the Fur-iron complex is reversible enough to allow expression of smcR to be induced by quorum sensing at high cell density under iron-rich conditions. Under iron-limiting conditions, Fur fails to bind either region and the expression of smcR is regulated solely by quorum sensing. These results suggest that two biologically important environmental signals, iron and quorum sensing, converge to direct the expression of smcR, which then coordinates the expression of virulence factors. PMID:23716618

Kim, In Hwang; Wen, Yancheng; Son, Jee-Soo; Lee, Kyu-Ho; Kim, Kun-Soo

2013-05-28

387

Deciphering bacterial universal language by detecting the quorum sensing signal, autoinducer-2, with a whole-cell sensing system.  

PubMed

Bacteria communicate with neighboring bacteria of the same species or of other species by means of chemical signaling molecules. The concentration of such signaling molecules is proportional to the bacterial population size; upon reaching a threshold concentration, corresponding to a threshold cell density, certain specialized genes are expressed. This system of communication among bacteria is known as quorum sensing (QS). QS regulates diverse behaviors, such as formation of biofilms and production of pathogenic factors. Autoinducer-2 (AI-2) is a QS signaling molecule that is used for interspecies communication by both Gram-positive and Gram-negative bacteria. Bacteria are known to play an important role in many diseases, from infections to chronic inflammation. Therefore, QS is involved in a variety of disorders of bacterial origin or where bacteria play a crucial pathogenic role. One such condition is inflammatory bowel disease (IBD), a chronic inflammation of the gastrointestinal (GI) tract that includes debilitating diseases, such as ulcerative colitis (UC) and Crohn's disease (CD). To date, noninvasive methods are unavailable for the diagnosis and monitoring of IBD. We hypothesized that detection of QS molecules in physiological samples, specifically saliva and stool specimens, would provide with a method for the noninvasive, early diagnosis and monitoring of IBD conditions. To that end, we developed and optimized a whole-cell sensing system for AI-2, which is based on Vibrio harveyi strain BB170. Furthermore, we standardized and applied the biosensing system for the quantitative detection of AI-2 in saliva, stool, and intestinal samples from IBD patients. PMID:24047052

Raut, Nilesh; Pasini, Patrizia; Daunert, Sylvia

2013-09-30

388

Secondary metabolites produced by the marine bacterium Halobacillus salinus that inhibit quorum sensing-controlled phenotypes in gram-negative bacteria.  

PubMed

Certain bacteria use cell-to-cell chemical communication to coordinate community-wide phenotypic expression, 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 in cocultivation experiments. With the use of bioassay-guided fractionation, two phenethylamide metabolites were identified as the active agents. The compounds additionally inhibit quorum sensing-regulated violacein biosynthesis by Chromobacterium violaceum CV026 and green fluorescent protein production by Escherichia coli JB525. Bacterial growth was unaffected at concentrations below 200 microg/ml. Evidence is presented that these nontoxic metabolites may act as antagonists of bacterial quorum sensing by competing with N-acyl homoserine lactones for receptor binding. PMID:19060172

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

2008-12-05

389

Targeting agr- and agr-Like quorum sensing systems for development of common therapeutics to treat multiple gram-positive bacterial infections.  

PubMed

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

2013-04-18

390

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

PubMed Central

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

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

2010-01-01

391

Isovaleryl-homoserine lactone, an unusual branched-chain quorum-sensing signal from the soybean symbiont Bradyrhizobium japonicum.  

PubMed

Many species of Proteobacteria communicate by using LuxI-LuxR-type quorum-sensing systems that produce and detect acyl-homoserine lactone (acyl-HSL) signals. Most of the known signals are straight-chain fatty acyl-HSLs, and evidence indicates that LuxI homologs prefer fatty acid-acyl carrier protein (ACP) over fatty acyl-CoA as the acyl substrate for signal synthesis. Two related LuxI homologs, RpaI and BtaI from Rhodopseudomonas palustris and photosynthetic stem-nodulating bradyrhizobia, direct production of the aryl-HSLs p-coumaroyl-HSL and cinnamoyl-HSL, respectively. Here we report that BjaI from the soybean symbiont Bradyrhizobium japonicum USDA110 is closely related to RpaI and BtaI and catalyzes the synthesis of isovaleryl-HSL (IV-HSL), a branched-chain fatty acyl-HSL. We show that IV-HSL induces expression of bjaI, and in this way IV-HSL functions like many other acyl-HSL quorum-sensing signals. Purified histidine-tagged BjaI was an IV-HSL synthase, which was active with isovaleryl-CoA but not detectably so with isovaleryl-ACP. This suggests that the RpaI-BtaI-BjaI subfamily of acyl-HSL synthases may use CoA- rather than ACP-linked substrates for acyl-HSL synthesis. The bjaI-linked bjaR(1) gene is involved in the response to IV-HSL, and BjaR(1) is sensitive to IV-HSL at concentrations as low as 10 pM. Low but sufficient levels of IV-HSL (about 5 nM) accumulate in B. japonicum culture fluid. The low levels of IV-HSL synthesis have likely contributed to the fact that the quorum-sensing signal from this bacterium has not been described elsewhere. PMID:21949379

Lindemann, Andrea; Pessi, Gabriella; Schaefer, Amy L; Mattmann, Margrith E; Christensen, Quin H; Kessler, Aline; Hennecke, Hauke; Blackwell, Helen E; Greenberg, E Peter; Harwood, Caroline S

2011-09-26

392

Inhibition of quorum sensing (QS) in Yersinia enterocolitica by an orange extract rich in glycosylated flavanones.  

PubMed

Flavanones, flavonoids abundant in Citrus , have been shown to interfere with quorum sensing (QS) and affect related physiological processes. We have investigated the QS-inhibitory effects of an orange extract enriched in O-glycosylated flavanones (mainly naringin, neohesperidin, and hesperidin). The QS-inhibitory capacity of this extract and its main flavanone components was first screened using the bacteriological monitoring system Chromobacterium violaceum . We next examined the ability of the orange extract and of some of the flavanones to (i) reduce the levels of the QS mediators produced by Y. enterocolitica using HPLC-MS/MS, (ii) inhibit biofilm formation, and (iii) inhibit swimming and swarming motility. Additionally, we evaluated changes in the expression of specific genes involved in the synthesis of the lactones (yenI, yenR) and in the flagellar regulon (flhDC, fleB, fliA) by RT-PCR. The results showed that the orange extract and its main flavanone components inhibited QS in C. violaceum, diminished the levels of lactones secreted by Y. enterocolitica to the media, and decreased QS-associated biofilm maturation without affecting bacterial growth. Among the tested compounds, naringin was found to inhibit swimming motility. Exposure to the orange extract and (or) to naringin was also found to be associated with induction of the transcription levels of yenR, flhDC, and fliA. This work shows the in vitro QS-inhibitory effects of an orange extract enriched in flavanones against a human enteropathogen at doses that can be achieved through the diet and suggests that consumption of these natural extracts may have a beneficial antipathogenic effect. PMID:22533445

Truchado, Pilar; Giménez-Bastida, Juan-Antonio; Larrosa, Mar; Castro-Ibáñez, Irene; Espín, Juan Carlos; Tomás-Barberán, Francisco A; García-Conesa, María Teresa; Allende, Ana

2012-05-02

393

A dual biosensor for 2-alkyl-4-quinolone quorum-sensing signal molecules.  

PubMed

Pseudomonas, Burkholderia and Alteromonas species produce diverse 2-alkyl-4-quinolones (AHQs) which inhibit the growth of bacteria, algae and phytoplankton, chelate iron, modulate mammalian host immune defences and act as quorum-sensing (QS) signal molecules. To facilitate the detection, identification and quantification of the major Pseudomonas aeruginosa AHQs 2-heptyl-3-hydroxy-4-quinolone (PQS) and 2-heptyl-4-quinolone (HHQ) we developed two different AHQ biosensors. These were constructed by introducing either a lecA::luxCDABE or a pqsA::luxCDABE reporter gene fusion into a P. aeruginosa pqsA mutant which cannot synthesize AHQs. While both biosensors responded similarly to PQS (EC(50) 18 +/- 4 microM), the pqsA::luxCDABE biosensor was most sensitively activated by HHQ (EC(50) 0.44 +/- 0.1 microM). This biosensor was also activated albeit less sensitively by (i) PQS analogues with alkyl chains varying from C1 to C11, (ii) HHQ analogues with C9 and C11 alkyl chains and (iii) 2-heptyl-4-hydroxyquinoline-N-oxide (HHQNO). The AHQ biosensor also responded differentially to the AHQs present in cell free culture supernatants prepared from PAO1 and isogenic strains carrying mutations in genes (pqsA, pqsH, lasR, lasI, rhlR, rhlI) known to influence AHQ production. The AHQ profiles of P. aeruginosa strains was also evaluated by overlaying thin layer chromatogram (TLC) plates with the pqsA::luxCDABE biosensor. In PAO1, three major bioluminescent spots were observed which correspond to PQS, HHQ and a mixture of 2 nonyl-4-quinolone and HHQNO. We also noted that on TLC plates the biosensor not only produced bioluminescence in response to AHQs but also the green pigment, pyocyanin which offers an alternative visual indicator for AHQ production. PMID:17922753

Fletcher, Matthew P; Diggle, Stephen P; Crusz, Shanika A; Chhabra, Siri Ram; Cámara, Miguel; Williams, Paul

2007-11-01

394

The Pseudomonas putida Lon protease is involved in N-acyl homoserine lactone quorum sensing regulation  

PubMed Central

Background In Pseudomonas putida and Pseduomonas aeruginosa, the similar PpuR/RsaL/PpuI and LasR/RsaL/LasI acyl homoserine lactones (AHLs) quorum sensing (QS) systems have been shown to be under considerable regulation by other global regulators. A major regulator is the RsaL protein which strongly directly represses the transcription of the P. putida ppuI and P. aeruginosa lasI AHL synthases. In this study we screened a transposon mutant bank of P. putida in order to identify if any other regulators were involved in negative regulation of AHL QS. Results In our screen we identified three Tn5 mutants which displayed overproduction of AHLs in P. putida strain WCS358. Two of the mutants had a Tn5 located in the rsaL gene, whereas in one mutant the transposon was located in the lon protease gene. Lon proteases play important roles in protein quality control via degradation of misfolded proteins. It was determined that in the P. putida lon mutant, AHL levels, PpuR levels and ppuI promoter activity all increased significantly; we therefore postulated that PpuR is a target for Lon. The Lon protease had no effect on AHL production in P. aeruginosa. Conclusion The Lon protease is a negative regulator of AHL production in P. putida WCS358. The Lon protease has also been shown by others to influence AHL QS in Vibrio fischeri and Agrobacterium tumefaciens and can thus become an important regulator of AHL QS timing and regulation in bacteria.

Bertani, Iris; Rampioni, Giordano; Leoni, Livia; Venturi, Vittorio

2007-01-01

395

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

PubMed

The quorum-sensing (QS) regulatory system of the gall-forming Pantoea agglomerans pv. gypsophilae was identified. Mass spectral analysis, together with signal-specific biosensors, demonstrated that P. agglomerans pv. gypsophilae produced N-butanoyl-l-homoserine lactone (C4-HSL) as a major and N-hexanoyl-l-homoserine lactone (C6-HSL) as a minor QS signal. Homologs of luxI and luxR regulatory genes, pagI and pagR, were characterized in strain P. agglomerans pv. gypsophilae Pag824-1 and shown to be convergently transcribed and separated by 14 bp. The deduced PagI (23.8 kDa) and PagR (26.9 kDa) show high similarity with SmaI (41% identity) and SmaR (43% identity), respectively, of Serratia sp. American Type Culture Collection 39006. PagR possesses characteristic autoinducer binding and a helix-turn-helix DNA-binding domain. Gall formation by P. agglomerans pv. gypsophilae depends on a plasmid-borne hrp/hrc gene cluster, type III effectors, and phytohormones. Disruption of pagI, pagR, or both genes simultaneously in Pag824-1 reduced gall size in gypsophila cuttings by 50 to 55% when plants were inoculated with 10(6) CFU/ml. Higher reductions in gall size (70 to 90%) were achieved by overexpression of pagI or addition of exogenous C4-HSL. Expression of the hrp/hrc regulatory gene hrpL and the type III effector pthG in the pagI mutant, as measured with quantitative reverse-transcriptase polymerase chain reaction, was reduced by 5.8 and 6.6, respectively, compared with the wild type, suggesting an effect of the QS system on the Hrp regulon. PMID:18616406

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

2008-08-01

396

Directed evolution of the quorum-sensing regulator EsaR for increased signal sensitivity.  

PubMed

The use of cell-cell communication or "quorum sensing (QS)" elements from Gram-negative Proteobacteria has enabled synthetic biologists to begin engineering systems composed of multiple interacting organisms. However, additional tools are necessary if we are to progress toward synthetic microbial consortia that exhibit more complex, dynamic behaviors. EsaR from Pantoea stewartii subsp. stewartii is a QS regulator that binds to DNA as an apoprotein and releases the DNA when it binds to its cognate signal molecule, 3-oxohexanoyl-homoserine lactone (3OC6HSL). In the absence of 3OC6HSL, EsaR binds to DNA and can act as either an activator or a repressor of transcription. Gene expression from P(esaR), which is repressed by wild-type EsaR, requires 100- to 1000-fold higher concentrations of signal than commonly used QS activators, such as LuxR and LasR. Here we have identified EsaR variants with increased sensitivity to 3OC6HSL using directed evolution and a dual ON/OFF screening strategy. Although we targeted EsaR-dependent derepression of P(esaR), our EsaR variants also showed increased 3OC6HSL sensitivity at a second promoter, P(esaS), which is activated by EsaR in the absence of 3OC6HSL. Here, the increase in AHL sensitivity led to gene expression being turned off at lower concentrations of 3OC6HSL. Overall, we have increased the signal sensitivity of EsaR more than 70-fold and generated a set of EsaR variants that recognize 3OC6HSL concentrations ranging over 4 orders of magnitude. QS-dependent transcriptional regulators that bind to DNA and are active in the absence of a QS signal represent a new set of tools for engineering cell-cell communication-dependent gene expression. PMID:23363022

Shong, Jasmine; Huang, Yao-Ming; Bystroff, Christopher; Collins, Cynthia H

2013-02-06

397

Regulation of Uptake and Processing of the Quorum-Sensing Autoinducer AI-2 in Escherichia coli  

PubMed Central

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 Typhimurium, the reduction in activity is due to import and processing of AI-2 by the Lsr transporter. We show that the Lsr transporter is functional in E. coli, and screening for mutants defective in AI-2 internalization revealed lsrK and glpD. Unlike the wild type, lsrK and glpD mutants do not activate transcription of the lsr operon in response to AI-2. lsrK encodes the AI-2 kinase, and the lsrK mutant fails to activate lsr expression because it cannot produce phospho-AI-2, which is the lsr operon inducer. glpD encodes the glycerol-3-phosphate (G3P) dehydrogenase, which is involved in glycerol and G3P metabolism. G3P accumulates in the glpD mutant and represses lsr transcription by preventing cyclic AMP (cAMP)-catabolite activator protein (CAP)-dependent activation. Dihydroxyacetone phosphate (DHAP) also accumulates in the glpD mutant, and DHAP represses lsr transcription by a cAMP-CAP-independent mechanism involving LsrR, the lsr operon repressor. The requirement for cAMP-CAP in lsr activation explains why AI-2 persists in culture fluids of bacteria grown in media containing sugars that cause catabolite repression. These findings show that, depending on the prevailing growth conditions, the amount of time that the AI-2 signal is present and, in turn, the time that a given community of bacteria remains exposed to this signal can vary greatly.

Xavier, Karina B.; Bassler, Bonnie L.

2005-01-01

398

Lyngbyoic acid, a "tagged" fatty acid from a marine cyanobacterium, disrupts quorum sensing in Pseudomonas aeruginosa†  

PubMed Central

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

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

2013-01-01

399

Farnesol, a Fungal Quorum-Sensing Molecule Triggers Apoptosis in Human Oral Squamous Carcinoma Cells1  

PubMed Central

Farnesol is a catabolite within the isoprenoid/cholesterol pathway that has exhibited significant antitumor activity. Farnesol was recently identified as a quorum-sensing molecule produced by the fungal pathogen Candida albicans. In this study, we hypothesize that synthetic and Candida-produced farnesol can induce apoptosis in vitro in oral squamous cell carcinoma (OSCC) lines. Cell proliferation, apoptosis, mitochondrial degradation, and survivin and caspase expressions were examined. In addition, global protein expression profiles were analyzed using proteomic analysis. Results demonstrated significant decrease in proliferation and increase in apoptosis in cells exposed to farnesol and C. albicans culture media. Concurrently, protein expression analysis demonstrated a significant decrease in survivin and an increase in cleaved-caspase expression, whereas fluorescent microscopy revealed the presence of active caspases with mitochondrial degradation in exposed cells. A total of 36 differentially expressed proteins were identified by proteomic analysis. Among the 26 up-regulated proteins were those involved in the inhibition of carcinogenesis, proliferation suppression, and aging. Most notable among the 10 down-regulated proteins were those involved in the inhibition of apoptosis and proteins overexpressed in epithelial carcinomas. This study demonstrates that farnesol significantly inhibits the proliferation of OSCCs and promotes apoptosis in vitro through both the intrinsic and extrinsic apoptotic signaling pathways. In addition, we report for the first time the ability of Candida-produced farnesol to induce a similar apoptotic response through the same pathways. The capability of farnesol to trigger apoptosis in cancer cells makes it a potential tool for studying tumor progression and an attractive candidate as a therapeutic agent.

Scheper, Mark A; Shirtliff, Mark E; Meiller, Timothy F; Peters, Brian M; Jabra-Rizk, Mary Ann

2008-01-01

400

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

2013-05-05

401

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

PubMed

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 P. aeruginosa prototrophic strain PAO1. Analysis of the biofilms by confocal laser scanning microscopy and COMSTAT image analysis at 1 and 7 days post-inoculation showed that the isolates produced diverse biofilms. In comparison with PAO1, the CI produced biofilms that scarcely or partially covered the surface at day 1, although CI-1 produced larger microcolonies. At day 7, CI-2 and CI-4 produced mature biofilms denser than that produced by PAO1, while the biofilm formed by CI-1 changed very little from day 1. CI-1 was defective in both swarming and twitching motilities, and immunoblotting analysis confirmed that it produced a reduced level of PilA protein. The twitching-motility defect of CI-1 was not complemented by a plasmid carrying intact pilA. In the 48 h colony biofilm assay, the CI varied in susceptibility to imipenem, gentamicin and piperacillin/tazobactam. These results suggest that: (1) the isolates produced biofilms with different structures and densities from that of PAO1; (2) biofilm formation by the isolates was not influenced by either the isolation site or the QS deficiencies of the isolates; (3) the behaviour of CI-1 in the different biofilm systems may be due to its lack of swarming motility and type IV pilus-related twitching motility. PMID:17510257

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

2007-06-01

402

Modulation of quorum sensing in Pseudomonas aeruginosa through alteration of membrane properties.  

PubMed

Changes in the cellular envelope are major physiological adaptations that occur when micro-organisms encounter extreme environmental conditions. An appropriate degree of membrane fluidity is crucial for survival, and alteration of membrane lipids is an essential adaptive response. Emerging data suggest that microbial cells may recognize alterations in their membrane viscosity resulting from certain environmental changes as a trigger for adaptive cellular responses. In Pseudomonas aeruginosa, the quorum-sensing (QS) system involves a complex regulatory circuitry that coordinates the expression of genes according to a critical population density. Interestingly, it has been shown that the QS system of P. aeruginosa can also be activated by nutritional stress, independently of the cell density, and therefore may be part of a more general adaptive response to stressful environmental conditions. In order to examine the proposed link between membrane properties and stress signalling, the effects of genetically engineered alterations of the membrane phospholipid composition of P. aeruginosa PAO1 on the activation of the stringent response and the QS system were examined. The lptA gene encoding a functional homologue of PlsC, an Escherichia coli enzyme that catalyses the second step of the phospholipid biosynthesis pathway, was identified and disrupted. Inactivation of lptA altered the fatty acid profile of phospholipids and the membrane properties, resulting in decreased membrane fluidity. This resulted in a premature production of the QS signals N-butanoyl- and N-hexanoyl-homoserine lactone (C4-HSL and C6-HSL) and a repression of 2-heptyl-3-hydroxy-4-quinolone (PQS) synthesis at later growth phases. The effects on C4- and C6-HSL depended upon the expression of relA, encoding the (p)ppGpp alarmone synthase, which was increased in the lptA mutant. Together, the findings support the concept that alterations in membrane properties can act as a trigger for stress-related gene expression. PMID:16079332

Baysse, Christine; Cullinane, Méabh; Dénervaud, Valérie; Burrowes, Elizabeth; Dow, J Maxwell; Morrissey, John P; Tam, Ling; Trevors, Jack T; O'Gara, Fergal

2005-08-01

403

Anaerobiosis-Induced Loss of Cytotoxicity Is Due to Inactivation of Quorum Sensing in Pseudomonas aeruginosa ? †  

PubMed Central

Pseudomonas aeruginosa, an opportunistic pathogen of clinical importance, causes chronic airway infections in patients with cystic fibrosis (CF). Current literature suggests that pockets with reduced oxygen tension exist in the CF airway mucus. However, virulence features of this opportunistic pathogen under such conditions are largely unknown. Cell-free supernatant of the standard laboratory P. aeruginosa strain PAO1 obtained from anaerobic culture, but not aerobic culture, failed to kill A549 human airway epithelial cells. Further investigation revealed that this reduced cytotoxicity upon anaerobiosis was due to the suppressed secretion of elastase, a virulence factor controlled by P. aeruginosa quorum sensing (QS). Both a lacZ-reporter fusion assay and quantitative real-time PCR (RT-PCR) analysis demonstrated that transcription of the elastase-encoding lasB gene was substantially decreased during anaerobic growth compared with aerobic growth. Moreover, transcription of other genes controlled by the LasI/R QS system, such as rhlR, vqsR, mvfR, and rsaL, was also repressed under the same anaerobic growth conditions. Importantly, synthesis of 3-oxo-C12-HSL (PAI-1), an autoinducer molecule that mediates induction of the LasI/R QS system, was >22-fold decreased during anaerobic growth while C4-HSL (PAI-2), which mediates RhlI/R QS, was nondetectable under the same growth conditions. Transcription of the lasB gene was restored by exogenous supplementation with autoinducers, with PAI-2 more effective than PAI-1 or Pseudomonas quinolone signal (PQS) at restoring transcription of the lasB gene. Together, these results suggest that anaerobiosis deprives P. aeruginosa of the ability to regulate its virulence via QS and this misregulation attenuates the pathogenic potential of this important pathogen.

Lee, Kang-Mu; Yoon, Mi Young; Park, Yongjin; Lee, Joon-Hee; Yoon, Sang Sun

2011-01-01

404

Staphylococcus aureus autoinducer-2 quorum sensing decreases biofilm formation in an icaR-dependent manner  

PubMed Central

Background Staphylococcus aureus is an important pathogen that causes biofilm-associated infection in humans. Autoinducer 2 (AI-2), a quorum-sensing (QS) signal for interspecies communication, has a wide range of regulatory functions in both Gram-positive and Gram-negative bacteria, but its exact role in biofilm formation in S. aureus remains unclear. Results Here we demonstrate that mutation of the AI-2 synthase gene luxS in S. aureus RN6390B results in increased biofilm formation compared with the wild-type (WT) strain under static, flowing and anaerobic conditions and in a mouse model. Addition of the chemically synthesized AI-2 precursor in the luxS mutation strain (?luxS) restored the WT phenotype. Real-time RT-PCR analysis showed that AI-2 activated the transcription of icaR, a repressor of the ica operon, and subsequently a decreased level of icaA transcription, which was presumably the main reason why luxS mutation influences biofilm formation. Furthermore, we compared the roles of the agr-mediated QS system and the LuxS/AI-2 QS system in the regulation of biofilm formation using the ?luxS strain, RN6911 and the ?agr ?luxS strain. Our data indicate a cumulative effect of the two QS systems on the regulation of biofilm formation in S. aureus. Conclusion These findings demonstrate that AI-2 can decrease biofilm formation in S. aureus via an icaR-activation pathway. This study may provide clues for therapy in S. aureus biofilm-associated infection.

2012-01-01

405

Mutational analysis of a nucleosidase involved in quorum-sensing autoinducer-2 biosynthesis.  

PubMed

5'-Methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) is important in a number of cellular functions such as polyamine biosynthesis, methionine salvaging, biological methylation, and quorum sensing. The nucleosidase is found in many microbes but not in mammalian systems, thus making MTAN a broad-spectrum antimicrobial drug target. Substrate binding and catalytic residues were identified from the crystal structure of MTAN complexed with 5'-methylthiotubercidin [Lee, J. E., Cornell, K. A., Riscoe, M. K. and Howell, P. L. (2003) J. Biol. Chem. 278 (10) 8761-8770]. The roles of active site residues Met9, Glu12, Ile50, Ser76, Val102, Phe105, Tyr107, Phe151, Met173, Glu174, Arg193, Ser196, Asp197, and Phe207 have been investigated by site-directed mutagenesis and steady-state kinetics. Mutagenesis of residues Glu12, Glu174, and Asp197 completely abolished activity. The location of Asp197 and Glu12 in the active site is consistent with their having a direct role in enzyme catalysis. Glu174 is suggested to be involved in catalysis by stabilizing the transition state positive charge at the O3', C2', and C3' atoms and by polarizing the 3'-hydroxyl to aid in the flow of electrons to the electron withdrawing purine base. This represents the first indication of the importance of the 3'-hydroxyl in the stabilization of the transition state. Furthermore, mutation of Arg193 to alanine shows that the nucleophilic water is able to direct its attack without assistance from the enzyme. This mutagenesis study has allowed a reevaluation of the catalytic mechanism. PMID:16101288

Lee, Jeffrey E; Luong, Winnie; Huang, David J T; Cornell, Kenneth A; Riscoe, Michael K; Howell, P Lynne

2005-08-23

406

Expression of the bviIR and cepIR Quorum-Sensing Systems of Burkholderia vietnamiensis  

Microsoft Academic Search

Burkholderia vietnamiensis has both the cepIR quorum-sensing system that is widely distributed among the Burkholderia cepacia complex (BCC) and the bviIR system. Comparison of the expression of cepI, cepR, bviI, and bviR-luxCDABE fusions in B. vietnamiensis G4 and the G4 cepR and bviR mutants determined that the expression of bviI requires both a functional cognate regulator, BviR, and functional CepR.

Rebecca J. Malott; Pamela A. Sokol

2007-01-01

407

AI2 does not function as a quorum sensing molecule in Campylobacter jejuni during exponential growth in vitro  

Microsoft Academic Search

Background  \\u000a Campylobacter jejunicontains a homologue of theluxSgene shown to be responsible for the production of the signalling molecule autoinducer-2 (AI-2) inVibrio harveyiandVibrio cholerae. The aim of this study was to determine whether AI-2 acted as a diffusible quorum sensing signal controllingC. jejunigene expression when it is produced at high levels during mid exponential growth phase.\\u000a \\u000a \\u000a \\u000a \\u000a Results  AI-2 activity was produced by

Kathryn Holmes; Tim J Tavender; Klaus Winzer; Jerry M Wells; Kim R Hardie

2009-01-01

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

Microsoft Academic Search

Background  Different models for biofilm in Streptococcus pneumoniae have been described in literature. To permit comparison of experimental