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Sample records for azithromycin blocks quorum

  1. Azithromycin blocks quorum sensing and alginate polymer formation and increases the sensitivity to serum and stationary growth phase killing of P. aeruginosa and attenuates chronic P. aeruginosa lung infection in Cftr -/--mice

    DEFF Research Database (Denmark)

    Hoffmann, N.; Lee, Bao le ri; Hentzer, Morten

    2007-01-01

    The consequences of O-acetylated alginate-producing Pseudomonas aeruginosa biofilms in the lungs of chronically infected cystic fibrosis (CF) patients are tolerance to both antibiotic treatments and effects on the innate and the adaptive defense mechanisms. In clinical trials, azithromycin (AZM...

  2. Azithromycin blocks autophagy and may predispose cystic fibrosis patients to mycobacterial infection

    Science.gov (United States)

    Renna, Maurizio; Schaffner, Catherine; Brown, Karen; Shang, Shaobin; Tamayo, Marcela Henao; Hegyi, Krisztina; Grimsey, Neil J.; Cusens, David; Coulter, Sarah; Cooper, Jason; Bowden, Anne R.; Newton, Sandra M.; Kampmann, Beate; Helm, Jennifer; Jones, Andrew; Haworth, Charles S.; Basaraba, Randall J.; DeGroote, Mary Ann; Ordway, Diane J.; Rubinsztein, David C.; Floto, R. Andres

    2011-01-01

    Azithromycin is a potent macrolide antibiotic with poorly understood antiinflammatory properties. Long-term use of azithromycin in patients with chronic inflammatory lung diseases, such as cystic fibrosis (CF), results in improved outcomes. Paradoxically, a recent study reported that azithromycin use in patients with CF is associated with increased infection with nontuberculous mycobacteria (NTM). Here, we confirm that long-term azithromycin use by adults with CF is associated with the development of infection with NTM, particularly the multi-drug-resistant species Mycobacterium abscessus, and identify an underlying mechanism. We found that in primary human macrophages, concentrations of azithromycin achieved during therapeutic dosing blocked autophagosome clearance by preventing lysosomal acidification, thereby impairing autophagic and phagosomal degradation. As a consequence, azithromycin treatment inhibited intracellular killing of mycobacteria within macrophages and resulted in chronic infection with NTM in mice. Our findings emphasize the essential role for autophagy in the host response to infection with NTM, reveal why chronic use of azithromycin may predispose to mycobacterial disease, and highlight the dangers of inadvertent pharmacological blockade of autophagy in patients at risk of infection with drug-resistant pathogens. PMID:21804191

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

    OpenAIRE

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

    2013-01-01

    With the emergence of antibiotic-resistant strains of bacteria, the available options for treating bacterial infections have become very limited, and the search for a novel general antibacterial therapy has received much greater attention. Quorum quenching can be used to control disease in a quorum sensing system by triggering the pathogenic phenotype. The interference with the quorum sensing system by the quorum quenching enzyme is a potential strategy for replacing traditional antibiotics b...

  4. Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Jensen, Peter Østrup; Rasmussen, Thomas B

    2005-01-01

    The opportunistic human pathogen Pseudomonas aeruginosa is the predominant micro-organism of chronic lung infections in cystic fibrosis patients. P. aeruginosa colonizes the lungs by forming biofilm microcolonies throughout the lung. Quorum sensing (QS) renders the biofilm bacteria highly toleran...

  5. Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Jensen, Peter Østrup; Rasmussen, Thomas B

    2005-01-01

    The opportunistic human pathogen Pseudomonas aeruginosa is the predominant micro-organism of chronic lung infections in cystic fibrosis patients. P. aeruginosa colonizes the lungs by forming biofilm microcolonies throughout the lung. Quorum sensing (QS) renders the biofilm bacteria highly tolerant...

  6. No proarrhythmic properties of the antibiotics Moxifloxacin or Azithromycin in anaesthetized dogs with chronic-AV block

    DEFF Research Database (Denmark)

    Thomsen, Morten Bækgaard; Beekman, J D M; Attevelt, N J M

    2006-01-01

    The therapeutically available quinolone antibiotic moxifloxacin has been used as a positive control for prolonging the QT interval in both clinical and non-clinical studies designed to assess the potential of new drugs to delay cardiac repolarization. Despite moxifloxacin prolonging QT, it has...... not been shown to cause torsades de pointes arrhythmias (TdP). Azithromycin is a macrolide antibiotic that has rarely been associated, clinically, with cases of proarrhythmia. As there is a lack of clinical data available, the cardiac safety of these drugs was assessed in a TdP-susceptible animal model...

  7. Quorum sensing inhibition

    DEFF Research Database (Denmark)

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

    2005-01-01

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

  8. Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections.

    Science.gov (United States)

    Bjarnsholt, Thomas; Jensen, Peter Østrup; Rasmussen, Thomas B; Christophersen, Lars; Calum, Henrik; Hentzer, Morten; Hougen, Hans-Petter; Rygaard, Jørgen; Moser, Claus; Eberl, Leo; Høiby, Niels; Givskov, Michael

    2005-12-01

    The opportunistic human pathogen Pseudomonas aeruginosa is the predominant micro-organism of chronic lung infections in cystic fibrosis patients. P. aeruginosa colonizes the lungs by forming biofilm microcolonies throughout the lung. Quorum sensing (QS) renders the biofilm bacteria highly tolerant to otherwise lethal doses of antibiotics, and protects against the bactericidal activity of polymorphonuclear leukocytes (PMNs). It has been previously demonstrated that QS is inhibited by garlic extract. In this study, the synergistic effects of garlic and tobramycin, and PMNs activities have been evaluated. P. aeruginosa was grown in vitro in continuous-culture once-through flow chambers with and without garlic extract. The garlic-treated biofilms were susceptible to both tobramycin and PMN grazing. Furthermore, the PMNs showed an increase in respiratory burst activation, when incubated with the garlic-treated biofilm. Garlic extract was administered as treatment for a mouse pulmonary infection model. Mice were treated with garlic extract or placebo for 7 days, with the initial 2 days being prophylactic before P. aeruginosa was instilled in the left lung of the mice. Bacteriology, mortality, histopathology and cytokine production were used as indicators. The garlic treatment initially provoked a higher degree of inflammation, and significantly improved clearing of the infecting bacteria. The results indicate that a QS-inhibitory extract of garlic renders P. aeruginosa sensitive to tobramycin, respiratory burst and phagocytosis by PMNs, as well as leading to an improved outcome of pulmonary infections.

  9. Azithromycin Causes a Novel Proarrhythmic Syndrome.

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    Yang, Zhenjiang; Prinsen, Joseph K; Bersell, Kevin R; Shen, Wangzhen; Yermalitskaya, Liudmila; Sidorova, Tatiana; Luis, Paula B; Hall, Lynn; Zhang, Wei; Du, Liping; Milne, Ginger; Tucker, Patrick; George, Alfred L; Campbell, Courtney M; Pickett, Robert A; Shaffer, Christian M; Chopra, Nagesh; Yang, Tao; Knollmann, Bjorn C; Roden, Dan M; Murray, Katherine T

    2017-04-01

    The widely used macrolide antibiotic azithromycin increases risk of cardiovascular and sudden cardiac death, although the underlying mechanisms are unclear. Case reports, including the one we document here, demonstrate that azithromycin can cause rapid, polymorphic ventricular tachycardia in the absence of QT prolongation, indicating a novel proarrhythmic syndrome. We investigated the electrophysiological effects of azithromycin in vivo and in vitro using mice, cardiomyocytes, and human ion channels heterologously expressed in human embryonic kidney (HEK 293) and Chinese hamster ovary (CHO) cells. In conscious telemetered mice, acute intraperitoneal and oral administration of azithromycin caused effects consistent with multi-ion channel block, with significant sinus slowing and increased PR, QRS, QT, and QTc intervals, as seen with azithromycin overdose. Similarly, in HL-1 cardiomyocytes, the drug slowed sinus automaticity, reduced phase 0 upstroke slope, and prolonged action potential duration. Acute exposure to azithromycin reduced peak SCN5A currents in HEK cells (IC 50 =110±3 μmol/L) and Na + current in mouse ventricular myocytes. However, with chronic (24 hour) exposure, azithromycin caused a ≈2-fold increase in both peak and late SCN5A currents, with findings confirmed for I Na in cardiomyocytes. Mild block occurred for K + currents representing I Kr (CHO cells expressing hERG; IC 50 =219±21 μmol/L) and I Ks (CHO cells expressing KCNQ1+KCNE1; IC 50 =184±12 μmol/L), whereas azithromycin suppressed L-type Ca ++ currents (rabbit ventricular myocytes, IC 50 =66.5±4 μmol/L) and I K1 (HEK cells expressing Kir2.1, IC 50 =44±3 μmol/L). Chronic exposure to azithromycin increases cardiac Na + current to promote intracellular Na + loading, providing a potential mechanistic basis for the novel form of proarrhythmia seen with this macrolide antibiotic. © 2017 American Heart Association, Inc.

  10. The Story of Azithromycin

    Directory of Open Access Journals (Sweden)

    Banić Tomišić, Z.

    2011-12-01

    Full Text Available The invention of azithromycin (1, Figure 1, the active pharmaceutical ingredient of the antibiotic Sumamed (Croatian brand name by PLIVA; Zithromax by Pfizer in the USA belongs among the great achievements in the history of science in Croatia. From the viewpoint of commercialization of research results, it may have been one of the greatest. In addition to contributing to science and to medicine, azithromycin has also brought about an improvement in the quality of life on the global level. Owing to its exceptional therapeutic properties, it has come to be one of the most successful antibiotics worldwide. Marking the 30th anniversary of the azithromycin Yugoslav patent application, this paper gives an overview of the research that led to its discovery and comes with a list of papers and patents through which the drug has been made known to the public (Table 1, Figures 4 and 6. The invention was due to the scientists from the Research Institute of the pharmaceutical company PLIVA in Zagreb, Croatia, D. Sc. S. Đokić, M. Sc. G. Kobrehel, D. Sc. G. Lazarevski, and D. Sc. Z. Tamburašev (Figure 3. Azithromycin became the first representative of the new class of 15-membered macrolides known as azalides after the introduction of nitrogen in the macrocycle of erythromycin A (2, Figure 1. Its synthesis involved several steps (Figure 2: oximation of erithromycin A, Beckmann rearrangement of erythromycin A oxime with aromatic sulphochlorides, reduction of the produced erithromycin A iminoether, and final methylation of the nitrogen introduced in the macrocycle of erythromycin A. Because of inadequate analytical support in the late 1970s and early 1980s, the precise structure of the LD product (Figure 5 in the Beckmann rearrangement step of azithromycin synthesis was confirmed only later as 7 and not 6 as assumed (Figure 5. Today, azithromycin is known under the common chemical name of 9-deoxo-9a-aza-9a-methyl-homoerythromycin A. This paper also deals with

  11. Neurodegenerative effects of azithromycin in differentiated PC12 cells.

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    Waetzig, Vicki; Riffert, Jeanette; Cordt, Justus; Reinecke, Kirstin; Haeusgen, Wiebke; Boehm, Ruwen; Cascorbi, Ingolf; Herdegen, Thomas

    2017-08-15

    Azithromycin is a widely used macrolide antibiotic with sustained and high tissue penetration and intracellular accumulation. While short-term exposure to low-dose azithromycin is usually well tolerated, prolonged treatment can lead to unwanted neurological effects like paresthesia and hearing loss. However, the mechanism causing neurodegeneration is still unknown. Here, we show that even low therapeutically relevant azithromycin concentrations like 1µg/ml decreased cell viability by 15% and induced neurite loss of 47% after 96h in differentiated PC12 cells, which are a well-established model system for neuronal cells. When higher concentrations were used, the drug-induced effects occurred earlier and were more pronounced. Thereby, azithromycin altered tropomyosin-related kinase A (TrkA) signaling and attenuated protein kinase B (Akt) activity, which subsequently induced autophagy. Simultaneously, the antibiotic impaired lysosomal functions by blocking the autophagic flux, and this concurrence reduced cell viability. In good agreement with reversible effects observed in patients, PC12 cells could completely recover if azithromycin was removed after 24h. In addition, the detrimental effects of azithromycin were limited to differentiated cells, as confirmed in the human neuronal model cell line SH-SY5Y. Thus, azithromycin alters cell surface receptor signaling and autophagy in neuronal cells, but does not automatically induce irreversible damage when used in low concentrations and for a short time. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Coprinuslactone protects the edible mushroom Coprinus comatus against biofilm infections by blocking both quorum-sensing and MurA.

    Science.gov (United States)

    de Carvalho, Maira P; Gulotta, Giuseppe; do Amaral, Matheus W; Lünsdorf, Heinrich; Sasse, Florenz; Abraham, Wolf-Rainer

    2016-11-01

    Pathogens embedded in biofilms are involved in many infections and are very difficult to treat with antibiotics because of higher resistance compared with planktonic cells. Therefore, new approaches for their control are urgently needed. One way to search for biofilm dispersing compounds is to look at defense strategies of organisms exposed to wet environments, which makes them prone to biofilm infections. It is reasonable to assume that mushrooms have developed mechanisms to control biofilms on their sporocarps (fruiting bodies). A preliminary screening for biofilms on sporocarps revealed several species with few or no bacteria on their sporocarps. From the edible mushroom Coprinus comatus where no bacteria on the sporocarp could be detected (3R,4S)-2-methylene-3,4-dihydroxypentanoic acid 1,4-lactone, named coprinuslactone, was isolated. Coprinuslactone interfered with quorum-sensing and dispersed biofilms of Pseudomonas aeruginosa, where it also reduced the formation of the pathogenicity factors pyocyanin and rhamnolipid B. Coprinuslactone also damaged Staphylococcus aureus cells in biofilms at subtoxic concentrations. Furthermore, it inhibited UDP-N-acetylglucosamine enolpyruvyl transferase (MurA), essential for bacterial cell wall synthesis. These two modes of action ensure the inhibition of a broad spectrum of pathogens on the fruiting body but may also be useful for future clinical applications. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  13. Quorum sensing inhibitors

    DEFF Research Database (Denmark)

    Rasmussen, Thomas Bovbjerg; Givskov, Michael Christian

    2006-01-01

    Many opportunistic pathogenic bacteria rely on quorum sensing (QS) circuits as central regulators of virulence expression. In Pseudomonas aeruginosa, QS-regulated gene expression contributes to the formation and maintenance of biofilms and their tolerance to conventional antimicrobials and the host...... of plant pathogens in several models....... innate immune system. Therefore, QS is an obvious target for a novel class of antimicrobial drugs which would function to efficiently block reception of the cognate QS signals in vivo, and thereby be capable of inducing chemical attenuation of pathogens. As QS is not directly involved in processes...

  14. Antivirulence activity of azithromycin in Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Francesco eImperi

    2014-04-01

    Full Text Available Antibiotics represent our bulwark to combat bacterial infections, but the spread of antibiotic resistance compromises their clinical efficacy. Alternatives to conventional antibiotics are urgently needed in order to complement the existing antibacterial arsenal. The macrolide antibiotic azithromycin (AZM provides a paradigmatic example of an unconventional antibacterial drug. Besides its growth-inhibiting activity, AZM displays potent anti-inflammatory properties, as well as antivirulence activity on some intrinsically resistant bacteria, such as Pseudomonas aeruginosa. In this bacterium, the antivirulence activity of AZM mainly relies on its ability to interact with the ribosome, resulting in direct and/or indirect repression of specific subsets of genes involved in virulence, quorum sensing, biofilm formation and intrinsic antibiotic resistance. Both clinical experience and clinical trials have shown the efficacy of AZM in the treatment of chronic pulmonary infections caused by P. aeruginosa. The aim of this review is to combine results from laboratory studies with evidence from clinical trials in order to unify the information on the in vivo mode of action of AZM in P. aeruginosa infection.

  15. Azithromycin Modulates 3',5'-cyclic Diguanylic Acid Signaling in Pseudomonas aeruginosa.

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    Kimura, Soichiro; Mori, Nobuaki; Kai, Toshihiro; Ishii, Yoshikazu; Yamaguchi, Keizo; Tateda, Kazuhiro

    2017-08-01

    Macrolides have been reported to exert a variety of effects on both host immunomodulation and repression of bacterial pathogenicity. In this study, we report that the 3',5'-cyclic diguanylic acid (c-di-GMP) signaling system, which regulates virulence in Pseudomonas aeruginosa, is affected by the macrolide azithromycin. Using DNA microarray analysis, we selected a gene encoding PA2567 related to c-di-GMP metabolism that was significantly affected by azithromycin treatment. Expression of the PA2567 gene was significantly repressed by azithromycin in a time- and dose-dependent manner, whereas no difference in PA2567 gene expression was observed in the absence of azithromycin. In-frame deletion of the PA2567 gene affected both virulence factors and the quorum-sensing system, and significantly decreased total bacteria in a mouse pneumonia model compared to the wild-type strain (P < 0.05). These results suggest that macrolides possess the ability to modulate c-di-GMP intracellular signaling in P. aeruginosa. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  16. Decreased Azithromycin Susceptibility of Neisseria gonorrhoeae Isolates in Patients Recently Treated with Azithromycin

    NARCIS (Netherlands)

    Wind, Carolien M.; de Vries, Esther; Schim van der Loeff, Maarten F.; van Rooijen, Martijn S.; van Dam, Alje P.; Demczuk, Walter H. B.; Martin, Irene; de Vries, Henry J. C.

    2017-01-01

    Background. Increasing azithromycin usage and resistance in Neisseria gonorrhoeae threatens current dual treatment. Because antimicrobial exposure influences resistance, we analyzed the association between azithromycin exposure and decreased susceptibility of N. gonorrhoeae. Methods. We included N.

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

    Science.gov (United States)

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

    2015-04-01

    Quorum sensing in Pseudomonas aeruginosa plays an imperative role in virulence factor, biofilm formation and antimicrobial resistance. Blocking quorum sensing pathways are viewed as viable anti-virulent therapy in association with traditional antimicrobial therapy. Anti-quorum sensing dietary phytochemicals with may prove to be a safe and viable choice as anti-virulent drug candidates. Previously, our lab proved zingerone as potent anti-biofilm agent hence; further its anti-virulent and anti-quorum activities were evaluated. Zingerone, besides decreasing swimming, swarming and twitching phenotypes of P. aeruginosa PAO1, reduced biofilm forming capacity and production of virulence factors including rhamnolipid, elastase, protease, pyocyanin, cell free and cell bound hemolysin (pquorum sensing signal molecules by clinical isolates of P. aeruginosa but also showed significant interference with the activation of QS reporter strains. To study the mechanism of blocking quorum sensing cascade, in silico analysis was carried out. Anti-QS activity was attributed to interference with the ligand receptor interaction of zingerone with QS receptors (TraR, LasR, RhlR and PqsR). Zingerone showed a good comparative docking score to respective autoinducer molecules which was even higher than that of vanillin, a proven anti-quorum sensing phytochemical. The results of the present study revealed the anti-quorum sensing activity of zingerone targeting ligand-receptor interaction, hence proposing zingerone as a suitable anti-virulent drug candidate against P. aeruginosa infections. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Azithromycin prophylaxis and treatment of murine toxoplasmosis.

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    Tabbara, Khalid F; Hammouda, Ehab; Tawfik, Abdulkader; Al-Omar, Othman M; Abu El-Asrar, Ahmed M

    2005-03-01

    To evaluate the azithromycin effects alone and in combination with other agents in the prophylaxis and treatment of murine toxoplasmosis. A total of 280 BALB/c mice were included, and 2 x 103 Toxoplasma organisms of the RH strain Toxoplasma gondii strain ATCC50174 were given intraperitoneally to each mouse. In experiment one, 40 animals were given azithromycin 200 milligram/kilogram/daily for 3 days starting the day of inoculation, 40 mice were control. In experiment 2, the treatment was started 48 hours after inoculation and given daily for 3 days: one group received azithromycin 200 milligram/kilogram/day, the second group received pyrimethamine 25 milligram/kilogram/day, and the sulfadiazine 100 milligram/kilogram/day. The third group was control. In experiment 3, 7 groups of animals received one of the following (1) none, (2) azithromycin 200 milligram/kilogram/day, (3) pyrimethamine 25 milligram/kilogram/day and sulfadiazine 100 milligram/kilogram/day, (4) azithromycin and sulfadiazine, (5) azithromycin and pyrimethamine, (6) azithromycin with sulfadiazine and pyrimethamine, (7) sulfadiazine alone. Treatment was initiated 72 hours after inoculation for 3 days. The study was conducted at the Animal Care Facility of King Saud University, Riyadh, Kingdom of Saudi Arabia. Animals that received azithromycin simultaneously with inoculation survived, and all control animals died. All animals died in groups receiving single drug therapy. Animals treated with azithromycin and sulfadiazine showed a survival rate of 40%, sulfadiazine and pyrimethamine 40%, or azithromycin with sulfadiazine and pyrimethamine 95% (p<0.0001). Azithromycin alone was found to be effective in the prophylaxis of murine toxoplasmosis. Combination therapy was effective in the treatment of murine toxoplasmosis.

  19. Evaluation of Enoyl-Acyl Carrier Protein Reductase Inhibitors as Pseudomonas aeruginosa Quorum-Quenching Reagents

    DEFF Research Database (Denmark)

    Yang, Liang; Liu, Yang; Sternberg, Claus

    2010-01-01

    which block the quorum-sensing process can facilitate development of novel treatment strategies for P. aeruginosa infections. We have used molecular dynamics simulation and experimental studies to elucidate the efficiencies of two potential quorum-quenching reagents, triclosan and green tea...

  20. Reducing Virulence and Biofilm of Pseudomonas aeruginosa by Potential Quorum Sensing Inhibitor Carotenoid: Zeaxanthin.

    Science.gov (United States)

    Gökalsın, Barış; Aksoydan, Busecan; Erman, Burak; Sesal, Nüzhet Cenk

    2017-08-01

    Pseudomonas aeruginosa can regulate its virulence gene expressions by using a signal system called quorum sensing. It is known that inhibition of quorum sensing can block biofilm formation and leave the bacteria defenseless. Therefore, it is necessary to determine natural sources to obtain potential quorum sensing inhibitors. This study aims to investigate an alternative treatment approach by utilizing the carotenoid zeaxanthin to reduce the expressions of P. aeruginosa virulence factors through quorum sensing inhibition. The inhibition potential of zeaxanthin was determined by in silico screening from a library of 638 lichen metabolites. Fluorescent monitor strains were utilized for quorum sensing inhibitor screens, and quantitative reverse-transcriptase PCR assay was performed for evaluating gene expression. Results indicate that zeaxanthin is a better inhibitor than the lichen secondary metabolite evernic acid, which was previously shown to be capable of inhibiting P. aeruginosa quorum sensing systems.

  1. Azithromycin

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    ... side effects.if you are taking antacids containing aluminum hydroxide or magnesium hydroxide (Maalox, Mylanta, Tums, others), ... to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in ...

  2. PA3297 Counteracts Antimicrobial Effects of Azithromycin in Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Hao eTan

    2016-03-01

    Full Text Available Pseudomonas aeruginosa causes acute and chronic infections in human. Its increasing resistance to antibiotics requires alternative treatments that are more effective than available strategies. Among the alternatives is the unconventional usage of conventional antibiotics, of which the macrolide antibiotic azithromycin (AZM provides a paradigmatic example. AZM therapy is associated with a small but consistent improvement in respiratory function of cystic fibrosis (CF patients suffering from chronic P. aeruginosa infection. Besides immunomodulating activities, AZM represses bacterial genes involved in virulence, quorum sensing, biofilm formation, and motility, all of which are due to stalling of ribosome and depletion of cellular tRNA pool. However, how P. aeruginosa responds to and counteracts the effects of AZM remain elusive. Here we found that deficiency of PA3297, a gene encoding a DEAH-box helicase, intensified AZM-mediated bacterial killing, suppression of pyocyanin production and swarming motility, and hypersusceptibility to hydrogen peroxide. We demonstrated that expression of PA3297 is induced by the interaction between AZM and ribosome. Importantly, mutation of PA3297 resulted in elevated levels of unprocessed 23S-5S rRNA in the presence of AZM, which might lead to increased susceptibility to AZM-mediated effects. Our results revealed one of the bacterial responses in counteracting the detrimental effects of AZM.

  3. Perinatal pharmacokinetics of azithromycin for cesarean prophylaxis.

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    Sutton, Amelia L; Acosta, Edward P; Larson, Kajal B; Kerstner-Wood, Corenna D; Tita, Alan T; Biggio, Joseph R

    2015-06-01

    Postpartum infections are polymicrobial and typically include Ureaplasma, an intracellular microbe that is treated by macrolides such as azithromycin. The aim of this study was to evaluate the perinatal pharmacokinetics of azithromycin after a single preincision dose before cesarean delivery. Thirty women who underwent scheduled cesarean delivery were assigned randomly to receive 500 mg of intravenous azithromycin that was initiated 15, 30, or 60 minutes before incision and infused over 1 hour. Serial maternal plasma samples were drawn from the end of infusion up to 8 hours after the infusion. Samples of amniotic fluid, umbilical cord blood, placenta, myometrium, and adipose tissue were collected intraoperatively. Breast milk samples were collected 12-48 hours after the infusion in 8 women who were breastfeeding. Azithromycin was quantified with high performance liquid chromatography separation coupled with tandem mass spectrometry detection. Plasma pharmacokinetic parameters were estimated with the use of noncompartmental analysis and compartmental modeling and simulations. The maximum maternal plasma concentration was reached within 1 hour and exceeded the in vitro minimum inhibitory concentration (MIC50) of 250 ng/mL of Ureaplasma spp in all 30 patients. The concentrations were sustained with a half-life of 6.7 hours. The median concentration of azithromycin in adipose tissue was 102 ng/g, which was below the MIC50. The median concentration in myometrium was 402 ng/g, which exceeded the MIC50. Azithromycin was detectable in both the umbilical cord plasma and amniotic fluid after the single preoperative dose. Azithromycin concentrations in breast milk were high and were sustained up to 48 hours after the single dose. Simulations demonstrated accumulation in breast milk after multiple doses. A single dose of azithromycin achieves effective plasma and tissue concentrations and is transported rapidly across the placenta. The tissue concentrations that are achieved

  4. Quorum Colorings of Graphs

    NARCIS (Netherlands)

    S.M. Heditniemi (Sandra); R.C. Laskar (R.C.); H.M. Mulder (Martyn)

    2012-01-01

    textabstractLet $G = (V,E)$ be a graph. A partition $\\pi = \\{V_1, V_2, \\ldots, V_k \\}$ of the vertices $V$ of $G$ into $k$ {\\it color classes} $V_i$, with $1 \\leq i \\leq k$, is called a {\\it quorum coloring} if for every vertex $v \\in V$, at least half of the vertices in the closed neighborhood

  5. Persistence of Mycoplasma genitalium following azithromycin therapy.

    Directory of Open Access Journals (Sweden)

    Catriona S Bradshaw

    Full Text Available BACKGROUND: To determine clinical outcomes and cure rates for M.genitalium genital infection in men and women following azithromycin 1 g. METHODOLOGY: Patients attending Melbourne Sexual Health Centre between March 2005 and November 2007 with urethritis/epididymitis, cervicitis/pelvic inflammatory disease and sexual contacts of M.genitalium were tested for M.genitalium by polymerase chain reaction (PCR. M.genitalium-infection was treated with 1 g of azithromycin and a test-of-cure (toc was performed one month post-azithromycin. Response to azithromycin, and response to moxifloxacin (400 mg daily for 10 days in individuals with persistent infection post-azithromycin, was determined. PRINCIPAL FINDINGS: Of 1538 males and 313 females tested, 161 males (11% and 30 females (10% were infected with M.genitalium. A toc was available on 131 (69% infected individuals (median = 36 days [range 12-373]. Of 120 individuals prescribed azithromycin only pre-toc, M.genitalium was eradicated in 101 (84%, 95% confidence intervals [CI]: 77-90% and persisted in 19 (16%, 95% CI: 10-23%. Eleven individuals with persistent infection (9%, 95% CI: 5-15% had no risk of reinfection from untreated-partners, while eight (7%, 95% CI: 3-12% may have been at risk of reinfection from doxycycline-treated or untreated-partners. Moxifloxacin was effective in eradicating persistent infection in all cases not responding to azithromycin. Patients with persistent-M.genitalium were more likely to experience persistent symptoms (91%, compared to patients in whom M.genitalium was eradicated (17%, p<0.0001. CONCLUSION: Use of azithromycin 1 g in M.genitalium-infected patients was associated with unacceptable rates of persistent infection, which was eradicated with moxifloxacin. These findings highlight the importance of follow-up in M.genitalium-infected patients prescribed azithromycin, and the need to monitor for the development of resistance. Research to determine optimal first and

  6. Bradycardia and Hypothermia Complicating Azithromycin Treatment.

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    Benn, Kerri; Salman, Sam; Page-Sharp, Madhu; Davis, Timothy M E; Buttery, Jim P

    2017-08-11

    BACKGROUND Azithromycin is a macrolide antibiotic widely used to treat respiratory, urogenital, and other infections. Gastrointestinal upset, headache, and dizziness are common adverse effects, and prolongation of the rate-corrected electrocardiographic QT interval and malignant arrhythmias have been reported. There are rare reports of bradycardia and hypothermia but not in the same patient. CASE REPORT A 4-year-old boy given intravenous azithromycin as part of treatment for febrile neutropenia complicating leukemia chemotherapy developed hypothermia (rectal temperature 35.2°C) and bradycardia (65 beats/minute) after the second dose, which resolved over several days post-treatment, consistent with persistence of high tissue azithromycin concentrations relative to those in plasma. A sigmoid Emax pharmacokinetic/pharmacodynamic model suggested a maximal azithromycin-associated reduction in heart rate of 23 beats/minute. Monitoring for these potential adverse effects should facilitate appropriate supportive care in similar cases. CONCLUSIONS Recommended azithromycin doses can cause at least moderate bradycardia and hypothermia in vulnerable pediatric patients, adverse effects that should prompt appropriate monitoring and which may take many days to resolve.

  7. Quorum Sensing of Periodontal Pathogens.

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    Plančak, Darije; Musić, Larisa; Puhar, Ivan

    2015-09-01

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

  8. A case of clinical and microbiological failure of azithromycin therapy in Salmonella enterica serotype Typhi despite low azithromycin MIC.

    Science.gov (United States)

    Manesh, Abi; Balaji, Veeraraghavan; Kumar, Devanga Ragupathi Naveen; Rupali, Priscilla

    2017-01-01

    Typhoid fever remains a serious problem in many developing countries. Due to resistance to multiple first line drugs, azithromycin has evolved as an important drug in the treatment of typhoid. While therapy with azithromycin is highly effective, no clinically validated mean inhibitory concentration (MIC) break points or disc diffusion cutoff guidelines are available so far. We describe an Indian adult with clinical and microbiological failure to azithromycin despite low azithromycin MIC. Copyright © 2016. Published by Elsevier Ltd.

  9. Pregnancy outcome following gestational exposure to azithromycin

    Directory of Open Access Journals (Sweden)

    Woodland C Cindy

    2006-05-01

    Full Text Available Abstract Background Azithromycin is an azalide antibiotic with an extensive range of indications and has become a common treatment option due to its convenient dosing regimen and therapeutic advantages. Human studies addressing gestational use of azithromycin have primarily focused on antibiotic efficacy rather than fetal safety. Our primary objective was to evaluate the possibility of teratogenic risk following gestational exposure to azithromycin. Methods There were 3 groups of pregnant women enrolled in our study: 1 women who took azithromycin. 2 women exposed to non-teratogenic antibiotics for similar indications, and 3 women exposed to non-teratogenic agents. They were matched for gestational age at time of call, maternal age, cigarette and alcohol consumption. Rates of major malformations and other endpoints of interest were compared among the three groups. Results Pregnancy outcome of 123 women in each group was ascertained. There were no statistically significant differences among the three groups in the rates of major malformations; 3.4% (exposed versus 2.3% (disease matched and 3.4% (non teratogen or any other endpoints that were examined. In the azithromycin group, 88 (71.6% women took the drug during the first trimester Conclusion Results suggest that gestational exposure to azithromycin is not associated with an increase in the rate of major malformations above the baseline of 1–3%. Our data adds to previous research showing that macrolide antibiotics, as a group, are generally safe in pregnancy and provides an evidence-based option for health professionals caring for populations with chlamydia.

  10. An inhibitor of bacterial quorum sensing reduces mortalities caused by vibriosis in rainbow trout (Oncorhynchus mykiss, Walbaum)

    DEFF Research Database (Denmark)

    Rasch, Maria; Buch, Christiane; Austin, B.

    2004-01-01

    The fish pathogen Vibrio anguillarum produces quorum sensing signal molecules, N-acyl homoserine lactones (AHLs), which in several Gram-negative human and plant pathogenic bacteria regulate virulence factors. Expression of these factors can be blocked using specific quorum-sensing inhibitors (QSIs...

  11. Evaluation of Enoyl-Acyl Carrier Protein Reductase Inhibitors as Pseudomonas aeruginosa Quorum-Quenching Reagents

    Directory of Open Access Journals (Sweden)

    Søren Molin

    2010-02-01

    Full Text Available Pseudomonas aeruginosa is an opportunistic pathogen which is responsible for a wide range of infections. Production of virulence factors and biofilm formation by P. aeruginosa are partly regulated by cell-to-cell communication quorum-sensing systems. Identification of quorum-quenching reagents which block the quorum-sensing process can facilitate development of novel treatment strategies for P. aeruginosa infections. We have used molecular dynamics simulation and experimental studies to elucidate the efficiencies of two potential quorum-quenching reagents, triclosan and green tea epigallocatechin gallate (EGCG, which both function as inhibitors of the enoyl-acyl carrier protein (ACP reductase (ENR from the bacterial type II fatty acid synthesis pathway. Our studies suggest that EGCG has a higher binding affinity towards ENR of P. aeruginosa and is an efficient quorum-quenching reagent. EGCG treatment was further shown to be able to attenuate the production of virulence factors and biofilm formation of P. aeruginosa.

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  13. Attenuation of Pseudomonas aeruginosa biofilm formation by Vitexin: A combinatorial study with azithromycin and gentamicin

    Science.gov (United States)

    Das, Manash C.; Sandhu, Padmani; Gupta, Priya; Rudrapaul, Prasenjit; de, Utpal C.; Tribedi, Prosun; Akhter, Yusuf; Bhattacharjee, Surajit

    2016-03-01

    Microbial biofilm are communities of surface-adhered cells enclosed in a matrix of extracellular polymeric substances. Extensive use of antibiotics to treat biofilm associated infections has led to the emergence of multiple drug resistant strains. Pseudomonas aeruginosa is recognised as a model biofilm forming pathogenic bacterium. Vitexin, a polyphenolic group of phytochemical with antimicrobial property, has been studied for its antibiofilm potential against Pseudomonas aeruginosa in combination with azithromycin and gentamicin. Vitexin shows minimum inhibitory concentration (MIC) at 260 μg/ml. It’s antibiofilm activity was evaluated by safranin staining, protein extraction, microscopy methods, quantification of EPS and in vivo models using several sub-MIC doses. Various quorum sensing (QS) mediated phenomenon such as swarming motility, azocasein degrading protease activity, pyoverdin and pyocyanin production, LasA and LasB activity of the bacteria were also evaluated. Results showed marked attenuation in biofilm formation and QS mediated phenotype of Pseudomonas aeruginosa in presence of 110 μg/ml vitexin in combination with azithromycin and gentamicin separately. Molecular docking of vitexin with QS associated LuxR, LasA, LasI and motility related proteins showed high and reasonable binding affinity respectively. The study explores the antibiofilm potential of vitexin against P. aeruginosa which can be used as a new antibiofilm agent against microbial biofilm associated pathogenesis.

  14. Attenuation of Pseudomonas aeruginosa biofilm formation by Vitexin: A combinatorial study with azithromycin and gentamicin

    Science.gov (United States)

    Das, Manash C.; Sandhu, Padmani; Gupta, Priya; Rudrapaul, Prasenjit; De, Utpal C.; Tribedi, Prosun; Akhter, Yusuf; Bhattacharjee, Surajit

    2016-01-01

    Microbial biofilm are communities of surface-adhered cells enclosed in a matrix of extracellular polymeric substances. Extensive use of antibiotics to treat biofilm associated infections has led to the emergence of multiple drug resistant strains. Pseudomonas aeruginosa is recognised as a model biofilm forming pathogenic bacterium. Vitexin, a polyphenolic group of phytochemical with antimicrobial property, has been studied for its antibiofilm potential against Pseudomonas aeruginosa in combination with azithromycin and gentamicin. Vitexin shows minimum inhibitory concentration (MIC) at 260 μg/ml. It’s antibiofilm activity was evaluated by safranin staining, protein extraction, microscopy methods, quantification of EPS and in vivo models using several sub-MIC doses. Various quorum sensing (QS) mediated phenomenon such as swarming motility, azocasein degrading protease activity, pyoverdin and pyocyanin production, LasA and LasB activity of the bacteria were also evaluated. Results showed marked attenuation in biofilm formation and QS mediated phenotype of Pseudomonas aeruginosa in presence of 110 μg/ml vitexin in combination with azithromycin and gentamicin separately. Molecular docking of vitexin with QS associated LuxR, LasA, LasI and motility related proteins showed high and reasonable binding affinity respectively. The study explores the antibiofilm potential of vitexin against P. aeruginosa which can be used as a new antibiofilm agent against microbial biofilm associated pathogenesis. PMID:27000525

  15. Quorum Sensing Inhibition, Relevance to Periodontics

    OpenAIRE

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

    2015-01-01

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

  16. Quorum sensing inhibition, relevance to periodontics.

    Science.gov (United States)

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

    2015-01-01

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

  17. Azithromycin Retards Pseudomonas aeruginosa Biofilm Formation

    Science.gov (United States)

    Gillis, Richard J.; Iglewski, Barbara H.

    2004-01-01

    Using a flow cell biofilm model, we showed that a sub-MIC of azithromycin (AZM) can delay but not inhibit Pseudomonas aeruginosa biofilm formation and results in the development of a stable AZM resistance phenotype. Furthermore, mature biofilms were not affected by AZM. PMID:15583321

  18. Azithromycin Failure in Mycoplasma genitalium Urethritis

    Science.gov (United States)

    Jensen, Jorgen S.; Tabrizi, Sepehr N.; Read, Timothy R.H.; Garland, Suzanne M.; Hopkins, Carol A.; Moss, Lorna M.; Fairley, Christopher K.

    2006-01-01

    We report significant failure rates (28%, 95% confidence interval 15%–45%) after administering 1 g azithromycin to men with Mycoplasma genitalium–positive nongonococcal urethritis. In vitro evidence supported reduced susceptibility of M. genitalium to macrolides. Moxifloxacin administration resulted in rapid symptom resolution and eradication of infection in all cases. These findings have implications for management of urethritis. PMID:16836839

  19. Adjunctive Azithromycin Prophylaxis for Cesarean Delivery.

    Science.gov (United States)

    Tita, Alan T N; Szychowski, Jeff M; Boggess, Kim; Saade, George; Longo, Sherri; Clark, Erin; Esplin, Sean; Cleary, Kirsten; Wapner, Ron; Letson, Kellett; Owens, Michelle; Abramovici, Adi; Ambalavanan, Namasivayam; Cutter, Gary; Andrews, William

    2016-09-29

    The addition of azithromycin to standard regimens for antibiotic prophylaxis before cesarean delivery may further reduce the rate of postoperative infection. We evaluated the benefits and safety of azithromycin-based extended-spectrum prophylaxis in women undergoing nonelective cesarean section. In this trial conducted at 14 centers in the United States, we studied 2013 women who had a singleton pregnancy with a gestation of 24 weeks or more and who were undergoing cesarean delivery during labor or after membrane rupture. We randomly assigned 1019 to receive 500 mg of intravenous azithromycin and 994 to receive placebo. All the women were also scheduled to receive standard antibiotic prophylaxis. The primary outcome was a composite of endometritis, wound infection, or other infection occurring within 6 weeks. The primary outcome occurred in 62 women (6.1%) who received azithromycin and in 119 (12.0%) who received placebo (relative risk, 0.51; 95% confidence interval [CI], 0.38 to 0.68; Pazithromycin group and the placebo group in rates of endometritis (3.8% vs. 6.1%, P=0.02), wound infection (2.4% vs. 6.6%, Pazithromycin was more effective than placebo in reducing the risk of postoperative infection. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; C/SOAP ClinicalTrials.gov number, NCT01235546 .).

  20. Azithromycin-induced Hiccups | Ayankunle | Highland Medical ...

    African Journals Online (AJOL)

    Background: Hiccups are not only known symptoms of some diseases but have been found to be induced by some drugs. In this report, we present a very rare case of azithromycin induced hiccups seen in a young male adult. Methods: The case records of a 34 year old male who was admitted and successfully managed for ...

  1. Cardiac Arrest in Pediatric Patients Receiving Azithromycin.

    Science.gov (United States)

    Valdés, Santiago O; Kim, Jeffrey J; Niu, Mary C; de la Uz, Caridad M; Miyake, Christina Y; Moffett, Brady S

    2017-03-01

    To compare outcomes of pediatric patients treated with azithromycin compared with penicillin or cephalosporin. We hypothesized that azithromycin use would not be associated with increased cardiac mortality in the pediatric population. Retrospective cohort study from the Pediatric Health Information System database between 2008 and 2012. Patients Azithromycin was used in 5039 (6.1%); penicillin or cephalosporin was used in 77 943 (93.9%). Overall prevalence of antibiotic-associated CPR was 0.14%. Patients receiving a macrolide antibiotic had a lower prevalence of CPR compared with patients receiving a penicillin or cephalosporin (0.04% vs 0.14%, P = .04), and there was no difference in mortality. Multivariable analysis did not find an association between macrolide use and CPR. In contrast to recent adult studies, among children hospitalized for community-acquired pneumonia, azithromycin use was not associated with a greater prevalence of cardiac arrest compared with penicillin or cephalosporin use. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    DEFF Research Database (Denmark)

    Hentzer, Morten; Riedel, K.; Rasmussen, Thomas Bovbjerg

    2002-01-01

    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...

  3. Cardiac risks associated with antibiotics: azithromycin and levofloxacin

    Science.gov (United States)

    Lu, Zhiqiang Kevin; Yuan, Jing; Li, Minghui; Sutton, S Scott; Rao, Gowtham A; Jacob, Sony; Bennett, Charles L

    2015-01-01

    Introduction Azithromycin and levofloxacin have been shown to be efficacious in treating infections. The adverse drug events associated with azithromycin and levofloxacin were considered rare. However, the US FDA released warnings regarding the possible risk of QT prolongation with azithromycin and levofloxacin. Areas covered Case reports/case series, observational studies and clinical trials assessing cardiovascular risks associated with azithromycin and levofloxacin were critically reviewed, including 15 case reports/series, 5 observational studies and 5 clinical trials that investigated the cardiac risks associated azithromycin and levofloxacin. Expert opinion Results are discordant. Two retrospective studies utilizing large databases demonstrated an increased risk of cardiovascular death with azithromycin, when azithromycin was compared with amoxicillin. Two other retrospective studies found no difference in cardiovascular death associated with azithromycin and other antibiotics. For levofloxacin, the increased risk of cardiovascular death was only found in one retrospective study. Therefore, the risks and benefits of antibacterial therapies should be considered when making prescription decisions. This study should not preclude clinicians from avoiding azithromycin and levofloxacin. If a patient has an indication to receive an antibiotic and if azithromycin or levofloxacin is needed, it may be used, but the potential risks must be understood. PMID:25494485

  4. Azithromycin in cystic fibrosis : pharmacokinetic and therapeutic aspects of maintenance therapy

    NARCIS (Netherlands)

    Wilms, E.B.

    2012-01-01

    This thesis describes the pharmacokinetics of azithromycin in cystic fibrosis (CF) patients during maintenance therapy, azithromycin drug-drug interactions and the effects of long term use of azithromycin on pulmonary function and microbial resistance. We studied pharmacokinetic parameters of

  5. Azithromycin for episodes with asthma-like symptoms in young children aged 1-3 years

    DEFF Research Database (Denmark)

    Stokholm, Jakob; Chawes, Bo L; Vissing, Nadja H

    2016-01-01

    BACKGROUND: Bacteria and viruses are equally associated with the risk of acute episodes of asthma-like symptoms in young children, suggesting antibiotics as a potential treatment for such episodes. We aimed to assess the effect of azithromycin on the duration of respiratory episodes in young...... examination by a study physician at the Copenhagen Prospective Studies on Asthma research unit. Each episode was randomly allocated independently of previous treatment from a computer-generated list of random numbers in blocks of ten (generated at the Pharmacy of Glostrup). Investigators and children were...... analysis) and placebo (24 [30%] of 79) groups (p=0·30), but we did not investigate bacterial resistance patterns after treatment. INTERPRETATION: Azithromycin reduced the duration of episodes of asthma-like symptoms in young children, suggesting that this drug could have a role in acute management...

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

    Science.gov (United States)

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

    2012-01-01

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

  7. Use and safety of azithromycin in neonates: a systematic review.

    Science.gov (United States)

    Smith, Coral; Egunsola, Oluwaseun; Choonara, Imti; Kotecha, Sailesh; Jacqz-Aigrain, Evelyne; Sammons, Helen

    2015-12-09

    To identify the use and adverse drug reactions associated with azithromycin in neonates. Databases MEDLINE (1948-August 2015), EMBASE (1980-August 2015) and Pubmed (August 2015) were searched for studies on azithromycin in neonates. All studies involving neonates (azithromycin for which safety was evaluated. The primary outcome was adverse event (AE) associated with use of azithromycin. Use of azithromycin in neonates was the secondary outcome. A total of 11 articles involving 473 neonates were identified. 371 AEs were reported. Adverse events were mainly respiratory (358/1000 neonate), neurological (273/1000 neonates) and gastrointestinal (196/1000 neonates) in origin. Azithromycin significantly reduced the risk of bronchopulmonary dysplasia (BPD) in extremely premature neonates (RR=0.83, 95% CI 0.71 to 0.98, p=0.02). There was no significant difference in the incidence of elevated liver enzymes between the azithromycin and placebo group (p=0.76). There were four cases of infantile hypertrophic pyloric stenosis (IHPS). Azithromycin significantly reduces the risk of BPD in preterm neonates. The relationship between azithromycin and IHPS requires further investigation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  8. Transport of Azithromycin into Extravascular Space in Rats.

    Science.gov (United States)

    Kobuchi, Shinji; Aoki, Miki; Inoue, Chiaki; Murakami, Hiroyuki; Kuwahara, Akiko; Nakamura, Tsutomu; Yasui, Hiroyuki; Ito, Yukako; Takada, Kanji; Sakaeda, Toshiyuki

    2016-11-01

    Recent clinical trials showed a prolonged retention of subinhibitory concentrations of unbound azithromycin in the interstitial fluid of soft tissues despite the fact that azithromycin is extensively distributed in tissues. In these clinical trials, interstitial fluid samples were obtained by using the microdialysis method, and it was established that drug concentrations represent protein-unbound drug concentrations. The present study was designed to measure total azithromycin concentrations in the interstitial fluid of the skin of rats by directly collecting interstitial fluid samples from a pore formed on the skin by a dissolving microneedle array. The total azithromycin concentrations in interstitial fluid of the skin were about 4 to 5 times higher than those in plasma throughout the experimental period, and stasis of the azithromycin concentration in interstitial fluid was observed when the concentration of azithromycin in plasma was at the lower limit of quantification. In addition, the skin/plasma concentration ratio transiently increased after dosing (from 4.3 to 83.1). Our results suggest that azithromycin was trapped inside white blood cells and/or phagocytic cells in not only blood but also interstitial fluid, resulting in a high total azithromycin concentration and the retention of its antimicrobial activity at the primary infection site. The stasis of azithromycin in interstitial fluid and skin would lead to long-lasting pharmacological effects (including those against skin infection) at concentrations exceeding the MIC. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

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

    DEFF Research Database (Denmark)

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

    2002-01-01

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

  10. Localized quorum sensing in Vibrio fischeri.

    Science.gov (United States)

    Parent, Mary E; Snyder, Charles E; Kopp, Nathaniel D; Velegol, Darrell

    2008-04-01

    Quorum sensing is almost always regarded as a population density effect in three-dimensional bulk samples of bacteria. Here we create two-dimensional samples of Vibrio fischeri cells adhered onto glass surfaces to examine the effect of local population densities on quorum sensing. This is done by measuring the luminescent response. The 2-D bacterial populations enable us to simultaneously account for time and distance effects on quorum sensing, which were previously very challenging to access in typical three-dimensional bulk samples. Thus, we are able to consider quorum sensing in terms of signal diffusion. A diffusion model of quorum sensing signals guides the experiments and shows that for a given cell spacing (density) and diffusion time there exists a "true quorum"- a number of cells necessary for quorum sensing. We find that quorum sensing can occur locally in 2-D surface samples and is a function of cell population density as well as signal diffusion time.

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

    Science.gov (United States)

    Jiang, Guoliang; Su, Mingxia

    2009-12-01

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

  12. Stability and thermophysical properties of azithromycin dihydrate

    Directory of Open Access Journals (Sweden)

    S. Timoumi

    2014-04-01

    Full Text Available The aim of this paper was to describe the temperature effect on the stability and the thermophysical properties of azithromycin (AZ. First, the density, the heat capacity and the solubility of original (commercial AZ were determined. Second, the original samples were heated at 50 °C and 80 °C and their PLM, DSC, TGA and XRD data were compared to those of the original AZ. According to our results, the original AZ was a dihydrate which converted to anhydrate when heated up to 80 °C. The dehydration induced a change of crystal habit while the crystalline lattice remained unchanged.

  13. Quorum sensing by farnesol revisited.

    Science.gov (United States)

    Polke, Melanie; Jacobsen, Ilse D

    2017-10-01

    Quorum sensing, a form of molecular communication in microbial communities, is relatively well studied in bacterial species, but poorly understood in fungi. Farnesol, a quorum sensing molecule secreted by the opportunistic human pathogenic fungus Candida albicans, was the first quorum sensing molecule described in a eukaryotic organism. However, despite considerable research efforts and advances in recent years, the mechanisms behind its action remain largely elusive. Only recently, we showed that deletion of the C. albicans gene EED1 (eed1Δ), which is essential for hyphal maintenance, resulted in both increased farnesol production and hypersensitivity to farnesol, providing a link between farnesol signaling and elongated hyphal growth. This finding raised several questions concerning farnesol signaling. In this short review we use the unique phenotype of the eed1Δ mutant to summarize current hypotheses and to speculate on possible mechanisms of quorum sensing in C. albicans and its implication in fungus-host interaction, by drawing comparisons to comparatively well-studied quorum sensing systems in bacteria.

  14. Optimal census by quorum sensing

    Science.gov (United States)

    Taillefumier, Thibaud

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

  15. Quorum sensing inhibition selects for virulence and cooperation in Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Thilo Köhler

    2010-05-01

    Full Text Available With the rising development of bacterial resistance the search for new medical treatments beyond conventional antimicrobials has become a key aim of public health research. Possible innovative strategies include the inhibition of bacterial virulence. However, consideration must be given to the evolutionary and environmental consequences of such new interventions. Virulence and cooperative social behaviour of the bacterium Pseudomonas aeruginosa rely on the quorum-sensing (QS controlled production of extracellular products (public goods. Hence QS is an attractive target for anti-virulence interventions. During colonization, non-cooperating (and hence less virulent P. aeruginosa QS-mutants, benefiting from public goods provided by wild type isolates, naturally increase in frequency providing a relative protection from invasive infection. We hypothesized that inhibition of QS-mediated gene expression removes this growth advantage and selection of less virulent QS-mutants, and maintains the predominance of more virulent QS-wild type bacteria. We addressed this possibility in a placebo-controlled trial investigating the anti-QS properties of azithromycin, a macrolide antibiotic devoid of bactericidal activity on P. aeruginosa, but interfering with QS, in intubated patients colonized by P. aeruginosa. In the absence of azithromycin, non-cooperating (and hence less virulent lasR (QS-mutants increased in frequency over time. Azithromycin significantly reduced QS-gene expression measured directly in tracheal aspirates. Concomitantly the advantage of lasR-mutants was lost and virulent wild-type isolates predominated during azithromycin treatment. We confirmed these results in vitro with fitness and invasion experiments. Azithromycin reduced growth rate of the wild-type, but not of the lasR-mutant. Furthermore, the lasR-mutant efficiently invaded wild-type populations in the absence, but not in the presence of azithromycin. These in vivo and in vitro

  16. Synthetic analogs of bacterial quorum sensors

    Energy Technology Data Exchange (ETDEWEB)

    Iyer, Rashi [Los Alamos, NM; Ganguly, Kumkum [Los Alamos, NM; Silks, Louis A [Los Alamos, NM

    2011-12-06

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

  17. Synthetic analogs of bacterial quorum sensors

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-01-08

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

  18. Economic Evaluation of Adjunctive Azithromycin Prophylaxis for Cesarean Delivery.

    Science.gov (United States)

    Harper, Lorie M; Kilgore, Meredith; Szychowski, Jeff M; Andrews, William W; Tita, Alan T N

    2017-08-01

    To compare the costs associated with adjunctive azithromycin compared with standard cefazolin antibiotic prophylaxis alone for unscheduled and scheduled cesarean deliveries. A decision analytic model was created to compare cefazolin alone with azithromycin plus cefazolin. Published incidences of surgical site infection after cesarean delivery were used to estimate the baseline incidence of surgical site infection in scheduled and unscheduled cesarean delivery using standard antibiotic prophylaxis. The effectiveness of adjunctive azithromycin prophylaxis was obtained from published randomized controlled trials for unscheduled cesarean deliveries. No randomized study of its use in scheduled procedures has been completed. Cost estimates were obtained from published literature, hospital estimates, and the Healthcare Cost and Utilization Project and considered costs of azithromycin and surgical site infections. A series of sensitivity analyses were conducted by varying parameters in the model based on observed distributions for probabilities and costs. The outcome was cost per cesarean delivery from a health system perspective. For unscheduled cesarean deliveries, cefazolin prophylaxis alone would cost $695 compared with $335 for adjunctive azithromycin prophylaxis, resulting in a savings of $360 (95% CI $155-451) per cesarean delivery. In scheduled cesarean deliveries, cefazolin prophylaxis alone would cost $254 compared with $111 for adjunctive azithromycin prophylaxis, resulting in a savings of $143 (95% CI 98-157) per cesarean delivery, if proven effective. These findings were robust to a multitude of inputs; as long as adjunctive azithromycin prevented as few as seven additional surgical site infections per 1,000 unscheduled cesarean deliveries and nine additional surgical site infections per 10,000 scheduled cesarean deliveries, adjunctive azithromycin prophylaxis was cost-saving. Adjunctive azithromycin prophylaxis is a cost-saving strategy in both unscheduled

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    of Aeromonas salmonicida strains. All 31 typical strains were AHL producers as were 21 of 26 atypical strains, but on a strain population basis, production of virulence factors such as protease, lipase, A-layer or pigment did not correlate with the production and accumulation of AHLs in the growth medium....... Pigment production was only observed in broth under highly aerated conditions. Quorum sensing inhibitors (QSIs) are compounds that specifically block QS systems without affecting bacterial growth and 2 such compounds, sulphur-containing AHL-analogues, reduced production of protease in a typical strain......Many pathogens control production of virulence factors by self-produced signals in a process called quorum sensing (QS). We demonstrate that acyl homoserine lactone (AHL) signals, which enable bacteria to express certain phenotypes in relation to cell density, are produced by a wide spectrum...

  20. Effect of Azithromycin plus Rifampin versus That of Azithromycin Alone on the Eradication of Chlamydia pneumoniae from Lung Tissue in Experimental Pneumonitis

    OpenAIRE

    Wolf, Katerina; Malinverni, Raffaele

    1999-01-01

    Azithromycin, doxycycline, and rifampin, alone or in combination, were tested in vitro against Chlamydia pneumoniae AR-39. The combination of azithromycin plus rifampin showed the strongest activity and produced higher rates of eradication of C. pneumoniae from lung tissues than azithromycin alone in experimental mouse pneumonitis.

  1. Azithromycin versus Doxycycline for Urogenital Chlamydia trachomatis Infection.

    Science.gov (United States)

    Geisler, William M; Uniyal, Apurva; Lee, Jeannette Y; Lensing, Shelly Y; Johnson, Shacondra; Perry, Raymond C W; Kadrnka, Carmel M; Kerndt, Peter R

    2015-12-24

    Urogenital Chlamydia trachomatis infection remains prevalent and causes substantial reproductive morbidity. Recent studies have raised concern about the efficacy of azithromycin for the treatment of chlamydia infection. We conducted a randomized trial comparing oral azithromycin with doxycycline for the treatment of urogenital chlamydia infection among adolescents in youth correctional facilities, to evaluate the noninferiority of azithromycin (1 g in one dose) to doxycycline (100 mg twice daily for 7 days). The treatment was directly observed. The primary end point was treatment failure at 28 days after treatment initiation, with treatment failure determined on the basis of nucleic acid amplification testing, sexual history, and outer membrane protein A (OmpA) genotyping of C. trachomatis strains. Among the 567 participants enrolled, 284 were randomly assigned to receive azithromycin, and 283 were randomly assigned to receive doxycycline. A total of 155 participants in each treatment group (65% male) made up the per-protocol population. There were no treatment failures in the doxycycline group. In the azithromycin group, treatment failure occurred in 5 participants (3.2%; 95% confidence interval, 0.4 to 7.4%). The observed difference in failure rates between the treatment groups was 3.2 percentage points, with an upper boundary of the 90% confidence interval of 5.9 percentage points, which exceeded the prespecified absolute 5-percentage-point cutoff for establishing the noninferiority of azithromycin. In the context of a closed population receiving directly observed treatment for urogenital chlamydia infection, the efficacy of azithromycin was 97%, and the efficacy of doxycycline was 100%. The noninferiority of azithromycin was not established in this setting. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00980148.).

  2. Interference in Bacterial Quorum Sensing: A Biopharmaceutical Perspective.

    Science.gov (United States)

    Rémy, Benjamin; Mion, Sonia; Plener, Laure; Elias, Mikael; Chabrière, Eric; Daudé, David

    2018-01-01

    Numerous bacteria utilize molecular communication systems referred to as quorum sensing (QS) to synchronize the expression of certain genes regulating, among other aspects, the expression of virulence factors and the synthesis of biofilm. To achieve this process, bacteria use signaling molecules, known as autoinducers (AIs), as chemical messengers to share information. Naturally occurring strategies that interfere with bacterial signaling have been extensively studied in recent years, examining their potential to control bacteria. To interfere with QS, bacteria use quorum sensing inhibitors (QSIs) to block the action of AIs and quorum quenching (QQ) enzymes to degrade signaling molecules. Recent studies have shown that these strategies are promising routes to decrease bacterial pathogenicity and decrease biofilms, potentially enhancing bacterial susceptibility to antimicrobial agents including antibiotics and bacteriophages. The efficacy of QSIs and QQ enzymes has been demonstrated in various animal models and are now considered in the development of new medical devices against bacterial infections, including dressings, and catheters for enlarging the therapeutic arsenal against bacteria.

  3. Interference in Bacterial Quorum Sensing: A Biopharmaceutical Perspective

    Directory of Open Access Journals (Sweden)

    Benjamin Rémy

    2018-03-01

    Full Text Available Numerous bacteria utilize molecular communication systems referred to as quorum sensing (QS to synchronize the expression of certain genes regulating, among other aspects, the expression of virulence factors and the synthesis of biofilm. To achieve this process, bacteria use signaling molecules, known as autoinducers (AIs, as chemical messengers to share information. Naturally occurring strategies that interfere with bacterial signaling have been extensively studied in recent years, examining their potential to control bacteria. To interfere with QS, bacteria use quorum sensing inhibitors (QSIs to block the action of AIs and quorum quenching (QQ enzymes to degrade signaling molecules. Recent studies have shown that these strategies are promising routes to decrease bacterial pathogenicity and decrease biofilms, potentially enhancing bacterial susceptibility to antimicrobial agents including antibiotics and bacteriophages. The efficacy of QSIs and QQ enzymes has been demonstrated in various animal models and are now considered in the development of new medical devices against bacterial infections, including dressings, and catheters for enlarging the therapeutic arsenal against bacteria.

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

    DEFF Research Database (Denmark)

    Bruhn, Jesper Bartholin; Dalsgaard, Inger; Nielsen, K.F.

    2005-01-01

    The aim of the present study was to investigate the production of quorum sensing signals (specifically acylated homoserine lactones, AHLs) among a selection of strains of Gram-negative fish bacterial pathogens. These signals are involved in the regulation of virulence factors in some human....... In conclusion, the production of quorum sensing signals, AHLs, is common among the strains that we examined. If the AHL molecules regulate the expression of the virulence phenotype in these bacteria, as shown to occur in some bacterial pathogens, novel disease control measures may be developed by blocking AHL...

  5. Size of quorum sensing communities

    DEFF Research Database (Denmark)

    Ferkinghoff-Borg, Jesper; Sams, Thomas

    2014-01-01

    Ensembles of bacteria are able to coordinate their phenotypic behavior in accordance with the size, density, and growth state of the ensemble. This is achieved through production and exchange of diffusible signal molecules in a cell–cell regulatory system termed quorum sensing. In the generic...... quorum sensor a positive feedback in the production of signal molecules defines the conditions at which the collective behavior switches on. In spite of its conceptual simplicity, a proper measure of biofilm colony ‘‘size’’ appears to be lacking. We establish that the cell density multiplied...... by a geometric factor which incorporates the boundary conditions constitutes an appropriate size measure. The geometric factor is the square of the radius for a spherical colony or a hemisphere attached to a reflecting surface. If surrounded by a rapidly exchanged medium, the geometric factor is divided by three...

  6. Use of azithromycin and risk of ventricular arrhythmia.

    Science.gov (United States)

    Trifirò, Gianluca; de Ridder, Maria; Sultana, Janet; Oteri, Alessandro; Rijnbeek, Peter; Pecchioli, Serena; Mazzaglia, Giampiero; Bezemer, Irene; Garbe, Edeltraut; Schink, Tania; Poluzzi, Elisabetta; Frøslev, Trine; Molokhia, Mariam; Diemberger, Igor; Sturkenboom, Miriam C J M

    2017-04-18

    There are conflicting findings from observational studies of the arrhythrogenic potential of azithromycin. Our aim was to quantify the association between azithromycin use and the risk of ventricular arrhythmia. We conducted a nested case-control study within a cohort of new antibiotic users identified from a network of 7 population-based health care databases in Denmark, Germany, Italy, the Netherlands and the United Kingdom for the period 1997-2010. Up to 100 controls per case were selected and matched by age, sex and database. Recency of antibiotic use and type of drug (azithromycin was the exposure of interest) at the index date (occurrence of ventricular arrhythmia) were identified. We estimated the odds of ventricular arrhythmia associated with current azithromycin use relative to current amoxicillin use or nonuse of antibiotics (≥ 365 d without antibiotic exposure) using conditional logistic regression, adjusting for confounders. We identified 14 040 688 new antibiotic users who met the inclusion criteria. Ventricular arrhythmia developed in 12 874, of whom 30 were current azithromycin users. The mean age of the cases and controls was 63 years, and two-thirds were male. In the pooled data analyses across databases, azithromycin use was associated with an increased risk of ventricular arrhythmia relative to nonuse of antibiotics (adjusted odds ratio [OR] 1.97, 95% confidence interval [CI] 1.35-2.86). This increased risk disappeared when current amoxicillin use was the comparator (adjusted OR 0.90, 95% CI 0.48-1.71). Database-specific estimates and meta-analysis confirmed results from the pooled data analysis. Current azithromycin use was associated with an increased risk of ventricular arrhythmia when compared with nonuse of antibiotics, but not when compared with current amoxicillin use. The decreased risk with an active comparator suggests significant confounding by indication. © 2017 Canadian Medical Association or its licensors.

  7. Structure And Specificity of a Quorum-Quenching Lactonase (AiiB) From Agrobacterium Tumefaciens

    Energy Technology Data Exchange (ETDEWEB)

    Liu, D.; Thomas, P.W.; Momb, J.; Hoang, Q.Q.; Petsko, G.A.; Ringe, D.; Fast, W.

    2009-06-03

    N-Acyl-l-homoserine lactone (AHL) mediated quorum-sensing regulates virulence factor production in a variety of Gram-negative bacteria. Proteins capable of degrading these autoinducers have been called 'quorum-quenching' enzymes, can block many quorum-sensing dependent phenotypes, and represent potentially useful reagents for clinical, agricultural, and industrial applications. The most characterized quorum-quenching enzymes to date are the AHL lactonases, which are metalloproteins that belong to the metallo-beta-lactamase superfamily. Here, we report the cloning, heterologous expression, purification, metal content, substrate specificity, and three-dimensional structure of AiiB, an AHL lactonase from Agrobacterium tumefaciens. Much like a homologous AHL lactonase from Bacillus thuringiensis, AiiB appears to be a metal-dependent AHL lactonase with broad specificity. A phosphate dianion is bound to the dinuclear zinc site and the active-site structure suggests specific mechanistic roles for an active site tyrosine and aspartate. To our knowledge, this is the second representative structure of an AHL lactonase and the first of an AHL lactonase from a microorganism that also produces AHL autoinducers. This work should help elucidate the hydrolytic ring-opening mechanism of this family of enzymes and also facilitate the design of more effective quorum-quenching catalysts.

  8. 32 CFR 150.4 - Quorum.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Quorum. 150.4 Section 150.4 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE REGULATIONS PERTAINING TO MILITARY JUSTICE COURTS OF CRIMINAL APPEALS RULES OF PRACTICE AND PROCEDURE § 150.4 Quorum. (a) In panel. When sitting in panel, a...

  9. Pregabalin- and azithromycin-induced rhabdomyolysis with purpura: An unrecognized interaction: A case report

    Directory of Open Access Journals (Sweden)

    Kazuya Kato, MD

    2016-01-01

    Conclusion: We report an extremely rare case of rhabdomyolysis with purpura caused by a drug interaction between pregabalin and azithromycin. However, the mechanisms of the interactions between azithromycin on the pregabalin are still unknown.

  10. Azithromycin as treatment for cryptosporidiosis in human immunodeficiency virus disease.

    Directory of Open Access Journals (Sweden)

    Kadappu K

    2002-07-01

    Full Text Available BACKGROUND: Cryptosporidiosis caused by the protozoa Cryptosporidium, is the common cause of diarrhoea in Acquired Immune Deficiency Syndrome (AIDS. AIM: To study the efficacy of short-term azithromycin in the management of cryptosporidiosis. SETTINGS AND DESIGN: Randomised, controlled trial. MATERIAL AND METHODS: All consecutive patients infected with Human Immunodeficiency Virus (HIV, who were positive for cryptosporidial oocysts were taken for this prospective randomised study. RESULT: Short-term azithromycin treatment for cryptosporidial diarrhoea in AIDS patients was associated with good clinical improvement but parasitological benefit was doubtful. All 13 patients, who had symptoms of cryptosporidiosis, symptomatically improved with 5 days of treatment with azithromycin and became asymptomatic after 7 days of antibiotic, but stool sample was positive for cryptosporidium even after 7 days of therapy. After 14 days of treatment with azithromycin in 13 patients, in five patients stool was free of cryptosporidial oocyst. The drug was well tolerated in all the patients. CONCLUSION: Short-term azithromycin can be used as a safe and effective treatment for symptomatic Cryptosporidiosis but not effective in eradicating Cryptosporidial infection.

  11. Quorum sensing and microbial drug resistance.

    Science.gov (United States)

    Chen, Yu-fan; Liu, Shi-yin; Liang, Zhi-bin; Lv, Ming-fa; Zhou, Jia-nuan; Zhang, Lian-hui

    2016-10-20

    Microbial drug resistance has become a serious problem of global concern, and the evolution and regulatory mechanisms of microbial drug resistance has become a hotspot of research in recent years. Recent studies showed that certain microbial resistance mechanisms are regulated by quorum sensing system. Quorum sensing is a ubiquitous cell-cell communication system in the microbial world, which associates with cell density. High-density microbial cells produce sufficient amount of small signal molecules, activating a range of downstream cellular processes including virulence and drug resistance mechanisms, which increases bacterial drug tolerance and causes infections on host organisms. In this review, the general mechanisms of microbial drug resistance and quorum-sensing systems are summarized with a focus on the association of quorum sensing and chemical signaling systems with microbial drug resistance mechanisms, including biofilm formation and drug efflux pump. The potential use of quorum quenching as a new strategy to control microbial resistance is also discussed.

  12. In vitro susceptibilities of Campylobacter jejuni and Campylobacter coli to azithromycin and erythromycin.

    OpenAIRE

    Taylor, D E; Chang, N

    1991-01-01

    MICs of azithromycin and erythromycin for 20 Campylobacter coli and 20 Campylobacter jejuni strains were determined. The results demonstrated that, for Campylobacter species, all high-level erythromycin-resistant strains were also resistant to azithromycin and that azithromycin did not exhibit increased potency in comparison with that of erythromycin.

  13. An evaluation strategy for potential QTc prolongation with chronic azithromycin therapy in cystic fibrosis.

    Science.gov (United States)

    Lenehan, Patrick John; Schramm, Craig M; Collins, Melanie Sue

    2016-03-01

    Chronic azithromycin therapy is recommended for CF patients with persistent Pseudomonas aeruginosa colonization. Other macrolide antibiotics have been reported to cause QT prolongation, but cardiac effects of azithromycin have not been studied in pediatric populations. We analyzed changes in QTc interval after starting chronic azithromycin in a pediatric CF population. Adolescent males showed increased QTc intervals after initiation of therapy. Given the possible effects of azithromycin on the QTc interval, particularly in patients predisposed to cardiac events, we suggest that the QTc interval of CF patients should be monitored throughout the course of chronic azithromycin. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  14. Quorum sensing in extreme environments.

    Science.gov (United States)

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

    2013-01-29

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

  15. Quorum Sensing in Extreme Environments

    Science.gov (United States)

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

    2013-01-01

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

  16. Azithromycin reduces inflammation in a rat model of acute conjunctivitis

    Science.gov (United States)

    Fernandez-Robredo, Patricia; Recalde, Sergio; Moreno-Orduña, Maite; García-García, Laura; Zarranz-Ventura, Javier; García-Layana, Alfredo

    2013-01-01

    Purpose Macrolide antibiotics are known to have various anti-inflammatory effects in addition to their antimicrobial activity, but the mechanisms are still unclear. The effect of azithromycin on inflammatory molecules in the lipopolysaccharide-induced rat conjunctivitis model was investigated. Methods Twenty-four Wistar rats were divided into two groups receiving topical ocular azithromycin (15 mg/g) or vehicle. In total, six doses (25 µl) were administered as one dose twice a day for three days before subconjunctival lipopolysaccharide injection (3 mg/ml). Before the rats were euthanized, mucus secretion, conjunctival and palpebral edema and redness were evaluated. Real-time polymerase chain reaction was used to determine gene expression for interleukin-6, cyclooxygenase-2, tumor necrosis factor-α, matrix metalloproteinase (MMP)-2, and MMP-9. Interleukin-6 was determined with enzyme-linked immunosorbent assay, nuclear factor-kappa B with western blot, and MMP-2 activity with gelatin zymogram. Four eyes per group were processed for histology and subsequent periodic acid-Schiff staining and CD68 for immunofluorescence. The Student t test or the Wilcoxon test for independent samples was applied (SPSS v.15.0). Results Azithromycin-treated animals showed a significant reduction in all clinical signs (pazithromycin group (p=0.063). Mucus secretion by goblet cells and the macrophage count in conjunctival tissue were also decreased in the azithromycin group (pazithromycin administration ameliorates induced inflammation effects in a rat model of acute conjunctivitis. PMID:23378729

  17. [National consensus regarding azithromycin use in cystic fibrosis].

    Science.gov (United States)

    Abely, M; Jubin, V; Bessaci-Kabouya, K; Chiron, R; Bui, S; Fayon, M

    2015-06-01

    To propose a formalized consensus agreement regarding the prescription of azithromycin in cystic fibrosis (CF). Application of the Delphi method in 5 thematic fields: indications, contra-indications, dosage, precautions for use and treatment follow-up. Thirty identified French CF centers participated in the process on 49 (61%), which comprised 3 rounds. Experts validated azithromycin as a long-term anti-inflammatory agent in children aged over 6 years, presenting with the classical form of CF, irrespective of the bacteriological status of the patient (except for non-tuberculous mycobacteria). Azithromycin administration should not be routine in the milder forms of the disease, and avoided in the presence of severe hepatic or renal involvement. In children whose weight is below 40 kg, a strong consensus recommended a single daily oral dose, administered three times weekly. However, in adults, the level of agreement was weaker. Minimal duration of treatment is 6 months, after which the drug should be discontinued if no observable effect is noted on clinical parameters, exacerbation rate and/or FEV1. Clinical monitoring of treatment tolerance is recommended (nausea, diarrhea, skin rash, tinnitus, deafness, arthropathy), without increasing the frequency of surveillance of sputum bacteria. However, it is essential to monitor sputum for fungi (expectoration, Aspergillus, broncho-pulmonary allergic aspergillosis). This consensus statement defines an area for the prescription of azithromycin in CF, with the aim of better harmonization of its use. Published by Elsevier Masson SAS.

  18. Effect of Gingivitis on Azithromycin Concentrations in Gingival Crevicular Fluid

    Science.gov (United States)

    Jain, Nidhi; Lai, Pin-Chuang; Walters, John D.

    2012-01-01

    Aim Macrolide antibiotics yield high concentrations in inflamed tissue, suggesting that their levels in gingival crevicular fluid (GCF) could be increased at gingivitis sites. However, the increased volume of GCF associated with gingivitis could potentially dilute macrolides. To determine whether these assumptions are correct, the bioavailability of systemically-administered azithromycin was compared in GCF from healthy and gingivitis sites. Materials and methods Experimental gingivitis was induced in one maxillary posterior sextant in nine healthy subjects. Contralateral healthy sextants served as controls. Subjects ingested 500 mg of azithromycin followed by a 250 mg dose 24 hours later. Four hours after the second dose, plaque was removed from experimental sites. GCF was collected from 8 surfaces in both the experimental and control sextants and pooled separately. GCF samples were subsequently collected on the 2nd, 3rd, 8th and 15th days and azithromycin content was determined by agar diffusion bioassay. Results On days 2 and 3, the pooled GCF volume at experimental sites was significantly higher than at control sites (P gingivitis sites and healthy sites, suggesting that the processes that regulate GCF azithromycin concentration can compensate for local inflammatory changes. PMID:22220766

  19. Caffeine as a Potential Quorum Sensing Inhibitor

    Directory of Open Access Journals (Sweden)

    Kok-Gan Chan

    2013-04-01

    Full Text Available 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.

  20. Risk factors for ocular chlamydia after three mass azithromycin distributions.

    Directory of Open Access Journals (Sweden)

    Berhan Ayele

    2011-12-01

    Full Text Available An important component of the World Health Organization's comprehensive trachoma elimination strategy is the provision of repeated annual mass azithromycin distributions, which are directed at reducing the burden of ocular chlamydia. Knowledge of characteristics associated with infection after mass antibiotic treatments could allow trachoma programs to focus resources to those most likely to be infected with ocular chlamydia.We monitored 12 communities in rural Ethiopia that had received 3 annual mass azithromycin treatments as part of a cluster-randomized trial for trachoma. One year after the third treatment, a random sample of children from each village received conjunctival examination for follicular trachomatous inflammation (TF and intense trachomatous inflammation (TI, conjunctival swabbing for chlamydial RNA and DNA, and a household survey. The primary outcome for this study was RNA evidence of ocular chlamydia, which we detected in 41 of 573 swabbed children (7.2%, 95%CI 2.7-17.8. In multivariate mixed effects logistic regression models, ocular chlamydial RNA was significantly associated with ocular discharge (OR 2.82, 95%CI 1.07-7.42, missing the most recent mass azithromycin treatment (OR 2.49, 95%CI 1.02-6.05, having a sibling with ocular chlamydia (OR 4.44, 95%CI 1.60-12.29, and above-median community population (OR 7.81, 95%CI 1.56-39.09. Ocular chlamydial infection was also independently associated with TF (OR 3.42, 95%CI 1.56-7.49 and TI (OR 5.39, 95%CI 2.43-11.98.In areas with highly prevalent trachoma treated with multiple rounds of mass azithromycin, trachoma programs could consider continuing mass azithromycin treatments in households that have missed prior mass antibiotic treatments, in households with clinically active trachoma, and in larger communities.

  1. Modulation of Quorum Sensing in a Gram Positive Pathogen by Linear Imprinted Copolymers with anti-Infective Properties

    NARCIS (Netherlands)

    Motib, Anfal; Guerreiro, Antonio; Al-Bayati, Firas; Piletska, Elena; Manzoor, Irfan; Shafeeq, Sulman; Kadam, Anagha; Kuipers, Oscar; Hiller, Luisa; Cowen, Todd; Piletsky, Sergey; Andrew, Peter; Yesilkaya, Hasan

    2017-01-01

    Here we describe the development, characterization and biological testing of a new type of linear molecularly imprinted polymer (LMIP) designed to act as anti-infective by blocking the quorum sensing (QS) mechanism and so preventing virulence of the pathogen Streptococcus pneumoniae. The LMIP is

  2. How to desynchronize quorum-sensing networks

    Science.gov (United States)

    Russo, Giovanni

    2017-04-01

    In this paper we investigate how so-called quorum-sensing networks can be desynchronized. Such networks, which arise in many important application fields, such as systems biology, are characterized by the fact that direct communication between network nodes is superimposed to communication with a shared, environmental variable. In particular, we provide a new sufficient condition ensuring that the trajectories of these quorum-sensing networks diverge from their synchronous evolution. Then, we apply our result to study two applications.

  3. An inhibitor of bacterial quorum sensing reduces mortalities caused by vibriosis in rainbow trout (Oncorhynchus mykiss, Walbaum)

    DEFF Research Database (Denmark)

    Rasch, Maria; Buch, Christiane; Austin, B.

    2004-01-01

    -100% in challenge controls to 4-40%, in treated groups. Furanone C-30 had no effect in an immersion challenge system, probably due to a very high water exchange and a rapid dilution of furanone C-30. Growth and Survival of V. anguillarum were not affected by the concentrations of furanone C-30 used in the challenge......The fish pathogen Vibrio anguillarum produces quorum sensing signal molecules, N-acyl homoserine lactones (AHLs), which in several Gram-negative human and plant pathogenic bacteria regulate virulence factors. Expression of these factors can be blocked using specific quorum-sensing inhibitors (QSIs...

  4. Quorum Quenching Revisited—From Signal Decays to Signalling Confusion

    Directory of Open Access Journals (Sweden)

    Kok-Gan Chan

    2012-04-01

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

  5. Fremmedlegemeinfektioner--nyt om biofilm og quorum sensing

    DEFF Research Database (Denmark)

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

    2007-01-01

    . Bacteria in biofilms communicate by means of quorum sensing which activates genes for virulence factors. Biofilms can be prevented by antibiotic prophylaxis or early therapy or by quorum sensing inhibitors which make them susceptible to antibiotics and phagocytosis....

  6. Azithromycin maintenance therapy in patients with cystic fibrosis : A dose advice based on a review of pharmacokinetics, efficacy, and side effects

    NARCIS (Netherlands)

    Wilms, Erik B.; Touw, Daniel J.; Heijerman, Harry G.M.; Van Der Ent, Cornelis K.

    Azithromycin maintenance therapy results in improvement of respiratory function in patients with cystic fibrosis (CF). In azithromycin maintenance therapy, several dosing schemes are applied. In this review, we combine current knowledge about azithromycin pharmacokinetics with the dosing schedules

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

    Science.gov (United States)

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

    2016-05-16

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

  8. Pharmaceutical development and optimization of azithromycin suppository for paediatric use

    Science.gov (United States)

    Kauss, Tina; Gaubert, Alexandra; Boyer, Chantal; Ba, Boubakar B.; Manse, Muriel; Massip, Stephane; Léger, Jean-Michel; Fawaz, Fawaz; Lembege, Martine; Boiron, Jean-Michel; Lafarge, Xavier; Lindegardh, Niklas; White, Nicholas J.; Olliaro, Piero; Millet, Pascal; Gaudin, Karen

    2013-01-01

    Pharmaceutical development and manufacturing process optimization work was undertaken in order to propose a potential paediatric rectal formulation of azithromycin as an alternative to existing oral or injectable formulations. The target product profile was to be easy-to-use, cheap and stable in tropical conditions, with bioavailability comparable to oral forms, rapidly achieving and maintaining bactericidal concentrations. PEG solid solution suppositories were characterized in vitro using visual, HPLC, DSC, FTIR and XRD analyses. In vitro drug release and in vivo bioavailability were assessed; a study in rabbits compared the bioavailability of the optimized solid solution suppository to rectal solution and intra-venous product (as reference) and to the previous, non-optimized formulation (suspended azithromycin suppository). The bioavailability of azithromycin administered as solid solution suppositories relative to intra-venous was 43%, which compared well to the target of 38% (oral product in humans). The results of 3-month preliminary stability and feasibility studies were consistent with industrial production scale-up. This product has potential both as a classical antibiotic and as a product for use in severely ill children in rural areas. Industrial partners for further development are being sought. PMID:23220079

  9. Pharmaceutical development and optimization of azithromycin suppository for paediatric use.

    Science.gov (United States)

    Kauss, Tina; Gaubert, Alexandra; Boyer, Chantal; Ba, Boubakar B; Manse, Muriel; Massip, Stephane; Léger, Jean-Michel; Fawaz, Fawaz; Lembege, Martine; Boiron, Jean-Michel; Lafarge, Xavier; Lindegardh, Niklas; White, Nicholas J; Olliaro, Piero; Millet, Pascal; Gaudin, Karen

    2013-01-30

    Pharmaceutical development and manufacturing process optimization work was undertaken in order to propose a potential paediatric rectal formulation of azithromycin as an alternative to existing oral or injectable formulations. The target product profile was to be easy-to-use, cheap and stable in tropical conditions, with bioavailability comparable to oral forms, rapidly achieving and maintaining bactericidal concentrations. PEG solid solution suppositories were characterized in vitro using visual, HPLC, DSC, FTIR and XRD analyses. In vitro drug release and in vivo bioavailability were assessed; a study in rabbits compared the bioavailability of the optimized solid solution suppository to rectal solution and intra-venous product (as reference) and to the previous, non-optimized formulation (suspended azithromycin suppository). The bioavailability of azithromycin administered as solid solution suppositories relative to intra-venous was 43%, which compared well to the target of 38% (oral product in humans). The results of 3-month preliminary stability and feasibility studies were consistent with industrial production scale-up. This product has potential both as a classical antibiotic and as a product for use in severely ill children in rural areas. Industrial partners for further development are being sought. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Azithromycin ameliorates airway remodeling via inhibiting airway epithelium apoptosis.

    Science.gov (United States)

    Liu, Yuanqi; Pu, Yue; Li, Diandian; Zhou, Liming; Wan, Lihong

    2017-02-01

    Azithromycin can benefit treating allergic airway inflammation and remodeling. In the present study, we hypothesized that azithromycin alleviated airway epithelium injury through inhibiting airway epithelium apoptosis via down regulation of caspase-3 and Bax/Bcl2 ratio in vivo and in vitro. Ovalbumin induced rat asthma model and TGF-β1-induced BEAS-2B cell apoptosis model were established, respectively. In vivo experiments, airway epithelium was stained with hematoxylin and eosin (HE) and periodic acid-Schiff (PAS) to histologically evaluate the airway inflammation and remodeling. Airway epithelium apoptotic index (AI) was further analyzed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), while expression of apoptosis related gene (Bax, Bcl2, Caspase-3) in lungs were measured by qRT-PCR and western blotting, respectively. In vitro experiments, apoptosis were evaluated by Flow cytometry (FCM) and TUNEL. Above apoptosis related gene were also measured by qRT-PCR and western blotting. Compared with the OVA group, azithromycin significantly reduced the inflammation score, peribronchial smooth muscle layer thickness, epithelial thickening and goblet cell metaplasia (Pazithromycin-treated rats (Pazithromycin significantly suppressed TGF-β1-induced BEAS-2B cells apoptosis (PAzithromycin is an attractive treatment option for reducing airway epithelial cell apoptosis by improving the imbalance of Bax/Bcl-2 ratio and inhibiting Caspase-3 level in airway epithelium. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Topical liposomal azithromycin in the treatment of acute cutaneous leishmaniasis.

    Science.gov (United States)

    Rajabi, Omid; Layegh, Pouran; Hashemzadeh, Sara; Khoddami, Mohsen

    2016-09-01

    Cutaneous leishmaniasis (CL) treatment is based on pentavalant antimony (sbv) drugs which are accompanied by many side effects and are facing ever-increasing resistance. Topical treatment of CL is an attractive alternative avoiding toxicities of parenteral therapy while being administered through a simple painless route. The liposomal formulations of different drugs have recently been increasingly used in the treatment of several types of leishmaniasis. The efficacy of a topical liposomal azithromycin formulation was compared with intralesional meglumine antimoniate (glucantime) in the treatment of CL. Sixty-six patients with 97 lesions who met our inclusion criteria were randomly divided into two groups. One group was administered with the topical liposomal form of azithromycin twice daily. The other group was treated by weekly intralesional injections of glucantime with a volume of 0.5-2 cm3 into each lesion till complete blanching of the lesion occurred. Clinical evaluations were performed weekly during the treatment course (8 weeks) by a single dermatologist for both groups. Per-protocol analysis showed no statistically significant difference between the two groups (p = 0.84, 95% confidence interval (CI) = 0.764 (0.714-0.821). Serious drug side effects were not observed in either group. Topical liposomal azithromycin has the same efficacy as intralesional glucantime in the treatment of CL. © 2016 Wiley Periodicals, Inc.

  12. The physical basis of bacterial quorum communication

    CERN Document Server

    2015-01-01

    This book aims to educate physical scientists and quantitatively-oriented biologists on the application of physical experimentation and analysis, together with appropriate modeling, to understanding and interpreting microbial chemical communication and especially quorum sensing (QS). Quorum sensing describes a chemical communication behavior that is nearly universal among bacteria. Individual cells release a diffusible small molecule (an autoinducer) into their environment. A high concentration of this autoinducer serves as a signal of high population density, triggering new patterns of gene expression throughout the population. However QS is often much more complex than simple census-taking. Many QS bacteria produce and detect multiple autoinducers, which generate quorum signal cross talk with each other and with other bacterial species. QS gene regulatory networks operate in physically complex environments and respond to a range of inputs in addition to autoinducer signals. While many individual QS systems ...

  13. Quorum sensing in nitrogen-fixing rhizobia.

    Science.gov (United States)

    González, Juan E; Marketon, Melanie M

    2003-12-01

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

  14. Quorum sensing in gram-negative bacteria

    DEFF Research Database (Denmark)

    Wu, H.; Song, Z.J.; Høiby, N.

    2004-01-01

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

  15. Quorum Sensing Regulation in Aeromonas hydrophila

    DEFF Research Database (Denmark)

    Garde, Christian; Bjarnsholt, Thomas; Givskov, Michael

    2010-01-01

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

  16. A randomised controlled trial of azithromycin therapy in bronchiolitis obliterans syndrome (BOS) post lung transplantation

    Science.gov (United States)

    Corris, Paul A; Ryan, Victoria A; Small, Therese; Lordan, James; Fisher, Andrew J; Meachery, Gerard; Johnson, Gail; Ward, Chris

    2015-01-01

    Background We conducted a placebo-controlled trial of azithromycin therapy in bronchiolitis obliterans syndrome (BOS) post lung transplantation. Methods We compared azithromycin (250 mg alternate days, 12 weeks) with placebo. Primary outcome was FEV1 change at 12 weeks. Results 48 patients were randomised; (25 azithromycin, 23 placebo). It was established, post randomisation that two did not have BOS. 46 patients were analysed as intention to treat (ITT) with 33 ‘Completers’. ITT analysis included placebo patients treated with open-label azithromycin after study withdrawal. Outcome The ITT analysis (n=46, 177 observations) estimated mean difference in FEV1 between treatments (azithromycin minus placebo) was 0.035 L, with a 95% CI of −0.112 L to 0.182 L (p=0.6). Five withdrawals, who were identified at the end of the study as having been randomised to placebo (four with rapid loss in FEV1, one withdrawn consent) had received rescue open-label azithromycin, with improvement in subsequent FEV1 at 12 weeks. Study Completers showed an estimated mean difference in FEV1 between treatment groups (azithromycin minus placebo) of 0.278 L, with 95% CI for the mean difference: 0.170 L to 0.386 L (p=azithromycin group had ≥10% gain in FEV1 from baseline. No patients in the placebo group had ≥10% gain in FEV1 from baseline while on placebo (p=0.002). Seven serious adverse events, three azithromycin, four in the placebo group, were deemed unrelated to study medication. Conclusions Azithromycin therapy improves FEV1 in patients with BOS and appears superior to placebo. This study strengthens evidence for clinical practice of initiating azithromycin therapy in BOS. Trial registration number EU-CTR, 2006-000485-36/GB. PMID:25714615

  17. Azithromycin Exhibits Bactericidal Effects on Pseudomonas aeruginosa through Interaction with the Outer Membrane

    Science.gov (United States)

    Imamura, Yoshifumi; Higashiyama, Yasuhito; Tomono, Kazunori; Izumikawa, Koichi; Yanagihara, Katsunori; Ohno, Hideaki; Miyazaki, Yoshitsugu; Hirakata, Yoichi; Mizuta, Yohei; Kadota, Jun-ichi; Iglewski, Barbara H.; Kohno, Shigeru

    2005-01-01

    The aim of the present study was to elucidate the effect of the macrolide antibiotic azithromycin on Pseudomonas aeruginosa. We studied the susceptibility to azithromycin in P. aeruginosa PAO1 using a killing assay. PAO1 cells at the exponential growth phase were resistant to azithromycin. In contrast, PAO1 cells at the stationary growth phase were sensitive to azithromycin. The divalent cations Mg2+ and Ca2+ inhibited this activity, suggesting that the action of azithromycin is mediated by interaction with the outer membranes of the cells, since the divalent cations exist between adjacent lipopolysaccharides (LPSs) and stabilize the outer membrane. The divalent cation chelator EDTA behaved in a manner resembling that of azithromycin; EDTA killed more PAO1 in the stationary growth phase than in the exponential growth phase. A 1-N-phenylnaphthylamine assay showed that azithromycin interacted with the outer membrane of P. aeruginosa PAO1 and increased its permeability while Mg2+ and Ca2+ antagonized this action. Our results indicate that azithromycin directly interacts with the outer membrane of P. aeruginosa PAO1 by displacement of divalent cations from their binding sites on LPS. This action explains, at least in part, the effectiveness of sub-MICs of macrolide antibiotics in pseudomonal chronic airway infection. PMID:15793115

  18. Azithromycin reduces spontaneous and induced inflammation in ΔF508 cystic fibrosis mice

    NARCIS (Netherlands)

    R. Legssyer (Rachida); F. Huaux (François); J. Lebacq (Jean); M. Delos (Monique); E. Marbaix (Etienne); P. Lebecque (Patrick); D. Lison (Dominique); B.J. Scholte (Bob); P. Wallemacq (Pierre); T. Leal (Teresinha)

    2006-01-01

    textabstractBackground: Inflammation plays a critical role in lung disease development and progression in cystic fibrosis. Azithromycin is used for the treatment of cystic fibrosis lung disease, although its mechanisms of action are poorly understood. We tested the hypothesis that azithromycin

  19. Novel antiviral properties of azithromycin in cystic fibrosis airway epithelial cells.

    Science.gov (United States)

    Schögler, Aline; Kopf, Brigitte S; Edwards, Michael R; Johnston, Sebastian L; Casaulta, Carmen; Kieninger, Elisabeth; Jung, Andreas; Moeller, Alexander; Geiser, Thomas; Regamey, Nicolas; Alves, Marco P

    2015-02-01

    Virus-associated pulmonary exacerbations, often associated with rhinoviruses (RVs), contribute to cystic fibrosis (CF) morbidity. Currently, there are only a few therapeutic options to treat virus-induced CF pulmonary exacerbations. The macrolide antibiotic azithromycin has antiviral properties in human bronchial epithelial cells. We investigated the potential of azithromycin to induce antiviral mechanisms in CF bronchial epithelial cells. Primary bronchial epithelial cells from CF and control children were infected with RV after azithromycin pre-treatment. Viral RNA, interferon (IFN), IFN-stimulated gene and pattern recognition receptor expression were measured by real-time quantitative PCR. Live virus shedding was assessed by assaying the 50% tissue culture infective dose. Pro-inflammatory cytokine and IFN-β production were evaluated by ELISA. Cell death was investigated by flow cytometry. RV replication was increased in CF compared with control cells. Azithromycin reduced RV replication seven-fold in CF cells without inducing cell death. Furthermore, azithromycin increased RV-induced pattern recognition receptor, IFN and IFN-stimulated gene mRNA levels. While stimulating antiviral responses, azithromycin did not prevent virus-induced pro-inflammatory responses. Azithromycin pre-treatment reduces RV replication in CF bronchial epithelial cells, possibly through the amplification of the antiviral response mediated by the IFN pathway. Clinical studies are needed to elucidate the potential of azithromycin in the management and prevention of RV-induced CF pulmonary exacerbations. Copyright ©ERS 2015.

  20. 28 CFR 2.63 - Quorum.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Quorum. 2.63 Section 2.63 Judicial Administration DEPARTMENT OF JUSTICE PAROLE, RELEASE, SUPERVISION AND RECOMMITMENT OF PRISONERS, YOUTH OFFENDERS... action authorized by law may be taken on a majority vote of the Commissioners holding office at the time...

  1. Targeting quorum sensing in Pseudomonas aeruginosa biofilms

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  2. A Strategy for Antagonizing Quorum Sensing

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-12-31

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

  3. Quorum sensing inhibitors disable bacterial biofilms

    DEFF Research Database (Denmark)

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

    2011-01-01

    defence systems in particular innate immunity. In the biofilm mode, bacteria use cell to cell communication termed quorum-sensing (QS) to coordinate expression of virulence, tolerance towards a number of antimicrobial agents and shielding against the host defence system. Chemical biology approaches may...

  4. CLINICAL EFFECTIVENESS OF AZITHROMYCIN IN THE TREATMENT OF PNEUMONIA IN CHILDREN

    Directory of Open Access Journals (Sweden)

    N.D. Soroka

    2006-01-01

    Full Text Available In the article the data on the morbidity of respiratory diseases (rd in the children of Saint Petersburg are presented, the significance of rd in children's pathology is estimated. The expediency of application of macrolides in the treatment of outpatient pneumonia is substantiated. the data on postmarketing clinical research of the azithromycin («sumamed» effectiveness in the treatment of moderate severe pneumonia in outpatient children are presented. High effectiveness of azithromycin as a starting antibacterial drug is pointed, as well as an alternative means for moderate severe variants of outpatient pneumonia. High efficiency of the combined antibacterial therapy with the application of azithromycin in severe variants of disease is revealed. Safety of azithromycin usage in frequently ill children with concomitant pediatric pathology is noted.Key words: pneumonia, children, antibacterial therapy, azithromycin.

  5. A single 2 g oral dose of extended-release azithromycin for treatment of gonococcal urethritis.

    Science.gov (United States)

    Yasuda, Mitsuru; Ito, Shin; Kido, Akira; Hamano, Kiminari; Uchijima, Yutaka; Uwatoko, Noriyasu; Kusuyama, Hiroyuki; Watanabe, Akiko; Miyamura, Ryuzou; Miyata, Kazutoyo; Deguchi, Takashi

    2014-11-01

    We treated gonococcal urethritis in men with a single 2 g dose of azithromycin extended-release formulation (azithromycin-SR) to determine its microbiological outcomes and tolerability. We enrolled 189 Japanese men with gonococcal urethritis between April 2009 and December 2013. The patients were given a single 2 g dose of azithromycin-SR. Microbiological efficacy was evaluated by the results of the post-treatment molecular testing of Neisseria gonorrhoeae. MIC testing was performed only for pretreatment isolates of N. gonorrhoeae collected from the patients. We evaluated 130 patients for microbiological outcomes. Of these patients, 122 (93.8%) were judged to be microbiologically cured on the basis of negative test results. All isolates for which the azithromycin MICs were ≤0.25 mg/L were eradicated, whereas 5 of 12 isolates for which the MICs were 1 mg/L persisted after the treatment. Forty-six adverse events occurred in 41 patients. However, all adverse events were classified as mild. The eradication rate of N. gonorrhoeae was 93.8% in men with gonococcal urethritis treated with a single 2 g dose of azithromycin-SR. The breakpoint MIC of a 2 g dose of azithromycin-SR for gonococcal urethritis associated with clinical treatment failures appeared to be 1 mg/L. With regard to side effects of higher doses of azithromycin, the 2 g dose of azithromycin-SR appeared to improve tolerability. However, the widespread use of a high-dose regimen of azithromycin might lead to the development of further resistance to azithromycin. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Azithromycin analogue CSY0073 attenuates lung inflammation induced by LPS challenge

    Science.gov (United States)

    Balloy, V; Deveaux, A; Lebeaux, D; Tabary, O; le Rouzic, P; Ghigo, J M; Busson, P F; Boëlle, P Y; Guez, J Guez; Hahn, U; Clement, A; Chignard, M; Corvol, H; Burnet, M; Guillot, L

    2014-01-01

    Background and Purpose Azithromycin is a macrolide antibiotic with anti-inflammatory and immunomodulating effects. Long-term azithromycin therapy in patients with chronic lung diseases such as cystic fibrosis has been associated with increased antimicrobial resistance, emergence of hypermutable strains, ototoxicity and cardiac toxicity. The aim of this study was to assess the anti-inflammatory effects of the non-antibiotic azithromycin derivative CSY0073. Experimental Approach We compared the effects of CSY0073 with those of azithromycin in experiments on bacterial cultures, Pseudomonas aeruginosa biofilm, lung cells and mice challenged intranasally with P. aeruginosa LPS. Key Results In contrast to azithromycin, CSY0073 did not inhibit the growth of P. aeruginosa, Staphylococcus aureus or Haemophilus influenzae and had no effect on an established P. aeruginosa biofilm. Bronchoalveolar lavage (BAL) fluids and lung homogenates collected after the LPS challenge in mice showed that CSY0073 and azithromycin (200 mg·kg−1, i.p.) decreased neutrophil counts at 24 h and TNF-α, CXCL1 and CXCL2 levels in the BAL fluid after 3 h and IL-6, CXCL2 and IL-1β levels in the lung after 3 h compared with the vehicle. However, only azithromycin reduced IL-1β levels in the lung 24 h post LPS challenge. CSY0073 and azithromycin similarly diminished the production of pro-inflammatory cytokines by macrophages, but not lung epithelial cells, exposed to P. aeruginosa LPS. Conclusions and Implications Unlike azithromycin, CSY0073 had no antibacterial effects but it did have a similar anti-inflammatory profile to that of azithromycin. Hence, CSY0073 may have potential as a long-term treatment for patients with chronic lung diseases. PMID:24417187

  7. Clinically and Microbiologically Derived Azithromycin Susceptibility Breakpoints for Salmonella enterica Serovars Typhi and Paratyphi A

    Science.gov (United States)

    Thieu, Nga Tran Vu; Dolecek, Christiane; Karkey, Abhilasha; Gupta, Ruchi; Turner, Paul; Dance, David; Maude, Rapeephan R.; Ha, Vinh; Tran, Chinh Nguyen; Thi, Phuong Le; Be, Bay Pham Van; Phi, La Tran Thi; Ngoc, Rang Nguyen; Ghose, Aniruddha; Dongol, Sabina; Campbell, James I.; Thanh, Duy Pham; Thanh, Tuyen Ha; Moore, Catrin E.; Sona, Soeng; Gaind, Rajni; Deb, Monorama; Anh, Ho Van; Van, Sach Nguyen; Tinh, Hien Tran; Day, Nicholas P. J.; Dondorp, Arjen; Thwaites, Guy; Faiz, Mohamed Abul; Phetsouvanh, Rattanaphone; Newton, Paul; Basnyat, Buddha; Farrar, Jeremy J.; Baker, Stephen

    2015-01-01

    Azithromycin is an effective treatment for uncomplicated infections with Salmonella enterica serovar Typhi and serovar Paratyphi A (enteric fever), but there are no clinically validated MIC and disk zone size interpretative guidelines. We studied individual patient data from three randomized controlled trials (RCTs) of antimicrobial treatment in enteric fever in Vietnam, with azithromycin used in one treatment arm, to determine the relationship between azithromycin treatment response and the azithromycin MIC of the infecting isolate. We additionally compared the azithromycin MIC and the disk susceptibility zone sizes of 1,640 S. Typhi and S. Paratyphi A clinical isolates collected from seven Asian countries. In the RCTs, 214 patients who were treated with azithromycin at a dose of 10 to 20 mg/ml for 5 to 7 days were analyzed. Treatment was successful in 195 of 214 (91%) patients, with no significant difference in response (cure rate, fever clearance time) with MICs ranging from 4 to 16 μg/ml. The proportion of Asian enteric fever isolates with an MIC of ≤16 μg/ml was 1,452/1,460 (99.5%; 95% confidence interval [CI], 98.9 to 99.7) for S. Typhi and 207/240 (86.3%; 95% CI, 81.2 to 90.3) (P azithromycin disk identified S. Typhi isolates with an MIC of ≤16 μg/ml with a sensitivity of 99.7%. An azithromycin MIC of ≤16 μg/ml or disk inhibition zone size of ≥13 mm enabled the detection of susceptible S. Typhi isolates that respond to azithromycin treatment. Further work is needed to define the response to treatment in S. Typhi isolates with an azithromycin MIC of >16 μg/ml and to determine MIC and disk breakpoints for S. Paratyphi A. PMID:25733500

  8. Emerging azithromycin-resistance among the Neisseria gonorrhoeae strains isolated in Hungary.

    Science.gov (United States)

    Brunner, Alexandra; Nemes-Nikodem, Eva; Jeney, Csaba; Szabo, Dora; Marschalko, Marta; Karpati, Sarolta; Ostorhazi, Eszter

    2016-09-20

    In the 1990s, azithromycin became the drug of choice for many infectious diseases but emerging resistance to the drug has only been reported in the last decade. In the last 5 years, the National Neisseria gonorrhoeae Reference Laboratory of Hungary (NNGRLH) has also observed an increased number of N. gonorrhoeae strains resistant to azithromycin. The aim of this study was to determine the most frequent sequence types (ST) of N. gonorrhoeae related to elevated levels of azithromycin MIC (minimal inhibitory concentration). Previously and currently isolated azithromycin-resistant strains have been investigated for the existence of molecular relationship. Maldi-Tof technic was applied for the identification of the strains isolated from outpatients attending the reference laboratory. Testing antibiotic susceptibility of azithromycin, cefixime, ceftriaxone, tetracycline, spectinomycin and ciprofloxacin was carried out for all the identified strains, using MIC strip test Liofilchem(®). N. gonorrhoeae multiantigen sequence typing (NG-MAST) was performed exclusively on azithromycin-resistant isolates. A phylogenetic tree was drawn using MEGA6 (Molecular Evolutionary Genetics Analysis Version 6.0) Neighbour-Joining method. Out of 192 N. gonorrhoeae isolates, 30.0 % (58/192) proved resistant to azithromycin (MIC > 0.5 mg/L). Of the azithromycin-resistant isolates, ST1407, ST4995 and ST11064 were the most prevalent. Based on the phylogenetic analysis, the latter two STs are closely related. In contrast to West-European countries, in our region, resistance to azithromycin has increased up to 30 % in the last 5 years, so the recommendation of the European Guideline -500 mg of ceftriaxone combined with 2 g of azithromycin as first choice therapy against N. gonorrhoeae- should be seriously considered in case of Hungary.

  9. Azithromycin May Antagonize Inhaled Tobramycin When Targeting Pseudomonas aeruginosa in Cystic Fibrosis

    Science.gov (United States)

    Nick, Jerry A.; Moskowitz, Samuel M.; Chmiel, James F.; Forssén, Anna V.; Kim, Sun Ho; Saavedra, Milene T.; Saiman, Lisa; Taylor-Cousar, Jennifer L.

    2014-01-01

    Rationale: Recent studies of inhaled tobramycin in subjects with cystic fibrosis (CF) find less clinical improvement than previously observed. Nonhuman data suggest that in some strains of Pseudomonas aeruginosa, azithromycin can antagonize tobramycin. Objectives: We tested the hypothesis that concomitant azithromycin use correlates with less improvement in key outcome measures in subjects receiving inhaled tobramycin while not affecting those receiving a comparative, nonaminoglycoside inhaled antibiotic. Methods: We studied a cohort of 263 subjects with CF enrolled in a recent clinical trial comparing inhaled tobramycin with aztreonam lysine. We performed a secondary analysis to examine key clinical and microbiologic outcomes based on concomitant, chronic azithromycin use at enrollment. Measurements and Main Results: The cohort randomized to inhaled tobramycin and reporting azithromycin use showed a significant decrease in the percent predicted FEV1 after one and three courses of inhaled tobramycin when compared with those not reporting azithromycin use (28 d: −0.51 vs. 3.43%, P azithromycin and inhaled tobramycin use was also associated with earlier need for additional antibiotics, lesser improvement in disease-related quality of life, and a trend toward less reduction in sputum P. aeruginosa density. Subjects randomized to inhaled aztreonam lysine had significantly greater improvement in these outcome measures, which were unaffected by concomitant azithromycin use. Outcomes in those not using azithromycin who received inhaled tobramycin were not significantly different from subjects receiving aztreonam lysine. Azithromycin also antagonized tobramycin but not aztreonam lysine in 40% of P. aeruginosa clinical isolates tested in vitro. Conclusions: Oral azithromycin may antagonize the therapeutic benefits of inhaled tobramycin in subjects with CF with P. aeruginosa airway infection. PMID:24476418

  10. Inhibition of bacterial quorum sensing by vanilla extract.

    Science.gov (United States)

    Choo, J H; Rukayadi, Y; Hwang, J-K

    2006-06-01

    The purpose of this study was to search for a novel quorum sensing inhibitor and analyse its inhibitory activity. Quorum sensing inhibition was monitored using the Tn-5 mutant, Chromobacterium violaceum CV026. Vanilla beans (Vanilla planifolia Andrews) were extracted using 75% (v/v) aqueous methanol and added to C. violaceum CV026 cultures. Inhibitory activity was measured by quantifying violacein production using a spectrophotometer. The results have revealed that vanilla extract significantly reduced violacein production in a concentration-dependent manner, indicating inhibition of quorum sensing. Vanilla, a widely used spice and flavour, can inhibit bacterial quorum sensing. The results suggest that the intake of vanilla-containing food materials might promote human health by inhibiting quorum sensing and preventing bacterial pathogenesis. Further studies are required to isolate specific substances from vanilla extract acting as quorum sensing inhibitors.

  11. Efficacy of azithromycin in the treatment of cutaneous leishmaniasis

    Directory of Open Access Journals (Sweden)

    Prata Aluízio

    2003-01-01

    Full Text Available The present open pilot study was conducted to assess the efficacy of azithromycin for the treatment of patients with cutaneous leishmaniasis in Araçuaí and Varzelândia, MG. Twenty-four patients with less of six months of disease evolution were treated after clinical examination, Montenegro test and a biopsy. The treatment schemes consisted of oral doses of 500 mg per day for 3, 5 and 10 days and of 1000 mg for two days. A clinical control was performed monthly and treatment cycles were repeated when necessary until full reepithelialization of the lesions. On the occasion of the final evaluation, 20 patients had completed the study and 17 of them (85% were cured. The time to obtain a cure was 60 days ifor 6 (30% patients, 90 days for 7 (35%, and 120 for 4 (20%. The three patients with treatment failure received a pentavalent antimonial for 20 days. No adverse reactions to the medication were observed and a 14 month follow-up did not show recurrence in any patient. These results suggest that azithromycin can be a good therapeutic option for the treatment of cutaneous leishmaniasis caused by Leishmania Viannia brasiliensis.

  12. Quorum signaling and sensing by nontypeable Haemophilus influenzae

    Directory of Open Access Journals (Sweden)

    W Edward Swords

    2012-07-01

    Full Text Available Quorum signals are diffusible factors produced by bacteria that coordinate communal responses. For Haemophilus influenzae, 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 H. influenzae, and identify specific topics for additional study.

  13. Quorum signaling and sensing by nontypeable Haemophilus influenzae.

    Science.gov (United States)

    Swords, W Edward

    2012-01-01

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

  14. Quorum Sensing Disruption in Vibrio harveyi Bacteria by Clay Materials.

    Science.gov (United States)

    Naik, Sajo P; Scholin, Jonathon; Ching, San; Chi, Fang; Herpfer, Marc

    2018-01-10

    This work describes the use of clay minerals as catalysts for the degradation of quorum sensing molecule N-(3-oxooctanoyl)-dl-homoserine lactone. Certain clay minerals as a result of their surface properties and porosity can catalytically degrade the quorum sensing molecule into smaller fragments. The disruption of quorum sensing by clay in a growing Gram-negative Vibrio harveyi bacteria culture was also studied by monitoring luminescence and population density of the bacteria, wherein quenching of bacterial quorum sensing activity was observed by means of luminescence reduction. The results of this study show that food-grade clays can be used as biocatalysts in disrupting bacterial activity in various media.

  15. Mass Azithromycin and Malaria Parasitemia in Niger: Results from a Community-Randomized Trial.

    Science.gov (United States)

    O'Brien, Kieran S; Cotter, Sun Y; Amza, Abdou; Kadri, Boubacar; Nassirou, Baido; Stoller, Nicole E; Zhou, Zhaoxia; Cotter, Chris; West, Sheila K; Bailey, Robin L; Rosenthal, Philip J; Gaynor, Bruce D; Porco, Travis C; Lietman, Thomas M

    2017-09-01

    Studies designed to determine the effects of mass administration of azithromycin on trachoma have suggested that mass azithromycin distributions may also reduce the prevalence of malaria. These studies have typically examined the impact of a small number of treatments over short durations. In this prespecified substudy of a cluster-randomized trial for trachoma, we compared malaria parasitemia prevalence in 24 communities in Niger randomized to receive either annual or biannual mass azithromycin distributions over 3 years. The 12 communities randomized to annual azithromycin received three treatments during the high-transmission season, and the 12 communities randomized to biannual azithromycin received a total of six treatments: three during the high-transmission season and three during the low-transmission season. Blood samples were taken to assess malariometric indices among children in all study communities at a single time point during the high-transmission season after 3 years of the intervention. No significant differences were identified in malaria parasitemia, parasite density, or hemoglobin concentration between the annual and biannual treatment arms. When compared with annual mass azithromycin alone, additional mass azithromycin distributions given during the low-transmission season did not significantly reduce the subsequent prevalence of malaria parasitemia or parasite density after 3 years, as measured during the high-transmission season.

  16. Intrahepatic cholestasis of pregnancy or azithromycin-induced intrahepatic cholestasis: A case report.

    Science.gov (United States)

    Han, Baoshi; Sheng, Yan; Wang, Li; Feng, Hao; Hou, Xianzeng; Li, Yan

    2017-12-01

    Azithromycin-induced liver injury has been rarely reported in adult individuals, let alone in a pregnant woman. Here, we describe the clinical features and outcomes of azithromycin-induced liver injury in a pregnant woman. A 30-year-old pregnant woman presented with generalized pruritus and elevated serum bile acid level (123.6 μmol/L) on day 4 of azithromycin administration. A diagnosis of intrahepatic cholestasis of pregnancy was made, and cesarean section was performed immediately. Interestingly, the alanine aminotransferase level (ALT) reached 211.2 U/L on day 9 after azithromycin administration. Therefore, drug-induced intrahepatic cholestasis was considered. (1) Azithromycin withdrawal after the patient hospitalized. (2) Termination of pregnancy by cesarean section was performed inmmediately to protect the fetus. (3) Silymarin capsules and bifendate are used to protect the liver after liver enzymes elevation was discovered. The liver enzymes recovered within 4 weeks without any symptoms after treatment with silymarin capsules and bifendate, which helps reduce ALT level and protects the liver from further injury. A pregnant woman developed azithromycin-induced intrahepatic cholestasis. Physicians should be aware of this side effect of azithromycin, which is widely prescribed. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  17. Azithromycin is able to control Toxoplasma gondii infection in human villous explants

    Science.gov (United States)

    2014-01-01

    Background Although Toxoplasma gondii infection is normally asymptomatic, severe cases of toxoplasmosis may occur in immunosuppressed patients or congenitally infected newborns. When a fetal infection is established, the recommended treatment is a combination of pyrimethamine, sulfadiazine and folinic acid (PSA). The aim of the present study was to evaluate the efficacy of azithromycin to control T. gondii infection in human villous explants. Methods Cultures of third trimester human villous explants were infected with T. gondii and simultaneously treated with either PSA or azithromycin. Proliferation of T. gondii, as well as production of cytokines and hormones by chorionic villous explants, was analyzed. Results Treatment with either azithromycin or PSA was able to control T. gondii infection in villous explants. After azithromycin or PSA treatment, TNF-α, IL-17A or TGF-β1 levels secreted by infected villous explants did not present significant differences. However, PSA-treated villous explants had decreased levels of IL-10 and increased IL-12 levels, while treatment with azithromycin increased production of IL-6. Additionally, T. gondii-infected villous explants increased secretion of estradiol, progesterone and HCG + β, while treatments with azithromycin or PSA reduced secretion of these hormones concurrently with decrease of parasite load. Conclusions In conclusion, these results suggest that azithromycin may be defined as an effective alternative drug to control T. gondii infection at the fetal-maternal interface. PMID:24885122

  18. Effects of dehydration on corneal tissue absorption of topical azithromycin in rabbits.

    Science.gov (United States)

    Tabbara, Khalid F; Kotb, Amgad A; Hammouda, Ehab F; Elkum, Naser

    2005-10-01

    To assess the corneal tissue absorption of azithromycin in desiccated and normal eyes of rabbits. A total of 25 New Zealand Albino rabbits weighing 2-3 kg each were included. One eye of each rabbit was desiccated. The other eye was left as control. Azithromycin 1.5% topical eyedrops were instilled in both eyes. Five rabbits were sacrificed at each of the following time points: 30 min, 3 hr, 6 hr, and 12 hr. Corneal tissues specimens were subjected to high-performance liquid chromatography mass spectrometry. A paired t test was used to evaluate the statistical difference in corneal tissue absorptions of azithromycin at each time point. The mean corneal tissue levels of azithromycin in dry eyes were 66.3 microg/ml, 92.6 microg/ml, 117.5 microg/ml, and 179.9 microg/ml, and the mean corneal tissue levels of azithromycin in normal eyes were 42.0 microg/ml, 43.4 microg/ml, 43.3 microg/ml, and 80.0 microg/ml at 30 min, 3 hr, 6 hr, and 12 hr respectively. Both groups showed increase in corneal tissue absorption overtime (p < 0.0001). Significantly higher levels of azithromycin were noted in dry eyes at each time point except at the 30-min time point. This study demonstrated that corneas exposed to desiccation showed statistically significant increase in azithromycin level compared to normal eyes.

  19. Oral azithromycin versus its combination with miltefosine for the treatment of experimental Old World cutaneous leishmaniasis.

    Science.gov (United States)

    Amer, Eglal I; Eissa, Maha M; Mossallam, Shereen F

    2016-06-01

    Leishmaniasis is one of the neglected infectious diseases included in the World Health Organization's list of the top guns of antimicrobial resistance. Miltefosine is the first and the only available oral effective therapy for leishmaniasis. For fear of its potential resistance, identification of alternative, effective and safe drugs is urgently needed. Therefore, in view of azithromycin promising activity against a number of Leishmania species, this work was carried out to evaluate the efficacy of oral azithromycin alone versus its combination with miltefosine against experimental Old World Cutaneous leishmaniasis thus, can provide another alternative oral therapy or for the first time an oral combination therapy for leishmaniasis. The experiment were carried out on Swiss strain albino mice which were treated either with miltefosine for 20 days, Azithromycin for 20 days or both drugs in combination therapy for shorter duration of 10 days. Efficacy of azithromycin mono and combination therapy with miltefosine was evaluated clinically, parasitologically and by examination of the cutaneous lesions by Transmission Electron Microscopy. The current work demonstrated superior activity of oral azithromycin over oral miltefosine in the treatment of experimentally infected mice with Leishmania major (MHOM/IL/81/FEBNI). Unfortunately, oral combination therapy of azithromycin and miltefosine for short duration though, induced dramatic clinical improvement yet, relapse rapidly developed after cessation of therapy. Oral azithromycin could be a promising oral antileishmanial agent. Further research is recommended to investigate its leishmanicidal activity against other Leishmania species thus; another alternative oral therapy for leishmaniasis can be rapidly available.

  20. Does mass azithromycin distribution impact child growth and nutrition in Niger? A cluster-randomized trial.

    Directory of Open Access Journals (Sweden)

    Abdou Amza

    2014-09-01

    Full Text Available Antibiotic use on animals demonstrates improved growth regardless of whether or not there is clinical evidence of infectious disease. Antibiotics used for trachoma control may play an unintended benefit of improving child growth.In this sub-study of a larger randomized controlled trial, we assess anthropometry of pre-school children in a community-randomized trial of mass oral azithromycin distributions for trachoma in Niger. We measured height, weight, and mid-upper arm circumference (MUAC in 12 communities randomized to receive annual mass azithromycin treatment of everyone versus 12 communities randomized to receive biannual mass azithromycin treatments for children, 3 years after the initial mass treatment. We collected measurements in 1,034 children aged 6-60 months of age.We found no difference in the prevalence of wasting among children in the 12 annually treated communities that received three mass azithromycin distributions compared to the 12 biannually treated communities that received six mass azithromycin distributions (odds ratio = 0.88, 95% confidence interval = 0.53 to 1.49.We were unable to demonstrate a statistically significant difference in stunting, underweight, and low MUAC of pre-school children in communities randomized to annual mass azithromycin treatment or biannual mass azithromycin treatment. The role of antibiotics on child growth and nutrition remains unclear, but larger studies and longitudinal trials may help determine any association.

  1. Home spirometry as early detector of azithromycin refractory bronchiolitis obliterans syndrome in lung transplant recipients.

    Science.gov (United States)

    de Wall, Claudia; Sabine, Dettmer; Gregor, Warnecke; Mark, Greer; Axel, Haverich; Thomas, Fuehner; Tobias, Welte; Jens, Gottlieb

    2014-02-01

    To evaluate the utility of home spirometry (HS) versus office spirometry (OS) in assessing treatment response to azithromycin in bronchiolitis obliterans syndrome (BOS). 239 Lung transplant recipients were retrospectively studied. ΔFEV1 ± 10% from FEV1 at azithromycin initiation for ≥7 consecutive days in HS or ≥2 measures in OS were taken as cut-off for response or progression. Based upon HS, 161/239 (67%) patients were progressive despite macrolide, 19 of who exhibited transient improvement in FEV1 (11%). Time to progression was 29 (13-96) days earlier with HS than in OS. Forty-six (19%) recipients responded in HS after median 81 (22-343) days, whilst 22% remained stable. Concordance in azithromycin treatment response between OS and HS was observed in 210 of 239 patients (88%). Response or stabilization conferred significant improvement in survival (p = 0.005). Transient azithromycin responders demonstrated improved survival when compared to azithromycin refractory patients (p = 0.034). HS identified azithromycin refractory patients significantly earlier than OS, possibly facilitating aggressive treatment escalation that may improve long-term outcome. Treatment response to azithromycin should be assessed 4 weeks after initiation. Responders demonstrated best survival, with even transient response conferring benefit. Macrolide-refractory BOS carried the worst prognosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Azithromycin differentially affects the IL-13-induced expression profile in human bronchial epithelial cells.

    Science.gov (United States)

    Mertens, Tinne C J; Hiemstra, Pieter S; Taube, Christian

    2016-08-01

    The T helper 2 (Th2) cytokine interleukin(IL)-13 is a central regulator in goblet cell metaplasia and induces the recently described Th2 gene signature consisting of periostin (POSTN), chloride channel regulator 1 (CLCA1) and serpin B2 (SERPINB2) in airway epithelial cells. This Th2 gene signature has been proposed as a biomarker to classify asthma into Th2-high and Th2-low phenotypes. Clinical studies have shown that the macrolide antibiotic azithromycin reduced clinical symptoms in neutrophilic asthma, but not in the classical Th2-mediated asthma despite the ability of azithromycin to reduce IL-13-induced mucus production. We therefore hypothesize that azithromycin differentially affects the IL-13-induced expression profile. To investigate this, we focus on IL-13-induced mucin and Th2-signature expression in human bronchial epithelial cells and how this combined expression profile is affected by azithromycin treatment. Primary bronchial epithelial cells were differentiated at air liquid interface in presence of IL-13 with or without azithromycin. Azithromycin inhibited IL-13-induced MUC5AC, which was accompanied by inhibition of IL-13-induced CLCA1 and SERPINB2 expression. In contrast, IL-13-induced expression of POSTN was further increased in cells treated with azithromycin. This indicates that azithromycin has a differential effect on the IL-13-induced Th2 gene signature. Furthermore, the ability of azithromycin to decrease IL-13-induced MUC5AC expression may be mediated by a reduction in CLCA1. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Blood, Tissue, and Intracellular Concentrations of Azithromycin during and after End of Therapy

    Science.gov (United States)

    Matzneller, P.; Krasniqi, S.; Kinzig, M.; Sörgel, F.; Hüttner, S.; Lackner, E.; Müller, M.

    2013-01-01

    Although azithromycin is extensively used in the treatment of respiratory tract infections as well as skin and skin-related infections, pharmacokinetics of azithromycin in extracellular space fluid of soft tissues, i.e., one of its therapeutic target sites, are not yet fully elucidated. In this study, azithromycin concentration-time profiles in extracellular space of muscle and subcutaneous adipose tissue, but also in plasma and white blood cells, were determined at days 1 and 3 of treatment as well as 2 and 7 days after the end of treatment. Of all compartments, azithromycin concentrations were highest in white blood cells, attesting for intracellular accumulation. However, azithromycin concentrations in both soft tissues were markedly lower than in plasma both during and after treatment. Calculation of the area under the concentration-time curve from 0 to 24 h (AUC0–24)/MIC90 ratios for selected pathogens suggests that azithromycin concentrations measured in the present study are subinhibitory at all time points in both soft tissues and at the large majority of observed time points in plasma. Hence, it might be speculated that azithromycin's clinical efficacy relies not only on elevated intracellular concentrations but possibly also on its known pleotropic effects, including immunomodulation and influence on bacterial virulence factors. However, prolonged subinhibitory azithromycin concentrations at the target site, as observed in the present study, might favor the emergence of bacterial resistance and should therefore be considered with concern. In conclusion, this study has added important information to the pharmacokinetic profile of the widely used antibiotic drug azithromycin and evidentiates the need for further research on its potential for induction of bacterial resistance. PMID:23357769

  4. Effect of azithromycin on Prevotella intermedia lipopolysaccharide-induced production of interleukin-6 in murine macrophages.

    Science.gov (United States)

    Choi, Eun-Young; Jin, Ji-Young; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2014-04-15

    Interleukin-6 (IL-6) is a key proinflammatory cytokine which plays a central role in the pathogenesis of periodontal disease. Host modulatory agents targeting at inhibiting IL-6, therefore, appear to be beneficial in slowing the progression of periodontal disease and potentially reducing destructive aspects of the host response. The present study was designed to investigate the effect of the macrolide antibiotic azithromycin on IL-6 generation in murine macrophages treated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in inflammatory periodontal disease, and its mechanisms of action. Azithromycin significantly suppressed IL-6 production as well as its mRNA expression in P. intermedia LPS-activated RAW264.7 cells. LPS-induced activation of JNK and p38 was not affected by azithromycin treatment. Azithromycin failed to prevent P. intermedia LPS from degrading IκB-α. Instead, azithromycin significantly diminished nuclear translocation and DNA binding activity of NF-κB p50 subunit induced with LPS. Azithromycin inhibited P. intermedia LPS-induced STAT1 and STAT3 phosphorylation. In addition, azithromycin up-regulated the mRNA level of SOCS1 in cells treated with LPS. In conclusion, azithromycin significantly attenuated P. intermedia LPS-induced production of IL-6 in murine macrophages via inhibition of NF-κB, STAT1 and STAT3 activation, which is possibly related to the activation of SOCS1 signaling. Further in vivo studies are required to better evaluate the potential of azithromycin in the treatment of periodontal disease. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2016-12-01

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

  6. Azithromycin for the Prevention of COPD Exacerbations: The Good, Bad, and Ugly.

    Science.gov (United States)

    Taylor, Stephanie Parks; Sellers, Eric; Taylor, Brice T

    2015-12-01

    Long-term azithromycin therapy has been shown to reduce exacerbations of chronic obstructive pulmonary disease (COPD), and is recommended by recent society guidelines for use in COPD patients who are at risk for recurrent exacerbations. However, concerns about adverse effects have limited its widespread adoption. Physicians deciding whether to use long-term azithromycin therapy must weigh each patient's individual risk of cardiovascular complications and both the individual and population impact of macrolide resistance against the expected benefit. This review will summarize evidence on the effectiveness and safety of chronic azithromycin for the prevention of COPD exacerbations. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Azithromycin as an adjuvant therapy in cryptogenic organizing pneumonia

    Directory of Open Access Journals (Sweden)

    A.P. Vaz

    2011-07-01

    Full Text Available There are data about the immunomodulatory properties of some macrolides in cryptogenic organizing pneumonia (COP as an alternative to corticosteroids in mild disease or as adjuvant to standard therapy.A sixty-year-old female, with a controlled intrinsic asthma, presented with COP and recurrent respiratory exacerbations despite corticosteroid and immunossupressant therapy. Azithromycin (500 mg, on alternate days as an adjuvant to steroids was then started, with clinical and functional improvement and regression of lung infiltrates. Withdrawal of steroids was possible in one year, without evidence of relapse in the next six months. Azithromycin was maintained (three times per week with no documentation of adverse side effects.This clinical case reinforces the potential role of macrolides anti-inflammatory properties in COP as corticosteroids adjuvant therapy. Resumo: Existem dados na literatura sobre o uso das propriedades imunomoduladoras de alguns macrólidos no tratamento da pneumonia organizativa criptogénica (COP como alternativa aos corticoesteróides na doença ligeira ou como adjuvantes da terapêutica padrão.Os autores descrevem o caso de uma mulher de 60 anos de idade, com asma intrínseca controlada, que apresentou uma COP e exacerbações respiratórias de repetição, apesar da corticoterapia e terapêutica imunossupressora instituídas. Após início de azitromicina (500 mg, dias alternados, como adjuvante da corticoterapia, verificou-se melhoria clínica e funcional e regressão dos infiltrados pulmonares. A suspensão dos corticoesteróides foi possível no período de um ano, sem evidência de recidiva nos seis meses seguintes. A azitromicina foi mantida (3 vezes/semana sem documentação de efeitos laterais adversos.Este caso clínico reforça o potencial papel das propriedades anti-inflamatórias dos macrólidos na COP, como terapêutica adjuvante dos corticoesteróides. Keywords: Cryptogenic organizing pneumonia, Macrolides

  8. Synthetic quorum sensing in model microcapsule colonies

    Science.gov (United States)

    Shum, Henry; Balazs, Anna C.

    2017-08-01

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

  9. Exploiting Quorum Sensing To Confuse Bacterial Pathogens

    Science.gov (United States)

    LaSarre, Breah

    2013-01-01

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

  10. Macrolide resistance and azithromycin failure in a Mycoplasma genitalium-infected cohort and response of azithromycin failures to alternative antibiotic regimens.

    Science.gov (United States)

    Bissessor, Melanie; Tabrizi, Sepehr N; Twin, Jimmy; Abdo, Houda; Fairley, Christopher K; Chen, Marcus Y; Vodstrcil, Lenka A; Jensen, Jorgen S; Hocking, Jane S; Garland, Suzanne M; Bradshaw, Catriona S

    2015-04-15

    Our aim was to determine the efficacy of 1 g azithromycin and alternative antibiotic regimens in a prospective cohort of Mycoplasma genitalium-infected participants, and factors associated with azithromycin failure. Consecutive eligible M. genitalium-infected men and women attending the Melbourne Sexual Health Centre between July 2012 and June 2013 were treated with 1 g of azithromycin and retested by polymerase chain reaction (PCR) on days 14 and 28. Cure was defined as PCR negative on day 28. Cases failing azithromycin were treated with moxifloxacin, and those failing moxifloxacin were treated with pristinamycin. Pre- and posttreatment samples were assessed for macrolide resistance mutations (MRMs) by high-resolution melt analysis. Mycoplasma genitalium samples from cases failing moxifloxacin were sequenced for fluoroquinolone resistance mutations. Multivariable analysis was used to examine associations with azithromycin failure. Of 155 participants treated with 1 g azithromycin, 95 (61% [95% confidence interval {CI}, 53%-69%]) were cured. Pretreatment MRM was detected in 56 (36% [95% CI, 28%-43%]) participants, and strongly associated with treatment failure (87% [95% CI, 76%-94%]; adjusted odds ratio, 47.0 [95% CI, 17.1-129.0]). All 11 participants who had MRM detected in posttreatment samples failed azithromycin. Moxifloxacin was effective in 53(88% [95% CI, 78%-94%]) of 60 cases failing azithromycin; all failures had gyrA and parC mutations detected in pretreatment samples. Six of 7 patients failing moxifloxacin treatment received pristinamycin, and all were PCR negative 28 days after pristinamycin treatment. We report a high azithromycin failure rate (39%) in an M. genitalium-infected cohort in association with high levels of pretreatment macrolide resistance. Moxifloxacin failure occurred in 12% of patients who received moxifloxacin; all had pretreatment fluoroquinolone mutations detected. Pristinamycin was highly effective in treating macrolide- and

  11. Glyceryl trinitrate is a novel inhibitor of quorum sensing in ...

    African Journals Online (AJOL)

    Objectives: Investigation of the possible inhibition of quorum sensing-regulated virulence of Pseudomonas aeruginosa by glyceryltrinitrate. Methods: The quorum sensing inhibiting activity of glyceryl trinitrate was assessed by inhibition of violacein production in Chromobacterium violaceum ATCC 12472. Its ability to inhibit ...

  12. Repurposing metformin as a quorum sensing inhibitor in ...

    African Journals Online (AJOL)

    Background: Quorum sensing is a mechanism of intercellular communication that controls the production of virulence factors in Pseudomonas aeruginosa. Inhibition of quorum sensing can disarm the virulence factors without exerting stress on bacterial growth that leads to emergence of antibiotic resistance. Objectives: ...

  13. Fremmedlegemeinfektioner--nyt om biofilm og quorum sensing

    DEFF Research Database (Denmark)

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

    2007-01-01

    . Bacteria in biofilms communicate by means of quorum sensing which activates genes for virulence factors. Biofilms can be prevented by antibiotic prophylaxis or early therapy or by quorum sensing inhibitors which make them susceptible to antibiotics and phagocytosis. Udgivelsesdato: 2007-Nov-26...

  14. Glyceryl trinitrate is a novel inhibitor of quorum sensing in ...

    African Journals Online (AJOL)

    GTN could inhibit the violacein pigment production that is under quorum-sensing control in the reporter strain. Chromobacterium violaceum ATCC 12472. This constitutes the biological evidence of the quorum sensing inhibit- ing activity of GTN. Moreover, molecular docking study showed that GTN is a competitive inhibitor ...

  15. Combination Therapy Strategy of Quorum Quenching Enzyme and Quorum Sensing Inhibitor in Suppressing Multiple Quorum Sensing Pathways of P. aeruginosa

    DEFF Research Database (Denmark)

    Fong, July; Zhang, Chaodong; Yang, Renliang

    2018-01-01

    The threat of antibiotic resistant bacteria has called for alternative antimicrobial strategies that would mitigate the increase of classical resistance mechanism. Many bacteria employ quorum sensing (QS) to govern the production of virulence factors and formation of drug-resistant biofilms....... Targeting the mechanism of QS has proven to be a functional alternative to conventional antibiotic control of infections. However, the presence of multiple QS systems in individual bacterial species poses a challenge to this approach. Quorum sensing inhibitors (QSI) and quorum quenching enzymes (QQE) have...

  16. Immunomodulatory indications of azithromycin in respiratory disease: a concise review for the clinician.

    Science.gov (United States)

    Cramer, Cassondra L; Patterson, Allie; Alchakaki, Abdulrazak; Soubani, Ayman O

    2017-06-01

    Azithromycin has a well-characterized bacteriostatic activity. However, it also has a robust immunomodulatory effect that has proven beneficial in a variety of chronic illnesses. This effect results in decreased production of pro-inflammatory cytokines in the acute phase and promotes resolution of chronic inflammation in the later phases. Specifically, azithromycin has direct activity on airway epithelial cells to maintain their function and reduce mucus secretion. These characteristics have resulted in the use of azithromycin in the management of a variety of chronic lung diseases including chronic obstructive pulmonary disease, cystic fibrosis (CF), non-CF bronchiectasis, bronchiolitis obliterans syndrome, diffuse panbronchiolitis, and asthma. In this review, we present the evidence supporting the role of azithromycin in these conditions with an emphasis on the clinical aspects for the practicing physician.

  17. ROLE OF AZITHROMYCIN IN COMPLEX TREATMENT OF RESPIRATORY DISEASES IN CHILDREN

    Directory of Open Access Journals (Sweden)

    E.V. Sereda

    2008-01-01

    Full Text Available The article contains the analysis of the role of azithromycin (sumamed in treatment of respiratory diseases in children. It is noted that azithromycin is an efficient antibacterial drug for treatment of extramural and uncomplicated pneumonia and is the drug of choice for atypical mycoplasmal and chlamidia trachomatis pneumonia, as well as for relapses of chronic bronchopulmonary diseases in children. High sensitivity to azithromycin of main pneumotropic and atypical agents, convenience of application, presence of children's pharmaceutical forms, reduction of administration to 1 time per day in case of short treatment schedules, high efficiency and absence of serious adverse events make it possible to recommend this antibiotic as an available means for treatment of respiratory diseases in infants and senior children not only as in patients but as out patients as well.Key words: children, azithromycin, treatment, respiratory diseases.

  18. Ocular surface distribution and pharmacokinetics of a novel ophthalmic 1% azithromycin formulation.

    Science.gov (United States)

    Akpek, Esen Karamursel; Vittitow, Jason; Verhoeven, Rozemarijn S; Brubaker, Kurt; Amar, Thierry; Powell, Kendall D; Boyer, José L; Crean, Christopher

    2009-10-01

    To investigate the ocular distribution of 1% azithromycin ophthalmic solution and the effect of polycarbophil-based mucoadhesive formulation on ocular tissue levels of azithromycin after single and multiple topical administrations in the rabbit eye. Rabbits were treated with either a single administration of 1% azithromycin solution with or without polycarbophil, or with multiple administrations of 1% azithromycin solution in polycarbophil. Drug concentrations were measured using LC/MS/MS. Conjunctiva, cornea, aqueous humor, and tear samples were analyzed over a period of 144 h after a single administration of azithromycin with or without polycarbophil. Eyelid, conjunctiva, cornea, aqueous humor, and tear samples were collected over a period of 288 h during and after multiple administrations of azithromycin. Azithromycin was rapidly absorbed and distributed in the ocular tissues, reaching within 5 min, concentrations of 10,539 microg/mL in tear film, 108 microg/g in conjunctiva, and 40 microg/g in the cornea. The drug demonstrated tissue-specific half-lives of 15, 63, and 67 h, respectively. Following multiple administrations, the drug gradually accumulated. The polycarbophil formulation increased the bioavailability of the drug, producing peak concentrations that were between 5- and 12-fold higher than those without polycarbophil. Azithromycin also distributed rapidly in the eyelids, reaching peak concentrations of 180 mug/g at the end of the 7-day treatment, and was eliminated with a half-life of 125 h. Six days after treatment was discontinued, eyelid levels of azithromycin were above 40 microg/g. Sustained and high concentrations were encountered with 7-day approved administration of 1% azithromycin formulation (AzaSite, Inspire Pharmaceuticals, Inc., Durham, NC) within all ocular surface tissues, particularly the lids. Many ocular surface disorders involving the tear film, eyelids, and adnexal structures are associated with chronic, low-grade bacterial

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

    Science.gov (United States)

    Defoirdt, Tom; Brackman, Gilles; Coenye, Tom

    2013-12-01

    Because of its promising effect as an alternative to antibiotics, quorum sensing disruption is an intensively studied field, and there are many studies that describe the quorum sensing inhibitory activity of natural and synthetic compounds. In this opinion article, we present an overview of recent literature with respect to quorum sensing inhibitors. Most of this research is based on experiments with quorum sensing signal molecule reporter strains. However, these experiments are prone to bias due to other effects compounds may have on reporter strains. We argue that researchers should perform adequate control experiments and should carefully assess toxicity of the compounds in the bacterial species they are working with in order to confirm that what they observe really is quorum sensing inhibition. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    Kimura, Nobutada

    2014-04-01

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

  1. Evaluation of baseline corrected QT interval and azithromycin prescriptions in an academic medical center.

    Science.gov (United States)

    Lee, Rachael A; Guyton, Allison; Kunz, Danielle; Cutter, Gary R; Hoesley, Craig J

    2016-01-01

    Azithromycin is used in the inpatient setting for a variety of conditions. In 2013, the US Food and Drug Administration released a warning regarding risk for corrected QT (QTc) prolongation and subsequent arrhythmias. Knowledge of inpatient prescribing patterns of QTc prolonging medications with respect to patient risk factors for adverse cardiovascular events can help recognize safe use in light of these new warnings. To assess inpatient prescribing patterns, risk factors for QTc prolongation, and relationship between drug-drug interactions and cardiac monitoring in patients receiving azithromycin. Retrospective cohort study. One hundred inpatients ≥ 19 years of age were randomly selected from 1610 patient encounters between October 2012 and April 2013 who were administered at least 1 dose of azithromycin. Length of stay, reason for use, therapy duration, and concomitant medications were recorded. Telemetry charges and baseline electrocardiogram (ECG) prior to administration were assessed. Seventy-nine percent of azithromycin use was empiric. Sixty-five percent of patients received a baseline ECG prior to prescribing azithromycin, of which 60% had borderline or abnormal QTc prolongation. Seventy-six percent of patients were prescribed 2 or more QTc prolonging medications, of which there were more abnormal ECGs at baseline (P = 0.03) despite having telemetry ordered less than half of the time. In a cohort of hospitalized patients, azithromycin was prescribed despite risk factors for QTc prolongation and administration of interacting medications. Selection of azithromycin by providers appears to be independent from these risk factors, and education and vigilance to drug-drug interactions may be useful in limiting cardiac events with prescribing azithromycin. © 2015 Society of Hospital Medicine.

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

    OpenAIRE

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

    2014-01-01

    Burkholderia thailandensis contains three acyl-homoserine lactone quorum sensing circuits and has two additional LuxR homologs. To identify B. thailandensis quorum sensing-controlled genes, we carried out transcriptome sequencing (RNA-seq) analyses of quorum sensing mutants and their parent. The analyses were grounded in the fact that we identified genes coding for factors shown previously to be regulated by quorum sensing among a larger set of quorum-controlled genes. We also found that gene...

  3. Azithromycin plus chloroquine: combination therapy for protection against malaria and sexually transmitted infections in pregnancy

    Science.gov (United States)

    Chico, R Matthew; Chandramohan, Daniel

    2011-01-01

    Introduction: The first-line therapy for the intermittent preventive treatment of malaria in pregnancy (IPTp) is sulphadoxine-pyrimethamine (SP). There is an urgent need to identify safe, well-tolerated and efficacious alternatives to SP due to widespread Plasmodium falciparum resistance. Combination therapy using azithromycin and chloroquine is one possibility that has demonstrated adequate parasitological response > 95% in clinical trials of non-pregnant adults in sub-Saharan Africa and where IPTp is a government policy in 33 countries. Areas covered: Key safety, tolerability and efficacy data are presented for azithromycin and chloroquine, alone and/or in combination, when used to prevent and/or treat P. falciparum, P. vivax, and several curable sexually transmitted and reproductive tract infections (STI/RTI). Pharmacokinetic evidence from pregnant women is also summarized for both compounds. Expert opinion: The azithromycin-chloroquine regimen that has demonstrated consistent efficacy in non-pregnant adults has been a 3-day course containing daily doses of 1 g of azithromycin and 600 mg base of chloroquine. The pharmacokinetic evidence of these compounds individually suggests that dose adjustments may not be necessary when used in combination for treatment efficacy against P. falciparum, P. vivax, as well as several curable STI/ RTI among pregnant women, although clinical confirmation will be necessary. Mass trachoma-treatment campaigns have shown that azithromycin selects for macrolide resistance in the pneumococcus, which reverses following the completion of therapy. Most importantly, no evidence to date suggests that azithromycin induces pneumococcal resistance to penicillin. PMID:21736423

  4. Prophylactic Azithromycin Therapy After Lung Transplantation: Post hoc Analysis of a Randomized Controlled Trial.

    Science.gov (United States)

    Ruttens, D; Verleden, S E; Vandermeulen, E; Bellon, H; Vanaudenaerde, B M; Somers, J; Schoonis, A; Schaevers, V; Van Raemdonck, D E; Neyrinck, A; Dupont, L J; Yserbyt, J; Verleden, G M; Vos, R

    2016-01-01

    Prophylactic azithromycin treatment has been demonstrated to improve freedom from bronchiolitis obliterans syndrome (BOS) 2 years after lung transplantation (LTx). In the current study, we re-evaluated the long-term effects of this prophylactic approach in view of the updated classification system for chronic lung allograft dysfunction (CLAD). A retrospective, intention-to-treat analysis of a randomized controlled trial comparing prophylactic treatment with placebo (n = 43) versus azithromycin (n = 40) after LTx was performed. Graft dysfunction (CLAD), graft loss (retransplantation, mortality), evolution of pulmonary function and functional exercise capacity were analyzed 7 years after inclusion of the last study subject. Following LTx, 22/43 (51%) patients of the placebo group and 11/40 (28%) patients of the azithromycin group ever developed CLAD (p = 0.043). CLAD-free survival was significantly longer in the azithromycin group (p = 0.024). No difference was present in proportion of obstructive versus restrictive CLAD between both groups. Graft loss was similar in both groups: 23/43 (53%) versus 16/40 (40%) patients (p = 0.27). Long-term pulmonary function and functional exercise capacity were significantly better in the azithromycin group (p azithromycin therapy reduces long-term CLAD prevalence and improves CLAD-free survival, pulmonary function, and functional exercise capacity after LTx. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  5. Azithromycin use and outcomes in severe sepsis patients with and without pneumonia.

    Science.gov (United States)

    Afshar, Majid; Foster, Clayton L; Layden, Jennifer E; Burnham, Ellen L

    2016-04-01

    Studies investigating the association between macrolides and outcomes in both pulmonary and nonpulmonary critically ill patients are limited. We aimed to examine the association between azithromycin use and clinical outcomes in severe sepsis patients with and without pneumonia receiving mechanical ventilation. A retrospective cohort of 105 patients admitted to an adult intensive care unit (ICU) with severe sepsis in an urban university hospital were included in the study. Multivariable linear regression was performed to assess the relationship between azithromycin use and the following outcomes: 28-day ICU-free days and 28-day ventilator-free days. In univariate analysis, patients receiving azithromycin had nearly 6 more ICU-free days on average than did patients not receiving azithromycin (P = .005). The increased ICU-free days remained in multivariable analysis adjusting for age, sex, race, ICU type, and presence of shock (P = .005). In stratified analysis examining the association of azithromycin use in severe sepsis patients without pneumonia (n = 74), the results were similar to the full cohort. Azithromycin was associated with more ICU-free days in severe sepsis patients with and without pneumonia. Further investigations are warranted to better elicit the association of macrolide use on clinical outcomes in severe sepsis patients, especially those without pneumonia. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Quorum sensing inhibitors disable bacterial biofilms

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  7. Analysis of Neisseria gonorrhoeae Azithromycin Susceptibility in the United States by the Gonococcal Isolate Surveillance Project, 2005 to 2013

    Science.gov (United States)

    Soge, Olusegun; Papp, John R.; Hook, Edward W.; del Rio, Carlos; Kubin, Grace; Weinstock, Hillard S.

    2014-01-01

    Azithromycin, administered with ceftriaxone, is recommended by the CDC for the treatment of gonorrhea. Many experts have expressed concern about the ease with which Neisseria gonorrhoeae can acquire macrolide resistance. We sought to describe gonococcal azithromycin susceptibility in the United States and to determine whether azithromycin susceptibility has changed over time. We analyzed data from 2005 to 2013 from the Gonococcal Isolate Surveillance Project, a CDC-supported sentinel surveillance network that monitors gonococcal antimicrobial susceptibility. A total of 44,144 N. gonorrhoeae isolates were tested for azithromycin susceptibility by agar dilution methods. The overall azithromycin MIC50 was 0.25 μg/ml, and the MIC90 was 0.5 μg/ml. There were no overall temporal trends in geometric means. Isolates from men who had sex with men had significantly higher geometric mean MICs than isolates from men who had sex exclusively with women. The overall prevalence of reduced azithromycin susceptibility (MIC, ≥2 μg/ml) was 0.4% and varied by year from 0.3% (2006 and 2009) to 0.6% (2013). We did not find a clear temporal trend in gonococcal azithromycin MICs in the United States, and the prevalence of reduced azithromycin susceptibility remains low. These findings support the continued use of azithromycin in a combination therapy regimen for gonorrhea. PMID:25451056

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

    Directory of Open Access Journals (Sweden)

    Antariksh Deep

    2011-01-01

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

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

    Science.gov (United States)

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

    2015-02-17

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

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

    Science.gov (United States)

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

    2016-02-01

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

  11. Long-term effects of azithromycin in patients with cystic fibrosis.

    Science.gov (United States)

    Samson, Clémentine; Tamalet, Aline; Thien, Hoang Vu; Taytard, Jessica; Perisson, Caroline; Nathan, Nadia; Clement, Annick; Boelle, Pierre-Yves; Corvol, Harriet

    2016-08-01

    Low-dose azithromycin has beneficial effects on severity of the lung disease in cystic fibrosis (CF) patients for a period of 6-12 months after initiation of the treatment. Although its impact in the longer term is uncertain, this treatment is frequently used chronically. The aim of this retrospective study was to investigate the effects of low-dose azithromycin treatment on the progression of CF lung disease in patients treated for more than 12 months. All of the CF patients followed in our pediatric center and who had been on low-dose azithromycin for more than 12 sequential months were included. The clinical data were collected for one year before and three years after the initiation of the azithromycin treatment. These data comprised lung function analyses, rates of exacerbations and of antibiotic courses, and changes in the airways' bacterial colonization. A total of 68 patients were included (mean age: 9.95 yrs (3.61)). After 12 months, significant reductions in the numbers of pulmonary exacerbations and antibiotic courses were present. However, this effect was not maintained in the subsequent periods, during which increased rates of both pulmonary exacerbations and antibiotic courses were observed. The lung function decline was not modified during the treatment, and a decreasing time-dependent trend typical of CF was observed for the various parameters. No differences in the airway colonization by pathogens such as Pseudomonas aeruginosa and methicillin-sensitive and/or -resistant Staphyloccocus aureus were observed during the treatment. However, isolated Staphyloccocus aureus strains became resistant to macrolides after 6 months of azithromycin and remained resistant thereafter. No clinical benefits of low-doses azithromycin were present after one year of treatment in young CF patients. Selection for macrolide-resistant strains of bacteria occurred, which should lead to a reconsideration of the duration of azithromycin treatment in CF. Copyright © 2016

  12. The antibiotic azithromycin is a motilin receptor agonist in human stomach: comparison with erythromycin

    Science.gov (United States)

    Broad, John; Sanger, Gareth J

    2013-01-01

    Background and Purpose The antibiotic azithromycin is a suggested alternative to erythromycin for treating patients with delayed gastric emptying. However, although hypothesized to activate motilin receptors, supportive evidence is unavailable. This was investigated using recombinant and naturally expressed motilin receptors in human stomach, comparing azithromycin with erythromycin. Experimental Approach [125I]-motilin binding and calcium flux experiments were conducted using human recombinant motilin receptors in CHO cells. Neuromuscular activities were studied using circular muscle of human gastric antrum, after electrical field stimulation (EFS) of intrinsic nerves. Key Results Azithromycin (1–100 μM) and erythromycin (3–30 μM) concentration-dependently displaced [125I]-motilin binding to the motilin receptor (52 ± 7 and 58 ± 18% displacement at 100 and 30 μM respectively). Azithromycin, erythromycin and motilin concentration-dependently caused short-lived increases in intracellular [Ca2+] in cells expressing the motilin receptor. EC50 values were, respectively, 2.9, 0.92 and 0.036 μM (n = 3 each); and maximal activities were similar. In human stomach, EFS evoked cholinergically mediated contractions, attenuated by simultaneous nitrergic activation. Azithromycin and erythromycin lactobionate (30–300 μM each) facilitated these contractions (apparent Emax values of 2007 ± 396 and 1924 ± 1375%, n = 3–4 each concentration, respectively). These actions were slow in onset and faded slowly. The higher concentrations also evoked short-lived muscle contraction. Contractions to a submaximally effective concentration of carbachol were unaffected by either drug. Conclusions and Implications Azithromcyin activates human recombinant motilin receptors in therapeutically relevant concentrations, similar to erythromycin. In humans, gastric antrum azithromycin caused long-lasting facilitation of cholinergic activity. These actions explain the gastric prokinetic

  13. Azithromycin attenuates airway inflammation in a mouse model of viral bronchiolitis

    Directory of Open Access Journals (Sweden)

    Brody Steven L

    2010-06-01

    Full Text Available Abstract Background Viral bronchiolitis is the leading cause of hospitalization in young infants. It is associated with the development of childhood asthma and contributes to morbidity and mortality in the elderly. Currently no therapies effectively attenuate inflammation during the acute viral infection, or prevent the risk of post-viral asthma. We hypothesized that early treatment of a paramyxoviral bronchiolitis with azithromycin would attenuate acute and chronic airway inflammation. Methods Mice were inoculated with parainfluenza type 1, Sendai Virus (SeV, and treated daily with PBS or azithromycin for 7 days post-inoculation. On day 8 and 21 we assessed airway inflammation in lung tissue, and quantified immune cells and inflammatory mediators in bronchoalveolar lavage (BAL. Results Compared to treatment with PBS, azithromycin significantly attenuated post-viral weight loss. During the peak of acute inflammation (day 8, azithromycin decreased total leukocyte accumulation in the lung tissue and BAL, with the largest fold-reduction in BAL neutrophils. This decreased inflammation was independent of changes in viral load. Azithromycin significantly attenuated the concentration of BAL inflammatory mediators and enhanced resolution of chronic airway inflammation evident by decreased BAL inflammatory mediators on day 21. Conclusions In this mouse model of paramyxoviral bronchiolitis, azithromycin attenuated acute and chronic airway inflammation. These findings demonstrate anti-inflammatory effects of azithromycin that are not related to anti-viral activity. Our findings support the rationale for future prospective randomized clinical trials that will evaluate the effects of macrolides on acute viral bronchiolitis and their long-term consequences.

  14. Azithromycin Is Equally Effective as Amoxicillin in Children with Solitary Erythema Migrans.

    Science.gov (United States)

    Arnež, Maja; Ružić-Sabljić, Eva

    2015-10-01

    Comparison of clinical efficacy and adverse effects of treatment with azithromycin and amoxicillin in children with solitary erythema migrans (EM). Consecutive patients younger than 15 years with untreated solitary EM referred to our institution 2002-2003 were included in this unblinded prospective clinical study in which patients were alternatively treated with either azithromycin for 5 days or amoxicillin for 14 days. The efficacy of treatment of acute disease, development of minor and major manifestations of Lyme borreliosis and adverse effects of treatment were surveyed by follow-up visits during the first year after inclusion. Eighty-four patients received azithromycin and 84 amoxicillin. Pretreatment characteristics in the 2 groups were comparable with the exception that patients in azithromycin group more often reported a tick bite at the site of later EM (69% versus 52%; P = 0.0400), had more often EM on the trunk (50% versus 26%; P = 0.0025) and reported longer duration of symptoms (median 3 versus 2 days; P = 0.0283). The posttreatment period revealed no significant differences between azithromycin and amoxicillin groups including the duration of EM (median 3 days; P = 0.8984) and the appearance of minor (12% versus 21%; P = 0.2146) and major manifestations (2.6% in each group) of Lyme borreliosis. Adverse effects of treatment were observed in 21% of patients treated with azithromycin and in 16% treated with amoxicillin, and the appearance of Jarisch-Herxheimer reaction was recorded in 7% and 15%, respectively (P = 0.1438). Comparison of azithromycin and amoxicillin for the treatment of children with solitary EM revealed comparable efficacy and adverse effects of treatment.

  15. Adding Azithromycin to Cephalosporin for Cesarean Delivery Infection Prophylaxis: A Cost-Effectiveness Analysis.

    Science.gov (United States)

    Skeith, Ashley E; Niu, Brenda; Valent, Amy M; Tuuli, Methodius G; Caughey, Aaron B

    2017-12-01

    To investigate the cost-effectiveness of adding azithromycin to standard cephalosporin regimens of cesarean delivery prophylaxis by considering the maternal outcomes in the current and potential subsequent pregnancies. A cost-effectiveness model was created using TreeAge to compare the outcomes of using azithromycin-cephalosporin with cephalosporin alone in a theoretical cohort of 700,000 women, the approximate number of nonelective cesarean deliveries annually in the United States that occur during labor or after membrane rupture. Outcomes examined included endometritis, wound infection, sepsis, venous thromboembolism, and maternal death in the current pregnancy and uterine rupture, cesarean hysterectomy, and maternal death in subsequent pregnancies, including cost and quality-adjusted life-years for both pregnancies. Probabilities, utilities, and costs were derived from the literature, and a cost-effectiveness threshold was set at $100,000 per quality-adjusted life-year. Sensitivity analyses were used to determine the robustness of our results. Compared with cephalosporin alone for prophylaxis, our model showed 16,100 fewer cases of endometritis, 17 fewer cases of sepsis, eight fewer cases of venous thromboembolism, and one fewer maternal death with azithromycin-cephalosporin. Additionally, this strategy prevented 36 uterine ruptures and four cesarean hysterectomies in the subsequent pregnancy. Overall, the addition of azithromycin led to both lower costs and higher quality-adjusted life-years when compared with standard cephalosporin prophylaxis. In sensitivity analysis, we found that as long as the cost of azithromycin remained below $930 (baseline cost $27), it was cost-effective. For women who undergo cesarean delivery in labor or after membrane rupture, compared with cephalosporin alone, the addition of azithromycin to cesarean delivery infection prophylaxis is less costly and leads to better maternal outcomes in the index delivery and subsequent deliveries

  16. Preparation of azithromycin nanosuspensions by reactive precipitation method.

    Science.gov (United States)

    Hou, Cheng-Dong; Wang, Jie-Xin; Le, Yuan; Zou, Hai-Kui; Zhao, Hong

    2012-07-01

    The aim of this work was to prepare azithromycin (AZI) nanosuspensions to increase the solubility and dissolution rate. AZI nanosuspensions were prepared by the combination of reactive precipitation and freeze-drying in presence of biocompatible stabilizer. Formulation and process variables affecting the characteristics of nanosuspensions were optimized. Various tests were carried out to study the physicochemical characteristics of AZI nanosuspensions. The nanosuspensions were parenterally acceptable and autoclavable, because soybean lecithin was the stabilizer of choice and no organic solvents were used during the preparation. The mean particle size and zeta potential of the AZI nanosuspensions were about 200 nm (±20 nm) and -36.7 mV (±7.6 mV), respectively. Solid nanoparticles were obtained by lyophilization of the nanosuspensions and nanosuspensions rapidly reconstituted when the nanoparticles were dispersed in water. X-ray diffraction and differential scanning calorimetry analysis showed that the crystal state of nanoparticles was amorphous. Solubility and in vitro release studies indicated that the saturated solubility and dissolution rate increased obviously in comparison of raw AZI. The nanoparticles were physically stable over a period of 5 months as demonstrated by unchanged crystallinity and stable particle size when stored at room temperature and protected from humidity. The results suggested that reactive precipitation is an effective way to prepare AZI nanosuspensions with increased solubility and dissolution rate.

  17. Quorum Sensing Communication Modules for Microbial Consortia.

    Science.gov (United States)

    Scott, Spencer R; Hasty, Jeff

    2016-09-16

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

  18. Quorum Quenching Agents: Resources for Antivirulence Therapy

    Directory of Open Access Journals (Sweden)

    Kaihao Tang

    2014-05-01

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

  19. Efficacy and safety of intravenous azithromycin followed by oral azithromycin for the treatment of acute pelvic inflammatory disease and perihepatitis in Japanese women.

    Science.gov (United States)

    Mikamo, Hiroshige; Iwasaku, Kazuhiro; Yamagishi, Yuka; Matsumizu, Miyako; Nagashima, Masahito

    2014-07-01

    Pelvic inflammatory disease (PID) is mainly caused by ascending infection from the vaginal flora including the sexually transmitted organisms, Neisseria gonorrhoeae and Chlamydia trachomatis, and lower genital tract endogenous anaerobes, leading to serious consequences including infertility and ectopic pregnancy. To evaluate the efficacy and safety of azithromycin in the treatment of PID that requires initial intravenous therapy, we conducted a multicenter, unblinded, non-comparative phase 3 trial. Intravenous azithromycin (500 mg, once daily) for 1 or 2 days followed by oral azithromycin (250 mg once daily) to complete a total of 7 days treatment was administered to 60 Japanese women with acute PID. The clinical and bacteriological responses were assessed at the end of treatment, and on Days 15 and 29. The most commonly detected baseline causative pathogens were C. trachomatis (12 strains), Prevotella bivia (10 strains), Streptococcus agalactiae (7 strains), N. gonorrhoeae and Peptostreptococcus anaerobius (6 strains each). The clinical success rate on Day 15 was 94.1% (48/51 subjects including perihepatitis). The clinical efficacy and bacterial eradication rates against C. trachomatis and N. gonorrhoeae (including 2 quinolone-resistant strains) were both 100%. Common treatment-related adverse events were diarrhoea, injection site pain, and nausea. All adverse events were mild or moderate in severity. Azithromycin intravenous-to-oral switch therapy demonstrated excellent clinical and bacteriological effects for PID caused by various etiologic agents including quinolone-resistant strains and strains with low susceptibility to azithromycin at in vitro testing. The therapy was well tolerated in the treatment of PID in Japanese women. NCT00871494. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  20. A Case-Control Study of Molecular Epidemiology in Relation to Azithromycin Resistance in Neisseria gonorrhoeae Isolates Collected in Amsterdam, the Netherlands, between 2008 and 2015

    NARCIS (Netherlands)

    Wind, Carolien M.; Bruisten, Sylvia M.; Schim van der Loeff, Maarten F.; Dierdorp, Mirjam; de Vries, Henry J. C.; van Dam, Alje P.

    2017-01-01

    Neisseria gonorrhoeae resistance to ceftriaxone and azithromycin is increasing, which threatens the recommended dual therapy. We used molecular epidemiology to identify N. gonorrhoeae clusters and associations with azithromycin resistance in Amsterdam, the Netherlands. N. gonorrhoeae isolates (n =

  1. Non-surgical periodontal therapy supplemented with systemically administered azithromycin: a systematic review of RCTs.

    Science.gov (United States)

    Buset, Sabrina L; Zitzmann, Nicola U; Weiger, Roland; Walter, Clemens

    2015-11-01

    Azithromycin may be an alternative adjunctive systemic antibiotic in non-surgical periodontal therapy. This study aims to identify randomized controlled trials evaluating non-surgical periodontal treatment of chronic and/or aggressive periodontitis supplemented with systemically administered azithromycin. A systematic literature search was performed for publications published by 31 March 2014 using electronic databases and hand search. Randomized controlled trials published in English or German language, with a follow-up ≥6 months were included. From 231 titles identified, nine publications were eligible for inclusion. Among the studies included, showing some risk of bias, seven reported on patients with chronic periodontitis and two with aggressive periodontitis. Minor adverse events were described in five studies. A synthesis of results using a vote counting method was applied. Significant (p azithromycin were shown in six studies for probing depth changes and in five studies for clinical attachment level changes. In contrast to aggressive periodontitis patients, data from this analysis indicate a potential benefit of systemic azithromycin as adjunctive to non-surgical periodontal therapy in chronic periodontitis patients. When contraindications for the standard antibiotics are present, azithromycin (AZM) may be considered as alternative systemically administered antibiotic drug in selected cases of chronic periodontitis.

  2. Comparison of minocycline and azithromycin for the treatment of mild scrub typhus in northern China.

    Science.gov (United States)

    Zhao, Minxing; Wang, Ting; Yuan, Xiaoyu; Du, Weiming; Lin, Miaoxin; Shen, Yanbo

    2016-09-01

    Scrub typhus, caused by Orientia tsutsugamushi, has recently emerged in northern China where the disease had not been known to exist. Although doxycycline and azithromycin are the recommended agents for the treatment of scrub typhus, clinical responses depend both on the susceptibilities of various O. tsutsugamushi strains and the severity of the disease. A retrospective analysis was conducted on patients diagnosed with mild scrub typhus from August 2013 to January 2016 in the Affiliated Hospital of Nantong University, northern China. A total of 40 patients who received minocycline treatment and 34 patients who received azithromycin treatment were included in the analysis. All patients except one defervesced within 120 h after initiating antimicrobial therapy. Kaplan-Meier curves in association with log-rank test showed that the median time to defervescence was significantly shorter for the minocycline-treated group than the azithromycin-treated group (P = 0.003). There were no serious adverse events during treatment. No relapse occurred in either group during the 1-month follow-up period. In conclusion, both minocycline and azithromycin are effective and safe for the treatment of mild scrub typhus, but minocycline is more active than azithromycin against O. tsutsugamushi infection acquired in northern China. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  3. Pseudomonas aeruginosa quorum sensing as a potential antimicrobial target

    Science.gov (United States)

    Smith, Roger S.; Iglewski, Barbara H.

    2003-01-01

    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. PMID:14617745

  4. 17 CFR 200.41 - Quorum of the Commission.

    Science.gov (United States)

    2010-04-01

    ...; CONDUCT AND ETHICS; AND INFORMATION AND REQUESTS Disposition of Commission Business § 200.41 Quorum of the... office; and provided further that on any matter of business as to which the number of members in office...

  5. Electronic implementation of a repressilator with quorum sensing feedback.

    Directory of Open Access Journals (Sweden)

    Edward H Hellen

    Full Text Available 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.

  6. Qualitative and Quantitative Determination of Quorum Sensing Inhibition In Vitro

    DEFF Research Database (Denmark)

    Jakobsen, Tim Holm; Alhede, Maria; Hultqvist, Louise Dahl

    2018-01-01

    The formation of biofilms in conjunction with quorum sensing (QS) regulated expression of virulence by opportunistic pathogens contributes significantly to immune evasion and tolerance to a variety of antimicrobial treatments. The present protocol describes methods to determine the in vitro...

  7. Quorum-Sensing Systems as Targets for Antivirulence Therapy.

    Science.gov (United States)

    Defoirdt, Tom

    2018-04-01

    The development of novel therapies to control diseases caused by antibiotic-resistant pathogens is one of the major challenges we are currently facing. Many important plant, animal, and human pathogens regulate virulence by quorum sensing, bacterial cell-to-cell communication with small signal molecules. Consequently, a significant research effort is being undertaken to identify and use quorum-sensing-interfering agents in order to control diseases caused by these pathogens. In this review, an overview of our current knowledge of quorum-sensing systems of Gram-negative model pathogens is presented as well as the link with virulence of these pathogens, and recent advances and challenges in the development of quorum-sensing-interfering therapies are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Bacterial gangs: United and strong by means of quorum sensing

    DEFF Research Database (Denmark)

    Kuipers, Oscar P.; Kovács, Ákos T.

    2017-01-01

    Microorganisms can effectively communicate with each other. They share information about their community size (quorum), and thereby their nutrient requirement, then take appropriate action such as moving away. They use signalling molecules to coordinate their behaviour. These compounds, like...

  9. Quorum-based Data Replication in Grid Environment

    Directory of Open Access Journals (Sweden)

    Rohaya Latip

    2009-12-01

    Full Text Available Replication is a useful technique for distributed database systems and can be implemented in a grid computation environment to provide a high availability, fault tolerant, and enhance the performance of the system. This paper discusses a new protocol named Diagonal Data Replication in 2D Mesh structure (DR2M protocol where the performance addressed are data availability which is compared with the previous replication protocols, Read-One Write-All (ROWA, Voting (VT, Tree Quorum (TQ, Grid Configuration (GC, and Neighbor Replication on Grid (NRG. DR2M protocol is organized in a logical two dimensional mesh structure and by using quorums and voting techniques to improve the performance and availability of the replication protocol where it reduce the number of copies of data replication for read or write operations. The data file is copied at the selected node of the diagonal site in a quorum. The selection of a replica depends on the diagonal location of the structured two dimensional mesh quorum where the middle node is selected because it is the best location to get a copy of the data if every node has the equal number of request and data accessing in the network. The algorithm in this paper also calculates the best number of nodes in each quorum and how many quorums are needed for N number of nodes in a network. DR2M protocol also ensures that the data for read and write operations is consistency, by proofing the quorum must not have a nonempty intersection quorum. To evaluate DR2M protocol, we developed a simulation model in Java. Our results prove that DR2M protocol improves the performance of the data availability compare to the previous data replication protocol, ROWA, VT, TQ, GC and NRG.

  10. 39 CFR 6.6 - Quorum and voting.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Quorum and voting. 6.6 Section 6.6 Postal Service....6 Quorum and voting. As provided by 39 U.S.C. 205(c), the Board acts by resolution upon a majority... the compensation and benefits of the Postmaster General and Deputy Postmaster General, 39 U.S.C. 205(c...

  11. Macrolide resistance of Staphylococcus aureus and Haemophilus species associated with long-term azithromycin use in cystic fibrosis

    NARCIS (Netherlands)

    S.J. Phaff (Sonja); H.A.W.M. Tiddens (Harm); H.A. Verbrugh (Henri); A. Ott (Alewijn)

    2006-01-01

    textabstractOBJECTIVES: Azithromycin is used to modulate exuberant inflammatory response in patients with cystic fibrosis (CF). The purpose of this study was to determine the association between long-term use of azithromycin in CF patients and change over time in macrolide susceptibility of

  12. Pharmacokinetics of azithromycin in plasma, blood, polymorphonuclear neutrophils and sputum during long-term therapy in patients with cystic fibrosis

    NARCIS (Netherlands)

    Wilms, E B; Touw, D J; Heijerman, H G M

    Chronic therapy with the macrolide antibiotic azithromycin (AZM) is widely practiced in the treatment of patients with cystic fibrosis (CF) and chronic lung infection with Pseudomonas aeruginosa. Azithromycin dosage is variable, based on published studies, and not supported by pharmacokinetic data.

  13. Meta-Analysis of the Adverse Effects of Long-Term Azithromycin Use in Patients with Chronic Lung Diseases

    Science.gov (United States)

    Li, Hui; Liu, Ding-Hui; Chen, Lu-Lu; Zhao, Qi; Yu, Yan-Zhe; Ding, Jing-Jing; Miao, Li-Yun; Xiao, Yong-Long; Zhang, De-Ping; Guo, Yu-Biao; Xie, Can-Mao

    2014-01-01

    The adverse effects of azithromycin on the treatment of patients with chronic lung diseases (CLD) were evaluated in the present study. MEDLINE and other databases were searched for relevant articles published until August 2013. Randomized controlled trials that enrolled patients with chronic lung diseases who received long-term azithromycin treatment were selected, and data on microbiological studies and azithromycin-related adverse events were abstracted from articles and analyzed. Six studies were included in the meta-analysis. The risk of bacterial resistance in patients receiving long-term azithromycin treatment was increased 2.7-fold (risk ratio [RR], 2.69 [95% confidence interval {95% CI}, 1.249, 5.211]) compared with the risk in patients receiving placebo treatment. On the other hand, the risk of bacterial colonization decreased in patients receiving azithromycin treatment (RR, 0.551 [95% CI, 0.460, 0.658]). Patients receiving long-term azithromycin therapy were at risk of increased impairment of hearing (RR, 1.168 [95% CI, 1.030, 1.325]). This analysis provides evidence supporting the idea that bacterial resistance can develop with long-term azithromycin treatment. Besides the increasingly recognized anti-inflammatory role of azithromycin used in treating chronic lung diseases, we should be aware of the potential for adverse events with its long-term use. PMID:24189261

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

    Science.gov (United States)

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

    2015-01-01

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

  15. Self-sensing in Bacillus subtilis quorum-sensing systems.

    Science.gov (United States)

    Bareia, Tasneem; Pollak, Shaul; Eldar, Avigdor

    2018-01-01

    Bacterial cell-cell signalling, or quorum sensing, is characterized by the secretion and groupwide detection of small diffusible signal molecules called autoinducers. This mechanism allows cells to coordinate their behaviour in a density-dependent manner. A quorum-sensing cell may directly respond to the autoinducers it produces in a cell-autonomous and quorum-independent manner, but the strength of this self-sensing effect and its impact on bacterial physiology are unclear. Here, we explore the existence and impact of self-sensing in the Bacillus subtilis ComQXP and Rap-Phr quorum-sensing systems. By comparing the quorum-sensing response of autoinducer-secreting and non-secreting cells in co-culture, we find that secreting cells consistently show a stronger response than non-secreting cells. Combining genetic and quantitative analyses, we demonstrate this effect to be a direct result of self-sensing and rule out an indirect regulatory effect of the autoinducer production genes on response sensitivity. In addition, self-sensing in the ComQXP system affects persistence to antibiotic treatment. Together, these findings indicate the existence of self-sensing in the two most common designs of quorum-sensing systems of Gram-positive bacteria.

  16. Azithromycin protects mice against ischemic stroke injury by promoting macrophage transition towards M2 phenotype.

    Science.gov (United States)

    Amantea, Diana; Certo, Michelangelo; Petrelli, Francesco; Tassorelli, Cristina; Micieli, Giuseppe; Corasaniti, Maria Tiziana; Puccetti, Paolo; Fallarino, Francesca; Bagetta, Giacinto

    2016-01-01

    To develop novel and effective treatments for ischemic stroke, we investigated the neuroprotective effects of the macrolide antibiotic azithromycin in a mouse model system of transient middle cerebral artery occlusion. Intraperitoneal administration of azithromycin significantly reduced blood-brain barrier damage and cerebral infiltration of myeloid cells, including neutrophils and inflammatory macrophages. These effects resulted in a dose-dependent reduction of cerebral ischemic damage, and in a remarkable amelioration of neurological deficits up to 7 days after the insult. Neuroprotection was associated with increased arginase activity in peritoneal exudate cells, which was followed by the detection of Ym1- and arginase I-immunopositive M2 macrophages in the ischemic area at 24-48 h of reperfusion. Pharmacological inhibition of peritoneal arginase activity counteracted azithromycin-induced neuroprotection, pointing to a major role for drug-induced polarization of migratory macrophages towards a protective, non-inflammatory M2 phenotype. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Screening paediatric rectal forms of azithromycin as an alternative to oral or injectable treatment

    Science.gov (United States)

    Kauss, Tina; Gaudin, Karen; Gaubert, Alexandra; Ba, Boubakar; Tagliaferri, Serena; Fawaz, Fawaz; Fabre, Jean-Louis; Boiron, Jean-Michel; Lafarge, Xavier; White, Nicholas J.; Olliaro, Piero L.; Millet, Pascal

    2012-01-01

    The aim of this study was to identify a candidate formulation for further development of a home or near-home administrable paediatric rectal form of a broad-spectrum antibiotic – specially intended for (emergency) use in tropical rural settings, in particular for children who cannot take medications orally and far from health facilities where injectable treatments can be given. Azithromycin, a broad-spectrum macrolide used orally or intravenously for the treatment of respiratory tract, skin and soft tissue infections, was selected because of its pharmacokinetic and therapeutic properties. Azithromycin in vitro solubility and stability in physiologically relevant conditions were studied. Various pharmaceutical forms, i.e. rectal suspension, two different rectal gels, polyethylene glycol (PEG) suppository and hard gelatin capsule (HGC) were assessed for in vitro dissolution and in vivo bioavailability in the rabbit. Azithromycin PEG suppository appears to be a promising candidate. PMID:22868232

  18. A comparative study of single-dose treatment of chancroid using thiamphenicol versus Azithromycin

    Directory of Open Access Journals (Sweden)

    Walter B. Junior

    Full Text Available A study was conducted in São Paulo, Brazil, to compare azithromycin with thiamphenicol for the single-dose treatment of chancroid. In all, 54 men with chancroid were tested. The etiology was determined by clinical characterization and direct bacterioscopy with Gram staining. None of the patients had positive serology or dark-field examination indicating active infection with Treponema pallidum. Genital infections due to Neisseria gonorrhoeae and herpes simplex virus were excluded by polymerase chain reaction testing. For 54 patients with chancroid, cure rates with single-dose treatment were 73% with azithromycin and 89% with thiamphenicol. HIV seropositivity was found to be associated with treatment failure (p=0.001. The treatment failed in all HIV positive patients treated with azithromycin (p=0.002 and this drug should be avoided in these co-infected patients. In the view of the authors, thiamphenicol is the most indicated single-dose regimen for chancroid treatment.

  19. Molecular Basis of Azithromycin-Resistant Pseudomonas aeruginosa Biofilms†

    Science.gov (United States)

    Gillis, Richard J.; White, Kimberly G.; Choi, Kyoung-Hee; Wagner, Victoria E.; Schweizer, Herbert P.; Iglewski, Barbara H.

    2005-01-01

    Pseudomonas aeruginosa biofilms are extremely recalcitrant to antibiotic treatment. Treatment of cystic fibrosis patients with azithromycin (AZM) has shown promise. We used DNA microarrays to identify differentially expressed transcripts in developing P. aeruginosa biofilms exposed to 2 μg/ml AZM. We report that transcripts for multiple restriction-nodulation-cell division (RND) efflux pumps, known to be involved in planktonic antibiotic resistance, and transcripts involved in type III secretion were upregulated in the resistant biofilms that developed in the presence of AZM. Interestingly, the MexAB-OprM and MexCD-OprJ efflux pumps, but not type III secretion, appear to be integral to biofilm formation in the presence of AZM, as evidenced by the fact that a mutant deleted in both mexAB-oprM and mexCD-oprJ was unable to form a biofilm in the presence of AZM. A mutant deleted in type III secretion was still able to form biofilms in the presence of drug. Furthermore, single mexAB-oprM- and mexCD-oprJ-null mutants were able to form a biofilm in the presence of drug, indicating that either of the pumps can confer resistance to AZM during biofilm development. In contrast to planktonically grown cells, where no mexC expression was detectable regardless of the presence of AZM, biofilms exhibited induction of mexC expression from the outset of their formation, but only in the presence of AZM. mexA, which is constitutively expressed in planktonic cells, was uniformly expressed in biofilms regardless of the presence of AZM. These data indicate that the MexCD-OprJ pump acts as a biofilm-specific mechanism for AZM resistance. PMID:16127063

  20. Azithromycin for episodes with asthma-like symptoms in young children aged 1-3 years: a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Stokholm, Jakob; Chawes, Bo L; Vissing, Nadja H; Bjarnadóttir, Elín; Pedersen, Tine M; Vinding, Rebecca K; Schoos, Ann-Marie M; Wolsk, Helene M; Thorsteinsdóttir, Sunna; Hallas, Henrik W; Arianto, Lambang; Schjørring, Susanne; Krogfelt, Karen A; Fischer, Thea K; Pipper, Christian B; Bønnelykke, Klaus; Bisgaard, Hans

    2016-01-01

    Bacteria and viruses are equally associated with the risk of acute episodes of asthma-like symptoms in young children, suggesting antibiotics as a potential treatment for such episodes. We aimed to assess the effect of azithromycin on the duration of respiratory episodes in young children with recurrent asthma-like symptoms, hypothesising that it reduces the duration of the symptomatic period. In this randomised, double-blind, placebo-controlled trial, we recruited children aged 1-3 years, who were diagnosed with recurrent asthma-like symptoms from the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort; a birth cohort consisting of the general Danish population of Zealand, including Copenhagen. Exclusion criteria were macrolide allergy, heart, liver, neurological, and kidney disease, and, before each treatment, one or more clinical signs of pneumonia (respiratory frequency of ≥50 breaths per min; fever of ≥39°C; C-reactive protein concentration of ≥476·20 nmol/L [≥50 mg/L]). Each episode of asthma-like symptoms lasting at least 3 days was randomly allocated to a 3-day course of azithromycin oral solution of 10 mg/kg per day or placebo after thorough examination by a study physician at the Copenhagen Prospective Studies on Asthma research unit. Each episode was randomly allocated independently of previous treatment from a computer-generated list of random numbers in blocks of ten (generated at the Pharmacy of Glostrup). Investigators and children were masked until the youngest child turned 3 years of age and throughout the data validation and analysis phases. The primary outcome was duration of the respiratory episode after treatment, verified by prospective daily diaries and analysed with Poisson regression. Analyses were per protocol (excluding those without a primary outcome measure or who did not receive treatment). This trial is registered with ClinicalTrials.gov, number NCT01233297. Between Nov 17, 2010, and Jan 28, 2014, we randomly

  1. Effects of oral florfenicol and azithromycin on gut microbiota and adipogenesis in mice.

    Science.gov (United States)

    Li, Rui; Wang, Hexing; Shi, Qingfeng; Wang, Na; Zhang, Zhijie; Xiong, Chenglong; Liu, Jianxiang; Chen, Yue; Jiang, Lufang; Jiang, Qingwu

    2017-01-01

    Certain antibiotics detected in urine are associated with childhood obesity. In the current experimental study, we investigated two representative antibiotics detected in urine, florfenicol and azithromycin, for their early effects on adipogenesis, gut microbiota, short-chain fatty acids (SCFAs), and bile acids in mice. Thirty C57BL/6 mice aged four weeks were randomly divided into three groups (florfenicol, azithromycin and control). The two experimental groups were administered florfenicol or azithromycin at 5 mg/kg/day for four weeks. Body weight was measured weekly. The composition of the gut microbiota, body fat, SCFAs, and bile acids in colon contents were measured at the end of the experiment. The composition of the gut microbiota was determined by sequencing the bacterial 16S rRNA gene. The concentration of SCFAs and bile acids was determined using gas chromatography and liquid chromatography coupled to tandem mass spectrometry, respectively. The composition of the gut microbiota indicated that the two antibiotics altered the gut microbiota composition and decreased its richness and diversity. At the phylum level, the ratio of Firmicutes/Bacteroidetes increased significantly in the antibiotic groups. At the genus level, there were declines in Christensenella, Gordonibacter and Anaerotruncus in the florfenicol group, in Lactobacillus in the azithromycin group, and in Alistipes, Desulfovibrio, Parasutterella and Rikenella in both the antibiotic groups. The decrease in Rikenella in the azithromycin group was particularly noticeable. The concentration of SCFAs and secondary bile acids decreased in the colon, but the concentration of primary bile acids increased. These findings indicated that florfenicol and azithromycin increased adipogenesis and altered gut microbiota composition, SCFA production, and bile acid metabolism, suggesting that exposure to antibiotics might be one risk factor for childhood obesity. More studies are needed to investigate the specific

  2. Effects of oral florfenicol and azithromycin on gut microbiota and adipogenesis in mice.

    Directory of Open Access Journals (Sweden)

    Rui Li

    Full Text Available Certain antibiotics detected in urine are associated with childhood obesity. In the current experimental study, we investigated two representative antibiotics detected in urine, florfenicol and azithromycin, for their early effects on adipogenesis, gut microbiota, short-chain fatty acids (SCFAs, and bile acids in mice. Thirty C57BL/6 mice aged four weeks were randomly divided into three groups (florfenicol, azithromycin and control. The two experimental groups were administered florfenicol or azithromycin at 5 mg/kg/day for four weeks. Body weight was measured weekly. The composition of the gut microbiota, body fat, SCFAs, and bile acids in colon contents were measured at the end of the experiment. The composition of the gut microbiota was determined by sequencing the bacterial 16S rRNA gene. The concentration of SCFAs and bile acids was determined using gas chromatography and liquid chromatography coupled to tandem mass spectrometry, respectively. The composition of the gut microbiota indicated that the two antibiotics altered the gut microbiota composition and decreased its richness and diversity. At the phylum level, the ratio of Firmicutes/Bacteroidetes increased significantly in the antibiotic groups. At the genus level, there were declines in Christensenella, Gordonibacter and Anaerotruncus in the florfenicol group, in Lactobacillus in the azithromycin group, and in Alistipes, Desulfovibrio, Parasutterella and Rikenella in both the antibiotic groups. The decrease in Rikenella in the azithromycin group was particularly noticeable. The concentration of SCFAs and secondary bile acids decreased in the colon, but the concentration of primary bile acids increased. These findings indicated that florfenicol and azithromycin increased adipogenesis and altered gut microbiota composition, SCFA production, and bile acid metabolism, suggesting that exposure to antibiotics might be one risk factor for childhood obesity. More studies are needed to

  3. Azithromycin is not associated with QT prolongation in hospitalized patients with community-acquired pneumonia.

    Science.gov (United States)

    Goldstein, Lee Hilary; Gabin, Ahmad; Fawaz, Abdallah; Freedberg, Nahum Adam; Schwartz, Naama; Elias, Mazen; Saliba, Walid

    2015-10-01

    Large data-based studies have reported excess cardiovascular mortality in high-risk patients treated with azithromycin, but whether or not azithromycin causes QT prolongation remains controversial. The purpose of this study was to examine the association of azithromycin treatment on QT prolongation in a cohort of patients hospitalized with community-acquired pneumonia (CAP) METHODS: One-hundred twenty-two hospitalized patients with CAP were enrolled in the study. We compared the baseline QTc, with daily post antibiotic QTc. Other risk factors for QT prolongation such as medication or electrolyte abnormalities were recorded. Ninety (73.8%) patients were treated with azithromycin (usually in combination with ceftriaxone), and 32 (26.2%) patients with other antibiotics (ampicillin-clavulanate, chloramphenicol, doxcycline, or ceftriaxone); 72.1% (88) of the cohort experienced QT lengthening; 72.7% with QT lengthening had a normal baseline QTc. Azithromycin was not associated with the post-antibiotic QTc. Wide (pathological) post-antibiotic QTc was associated with the pneumonia score. Every 10-point increase in the pneumonia score raised the risk for a pathological post antibiotic QTc by 1.249 (95%CI: 1.050-1.486). Analysis of patients with non-pathological baseline QTc revealed that pathological post-antibiotic QTc was only associated with previous stroke and not with the type of antibiotic. Azithromycin treatment was not associated with QT prolongation in patients with severe CAP. Nonetheless, in a large majority of hospitalized CAP patients, QT prolongation and pathological QTc develop regardless of the antibiotic used, especially in patients with previous stroke or a higher pneumonia score. Copyright © 2015 John Wiley & Sons, Ltd.

  4. Quorum Sensing in Marine Microbial Environments

    Science.gov (United States)

    Hmelo, Laura R.

    2017-01-01

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

  5. Mutations in 23S rRNA confer resistance against azithromycin in Pseudomonas aeruginosa.

    Science.gov (United States)

    Marvig, Rasmus Lykke; Søndergaard, Mette S R; Damkiær, Søren; Høiby, Niels; Johansen, Helle Krogh; Molin, Søren; Jelsbak, Lars

    2012-08-01

    The emergence of antibiotic-resistant Pseudomonas aeruginosa is an important concern in the treatment of long-term airway infections in cystic fibrosis patients. In this study, we report the occurrence of azithromycin resistance among clinical P. aeruginosa DK2 isolates. We demonstrate that resistance is associated with specific mutations (A2058G, A2059G, and C2611T in Escherichia coli numbering) in domain V of 23S rRNA and that introduction of A2058G and C2611T into strain PAO1 results in azithromycin resistance.

  6. Childhood Mortality in a Cohort Treated With Mass Azithromycin for Trachoma

    Science.gov (United States)

    Ayele, Berhan; Gebre, Teshome; Zerihun, Mulat; Zhou, Zhaoxia; House, Jenafir I.; Gaynor, Bruce D.; Porco, Travis C.; Emerson, Paul M.; Lietman, Thomas M.

    2011-01-01

    Background. Mass azithromycin distributions are used to clear ocular strains of chlamydia that cause trachoma, but treatments may also affect respiratory infections, diarrhea, and malaria. Here, we monitor a large cohort in which almost 90% of individuals received azithromycin. We assess whether receiving treatment is associated with reduced all-cause and infectious childhood mortality. Methods. As part of a clinical trial for trachoma, a census was conducted in 24 communities in rural Ethiopia. All individuals ≥1 year of age were eligible for single-dose oral azithromycin, although antibiotic coverage was not universal. A follow-up census was performed 26 months after treatment to estimate all-cause mortality among children 1–5 years of age, and verbal autopsies were performed to identify infectious mortality. Results. The cohort included 35,052 individuals ≥1 year of age and 5507 children 1–5 years of age, of whom 4914 received a dose of azithromycin. All-cause mortality was significantly lower among those 1–5-year-old children who received azithromycin (odds ratio [OR] = 0.35 [95% confidence interval {CI}, 0.17–0.74]), as was infectious mortality (OR = 0.20 [95% CI, 0.07–0.58]). When individuals were compared only with members of the same household, azithromycin treatment was still associated with reduced all-cause mortality in children 1–5 years of age (OR = 0.40 [95% CI, 0.16–0.96]), although this relationship was not statistically significant for infectious mortality (OR = 0.35 [95% CI, 0.10–1.28]). Conclusions. This study demonstrated an association between mass oral azithromycin treatment and reduced all-cause and infectious childhood mortality. This relationship could not be attributed to bias at the level of the household. Mass azithromycin distributions may have benefits unrelated to trachoma. PMID:21427395

  7. Association of azithromycin with mortality and cardiovascular events among older patients hospitalized with pneumonia

    Science.gov (United States)

    Mortensen, Eric M.; Halm, Ethan A.; Pugh, Mary Jo; Copeland, Laurel A.; Metersky, Mark; Fine, Michael J.; Johnson, Christopher S.; Alvarez, Carlos A.; Frei, Christopher R.; Good, Chester; Restrepo, Marcos I.; Downs, John R.; Anzueto, Antonio

    2014-01-01

    Importance Although clinical practice guidelines recommend combination therapy with macrolides, including azithromycin, as first line therapy for patients hospitalized with pneumonia, recent research suggests that azithromycin may be associated with increased cardiovascular events. Objective The purpose of this study was to examine the association of azithromycin use with all-cause mortality and cardiovascular events for patients hospitalized with pneumonia. Design Retrospective, cohort study comparing older patients hospitalized with pneumonia between fiscal years 2002–2012 prescribed azithromycin therapy and patients receiving other guideline-concordant antibiotic therapy Setting This study was conducted using national Department of Veterans Affairs administrative data of patients hospitalized at any Veterans Administration acute care hospital. Participants Patients were included if they were ≥65 years of age hospitalized with pneumonia and received antibiotic therapy concordant with national clinical practice guidelines. Main Outcome Measures Outcomes included 30 and 90-day all-cause mortality, and 90-day cardiac arrhythmias, heart failure, myocardial infarction, and any cardiac event. Propensity score matching was used to control for the possible effects of known confounders with conditional logistic regression. Results Out of the 73,690 patients from 118 hospitals identified, propensity-matched groups were composed of 31,863 azithromycin-exposed and 31,863 matched unexposed. There were no significant differences in potential confounders between groups after matching. 90-day mortality was significantly lower in those who received azithromycin (exposed- 17.4% vs. unexposed- 22.3%, odds ratio [OR] 0.73, 95% confidence interval [CI] 0.70–0.76). However, we found significant increased odds of myocardial infarctions (5.1% vs. 4.4%, OR 1.17, 95% CI 1.08–1.25) but not any cardiac event (43.0% vs. 42.7%, OR 1.01, 95% CI 0.98–1.05), cardiac arrhythmias (25

  8. Mutations in 23S rRNA Confer Resistance against Azithromycin in Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Marvig, Rasmus Lykke; Søndergaard, Mette S. R.; Pedersen, Søren Damkiær

    2012-01-01

    The emergence of antibiotic-resistant Pseudomonas aeruginosa is an important concern in the treatment of long-term airway infections in cystic fibrosis patients. In this study, we report the occurrence of azithromycin resistance among clinical P. aeruginosa DK2 isolates. We demonstrate...... that resistance is associated with specific mutations (A2058G, A2059G, and C2611T in Escherichia coli numbering) in domain V of 23S rRNA and that introduction of A2058G and C2611T into strain PAO1 results in azithromycin resistance....

  9. Multidrug-resistant Neisseria gonorrhoeae infection with ceftriaxone resistance and intermediate resistance to azithromycin, Denmark, 2017

    DEFF Research Database (Denmark)

    Terkelsen, David; Tolstrup, Jacob; Johnsen, Camilla Hundahl

    2017-01-01

    We describe a multidrug-resistant Neisseria gonorrhoeae infection with ceftriaxone resistance and azithromycin intermediate resistance in a heterosexual man in Denmark, 2017. Whole genome sequencing of the strain GK124 identified MSLT ST1903, NG-MAST ST1614 and all relevant resistance determinants...... including similar penA resistance mutations previously described in ceftriaxone-resistant gonococcal strains. Although treatment with ceftriaxone 0.5 g plus azithromycin 2 g was successful, increased awareness of spread of gonococcal strains threatening the recommended dual therapy is crucial....

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

    Science.gov (United States)

    Gökalsın, Barış; Sesal, Nüzhet Cenk

    2016-09-01

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

  11. Effects of food on a gastrically degraded drug: azithromycin fast-dissolving gelatin capsules and HPMC capsules.

    Science.gov (United States)

    Curatolo, William; Liu, Ping; Johnson, Barbara A; Hausberger, Angela; Quan, Ernest; Vendola, Thomas; Vatsaraj, Neha; Foulds, George; Vincent, John; Chandra, Richa

    2011-07-01

    Commercial azithromycin gelatin capsules (Zithromax®) are known to be bioequivalent to commercial azithromycin tablets (Zithromax®) when dosed in the fasted state. These capsules exhibit a reduced bioavailability when dosed in the fed state, while tablets do not. This gelatin capsule negative food effect was previously proposed to be due to slow and/or delayed capsule disintegration in the fed stomach, resulting in extended exposure of the drug to gastric acid, leading to degradation to des-cladinose-azithromycin (DCA). Azithromycin gelatin capsules were formulated with "superdisintegrants" to provide fast-dissolving capsules, and HPMC capsule shells were substituted for gelatin capsule shells, in an effort to eliminate the food effect. Healthy volunteers were dosed with these dosage forms under fasted and fed conditions; pharmacokinetics were evaluated. DCA pharmacokinetics were also evaluated for the HPMC capsule subjects. In vitro disintegration of azithromycin HPMC capsules in media containing food was evaluated and compared with commercial tablets and commercial gelatin capsules. When the two fast-dissolving capsule formulations were dosed to fed subjects, the azithromycin AUC was 38.9% and 52.1% lower than after fasted-state dosing. When HPMC capsules were dosed to fed subjects, the azithromycin AUC was 65.5% lower than after fasted-state dosing. For HPMC capsules, the absolute fasting-state to fed-state decrease in azithromycin AUC (on a molar basis) was similar to the increase in DCA AUC. In vitro capsule disintegration studies revealed extended disintegration times for commercial azithromycin gelatin capsules and HPMC capsules in media containing the liquid foods milk and Ensure®. Interaction of azithromycin gelatin and HPMC capsules with food results in slowed disintegration in vitro and decreased bioavailability in vivo. Concurrent measurement of serum azithromycin and the acid-degradation product DCA demonstrates that the loss of azithromycin

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

    Science.gov (United States)

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

    2015-01-01

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

  13. Methods for Measuring the Production of Quorum Sensing Signal Molecules.

    Science.gov (United States)

    Alcalde-Rico, Manuel; Martínez, José Luis

    2018-01-01

    One relevant aspect for understanding the bottlenecks that modulate the spread of resistance among bacterial pathogens consists in the effect that the acquisition of resistance may have on the microbial physiology . Whereas studies on the effect of acquiring resistance of bacterial growth are frequently performed, more detailed analyses aiming to understand in depth the cross talk between resistance and virulence, including bacterial communication are less frequent. The bacterial quorum sensing system, is an important intraspecific and interspecific communication system highly relevant for many physiological processes, including virulence and bacterial/host interactions. Some works have shown that the acquisition of antibiotic resistance may impair the quorum sensing response. In addition, some antibiotics as antimicrobial peptides can affect the production and accumulation of the quorum sensing signal molecules. Given the relevance that this system has in the bacterial behavior in the human host, it is important to study the effect that the acquisition of antibiotic resistance may have on the production of quorum sensing signals. In this chapter we present a set of methods for measuring quorum sensing signals based on the use of biosensor strains, either coupled to Thin Layer Chromatography or for performing automated luminometry/spectrophotometry assays. We use Pseudomonas aeruginosa as bacterial model because it has a complex quorum system than encloses different signals. Namely, P. aeruginosa quorum sensing system consists in three different interconnected regulatory networks, each one presenting a specific autoinducer molecule: the las system, which signal is N-(3-oxo-dodecanoyl)-L-homoserine lactone, the rhl system, which signal is N-butanoyl-homoserine lactone and the pqs system, which signals are 2-heptyl-3-hydroxy-4(1H)-quinolone together with its immediate precursor 2-heptyl-4-hydroxy-quinoline.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    R, and a quorum-sensing receptor agonist. Six top-ranking compounds, all recognized drugs, were identified and tested for quorum-sensing-inhibitory activity. Three compounds, salicylic acid, nifuroxazide, and chlorzoxazone, showed significant inhibition of quorum-sensing-regulated gene expression and related...

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

    Science.gov (United States)

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

    2016-04-01

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

  16. Azithromycin Resistance and Decreased Ceftriaxone Susceptibility in Neisseria gonorrhoeae, Hawaii, USA.

    Science.gov (United States)

    Papp, John R; Abrams, A Jeanine; Nash, Evelyn; Katz, Alan R; Kirkcaldy, Robert D; O'Connor, Norman P; O'Brien, Pamela S; Harauchi, Derek H; Maningas, Eloisa V; Soge, Olusegun O; Kersh, Ellen N; Komeya, Alan; Tomas, Juval E; Wasserman, Glenn M; Kunimoto, Gail Y; Trees, David L; Whelen, A Christian

    2017-05-01

    During 2016, eight Neisseria gonorrhoeae isolates from 7 patients in Hawaii were resistant to azithromycin; 5 had decreased in vitro susceptibility to ceftriaxone. Genomic analysis demonstrated a distinct phylogenetic clade when compared with local contemporary strains. Continued evolution and widespread transmission of these strains might challenge the effectiveness of current therapeutic options.

  17. A meta-analysis of the efficacy of azithromycin and benzathine ...

    African Journals Online (AJOL)

    Purpose: To systematically analyze the efficacy of azithromycin and benzathine penicillin in early syphilis, and provide guidance for diagnosis and treatment. Methods: Databases were searched for randomized controlled trials (RCTs) and control studies according to keywords, and inclusion and exclusion criteria. Related ...

  18. Encapsulation of azithromycin into polymeric microspheres by reduced pressure-solvent evaporation method

    DEFF Research Database (Denmark)

    Li, Xiujuan; Chang, Si; Du, Guangsheng

    2012-01-01

    Azithromycin loaded microspheres with blends of poly-l-lactide and ploy-D,L-lactide-co-glycolide as matrices were prepared by the atmosphere-solvent evaporation (ASE) and reduced pressure-solvent evaporation (RSE) method. Both the X-ray diffraction spectra and DSC thermographs demonstrated...

  19. Treatment of adenotonsillar hypertrophy: A prospective randomized trial comparing azithromycin vs. fluticasone

    Directory of Open Access Journals (Sweden)

    Seyed Mostafa Hashemi Jazi

    2011-01-01

    Conclusions: It could explain that though both of the improved and mentioned symptoms comparing within initial status, Azithromycin seems to be more effective than fluticasone in improving AH-related symptoms. Short term efficacy of the antibiotic is much significant than its long term effect.

  20. Antimicrobial susceptibility to azithromycin among Salmonella enterica isolated from the United States

    Science.gov (United States)

    Due to emerging resistance to traditional antimicrobial agents such as ampicillin, trimethoprim-sulfamethoxazole and chloramphenicol, azithromycin is increasingly used for the treatment of invasive Salmonella infections. In the present study, 696 isolates of non-Typhi Salmonella collected from human...

  1. Azithromycin as an adjunct to non-surgical periodontal therapy: a systematic review.

    Science.gov (United States)

    O'Rourke, V J

    2017-03-01

    The aim of this study was to investigate the current published work relating to the clinical benefits of the use of systemic azithromycin as an adjunct to non-surgical periodontal therapy. A published work search of PubMed, EMBASE and Cochrane Register of Controlled Trials up to 27 April 2016 was undertaken. The large degree of heterogeneity in the types of studies, treatment protocols, test subjects, sample size and exclusion criteria indicated that the use of narrative synthesis of all relevant studies was a valid method of review. Of the 194 eligible studies, 15 were found to be of relevance. The majority of studies demonstrated an additional clinical benefit when azithromycin is used as an adjunct to non-surgical periodontal therapy, particularly in deeper pockets (≥6 mm). In conclusion, the current body of research on the adjunctive use of systemic azithromycin in non-surgical periodontal therapy suggests there is a clinical benefit and that this benefit is greatest in deeper initial pockets (≥6 mm). The findings also suggest that future studies need to be more careful in subject selection to identify susceptible patients or at risk sites, both the immunoregulatory effects and antibiotic resistance of azithromycin needs to be reported, and that study populations need to be more homogeneous. © 2016 Australian Dental Association.

  2. Azithromycin in Chronic Fatigue Syndrome (CFS, an analysis of clinical data

    Directory of Open Access Journals (Sweden)

    Scholte Hans R

    2006-08-01

    Full Text Available Abstract Background CFS is a clinical state with defined symptoms, but undefined cause. The patients may show a chronic state of immune activation and treatment with an antibiotic in this subgroup has been suggested. Methods In a retrospective study, the response of CFS patients to azithromycin, an antibiotic and immunomodulating drug, has been scored from the patients records and compared with clinical and laboratory data. Azithromycin was not the first choice therapy, but offered when the effect of counseling and L-carnitine was considered insufficient by the patient and the clinician. Results Of the 99 patients investigated, 58 reported a decrease in the symptoms by the use of azithromycin. These responding patients had lower levels of plasma acetylcarnitine. Conclusion The efficacy of azithromycin in the responsive patients could be explained by the modulating effect on a chronic primed state of the immune cells of the brain, or the activated peripheral immune system. Their lower acetylcarnitine levels may reflect a decreased antioxidant defense and/or an increased consumption of acetylcarnitine caused by oxidative stress.

  3. Medical Management of Cyclosporine-Induced Gingival Overgrowth Using Oral Azithromycin in Six Dogs

    Directory of Open Access Journals (Sweden)

    Alison Diesel

    2015-02-01

    Full Text Available Gingival overgrowth is an uncommon adverse effect of cyclosporine administration in veterinary species. In people, gingival overgrowth is a common complication of cyclosporine administration for immunosuppression, generally following transplant procedures. Azithromycin has been used successfully for managing gingival overgrowth in human transplant patients when cyclosporine administration cannot be reduced or discontinued. This case series describes six dogs being administered cyclosporine for various dermatologic diseases that developed gingival overgrowth. The dogs were prescribed systemic azithromycin, with or without concurrent dose reduction of cyclosporine. Oral administration of 6.6–10.8 mg/kg of azithromycin once daily for 4–14 weeks was effective for complete clinical resolution of gingival overgrowth. In most cases, gingival overgrowth did not recur even with continued cyclosporine administration long-term. Adverse events of long-term azithromycin administration did not occur in any of the dogs. This series highlights a potentially beneficial medical treatment option for gingival overgrowth even when cyclosporine dose reduction is not possible or elected, without the need for surgical resection of proliferative gingival tissue.

  4. Creatinine-based non-phospholipid vesicular carrier for improved oral bioavailability of Azithromycin.

    Science.gov (United States)

    Ullah, Shafi; Shah, Muhammad Raza; Shoaib, Mohammad; Imran, Muhammad; Shah, Syed Wadood Ali; Ali, Imdad; Ahmed, Farid

    2017-06-01

    Novel, safe, efficient and cost effective nano-carriers from renewable resources have got greater interest for enhancing solubility and bioavailability of hydrophobic dugs. This study reports the synthesis of a novel biocompatible non-phospholipid human metabolite "Creatinine" based niosomal delivery system for Azithromycin improved oral bioavailability. Synthesized surfactant was characterized through spectroscopic and spectrometric techniques and then the potential for niosomal vesicle formation was evaluated using Azithromycin as model drug. Drug loaded vesicles were characterized for size, polydispersity index (PDI), shape, drug encapsulation efficiency (EE), in vitro release and drug-excipient interaction using zetasizer, atomic force microscope (AFM), LC-MS/MS and FTIR. The biocompatibility of surfactant was investigated through cells cytotoxicity, blood hemolysis and acute toxicity. Azithromycin encapsulated in niosomes was investigated for in vivo bioavailability in rabbits. The vesicles were spherical with 247 ± 4.67 nm diameter hosting 73.29 ± 3.51% of the drug. Surfactant was nontoxic against cell cultures and caused 5.80 ± 0.51% hemolysis at 1000 µg/mL. It was also found safe in mice up to 2.5 g/kg body weight. Synthesized surfactant based niosomal vesicles revealed enhanced oral bioavailability of Azithromycin in rabbits. The results of the present study confirm that the novel surfactant is highly biocompatible and the niosomal vesicles can be efficiently used for improving the oral bioavailability of poor water soluble drugs.

  5. Effect of azithromycin on acid reflux, hiatus hernia and proximal acid pocket in the postprandial period

    NARCIS (Netherlands)

    Rohof, W. O.; Bennink, R. J.; de Ruigh, A. A.; Hirsch, D. P.; Zwinderman, A. H.; Boeckxstaens, G. E.

    2012-01-01

    Background The risk for acidic reflux is mainly determined by the position of the gastric acid pocket. It was hypothesised that compounds affecting proximal stomach tone might reduce gastro-oesophageal reflux by changing the acid pocket position. Objective To study the effect of azithromycin (Azi)

  6. Azithromycin 1.5% ophthalmic solution: efficacy and treatment modalities in chronic blepharitis

    Directory of Open Access Journals (Sweden)

    Ali Fadlallah

    2012-06-01

    Full Text Available PURPOSE: To assess the efficacy of topical 1.5% azithromycin in the treatment of moderate to severe chronic blepharitis and to compare the efficacy of two different treatment modalities. METHODS: A randomized clinical trial included 67 patients with chronic anterior and/or posterior blepharitis, followed-up for 3 months. Signs and symptoms were graded according to severity. Patients were randomized into two groups: 33 patients in group I and 34 patients in group II. Group I patients were treated with topical 1.5% azithromycin twice a day for three days, and Group II patients were treated with topical 1.5% azithromycin twice a day for three days then at bedtime for the rest of the month. All patients were instructed to apply warm compresses and an eye-friendly soap twice daily. RESULTS: Patients in both groups tolerated the treatment with minimal irritation. A significant improvement in signs and symptoms was noted at the one week follow-up visit. Group II showed a more pronounced and longer-lasting improvement that persisted after three months of follow-up. CONCLUSION: Topical 1.5% azithromycin ophthalmic solution is an effective treatment option for chronic blepharitis. In moderate to severe blepharitis, a one month treatment is safe and shows better improvement than the three-day protocol with no significant relapse until three months of follow-up.

  7. Role of quorum sensing in Sinorhizobium meliloti-Alfalfa symbiosis.

    Science.gov (United States)

    Gurich, Nataliya; González, Juan E

    2009-07-01

    The ExpR/Sin quorum-sensing system of the gram-negative soil bacterium Sinorhizobium meliloti plays an important role in the establishment of symbiosis with its host plant Medicago sativa. A mutant unable to produce autoinducer signal molecules (sinI) is deficient in its ability to invade the host, but paradoxically, a strain lacking the quorum-sensing transcriptional regulator ExpR is as efficient as the wild type. We compared the whole-genome expression profile of the wild-type strain with strains missing one of the quorum-sensing regulatory components to identify genes controlled by the ExpR/Sin system throughout the different phases of the bacterial growth cycle, as well as in planta. Our analyses revealed that ExpR is a highly versatile regulator with a unique ability to show different regulatory capabilities in the presence or absence of an autoinducer. In addition, this study provided us with insight into the plant invasion defect displayed by the autoinducer mutant. We also discovered that the ExpR/Sin quorum-sensing system is repressed after plant invasion. Therefore, quorum sensing plays a crucial role in the regulation of many cell functions that ensures the successful invasion of the host and is inactivated once symbiosis is established.

  8. ANTI-QUORUM SENSING ACTIVITY OF SOME MEDICINAL PLANTS.

    Science.gov (United States)

    Al-Haidari, Rwaida A; Shaaban, Mona I; Ibrahim, Sabrin R M; Mohamed, Gamal A

    2016-01-01

    Quorum sensing is the key regulator of virulence factors of Pseudomonas aeruginosa such as biofilm formation, motility, productions of proteases, hemolysin, pyocyanin, and toxins. The aim of this study was to explore the effect of the extracts from some medicinal plants on quorum sensing and related virulence factors of P. aeruginosa . Quorum sensing inhibitory (OSI) effect of the alcohol extracts of 20 medicinal plants was evaluated by Chromobacterium violaceum reporter using agar cup diffusion method. The efficient QSI extracts were tested for their activity against biofilm synthesis, motility, and synthesis of pyocyanin from P. aeruginosa PA14. The extracts of Citrus sinensis, Laurus nobilis, Elettaria cardamomum, Allium cepa , and Coriandrum sativum exhibited potent quorum quenching effect. On the other hand, Psidium guajava and Mentha longifolia extracts showed lower QSI activity. These extracts exhibited significant elimination of pyocyanin formation and biofilm development of Pseudomonas aeruginosa PA14. In addition, they significantly inhibited twitching and swimming motilities of P. aeruginosa PA14. This study illustrated, for the first time, the importance of C. sinensis, L. nobilis, E. cardamomum, A. cepa , and C. sativum as quorum sensing inhibitors and virulence suppressors of P. aeruginosa . Thus, these plants could provide a natural source for the elimination of Pseudomonas pathogenesis.

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

    Science.gov (United States)

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

    2015-05-01

    Bacterial phenotypes, such as biofilm formation, antibiotic resistance and virulence expression, are associated with quorum sensing. Quorum sensing is a density-dependent regulatory system of gene expression controlled by specific signal molecules, such as N-acyl homoserine lactones (AHLs), produced and released by bacteria. This study reports the development of linear polymers capable to attenuate quorum sensing by adsorption of AHLs. Linear polymers were synthesized using MMA as backbone monomer and methacrylic acid and itaconic acid as functional monomers. Two different quorum sensing-controlled phenotypes, Vibrio fischeri bioluminescence and Aeromonas hydrophila biofilm formation, were evaluated to test the polymers' efficiency. Results showed that both phenotypes were significantly affected by the polymers, with the itaconic acid-containing material being more effective than the methacrylic acid one. The polymer inhibitory effects were reverted by the addition of lactones, confirming attenuation of quorum sensing through sequestration of signal molecules. The polymers also showed no cytotoxicity when tested using a mammalian cell line. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. RND efflux pump and its interrelationship with quorum sensing system.

    Science.gov (United States)

    Liang, Zhi-bin; Chen, Yu-mei; Chen, Yu-fan; Cheng, Ying-ying; Zhang, Lian-hui

    2016-10-20

    Antibiotic resistance has become a serious concern in treatment of bacterial infections. Overexpression of efflux pump is one of the important mechanisms in antibiotic resistance. In Gram negative bacteria, RND (Resistance-nodulation-cell division) superfamily efflux pump plays a vital important role in antibiotics resistance. Recent research progress unveils an intriguing interrelationship between RND efflux pump and the bacterial quorum sensing system, whose regulation is dependent on small signal molecules. This article reviews the latest findings on the structure and transport mechanism of RND efflux pump, as well as the general features and regulatory mechanisms of quorum sensing, with a special focus on the role and mechanism of quorum sensing system in regulation of RND efflux pump, and the influence of efflux pump on quorum sensing signal transportation. Further investigation of the interrelationship between RND efflux pumps and the bacterial quorum sensing systems is critical for elucidation of the regulatory mechanisms that govern the expression of the RND efflux pumps genes, and may also provide useful clues to overcome the efflux pump mediated antibiotic resistance.

  11. Comparative effectiveness of azithromycin for treating scrub typhus: A PRISMA-compliant systematic review and meta-analysis.

    Science.gov (United States)

    Lee, Szu-Chia; Cheng, Yu-Jyun; Lin, Chao-Hsu; Lei, Wei-Te; Chang, Hung-Yang; Lee, Ming-Dar; Liu, Jui-Ming; Hsu, Ren-Jun; Chiu, Nan-Chang; Chi, Hsin; Peng, Chun-Chih; Tsai, Te-Lung; Lin, Chien-Yu

    2017-09-01

    Scrub typhus is a zoonotic disease that remains an important health threat in endemic areas. Appropriate anti-rickettsial treatment ensures a successful recovery. Doxycycline is a recommended drug, but it is contraindicated in pregnant women and young children. Azithromycin is a safer alternative drug, but its effectiveness remains largely unclear. Herein, we conducted a systematic review and meta-analysis to determine the effectiveness of azithromycin. Studies that investigated azithromycin in treating scrub typhus were systematically identified from electronic databases up to December 2016. Information regarding study population, disease severity, treatment protocols, and responses was extracted and analyzed. In this review, 5 studies were included, which comprised a total of 427 patients. When comparing the treatment failure rate, we observed a favorable outcome in patients treated with azithromycin (risk ratio [RR] 0.83, 95% confidence interval [CI] 0.23-2.98). However, patients in the azithromycin group had longer time to defervescence (mean difference 4.38 hours, 95% CI -2.51 to 11.27) and higher rate of fever for more than 48 hours (RR 1.31, 95% CI 0.81-2.12). Moreover, patients treated with azithromycin had less adverse effects (RR 0.8, 95% CI 0.42-1.52). Azithromycin is as effective as other anti-rickettsial drugs with higher treatment success rates, lower frequency of adverse effects, and longer time to defervescence (GRADE 2B). Therefore, it is reasonable to use azithromycin as the first-line treatment against scrub typhus. Further studies are warranted to elucidate the effectiveness of azithromycin in specific patient groups, at high dose and influence of drug resistance.

  12. Influence of Body Weight, Ethnicity, Oral Contraceptives, and Pregnancy on the Pharmacokinetics of Azithromycin in Women of Childbearing Age

    Science.gov (United States)

    Habibi, Mitra; Kilpatrick, Sarah J.; Tuomala, Ruth E.; Shier, Janice M.; Wollett, Lori; Fischer, Patricia A.; Khorana, Kinnari S.; Rodvold, Keith A.

    2012-01-01

    Women of childbearing age commonly receive azithromycin for the treatment of community-acquired infections, including during pregnancy. This study determined azithromycin pharmacokinetics in pregnant and nonpregnant women and identified covariates contributing to pharmacokinetic variability. Plasma samples were collected by using a sparse-sampling strategy from pregnant women at a gestational age of 12 to 40 weeks and from nonpregnant women of childbearing age receiving oral azithromycin for the treatment of an infection. Pharmacokinetic data from extensive sampling conducted on 12 healthy women were also included. Plasma samples were assayed for azithromycin by high-performance liquid chromatography. Population data were analyzed by nonlinear mixed-effects modeling. The population analysis included 53 pregnant and 25 nonpregnant women. A three-compartment model with first-order absorption and a lag time provided the best fit of the data. Lean body weight, pregnancy, ethnicity, and the coadministration of oral contraceptives were covariates identified as significantly influencing the oral clearance of azithromycin and, except for oral contraceptive use, intercompartmental clearance between the central and second peripheral compartments. No other covariate relationships were identified. Compared to nonpregnant women not receiving oral contraceptives, a 21% to 42% higher dose-adjusted azithromycin area under the plasma concentration-time curve (AUC) occurred in non-African American women who were pregnant or receiving oral contraceptives. Conversely, azithromycin AUCs were similar between pregnant African American women and nonpregnant women not receiving oral contraceptives. Although higher levels of maternal and fetal azithromycin exposure suggest that lower doses be administered to non-African American women during pregnancy, the consideration of azithromycin pharmacodynamics during pregnancy should guide any dose adjustments. PMID:22106226

  13. Effect of Azithromycin on Airflow Decline–Free Survival After Allogeneic Hematopoietic Stem Cell Transplant

    Science.gov (United States)

    Chevret, Sylvie; Granata, Angela; Chevallier, Patrice; Vincent, Laure; Huynh, Anne; Tabrizi, Reza; Labussiere-Wallet, Hélène; Bernard, Marc; Chantepie, Sylvain; Bay, Jacques-Olivier; Thiebaut-Bertrand, Anne; Thepot, Sylvain; Contentin, Nathalie; Fornecker, Luc-Matthieu; Maillard, Natacha; Risso, Karine; Berceanu, Ana; Blaise, Didier; Peffault de La Tour, Regis; Chien, Jason W.; Coiteux, Valérie; Socié, Gérard

    2017-01-01

    Importance Bronchiolitis obliterans syndrome has been associated with increased morbidity and mortality after allogeneic hematopoietic stem cell transplant (HSCT). Previous studies have suggested that azithromycin may reduce the incidence of post–lung transplant bronchiolitis obliterans syndrome. Objective To evaluate if the early administration of azithromycin can improve airflow decline–free survival after allogeneic HSCT. Design, Setting, and Participants The ALLOZITHRO parallel-group trial conducted in 19 French academic transplant centers and involving participants who were at least 16 years old, had undergone allogeneic HSCT for a hematological malignancy, and had available pretransplant pulmonary function test results. Enrollment was from February 2014 to August 2015 with follow-up through April 26, 2017. Interventions Patients were randomly assigned to receive 3 times a week either 250 mg of azithromycin (n = 243) or placebo (n = 237) for 2 years, starting at the time of the conditioning regimen. Main Outcomes and Measures The primary efficacy end point was airflow decline–free survival at 2 years after randomization. Main secondary end points were overall survival and bronchiolitis obliterans syndrome at 2 years. Results Thirteen months after enrollment, the independent data and safety monitoring board detected an unanticipated imbalance across blinded groups in the number of hematological relapses, and the treatment was stopped December 26, 2016. Among 480 randomized participants, 465 (97%) were included in the modified intention-to-treat analysis (mean age, 52 [SD, 14] years; 75 women [35%]). At the time of data cutoff, 104 patients (22%; 54 azithromycin vs 50 placebo) had experienced an airflow decline; 138 patients (30%) died (78 azithromycin vs 60 placebo). Two-year airflow decline–free survival was 32.8% (95% CI, 25.9%-41.7%) with azithromycin and 41.3% (95% CI, 34.1%-50.1%) with placebo (unadjusted hazard ratio [HR], 1.3; 95% CI, 1

  14. Azithromycin in Labor Lowers Clinical Infections in Mothers and Newborns: A Double-Blind Trial.

    Science.gov (United States)

    Oluwalana, Claire; Camara, Bully; Bottomley, Christian; Goodier, Sean; Bojang, Abdoulie; Kampmann, Beate; Ceesay, Samba; D'Alessandro, Umberto; Roca, Anna

    2017-02-01

    We have recently completed a proof-of-concept trial showing that bacterial colonization decreased in women and newborns after the administration of azithromycin during labor. Here, we aim to assess the effect of the intervention on maternal and neonatal clinical infections. This was a double-blind, placebo-controlled randomized trial. Gambian women in labor were given either an oral dose of azithromycin (2 g) or placebo. Follow-up was conducted for 8 weeks after delivery. From April 2013 to April 2014, we recruited 829 mothers and their 830 newborns. Sixteen infants died during the follow-up period (8 per arm). No maternal deaths or serious adverse events related to the intervention were reported. Maternal infections were lower in the azithromycin group (3.6% vs 9.2%; relative risk [RR], 0.40; 95% confidence interval [CI], 0.22-0.71; P = .002), as was the prevalence of mastitis (1.4% vs 5.1%; RR, 0.29; 95% CI, 0.12-0.70; P = .005) and fever (1.9% vs 5.8%; RR, 0.33; 95% CI, 0.15-0.74; P = .006). Among newborns, the overall prevalence of infections was also lower in the azithromycin group (18.1% vs 23.8%; RR, 0.76; 95% CI, 0.58-0.99; P = .052) and there was a marked difference in prevalence of skin infections (3.1% vs 6.4%; RR, 0.49; 95% CI, 0.25-0.93; P = .034). Azithromycin given to women in labor decreases infections in both women and newborns during the puerperal period. Larger studies designed to evaluate the effect of the intervention on severe morbidity and mortality are warranted. Copyright © 2017 by the American Academy of Pediatrics.

  15. Variations in Antibiotic and Azithromycin Prescribing for Children by Geography and Specialty-United States, 2013.

    Science.gov (United States)

    Fleming-Dutra, Katherine E; Demirjian, Alicia; Bartoces, Monina; Roberts, Rebecca M; Taylor, Thomas H; Hicks, Lauri A

    2018-01-01

    Using antibiotics appropriately is critical to slow spread of antibiotic resistance, a major public health problem. Children, especially young children, receive more antibiotics than other age groups. Our objective was to describe antibiotic use in children in the United States and use of azithromycin, which is recommended infrequently for pediatric conditions. We used QuintilesIMS Xponent 2013 data to calculate the number and rate of oral antibiotic prescriptions for children by age (0-2, 3-9 and 10-19 years) and agent. We used log-binomial regression to calculate adjusted prevalence ratios and 95% confidence intervals to determine if specialty and patient age were associated with azithromycin selection when an antibiotic was prescribed. In 2013, 66.8 million antibiotics were prescribed to US children ≤19 years of age (813 antibiotic prescriptions per 1000 children). Amoxicillin and azithromycin were the 2 most commonly prescribed agents (23.1 million courses, 35% of all antibiotics; 12.2 million, 18%, respectively). Most antibiotics for children were prescribed by pediatricians (39%) and family practitioners (15%). Family practitioners were more likely to select azithromycin when an antibiotic was prescribed in all age groups than pediatricians (for children 0-2 years of age: prevalence ratio: 1.79, 95% confidence interval: 1.78-1.80; 3-9 years: 1.40, 1.40-1.40 and 10-19 years: 1.18, 1.18-1.18). Despite infrequent pediatric recommendations, variations in pediatric azithromycin use may suggest inappropriate antibiotic selection. Public health interventions focused on improving antibiotic selection in children as well as reducing antibiotic overuse are needed.

  16. Treatment of adults with acute uncomplicated malaria with azithromycin and chloroquine in India, Colombia, and Suriname

    Directory of Open Access Journals (Sweden)

    Kshirsagar NA

    2017-10-01

    Full Text Available Nilima A Kshirsagar,1 Nithya J Gogtay,1 Diego Moran,2 Gregory Utz,3 Ashok Sethia,4 Shirsendu Sarkar,5 Pol Vandenbroucke6 1Seth G S Medical College and KEM Hospital, Mumbai, India; 2Hospital San Andrés de Tumaco, Narino, Colombia; 3US Naval Medical Research Unit 6, Lima, Peru; 4Gita Bhawan Hospital and Research Centre, Indore, 5Pfizer, Mumbai, India; 6Pfizer, New York, NY, USA Background: To explore the use of azithromycin–chloroquine (AZCQ for the treatment of malaria, we conducted double-blind, randomized, non-inferiority studies in India, Colombia, and Suriname comparing the combination of azithromycin 1 g and chloroquine (CQ 600 mg base once daily (QD for 3 days versus atovaquone–proguanil (AP or chloroquine plus sulfadoxine–pyrimethamine (SPCQ in adults with acute uncomplicated Plasmodium falciparum malaria.Methods: Patients were hospitalized until three documented negative blood smears and followed through Day 42. The primary end point was parasitologic cure at Day 28.Results: In India, parasite clearance rates were 84% and 94% for AZCQ and SPCQ, respectively (95% confidence interval [CI] for the difference: –22.6, 0.8. In Colombia and Suriname, parasite clearance rates were 57% and 99% for AZCQ and AP, respectively (95% CI: –52, –32. A subsequent open-label, non-comparative third study using a 2 g dose of azithromycin and 600 mg of CQ in India and Colombia resulted in an overall efficacy rate of 97%.Conclusion: In India, Colombia, and Suriname, 1 g azithromycin with CQ QD for 3 days was inferior to established comparator agents. An improved response rate was observed when the dose of azithromycin was increased to 2 g. Keywords: acute, uncomplicated malaria, antimalarial, azithromycin, chloroquine, malaria, parasitologic cure rate, plasmodium

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

    Directory of Open Access Journals (Sweden)

    Bindu Subhadra

    2016-02-01

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

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

    Science.gov (United States)

    Zhu, Peng; Li, Minyong

    2012-01-01

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

  19. Differential Equations Models to Study Quorum Sensing.

    Science.gov (United States)

    Pérez-Velázquez, Judith; Hense, Burkhard A

    2018-01-01

    Mathematical models to study quorum sensing (QS) have become an important tool to explore all aspects of this type of bacterial communication. A wide spectrum of mathematical tools and methods such as dynamical systems, stochastics, and spatial models can be employed. In this chapter, we focus on giving an overview of models consisting of differential equations (DE), which can be used to describe changing quantities, for example, the dynamics of one or more signaling molecule in time and space, often in conjunction with bacterial growth dynamics. The chapter is divided into two sections: ordinary differential equations (ODE) and partial differential equations (PDE) models of QS. Rates of change are represented mathematically by derivatives, i.e., in terms of DE. ODE models allow describing changes in one independent variable, for example, time. PDE models can be used to follow changes in more than one independent variable, for example, time and space. Both types of models often consist of systems (i.e., more than one equation) of equations, such as equations for bacterial growth and autoinducer concentration dynamics. Almost from the onset, mathematical modeling of QS using differential equations has been an interdisciplinary endeavor and many of the works we revised here will be placed into their biological context.

  20. Role of quorum sensing in bacterial infections

    Science.gov (United States)

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

    2015-01-01

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

  1. Why Quorum Sensing Controls Private Goods

    Directory of Open Access Journals (Sweden)

    Martin Schuster

    2017-05-01

    Full Text Available Cell-cell communication, also termed quorum sensing (QS, is a widespread process that coordinates gene expression in bacterial populations. The generally accepted view is that QS optimizes the cell density-dependent benefit attained from cooperative behaviors, often in the form of secreted products referred to as “public goods.” This view is challenged by an increasing number of cell-associated products or “private goods” reported to be under QS-control for which a collective benefit is not apparent. A prominent example is nucleoside hydrolase from Pseudomonas aeruginosa, a periplasmic enzyme that catabolizes adenosine. Several recent studies have shown that private goods can function to stabilize cooperation by co-regulated public goods, seemingly explaining their control by QS. Here we argue that this property is a by-product of selection for other benefits rather than an adaptation. Emphasizing ecophysiological context, we propose alternative explanations for the QS control of private goods. We suggest that the benefit attained from private goods is associated with high cell density, either because a relevant ecological condition correlates with density, or because the private good is, directly or indirectly, involved in cooperative behavior. Our analysis helps guide a systems approach to QS, with implications for antivirulence drug design and synthetic biology.

  2. Biomimicry of quorum sensing using bacterial lifecycle model.

    Science.gov (United States)

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

    2013-01-01

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

  3. The evolution of quorum sensing in bacterial biofilms.

    Directory of Open Access Journals (Sweden)

    Carey D Nadell

    2008-01-01

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

  4. Population Blocks.

    Science.gov (United States)

    Smith, Martin H.

    1992-01-01

    Describes an educational game called "Population Blocks" that is designed to illustrate the concept of exponential growth of the human population and some potential effects of overpopulation. The game material consists of wooden blocks; 18 blocks are painted green (representing land), 7 are painted blue (representing water); and the remaining…

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

    Science.gov (United States)

    Hammond, John H; Dolben, Emily F; Smith, T Jarrod; Bhuju, Sabin; Hogan, Deborah A

    2015-09-01

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

  6. Qualitative and quantitative determination of quorum sensing inhibition in vitro

    DEFF Research Database (Denmark)

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

    2011-01-01

    The formation of biofilms in conjunction with quorum sensing (QS)-regulated expression of virulence by opportunistic pathogens contributes significantly to immune evasion and tolerance to a variety of antimicrobial treatments. The present protocol describes methods to determine the in vitro...... efficacy of potential quorum sensing inhibitors (QSIs). Work on Pseudomonas aeruginosa has shown that chemical blockage of QS is a promising new antimicrobial strategy. Several live bacterial reporter systems been developed to screen extracts and pure compounds for QSI activity. Here we describe the usage...

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

    Science.gov (United States)

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

    2016-09-01

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

  8. Azithromycin for Acute Exacerbations of Asthma : The AZALEA Randomized Clinical Trial.

    Science.gov (United States)

    Johnston, Sebastian L; Szigeti, Matyas; Cross, Mary; Brightling, Christopher; Chaudhuri, Rekha; Harrison, Timothy; Mansur, Adel; Robison, Laura; Sattar, Zahid; Jackson, David; Mallia, Patrick; Wong, Ernie; Corrigan, Christopher; Higgins, Bernard; Ind, Philip; Singh, Dave; Thomson, Neil C; Ashby, Deborah; Chauhan, Anoop

    2016-11-01

    Guidelines recommend against antibiotic use to treat asthma attacks. A study with telithromycin reported benefit, but adverse reactions limit its use. To determine whether azithromycin added to standard care for asthma attacks in adults results in clinical benefit. The Azithromycin Against Placebo in Exacerbations of Asthma (AZALEA) randomized, double-blind, placebo-controlled clinical trial, a United Kingdom-based multicenter study in adults requesting emergency care for acute asthma exacerbations, ran from September 2011 to April 2014. Adults with a history of asthma for more than 6 months were recruited within 48 hours of presentation to medical care with an acute deterioration in asthma control requiring a course of oral and/or systemic corticosteroids. Azithromycin 500 mg daily or matched placebo for 3 days. The primary outcome was diary card symptom score 10 days after randomization, with a hypothesized treatment effect size of -0.3. Secondary outcomes were diary card symptom score, quality-of-life questionnaires, and lung function changes, all between exacerbation and day 10, and time to a 50% reduction in symptom score. Of 4582 patients screened at 31 centers, 199 of a planned 380 were randomized within 48 hours of presentation. The major reason for nonrecruitment was receipt of antibiotics (2044 [44.6%] screened patients). Median time from presentation to drug administration was 22 hours (interquartile range, 14-28 hours). Exacerbation characteristics were well balanced across treatment arms and centers. The primary outcome asthma symptom scores were mean (SD), 4.14 (1.38) at exacerbation and 2.09 (1.71) at 10 days for the azithromycin group and 4.18 (1.48) and 2.20 (1.51) for the placebo group, respectively. Using multilevel modeling, there was no significant difference in symptom scores between azithromycin and placebo at day 10 (difference, -0.166; 95% CI, -0.670 to 0.337), nor on any day between exacerbation and day 10. No significant between

  9. Long-term azithromycin ameliorates not only airway inflammation but also remodeling in a murine model of chronic asthma.

    Science.gov (United States)

    Kang, Ji Young; Jo, Mi Ran; Kang, Hyeon Hui; Kim, Sung Kyoung; Kim, Myoung Sook; Kim, Yong Hyun; Kim, Seok Chan; Kwon, Soon Seog; Lee, Sook Young; Kim, Jin Woo

    2016-02-01

    We investigated the effect of long-term treatment with azithromycin on the pathogenesis of chronic asthma with airway remodeling. Six-week-old-BALB/c mice were sensitized with ovalbumin (OVA) combined with lipopolysaccharide (LPS) for 1 month, then challenged with OVA for 3 months. Azithromycin at 75 mg/kg was administered via oral gavage five times a week during the challenge period. Inflammatory cells, T helper 2 cytokines in bronchoalveolar lavage fluid (BAL) fluid, and airway hyperresponsiveness (AHR) were measured. Parameters related to airway remodeling were evaluated. The levels of neutrophil elastase, Interleukin (IL)-8, and BRP-39 (human homologue YKL-40) were assessed. The expression of MAPK and NF-κB signaling were investigated. Long-term treatment with azithromycin improved AHR and airway inflammation compared with the OVA and the OVA/LPS groups. The concentrations of IL-5 and IL-13 in the OVA/LPS group decreased significantly after azithromycin administration. The levels of neutrophil elastase and IL-8, as surrogate markers of neutrophil activation, were reduced in the azithromycin group compared with the OVA/LPS group. Goblet cell hyperplasia and the smooth muscle thickening of airway remodeling were attenuated after azithromycin treatment. The expression of MAPK/NF-kappaB signal and the level of BRP-39 in the lung decreased remarkably in the OVA/LPS with azithromycin-treated group. This study suggests that in a murine model of chronic asthma, long-term azithromycin treatment ameliorates not only airway inflammation but also airway remodeling by influencing on neutrophilc-related mediators, BRP-39 and MAPK/NF-κB signal pathways. Macrolide therapy might be an effective adjuvant therapy in a chronic, severe asthma with remodeling airway. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Comparison of Azithromycin and Amoxicillin Before Dental Implant Placement: An Exploratory Study of Bioavailability and Resolution of Postoperative Inflammation.

    Science.gov (United States)

    Escalante, Mariana Gil; Eubank, Tim D; Leblebicioglu, Binnaz; Walters, John D

    2015-11-01

    Studies suggest that a single prophylactic dose of amoxicillin reduces early implant complications, but it is unclear whether other antibiotics are also effective. This study compared the local antimicrobial and anti-inflammatory effects resulting from a single dose of azithromycin or amoxicillin before surgical placement of one-stage dental implants. Healthy adult patients requiring one-stage dental implant placement were allocated randomly to receive either 2 g amoxicillin (n = 7) or 500 mg azithromycin (n = 6) before surgery. Peri-implant crevicular fluid (PICF) samples from the new implant and gingival crevicular fluid (GCF) from adjacent teeth were sampled on postoperative days 6, 13, and 20. Inflammatory mediators in the samples were analyzed by immunoassay, and antibiotic levels were measured by bioassay. On day 6, azithromycin concentrations in GCF and PICF were 3.39 ± 0.73 and 2.77 ± 0.90 μg/mL, respectively, whereas amoxicillin was below the limit of detection. During early healing, patents in the azithromycin group exhibited a significantly greater decrease in GCF volume (P = 0.03, analysis of variance). At specific times during healing, the azithromycin group exhibited significantly lower levels of interleukin (IL)-6 and IL-8 in GCF than the amoxicillin group and exhibited significantly lower levels of granulocyte colony stimulating factor, IL-8, macrophage inflammatory protein-1β, and interferon-gamma-inducible protein-10 in PICF. Azithromycin was available at the surgical site for a longer period of time than amoxicillin, and patients taking azithromycin exhibited lower levels of specific proinflammatory cytokines and chemokines in GCF and PICF. Thus, preoperative azithromycin may enhance resolution of postoperative inflammation to a greater extent than amoxicillin.

  11. Single dose oral azithromycin versus seven day doxycycline in the treatment of non-gonococcal mucopurulent endocervicitis.

    Science.gov (United States)

    Sendağ, F; Terek, C; Tuncay, G; Ozkinay, E; Güven, M

    2000-02-01

    The aim of this study was to compare single dose oral azithromycin versus seven-day doxycycline in the treatment of non-gonococcal mucopurulent cervicitis (MPC). One hundred and thirty-one women with non-gonococcal MPC were enrolled in a prospective-randomised study to compare the efficacy and safety of a single oral dose of 1 g azithromycin and a seven-day course of 100 mg doxycycline twice daily. Clinical examination and culture samples for Chlamydia trachomatis and other microorganisms were performed before and approximately 14 days after starting the treatment. Of the 131 women recruited (67 in the azithromycin group and 64 in the doxycycline group), Ureaplasma urealyticum was isolated from 21 (16%); Chlamydia trachomatis from 15 (11.5%); and Mycoplasma hominis from 3 (2.3%) of the patients at the initial examination. The eradication rate of baseline culture-positive cases at the follow-up visit in the azithromycin group was 71.4%, and 77.3% in the doxycycline group. There was no statistically significant difference in efficacy between the single dose azithromycin and seven-day course of doxycycline in the treatment of culture-positive cases. Azithromycin 1 g appears to be an effective and safe alternative to doxycycline for the treatment of non-gonococcal MPC.

  12. Chloroquine-Azithromycin Combination Antimalarial Treatment Decreases Risk of Respiratory- and Gastrointestinal-Tract Infections in Malawian Children

    Science.gov (United States)

    Gilliams, Elizabeth A.; Jumare, Jibreel; Claassen, Cassidy W.; Thesing, Phillip C.; Nyirenda, Osward M.; Dzinjalamala, Fraction K.; Taylor, Terrie; Plowe, Christopher V.; Tracy, LaRee A.; Laufer, Miriam K.

    2014-01-01

    Background. Chloroquine-azithromycin is being evaluated as combination therapy for malaria. It may provide added benefit in treating or preventing bacterial infections that occur in children with malaria. Objective. We aim to evaluate the effect of treating clinical malaria with chloroquine-azithromycin on the incidence of respiratory-tract and gastrointestinal-tract infections compared to treatment with chloroquine monotherapy. Methods. We compared the incidence density and time to first events of respiratory-tract and gastrointestinal-tract infections among children assigned to receive chloroquine-azithromycin or chloroquine for all symptomatic malaria episodes over the course of 1 year in a randomized longitudinal trial in Blantyre, Malawi. Results. The incidence density ratios of total respiratory-tract infections and gastrointestinal-tract infections comparing chloroquine-azithromycin to chloroquine monotherapy were 0.67 (95% confidence interval [CI], .48, .94) and 0.74 (95% CI, .55, .99), respectively. The time to first lower-respiratory-tract and gastrointestinal-tract infections were significantly longer in the chloroquine-azithromycin arm compared to the chloroquine arm (P = .04 and P = .02, respectively). Conclusions. Children treated routinely with chloroquine-azithromycin had fewer respiratory and gastrointestinal-tract infections than those treated with chloroquine alone. This antimalarial combination has the potential to reduce the burden of bacterial infections among children in malaria-endemic countries. PMID:24652498

  13. Impact of azithromycin on the clinical and antimicrobial effectiveness of tobramycin in the treatment of cystic fibrosis.

    Science.gov (United States)

    Nichols, Dave P; Happoldt, Carrie L; Bratcher, Preston E; Caceres, Silvia M; Chmiel, James F; Malcolm, Kenneth C; Saavedra, Milene T; Saiman, Lisa; Taylor-Cousar, Jennifer L; Nick, Jerry A

    2017-05-01

    Concomitant use of oral azithromycin and inhaled tobramycin occurs in approximately half of US cystic fibrosis (CF) patients. Recent data suggest that this combination may be antagonistic. Test the hypothesis that azithromycin reduces the clinical benefits of tobramycin by analyses of clinical trial data, in vitro modeling of P. aeruginosa antibiotic killing, and regulation of the MexXY efflux pump. Ongoing administration of azithromycin associates with reduced ability of inhaled tobramycin, as compared with aztreonam, to improve lung function and quality of life in a completed clinical trial. In users of azithromycin FEV 1 (L) increased 0.8% during a 4-week period of inhaled tobramycin and an additional 6.4% during a subsequent 4-week period of inhaled aztreonam (Pazithromycin had similar improvement in lung function and quality of life scores during inhaled tobramycin and inhaled aztreonam. In vitro, azithromycin selectively reduced the bactericidal effects tobramycin in cultures of clinical strains of P. aeruginosa, while up regulating antibiotic resistance through MexXY efflux. Azithromycin appears capable of reducing the antimicrobial benefits of tobramycin by inducing adaptive bacterial stress responses in P. aeruginosa, suggesting that these medications together may not be optimal chronic therapy for at least some patients. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  14. Thin-section computed tomography findings before and after azithromycin treatment of neutrophilic reversible lung allograft dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Jong, Pim A. de [Department of Radiology, Katholieke Universiteit Leuven, Leuven (Belgium); Lung Transplantation Unit, Katholieke Universiteit Leuven, Leuven (Belgium); University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Vos, Robin; Verleden, Geert M.; Vanaudenaerde, Bart M. [Lung Transplantation Unit, Katholieke Universiteit Leuven, Leuven (Belgium); Verschakelen, Johny A. [Department of Radiology, Katholieke Universiteit Leuven, Leuven (Belgium)

    2011-12-15

    Recently a novel subgroup of bronchiolitis obliterans syndrome (BOS) has been described in patients after lung transplantation with high neutrophil counts in broncho-alveolar lavage and recovery of lung functional decline with azithromycin treatment. We aimed to describe the thin-section computed tomography (CT) findings of these neutrophilic reversible allograft dysfunction (NRAD) patients before and after azithromycin. A cohort of 100 lung transplant recipients with BOS were treated with azithromycin and underwent lung function testing, broncho-alveolar lavage and CT before azithromycin treatment and during follow-up. The 200 CT data sets were scored for bronchial dilatation, mucus plugging, centrilobular abnormalities, airway wall thickening, consolidation, ground glass and end-expiratory air trapping. NRAD was characterized by more centrilobular abnormalities on CT (p = 0.03 for prevalence and p = 0.06 for severity) compared to non-responders. At follow-up NRAD patients showed improvement in all CT abnormalities including air trapping, but the degree of improvement in all CT abnormalities was significantly different between responders and non-responders (who showed progression of bronchus dilatation, consolidation and air trapping). Within BOS patients those with NRAD differ from azithromycin non-responders by more centrilobular abnormalities on CT before azithromycin and improvement in bronchus dilatation, consolidation and air trapping during treatment. (orig.)

  15. Azithromycin for the Treatment of Obliterative Bronchiolitis after Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Yadav, Hemang; Peters, Steve G; Keogh, Karina A; Hogan, William J; Erwin, Patricia J; West, Colin P; Kennedy, Cassie C

    2016-12-01

    Obliterative bronchiolitis (OB) is a major cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). Our objective was to perform a systematic review and meta-analysis of the impact of azithromycin on change in forced expiratory volume in 1 second (FEV 1 ). We searched MEDLINE, EMBASE, Web of Science, Cochrane CENTRAL and Scopus databases and included studies that compared azithromycin with placebo or no intervention in the treatment of OB or bronchiolitis obliterans syndrome (BOS) in patients who had undergone allogeneic HSCT. Ninety-one unique publications were identified, and 4 studies met inclusion criteria, with a total of 90 patients. Changes in FEV 1 were measured between 12 and 24 weeks after initiation of treatment. The meta-analysis demonstrated a mean increase in FEV 1 of 30 mL (95% confidence interval, -260 to +330 mL; P = .82) after initiation of azithromycin. One patient death was reported but not attributed to azithromycin therapy. In conclusion, current evidence can neither support nor refute the use of azithromycin in the treatment of patients who develop OB/BOS after HSCT. Further studies are needed to determine whether azithromycin is beneficial for the treatment of OB/BOS in this setting. Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  16. The efficacy of azithromycin and doxycycline for the treatment of rectal chlamydia infection: a systematic review and meta-analysis.

    Science.gov (United States)

    Kong, Fabian Yuh Shiong; Tabrizi, Sepehr N; Fairley, Christopher Kincaid; Vodstrcil, Lenka A; Huston, Wilhelmina M; Chen, Marcus; Bradshaw, Catriona; Hocking, Jane S

    2015-05-01

    There are increasing concerns about treatment failure following treatment for rectal chlamydia with 1 g of azithromycin. A systematic review and meta-analysis was conducted to investigate the efficacy of 1 g of azithromycin as a single dose or 100 mg of doxycycline twice daily for 7 days for the treatment of rectal chlamydia. Medline, Embase, PubMed, Cochrane Controlled Trials Register, Australia New Zealand Clinical Trial Register and ClinicalTrials.gov were searched to the end of April 2014. Studies using 1 g of azithromycin or 7 days of doxycycline for the treatment of rectal chlamydia were eligible. Gender, diagnostic test, serovar, symptomatic status, other sexually transmitted infections, follow-up time, attrition and microbial cure were extracted. Meta-analysis was used to calculate pooled (i) azithromycin and doxycycline efficacy and (ii) efficacy difference. All eight included studies were observational. The random-effects pooled efficacy for azithromycin (based on eight studies) was 82.9% (95% CI 76.0%-89.8%; I(2) = 71.0%; P azithromycin may be considerably lower than 1 week of doxycycline for treating rectal chlamydia. However, the available evidence is very poor. Robust randomized controlled trials are urgently required. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. Azithromycin for the treatment of obliterative bronchiolitis following hematopoietic stem cell transplantation: a systematic review and meta-analysis

    Science.gov (United States)

    Yadav, Hemang; Peters, Steve G.; Keogh, Karina A.; Hogan, William J.; Erwin, Patricia J.; West, Colin P.; Kennedy, Cassie C.

    2016-01-01

    Obliterative bronchiolitis (OB) is a major cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). Our objective was to perform a systematic review and meta-analysis of the impact of azithromycin on change in forced expiratory volume in 1 second (FEV1). We searched MEDLINE, EMBASE, Web of Science, Cochrane CENTRAL and Scopus databases. We included studies that compared azithromycin to placebo or no intervention in the treatment of OB or BOS in patients who had undergone allogeneic HSCT. 91 unique publications were identified. 4 studies met inclusion criteria, with a total of 90 patients. Changes in FEV1 were measured between 12 weeks and 24 weeks after initiation of treatment. The meta-analysis demonstrated a mean increase in FEV1 of 30 ml (95% Confidence Interval: -260 to +330 ml, p = 0.82) following initiation of azithromycin. One patient death was reported, but not attributed to azithromycin therapy. In conclusion, current evidence can neither support nor refute the use of azithromycin in the treatment of patients who develop OB/BOS following HSCT. Further studies are needed to determine whether azithromycin is beneficial for the treatment of OB/BOS in this setting. PMID:27575542

  18. High Resistance to Azithromycin in Clinical Samples from Patients with Sexually Transmitted Diseases in Guangxi Zhuang Autonomous Region, China.

    Science.gov (United States)

    Zhu, Bangyong; Bu, Jin; Li, Wei; Zhang, Jie; Huang, Geng; Cao, Juan; Tang, Zhongshu; Gan, Quan; Wei, Pingjiang

    2016-01-01

    Azithromycin is used as an alternative medicine in patients with syphilis who are intolerant to penicillin. Nevertheless, the report of treatment failure of azithromycin for patients with syphilis has raised concerns in China in the past years. In this study, 178 patients with early syphilis, who were treated in sexually transmitted infections clinics in four cities in Guangxi Zhuang Autonomous Region were enrolled to investigate the regional prevalence of Treponema pallidum strain resistant to azithromycin. Nested PCR was performed to amplify the 23S ribosomal RNA (23SrRNA) gene. The point mutation of A2058G in 23SrRNA, which confers Treponema pallidum resistance to azithromycin, was measured by endonuclease digestion of PCR amplification products using MboII. A2058G point mutation was detected in 91.0% (162/178; 95% CI, 86.8%, 95.2%) of the specimens, but no difference in prevalence of azithromycin resistance was found between the patients who had taken antibiotics before enrollment and the patients who had not (91.8% vs. 89.4%), nor between the patients with and without past sexually transmitted infections (87.1% vs. 93.1%). We concluded that azithromycin may not be suitable for syphilis as a treatment option in Guangxi Zhuang Autonomous Region because of the extremely high prevalence of resistance in the general syphilis population.

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

    Science.gov (United States)

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

    2014-01-01

    Burkholderia thailandensis contains three acyl-homoserine lactone quorum sensing circuits and has two additional LuxR homologs. To identify B. thailandensis quorum sensing-controlled genes, we carried out transcriptome sequencing (RNA-seq) analyses of quorum sensing mutants and their parent. The analyses were grounded in the fact that we identified genes coding for factors shown previously to be regulated by quorum sensing among a larger set of quorum-controlled genes. We also found that genes coding for contact-dependent inhibition were induced by quorum sensing and confirmed that specific quorum sensing mutants had a contact-dependent inhibition defect. Additional quorum-controlled genes included those for the production of numerous secondary metabolites, an uncharacterized exopolysaccharide, and a predicted chitin-binding protein. This study provides insights into the roles of the three quorum sensing circuits in the saprophytic lifestyle of B. thailandensis, and it provides a foundation on which to build an understanding of the roles of quorum sensing in the biology of B. thailandensis and the closely related pathogenic Burkholderia pseudomallei and Burkholderia mallei. PMID:24464461

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

    Science.gov (United States)

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

    2014-11-01

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

  1. Quorum-sensing control of antibiotic resistance stabilizes cooperation in Chromobacterium violaceum.

    Science.gov (United States)

    Evans, Kara C; Benomar, Saida; Camuy-Vélez, Lennel A; Nasseri, Ellen B; Wang, Xiaofei; Neuenswander, Benjamin; Chandler, Josephine R

    2018-01-26

    Many Proteobacteria use quorum sensing to regulate production of public goods, such as antimicrobials and proteases, that are shared among members of a community. Public goods are vulnerable to exploitation by cheaters, such as quorum sensing-defective mutants. Quorum sensing- regulated private goods, goods that benefit only producing cells, can prevent the emergence of cheaters under certain growth conditions. Previously, we developed a laboratory co-culture model to investigate the importance of quorum-regulated antimicrobials during interspecies competition. In our model, Burkholderia thailandensis and Chromobacterium violaceum each use quorum sensing-controlled antimicrobials to inhibit the other species' growth. Here, we show that C. violaceum uses quorum sensing to increase resistance to bactobolin, a B. thailandensis antibiotic, by increasing transcription of a putative antibiotic efflux pump. We demonstrate conditions where C. violaceum quorum-defective cheaters emerge and show that in these conditions, bactobolin restrains cheaters. We also demonstrate that bactobolin restrains quorum-defective mutants in our co-culture model, and the increase in antimicrobial-producing cooperators drives the C. violaceum population to become more competitive. Our results describe a mechanism of cheater restraint involving quorum control of efflux pumps and demonstrate that interspecies competition can reinforce cooperative behaviors by placing constraints on quorum sensing-defective mutants.

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

    Science.gov (United States)

    Avbelj, Martina; Zupan, Jure; Raspor, Peter

    2016-09-01

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

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

    Science.gov (United States)

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

    2014-04-01

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

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

    Science.gov (United States)

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

    2015-09-01

    In many countries, infectious diseases are a considerable threat to aquaculture. The pathogenicity of micro-organisms that infect aquaculture systems is closely related to the release of virulence factors and the formation of biofilms, both of which are regulated by quorum sensing (QS). Thus, QS disruption is a potential strategy for preventing disease in aquaculture systems. QS inhibitors (QSIs) not only inhibit the expression of virulence-associated genes but also attenuate the virulence of aquaculture pathogens. In this review, we discuss QS systems in important aquaculture pathogens and focus on the relationship between QS mechanisms and bacterial virulence in aquaculture. We further elucidate QS disruption strategies for targeting aquaculture pathogens. Four main types of QSIs that target aquaculture pathogens are discussed based on their mechanisms of action. © 2014 John Wiley & Sons Ltd.

  5. Detection of quorum sensing molecules from Vibrio harveyi and use ...

    African Journals Online (AJOL)

    This paper explores the extraction and detection processes of quorum sensing molecules such as N-aceyl homoserine lactone compounds (AHL) from marine Vibrio harveyi. The spent culture of V. harveyi was solvent partitioned for AHL, rotary evaporated and re-suspended in 50% acetonitrile then detected with reporter ...

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

    DEFF Research Database (Denmark)

    Johansen, Pernille; Jespersen, Lene

    2017-01-01

    The quality of fermented food highly dependents on the microorganisms involved, their metabolic activities and interactions. Recently, focus has been on quorum sensing (QS) being a cell density-dependent mechanism allowing adaptive responses. Specific QS molecules in prokaryotes and eukaryotes...

  7. Quorum sensing inhibitory activity of sub-inhibitory concentrations of ...

    African Journals Online (AJOL)

    Introduction: The virulence factors of Pseudomonas aeruginosa are under the control of quorum sensing (QS) signals. Hence, interference with QS prevents its pathogenesis. Objective: The aim of the present research is to assess the influence of some β-lactam antibiotics on cell communication and the release of different ...

  8. Deciphering Physiological Functions of AHL Quorum Quenching Acylases

    NARCIS (Netherlands)

    Utari, Putri D.; Vogel, Jan; Quax, Wim J.

    2017-01-01

    N-Acylhomoserine lactone (AHL)-acylase (also known as amidase or amidohydrolase) is a class of enzyme that belongs to the Ntn-hydrolase superfamily. As the name implies, AHL-acylases are capable of hydrolysing AHLs, the most studied signaling molecules for quorum sensing in Gram-negative bacteria.

  9. Exploring the chemical space of quorum sensing peptides.

    Science.gov (United States)

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

    2015-09-01

    Quorum sensing peptides are signalling molecules that are produced by mainly gram-positive bacteria. These peptides can exert different effects, ranging from intra- and interspecies bacterial virulence to bacterial-host interactions. To better comprehend these functional differences, we explored their chemical space, bacterial species distribution and receptor-binding properties using multivariate data analyses, with information obtained from the Quorumpeps database. The quorum sensing peptides can be categorized into three main clusters, which, in turn, can be divided into several subclusters: the classification is based on characteristic chemical properties, including peptide size/compactness, hydrophilicity/lipophilicity, cyclization and the presence of (unnatural) S-containing and aromatic amino acids. Most of the bacterial species synthesize peptides located into one cluster. However, some Streptococcus, Stapylococcus, Clostridium, Bacillus and Lactobacillus species produce peptides that are distributed over more than one cluster, with the quorum sensing peptides of Bacillus subtilis even occupying the total peptide space. The AgrC, FsrC and LamC receptors are only activated by cyclic (thio)lacton or lactam quorum sensing peptides, while the lipophilic isoprenyl-modified peptides solely bind the ComP receptor in Bacillus species. © 2015 Wiley Periodicals, Inc.

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

    DEFF Research Database (Denmark)

    Hultqvist, Louise Dahl; Alhede, Maria; Jakobsen, Tim Holm

    2018-01-01

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

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

    NARCIS (Netherlands)

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

    1998-01-01

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  13. Controlling the activity of quorum sensing autoinducers with light

    NARCIS (Netherlands)

    Van der Berg, J. P.; Velema, W. A.; Szymanski, W.; Driessen, A. J. M.; Feringa, B. L.

    2015-01-01

    Bacteria use a communication system, called quorum sensing (QS), to organize into communities and synchronize gene expression to promote virulence and secure survival. Here we report on a proof-of-principle for externally interfering with this bacterial communication system, using light. By

  14. Methods to Study Solo/Orphan Quorum-Sensing Receptors.

    Science.gov (United States)

    Venturi, Vittorio; Subramoni, Sujatha; Sabag-Daigle, Anice; Ahmer, Brian M M

    2018-01-01

    LuxR solos/orphans are very widespread among Proteobacteria; however they are surprisingly understudied given that they are likely to play a major role in cell-cell communication in bacteria. Here we describe three simple methodologies/approaches that can be used in order to begin to study this subgroup of quorum sensing-related LuxR receptors.

  15. Page | 82 CRITICAL EXAMINATION OF THE QUORUM OF CODE ...

    African Journals Online (AJOL)

    Fr. Ikenga

    Abstract. This paper critically examines the quorum of Code of Conduct Tribunal, and compares it to those of other tribunals and courts. The paper argues that since the Code of Conduct Bureau and Tribunal Act and the Nigerian Constitution provide for the establishment or composition of the Tribunal only, and.

  16. Azithromycin Dose To Maximize Efficacy and Suppress Acquired Drug Resistance in Pulmonary Mycobacterium avium Disease.

    Science.gov (United States)

    Deshpande, Devyani; Pasipanodya, Jotam G; Gumbo, Tawanda

    2016-04-01

    Mycobacterium aviumcomplex is now the leading mycobacterial cause of chronic pneumonia in the United States. Macrolides and ethambutol form the backbone of the regimen used in the treatment of pulmonary disease. However, therapy outcomes remain poor, with microbial cure rates of 4% in cavitary disease. The treatment dose of azithromycin has mostly been borrowed from that used to treat other bacterial pneumonias; there are no formal dose-response studies in pulmonaryM. aviumdisease and the optimal dose is unclear. We utilized population pharmacokinetics and pharmacokinetics/pharmacodynamics-derived azithromycin exposures associated with optimal microbial kill or resistance suppression to perform 10,000 patient Monte Carlo simulations of dose effect studies for daily azithromycin doses of 0.5 to 10 g. The currently recommended dose of 500 mg per day achieved the target exposures in 0% of patients. Exposures associated with optimal kill and resistance suppression were achieved in 87 and 54% of patients, respectively, only by the very high dose of 8 g per day. The azithromycin susceptibility breakpoint above which patients failed therapy on the very high doses of 8 g per day was an MIC of 16 mg/liter, suggesting a critical concentration of 32 mg/liter, which is 8-fold lower than the currently used susceptibility breakpoint of 256 mg/liter. If the standard dose of 500 mg a day were used, then the critical concentration would fall to 2 mg/liter, 128-fold lower than 256 mg/liter. The misclassification of resistant isolates as susceptible could explain the high failure rates of current doses. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  17. Effect of Smilax China Capsules and azithromycin combined therapy on chronic annexitis

    Directory of Open Access Journals (Sweden)

    Rong-Jun Cong

    2016-11-01

    Full Text Available Objective: To explore the mechanism of Smilax China (Chinese spelling: Jingangteng Capsules and Azithromycin combined therapy for chronic annexitis, and offer help to patients with chronic annexitis on relevant clinical therapies. Methods: A total of 170 cases of patients with chronic annexitis were selected from the gynecological department in our hospital, and randomly divided to be the combination therapy group and the control group by digital table, 85 cases for each group. Patients in control group were treated with Azithromycin. Patients in combination therapy group were treated by giving Smilax China capsules based on the Azithromycin treatment. Relevant indexes of lymphocyte subsets (CD3+ , CD4+ , CD8+ and CD4+ /CD8+ , cytokines (TNF-α, IL-2, IL-6 and IL-10 and hemorheology (blood viscosity, plasma viscosity, hematocrit, red blood cell aggregation index in patients of the two groups were detected before and after treatment. Results: Before treatment, no statistical significance found on the differences of lymphocyte subsets, cytokines and hemorheology between the two groups of patients (P>0.05; After treatment received on the two groups of patients, indexes of CD3+ , CD4+ and CD4+ /CD8+ were dramatically increased, CD8+ , cytokines (TNF-α, IL-2, IL-6 and IL-10 and hemorheology in the combination therapy group were significantly decreased compared with patients in the control group; Statistical significance existed in differences between the two groups (P<0.05. Conclusions: Patients who received Azithromycin therapy added with Smilax China capsules concurrently could be significantly improved levels of lymphocyte subsets, cytokines and hemorheology index. It is of clinical importance for treatment of patients with chronic annexitis.

  18. Detection of quorum-sensing-related molecules in Vibrio scophthalmi

    Directory of Open Access Journals (Sweden)

    Riedel Kathrin

    2008-08-01

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

  19. Assessment of Azithromycin in Pharmaceutical Formulation by Fourier-transform Infrared (FT-IR Transmission Spectroscopy

    Directory of Open Access Journals (Sweden)

    Muhammad Ali Mallah

    2011-12-01

    Full Text Available A simple, rapid and economical method for azithromycin quantification in solid tablet and capsule formulations has been developed by applying Fourier-transform Infrared (FT-IR transmission spectroscopy for regular quality monitoring. The newly developed method avoids the sample preparation, except grinding for pellet formation and does not involve consumption of any solvent as it absolutely eliminates the need of extraction. KBr pellets were employed for the appraisal of azithromycin while acquiring spectra of standards as well as samples on FT-IR. By selecting the FT-IR carbonyl band (C=O in the region 1,744–1,709 cm−1 the calibration model was developed based on simple Beer’s law. The excellent regression coefficient (R2 0.999 was accomplished for calibration set having standard error of calibration equal to 0.01 mg. The current work exposes that transmission FT-IR spectroscopy can definitely be applied to determine the exact amount of azithromycin to control the processing and quality of solid formulations with reduced cost and short analysis time.

  20. The efficacy of azithromycin in pityriasis rosea: A randomized, double-blind, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Deepika Pandhi

    2014-01-01

    Full Text Available Background: Macrolides are prescribed in the treatment of pityriasis rosea despite conflicting results of the limited number of studies evaluating their role in its treatment. Aim: A randomized double-blind placebo-controlled trial was conducted to evaluate the effect of azithromycin on the clinical course of pityriasis rosea. Methods: Seventy patients of pityriasis rosea were given either azithromycin (n = 35 or placebo (n = 35 and were followed-up at 2, 4 and 6 weeks. Pruritus was assessed in both groups using the visual analogue scale (VAS . Change in the pityriasis rosea severity score (PRSS and in the VAS were recorded as outcome measures and were compared statistically. Results: The decrease in PRSS from baseline through 2, 4 and 6 weeks within both treatment (P < 0.001 and placebo (P < 0.001 arms was found to be statistically significant; however, this change was not significantly different in the two groups (P = 0.179. Similarly, the decrease in VAS was found to be statistically significant within both groups (P < 0.001; however, the change was comparable between the two groups (P < 0.937. Analysis by Fisher′s exact test did not find a significant difference between the two groups for PRSS and VAS. Conclusion: Azithromycin is not effective in pityriasis rosea and the use of macrolides for this disease should not be encouraged in clinical practice.

  1. Synthesis and antibacterial activity of 4″-O-(trans-β-arylacrylamido)carbamoyl azithromycin analogs.

    Science.gov (United States)

    Yan, Mi; Ma, Xiaodong; Dong, Ruiqian; Li, Xin; Zhao, Can; Guo, Zhenzhen; Shen, Yan; Liu, Fang; Ma, Ruixin; Ma, Shutao

    2015-10-20

    Novel 4″-O-(trans-β-arylacrylamido)carbamoyl azithromycin analogs were designed, synthesized and evaluated for their antibacterial activity against nine significant pathogens using broth microdilution method. A majority of these derivatives maintained the activity of azithromycin against susceptible Streptococcus pyogenes and all the compounds demonstrated remarkably improved activity compared with the references against all the three phenotypes of resistant Streptococcus pneumoniae. In particular, compound 24 exhibited the most potent activity against susceptible Staphylococcus aureus (MIC = 0.5 μg/mL), S. pneumoniae (MIC = 0.06 μg/mL) and S. pyogenes (MIC = 0.25 μg/mL). The most active compound 7 (MIC = 0.015 μg/mL) against resistant S. pneumoniae expressing the mefA gene, exhibited 512 and 256-fold more potent activity than erythromycin and azithromycin, respectively. Compounds 28 (MIC = 0.5 μg/mL), 29 (MIC = 0.25 μg/mL) and 30 (MIC = 0.5 μg/mL) demonstrated potent activity against resistant S. pneumoniae expressing the ermB gene, which were 256, 512 and 256-fold better than the references, respectively. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  2. Azithromycin and Doxycycline Attenuation of Acanthamoeba Virulence in a Human Corneal Tissue Model.

    Science.gov (United States)

    Purssell, Andrew; Lau, Rachel; Boggild, Andrea K

    2017-04-15

    Amoebic keratitis is a potentially blinding eye infection caused by ubiquitous, free-living, environmental acanthamoebae, which are known to harbor bacterial endosymbionts. A Chlamydia-like endosymbiont has previously enhanced Acanthamoeba virulence in vitro. We investigated the potential effect of Acanthamoeba-endosymbiont coinfection in a human corneal tissue model representing clinical amoebic keratitis infection. Environmental and corneal Acanthamoeba isolates from the American Type Culture Collection were screened for endosymbionts by amplifying and sequencing bacterial 16S as well as Chlamydiales-specific DNA. Each Acanthamoeba isolate was used to infect EpiCorneal cells, a 3-dimensional human corneal tissue model. EpiCorneal cells were then treated with azithromycin, doxycycline, or control medium to determine whether antibiotics targeting common classes of bacterial endosymbionts attenuated Acanthamoeba virulence, as indicated by decreased observed cytopathic effect and inflammatory biomarker production. A novel endosymbiont closely related to Mycobacterium spp. was identified in Acanthamoeba polyphaga 50495. Infection of EpiCorneal cells with Acanthamoeba castellanii 50493 and A. polyphaga 50372 led to increased production of inflammatory cytokines and cytopathic effects visible under microscopy. These increases were attenuated by azithromycin and doxycycline. Our findings suggest that azithromycin and doxycycline may be effective adjuvants to standard antiacanthamoebal chemotherapy by potentially abrogating virulence-enhancing properties of bacterial endosymbionts. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  3. Subantibiotic dose of azithromycin attenuates alveolar bone destruction and improves trabecular microarchitectures in a rat model of experimental periodontitis: A study using micro-computed tomography.

    Science.gov (United States)

    Park, Hye-Shin; Lee, Yong Sun; Choi, Eun-Young; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2017-06-01

    Azithromycin, a macrolide antibiotic, has anti-inflammatory and immunomodulatory activities apart from its antibacterial properties. In this study, we examined the efficacy of subantibiotic dose of azithromycin on ligature-induced periodontitis in rats using micro-computed tomography (micro-CT) imaging and bone parameter analysis. Male Sprague-Dawley rats were allocated to the following four groups: non-ligation (NL) group; ligation-only (L) group; ligation-plus-subantibiotic dose azithromycin (SA) group; and 4) ligation-plus-antibiotic dose azithromycin (AA) group. The rats from Groups L, SA and AA were subjected to periodontitis by placing a ligature around lower right first molar. Immediately after ligation, the rats in SA and AA groups received daily intraperitoneal injections of azithromycin at a dosage of 3.5 or 10mg/kg body weight, respectively. The ligatures were maintained for 2weeks at which time the rats had their mandibles hemisected for micro-CT analysis. Subantibiotic dose of azithromycin strongly suppressed reductions in alveolar bone height and bone volume fraction caused by experimental periodontitis. When subantibiotic dosage of azithromycin was administered to rats, ligature-induced alterations in microarchitectural parameters of trabecular bone were significantly reversed. Rats treated with subantibiotic dose of azithromycin presented no significant difference compared to rats with antibiotic dosage in all parameters. While further studies are necessary, subantibiotic dose of azithromycin could be utilized as a host modulator for the treatment of periodontitis. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. The timing of azithromycin treatment is not associated with the clinical prognosis of childhood Mycoplasma pneumoniae pneumonia in high macrolide-resistant prevalence settings.

    Science.gov (United States)

    Yang, Dehua; Chen, Linghong; Chen, Zhimin

    2018-01-01

    Mycoplasma pneumoniae infection is a major cause of community-acquired pneumonia in children. We performed a retrospective study to evaluate the clinical impact of the timing of azithromycin treatment in children with Mycoplasma pneumoniae pneumonia in high macrolide-resistant prevalence settings. A total of 623 patients were enrolled in this study and were divided into 2 groups according to the timing of azithromycin therapy. Children who received azithromycin within 3 days (72 hours) after the onset of Mycoplasma pneumoniae pneumonia were classified into the early azithromycin treatment group (n = 174), whereas the late azithromycin treatment group (n = 449) comprised children treated with azithromycin more than 72 hours after symptom onset. We evaluated clinical prognosis according to demographic, clinical and laboratory characteristics. Although the early azithromycin treatment group exhibited a longer fever duration after azithromycin administration (7.17±4.12 versus 4.82±3.99 days, Pazithromycin therapy, the two groups exhibited no significant differences with respect to improvements in the laboratory and radiological findings (all P>0.05). The timing of azithromycin treatment is not associated with the clinical prognosis of Mycoplasma pneumoniae pneumonia in children in high macrolide-resistant Mycoplasma pneumoniae prevalence settings.

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

    Directory of Open Access Journals (Sweden)

    Christopher N LaRock

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

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    The role of quorum sensing in Pseudomonas aeruginosa biofilm formation is unclear. Some researchers have shown that quorum sensing is important for biofilm development, while others have indicated it has little or no role. In this study, the contribution of quorum sensing to biofilm development...... was found to depend upon the nutritional environment. Depending upon the carbon source, quorum-sensing mutant strains (lasIrhlI and lasRrhlR) either exhibited a pronounced defect early in biofilm formation or formed biofilms identical to the wild-type strain. Quorum sensing was then shown to exert its...... the contributions of quorum sensing and swarming motility at a key juncture early in biofilm development....

  7. Pharmacokinetics of azithromycin in lactating dairy cows with subclinical mastitis caused by Staphylococcus aureus.

    Science.gov (United States)

    Lucas, M F; Errecalde, J O; Mestorino, N

    2010-04-01

    Azithromycin is a time-dependent antimicrobial with long persistence. The main characteristics of azithromycin suggest that it could be useful for treating bovine mastitis caused by Staphylococcus aureus. To investigate this possibility, its pharmacokinetic (PK) behavior was studied. Six Holstein lactating cows with subclinical mastitis were administered two 10 mg/kg intramuscular (i.m.) doses of azithromycin, with a 48-h interval. Milk and plasma concentrations were measured by microbiological assay. The MIC(90) was determined in 51 S. aureus isolations to calculate pharmacokinetic/pharmacodynamic (PK/PD) parameters. Milk maximal concentration (C(max)) was 7.76 +/- 1.76 microg/mL (16.67 h post-first administration) and 7.82 +/- 2.18 microg/mL (14 h post-2(nd) administration). In plasma C(max) was 0.18 +/- 0.03 microg/mL (2 h post-1(rst) administration) and 0.11 +/- 0.03 microg/mL (14 h post-2(nd) administration). Azithromycin was eliminated from the milk with a half-life (T(1/2)lambda) of 158.26 +/- 137.7 h after 2(nd) administration, meanwhile plasma T(1/2)lambda resulted shorter(13.97 +/- 11.1 h). The mean area under the concentration vs. time curve from 0 to 24 h (AUC(0-24h)) was 153.82 +/- 34.66 microg.h/mL in milk secretion and 2.61 +/- 0.59 microgxh/mL in plasma. Infection presence in the quarters had a significant effect (P time curve from 0 to infinity (AUC(0-infinity)) and clearance from the mammary gland (Cl(mam)/F). Moreover, it had influence on milk bioavailability (F(milk)), T(1/2)lambda, AUC(0-infinity) and mean residence time (MRT) in milk, which values resulted increased in mastitic quarters. In this study, it was determined that the production level and the mammary health status have an influence on PK parameters of azithromycin treatments in bovine mastitis.

  8. 3-D Numerical Simulations of Biofilm Dynamics with Quorum Sensing in a Flow Cell

    Science.gov (United States)

    2014-01-01

    bacterial systems, such as vibrio fischeri [?], where quorum sensing was first observed, Pseudomonas aeruginosa, Escherichia coli and so on. This...fraction. τ is the threshold AHL concentration locally required for quorum sensing induction to occur. The exponent n describes the degree of... Quorum sensing controls biofilm formation in vibrio chel- erae. Molecular Microbiology, 50(1):101–114, 2003. [10] Douglas M. Heithoff and Michael J

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

    Science.gov (United States)

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

    2017-10-01

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

  10. Fusaric acid and analogues as Gram-negative bacterial quorum sensing inhibitors.

    Science.gov (United States)

    Tung, Truong Thanh; Jakobsen, Tim Holm; Dao, Trong Tuan; Fuglsang, Anja Thoe; Givskov, Michael; Christensen, Søren Brøgger; Nielsen, John

    2017-01-27

    Taking advantage of microwave-assisted synthesis, efficient and expedite procedures for preparation of a library of fusaric acid and 39 analogues are reported. The fusaric acid analogues were tested in cell-based screening assays for inhibition of the las and rhl quorum sensing system in Pseudomonas aeruginosa and the lux quorum sensing system in Vibrio fischeri. Eight of the 40 compounds in the library including fusaric acid inhibited lux quorum sensing and one compound inhibited activity of the las quorum sensing system. To our delight, none of the compounds showed growth inhibitory effects in the tested concentration ranges. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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

    Science.gov (United States)

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

    2015-12-09

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

  12. Staphylococcus aureus Quorum Regulator SarA Targeted Compound, 2-[(Methylaminomethyl]phenol Inhibits Biofilm and Down-Regulates Virulence Genes

    Directory of Open Access Journals (Sweden)

    P. Balamurugan

    2017-07-01

    Full Text Available Staphylococcus aureus is a widely acknowledged Gram-positive pathogen for forming biofilm and virulence gene expressions by quorum sensing (QS, a cell to cell communication process. The quorum regulator SarA of S. aureus up-regulates the expression of many virulence factors including biofilm formation to mediate pathogenesis and evasion of the host immune system in the late phases of growth. Thus, inhibiting the production or blocking SarA protein might influence the down-regulation of biofilm and virulence factors. In this context, here we have synthesized 2-[(Methylaminomethyl]phenol, which was specifically targeted toward the quorum regulator SarA through in silico approach in our previous study. The molecule has been evaluated in vitro to validate its antibiofilm activity against clinical S. aureus strains. In addition, antivirulence properties of the inhibitor were confirmed with the observation of a significant reduction in the expression of representative virulence genes like fnbA, hla and hld that are governed under S. aureus QS. Interestingly, the SarA targeted inhibitor showed negligible antimicrobial activity and markedly reduced the minimum inhibitory concentration of conventional antibiotics when used in combination making it a more attractive lead for further clinical tests.

  13. Mechanism of the Quorum-Quenching Lactonase (AiiA) from Bacillus thuringiensis. 1. Product-Bound Structures

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Dali; Momb, Jessica; Thomas, Pei W.; Moulin, Aaron; Petsko, Gregory A.; Fast, Walter; Ringe, Dagmar (Brandeis); (Texas)

    2008-08-06

    Enzymes capable of hydrolyzing N-acyl-l-homoserine lactones (AHLs) used in some bacterial quorum-sensing pathways are of considerable interest for their ability to block undesirable phenotypes. Most known AHL hydrolases that catalyze ring opening (AHL lactonases) are members of the metallo-{beta}-lactamase enzyme superfamily and rely on a dinuclear zinc site for catalysis and stability. Here we report the three-dimensional structures of three product complexes formed with the AHL lactonase from Bacillus thuringiensis. Structures of the lactonase bound with two different concentrations of the ring-opened product of N-hexanoyl-l-homoserine lactone are determined at 0.95 and 1.4 {angstrom} resolution and exhibit different product configurations. A structure of the ring-opened product of the non-natural N-hexanoyl-l-homocysteine thiolactone at 1.3 {angstrom} resolution is also determined. On the basis of these product-bound structures, a substrate-binding model is presented that differs from previous proposals. Additionally, the proximity of the product to active-site residues and observed changes in protein conformation and metal coordination provide insight into the catalytic mechanism of this quorum-quenching metalloenzyme.

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

    Science.gov (United States)

    Mellbye, Brett L; Giguere, Andrew T; Bottomley, Peter J; Sayavedra-Soto, Luis A

    2016-10-25

    Quorum sensing (QS) is a widespread process in bacteria used to coordinate gene expression with cell density, diffusion dynamics, and spatial distribution through the production of diffusible chemical signals. To date, most studies on QS have focused on model bacteria that are amenable to genetic manipulation and capable of high growth rates, but many environmentally important bacteria have been overlooked. For example, representatives of proteobacteria that participate in nitrification, the aerobic oxidation of ammonia to nitrate via nitrite, produce QS signals called acyl-homoserine lactones (AHLs). Nitrification emits nitrogen oxide gases (NO, NO 2 , and N 2 O), which are potentially hazardous compounds that contribute to global warming. Despite considerable interest in nitrification, the purpose of QS in the physiology/ecology of nitrifying bacteria is poorly understood. Through a quorum quenching approach, we investigated the role of QS in a well-studied AHL-producing nitrite oxidizer, Nitrobacter winogradskyi We added a recombinant AiiA lactonase to N. winogradskyi cultures to degrade AHLs to prevent their accumulation and to induce a QS-negative phenotype and then used mRNA sequencing (mRNA-Seq) to identify putative QS-controlled genes. Our transcriptome analysis showed that expression of nirK and nirK cluster genes (ncgABC) increased up to 19.9-fold under QS-proficient conditions (minus active lactonase). These data led to us to query if QS influenced nitrogen oxide gas fluxes in N. winogradskyi Production and consumption of NO x increased and production of N 2 O decreased under QS-proficient conditions. Quorum quenching transcriptome approaches have broad potential to identify QS-controlled genes and phenotypes in organisms that are not genetically tractable. Bacterial cell-cell signaling, or quorum sensing (QS), is a method of bacterial communication and gene regulation that is well studied in bacteria. However, little is known about the purpose of QS

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

    Science.gov (United States)

    Paul, Diby

    2014-01-01

    Membrane biofouling remains a severe problem to be addressed in wastewater treatment systems affecting reactor performance and economy. The finding that many wastewater bacteria rely on N-acyl homoserine lactone-mediated quorum sensing to synchronize their activities essential for biofilm formations; the quenching bacterial quorum sensing suggests a promising approach for control of membrane biofouling. A variety of quorum quenching compounds of both synthetic and natural origin have been identified and found effective in inhibition of membrane biofouling with much less environmental impact than traditional antimicrobials. Work over the past few years has demonstrated that enzymatic quorum quenching mechanisms are widely conserved in several prokaryotic organisms and can be utilized as a potent tool for inhibition of membrane biofouling. Such naturally occurring bacterial quorum quenching mechanisms also play important roles in microbe-microbe interactions and have been used to develop sustainable nonantibiotic antifouling strategies. Advances in membrane fabrication and bacteria entrapment techniques have allowed the implication of such quorum quenching bacteria for better design of membrane bioreactor with improved antibiofouling efficacies. In view of this, the present paper is designed to review and discuss the recent developments in control of membrane biofouling with special emphasis on quorum quenching bacteria that are applied in membrane bioreactors. PMID:25147787

  16. A quorum-sensing-induced bacteriophage defense mechanism

    DEFF Research Database (Denmark)

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

    2013-01-01

    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...... of uninfected survivor cells after a potent attack by virulent phages. Notably, this mechanism may apply to a broader range of phages, as AHLs also reduce the risk of ¿ phage infection through a different receptor. IMPORTANCE To enable the successful manipulation of bacterial populations, a comprehensive...... understanding of the factors that naturally shape microbial communities is required. One of the key factors in this context is the interactions between bacteria and the most abundant biological entities on Earth, namely, the bacteriophages that prey on bacteria. This proof-of-principle study shows that quorum...

  17. Quorum Sensing and Bacterial Social Interactions in Biofilms

    Science.gov (United States)

    Li, Yung-Hua; Tian, Xiaolin

    2012-01-01

    Many bacteria are known to regulate their cooperative activities and physiological processes through a mechanism called quorum sensing (QS), in which bacterial cells communicate with each other by releasing, sensing and responding to small diffusible signal molecules. The ability of bacteria to communicate and behave as a group for social interactions like a multi-cellular organism has provided significant benefits to bacteria in host colonization, formation of biofilms, defense against competitors, and adaptation to changing environments. Importantly, many QS-controlled activities have been involved in the virulence and pathogenic potential of bacteria. Therefore, understanding the molecular details of quorum sensing mechanisms and their controlled social activities may open a new avenue for controlling bacterial infections. PMID:22736963

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2013-12-01

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

  20. Quorum sensing inhibitors from Leucetta chagosensis Dendy, 1863.

    Science.gov (United States)

    Mai, T; Tintillier, F; Lucasson, A; Moriou, C; Bonno, E; Petek, S; Magré, K; Al Mourabit, A; Saulnier, D; Debitus, C

    2015-10-01

    Sponges are a rich source for investigation of bioactive small molecules. They have been mostly investigated for the search of new pharmacological models or therapeutic agents for the treatment of human diseases. Micro-organisms can also represent a virulent pathogen for marine invertebrates such as sponges, which need to protect themselves against these microbes. Sponges' self defence mechanisms involving dialogue molecules thus represent a pertinent research track for potent anti-infective and anti-biofilm activities such as quorum sensing inhibitors (QSIs). The investigation of the QSI crude extract of Leucetta chagosensis Dendy, 1863 led to the isolation of three new alkaloids, isonaamine D, di-isonaamidine A and leucettamine D, along with the known isonaamine A and isonaamidine A. Isonaamidine A and isonaamine D were identified as inhibitors of the three quorum sensing pathways of Vibrio harveyi (CAI-1, AI-2 and harveyi auto inducer), but isonaamidine A displayed the strongest activity on AI-2 biosensor. Both compounds are new examples of natural QSIs of V. harveyi. These results outline the importance of these secondary metabolites for their producing organisms themselves in their natural environment, as well as the potential of the marine resource for aquaculture needs. A new type of quorum sensing inhibitors was isolated from the sponge Leucetta chagosensis. One of them inhibits strongly the AI-2 channel of Vibrio harveyi, a marine pathogen of special importance in aquaculture. The activity of five different related compounds, including three new natural products discovered there, was investigated leading to structure-activity relationships which are useful for the design of new quorum sensing inhibitors to control marine infectious pathogens. © 2015 The Society for Applied Microbiology.

  1. Mitigating Seawater Desalination Membrane Biofouling using Quorum Sensing Inhibitors

    OpenAIRE

    Katebian, Leda

    2016-01-01

    Coastal seawater desalination using reverse osmosis (RO) membranes has the potential to alleviate water stress in arid regions. However, membrane biofouling, caused by bacterial biofilm formation, is a significant challenge for seawater desalination plants. Biofilm formation is regulated by quorum sensing (QS) pathways where bacteria secrete auto-inducer molecules to communicate with neighboring bacteria to activate biofilm formation. This research investigated the role of the QS system and t...

  2. Failure of azithromycin 2.0 g in the treatment of gonococcal urethritis caused by high-level resistance in California.

    Science.gov (United States)

    Gose, Severin O; Soge, Olusegun O; Beebe, James L; Nguyen, Duylinh; Stoltey, Juliet E; Bauer, Heidi M

    2015-05-01

    We report a treatment failure to azithromycin 2.0 g caused by a urethral Neisseria gonorrhoeae isolate with high-level azithromycin resistance in California. This report describes the epidemiological case investigation and phenotypic and genetic characterization of the treatment failure isolate.

  3. The long-term safety of chronic azithromycin use in patients with cystic fibrosis regarding the condition of the kidney, liver and heart

    NARCIS (Netherlands)

    Möhlmann, J.E.; Majoor, C.J.; Van Der Vaart, H.; Touw, D.

    2016-01-01

    Background: Azithromycin is a widely used macrolide antibiotic in cystic fibrosis (CF), but little is known about the safety of long-term use. Reported side effects only apply to short-term use. The aim of this study is to investigate possible azithromycin-induced toxicity of the kidney, liver and

  4. Antimicrobial Activities and Postantibiotic Effects of Clarithromycin, 14-Hydroxy-Clarithromycin, and Azithromycin in Epithelial Cell Lining Fluid against Clinical Isolates of Haemophilus influenzae and Streptococcus pneumoniae

    OpenAIRE

    Bergman, Kimberly L.; Olsen, Keith M.; Peddicord, Tom E.; Fey, Paul D.; Rupp, Mark E.

    1999-01-01

    The antimicrobial activity of concentrations of selected macrolides found in epithelial cell lining fluid was investigated. Clarithromycin demonstrated greater potency and a significantly longer postantibiotic effect (PAE) than azithromycin against Streptococcus pneumoniae. Azithromycin displayed greater potency, faster killing, and a longer PAE than clarithromycin against Haemophilus influenzae. Drug concentrations in epithelial cell lining fluid similar to those found in tissue did not impr...

  5. Stereochemical insignificance discovered in Acinetobacter baumannii quorum sensing.

    Directory of Open Access Journals (Sweden)

    Amanda L Garner

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

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

    Science.gov (United States)

    Singh, Harpartap; Parmananda, P.

    2013-10-01

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

  7. On the pathway to better birth outcomes? A systematic review of azithromycin and curable sexually transmitted infections

    Science.gov (United States)

    Chico, R Matthew; Hack, Berkin B; Newport, Melanie J; Ngulube, Enesia; Chandramohan, Daniel

    2013-01-01

    The WHO recommends the administration of sulfadoxine-pyrimethamine (SP) to all pregnant women living in areas of moderate (stable) to high malaria transmission during scheduled antenatal visits, beginning in the second trimester and continuing to delivery. Malaria parasites have lost sensitivity to SP in many endemic areas, prompting the investigation of alternatives that include azithromycin-based combination (ABC) therapies. Use of ABC therapies may also confer protection against curable sexually transmitted infections and reproductive tract infections (STIs/RTIs). The magnitude of protection at the population level would depend on the efficacy of the azithromycin-based regimen used and the underlying prevalence of curable STIs/RTIs among pregnant women who receive preventive treatment. This systematic review summarizes the efficacy data of azithromycin against curable STIs/RTIs. PMID:24191955

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

    KAUST Repository

    Scarascia, Giantommaso

    2016-12-15

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

  9. Azithromycin Treatment Failure for Chlamydia trachomatis Among Heterosexual Men With Nongonococcal Urethritis.

    Science.gov (United States)

    Kissinger, Patricia J; White, Scott; Manhart, Lisa E; Schwebke, Jane; Taylor, Stephanie N; Mena, Leandro; Khosropour, Christine M; Wilcox, Larissa; Schmidt, Norine; Martin, David H

    2016-10-01

    Three recent prospective studies have suggested that the 1-g dose of azithromycin for Chlamydia trachomatis (Ct) was less effective than expected, reporting a wide range of treatment failure rates (5.8%-22.6%). Reasons for the disparate results could be attributed to geographic or methodological differences. The purpose of this study was to reexamine the studies and attempt to harmonize methodologies to reduce misclassification as a result of false positives from early test-of-cure (TOC) or reinfection as a result of sexual exposure rather than treatment failure. Men who had sex with women, who received 1-g azithromycin under directly observed therapy for presumptive treatment of nongonococcal urethritis with confirmed Ct were included. Baseline screening was performed on urethral swabs or urine, and TOC screening was performed on urine using nucleic acid amplification tests. Posttreatment vaginal sexual exposure was elicited at TOC. Data from the 3 studies were obtained and reanalyzed. Rates of Ct retest positive were examined for all cases, and a sensitivity analysis was conducted to either reclassify potential false positives/reinfections as negative or remove them from the analysis. The crude treatment failure rate was 12.8% (31/242). The rate when potential false positives/reinfections were reclassified as negative was 6.2% (15/242) or when these were excluded from analysis was 10.9% (15/138). In these samples of men who have sex with women with Ct-related nongonococcal urethritis, azithromycin treatment failure was between 6.2% and 12.8%. This range of failure is lower than previously published but higher than the desired World Health Organization's target chlamydia treatment failure rate of < 5%.

  10. Azithromycin in the treatment of mucosal leishmaniasis Azitromicina no tratamento da leishmaniose mucosa

    Directory of Open Access Journals (Sweden)

    Mario León Silva-Vergara

    2004-06-01

    Full Text Available This report describes three elderly patients with mucosal form of American tegumentary leishmaniasis associated with chronic cardiopathy. Due to the known toxicity of classical drugs with activity against Leishmania sp., the patients received three oral courses of azithromycin therapy in single 500 mg daily dose during ten days, every other month. All lesions healed after the third series. One of the patients relapsed and a new series of azithromycin was prescribed. Azithromycin may be an alternative drug for the treatment of leishmaniasis in special situations due to its optimal mucosal and intraphagocyte concentration, single daily posology, high tolerance and oral administration. The mechanism of this drug on Leishmania sp. is unknown at present.O presente relato descreve três pacientes idosos com leishmaniose mucosa de longa evolução, os quais eram portadores de cardiopatia crônica. Pela alta freqüência de efeitos secundários e tóxicos dos medicamentos utilizados no tratamento clássico, esses pacientes receberam azitromicina. Este medicamento foi administrado pela via oral, em dose única diária de 500 mg, durante dez dias, em três séries com intervalo de um mês. Em todos, houve cicatrização das lesões depois da terceira série. Um dos pacientes apresentou recidiva após seis meses e uma nova série de azitromicina fez regredir novamente o quadro. Azitromicina pode ser uma alternativa para o tratamento das leishmanioses, principalmente pela concentração adequada em mucosas e nos fagócitos, posologia única diária, boa tolerância e administração oral.

  11. Development of low density azithromycin-loaded polycaprolactone microparticles for pulmonary delivery.

    Science.gov (United States)

    Kasten, Georgia; Silva, Luis Felipe Costa; Lemos-Senna, Elenara

    2016-05-01

    The development of low-density polymeric microparticles may be a useful approach to deliver antibiotics such as azithromycin into the lung. The aim of this study was to develop azithromycin-loaded low density polycaprolactone microparticles by the double emulsion/solvent evaporation method. Microparticles were prepared and characterized according to their physicochemical properties, drug loading, and drug release profiles. A full 2 3 factorial design was used to evaluate the effect of some independent variables on the drug loading and aerodynamic diameter of the particles. An in silico pulmonary deposition model was used to predict the lung deposition profiles for the formulations. The resulting particles presented drug loading up to 23.1% (wt%) and mean geometric diameters varying from 4.0 µm to 15.4 µm. Bulk and tapped densities were low, resulting in good or excellent flow properties. SEM images showed spherical particles with a smooth surface. However, hollow inner structures were observed, which may explain the low values of bulk density. The estimated aerodynamic diameters ranged from 2.3 µm to 8.9 µm. The in silico pulmonary deposition profiles indicated, for some formulations, that a significant fraction of the particles would be deposited in the deeper lung regions. Statistical analysis demonstrated that not only drug loading but also the aerodynamic diameter of the microparticles is greatly affected by the preparation conditions. Overall, the results indicated that the low-density azithromycin-loaded microparticles with a relatively high respirable fraction may be obtained for the local treatment of lung infections.

  12. Single-Dose Azithromycin for the Treatment of Haemophilus ducreyi Skin Ulcers in Papua New Guinea.

    Science.gov (United States)

    González-Beiras, Camila; Kapa, August; Vall-Mayans, Marti; Paru, Raymond; Gavilán, Sergi; Houinei, Wendy; Bieb, Sibauk; Sanz, Sergi; Martins, Rosario; Mitjà, Oriol

    2017-11-29

    Haemophilus ducreyi (HD) and Treponema pallidum subspecies pertenue (TP) are major causative agents of cutaneous ulcer (CU) in the tropics. Azithromycin is recommended to treat sexually transmitted HD infections and has good in vitro activity against HD strains from both genital and skin ulcers. We investigated the efficacy of oral single-dose azithromycin on HD-CU. We conducted a community-based cohort study in Lihir Island, Papua New Guinea, from October 2014 through May 2016. Consenting patients with skin ulcers >1 cm in diameter were eligible for this study and had collected a lesional swab for polymerase chain reaction (PCR). All participants were treated with single-dose azithromycin (30 mg/kg) and were followed up for assessment of clinical resolution. We retrospectively classified patients according to PCR results into HD, TP, and PCR-negative groups. The primary endpoint was healing rates of HD-CU at 14 days after treatment. We obtained full outcome data from 246 patients; 131 (53.3%) were HD PCR positive, 37 (15.0%) were TP positive, and 78 (31.7%) were negative for all tests. Healing rates were 88.5% (95% confidence interval [CI], .82-.93) in the HD group, 78.4% [95% CI, .63-.89] in the TP group, and 74.4% (95% CI, .64-.83) in the PCR-negative group. If we included the participants with improved ulcers, the healing rates increased to 94.7%, 97.3%, and 89.7% respectively. HD cases classified as not healed all converted to HD-negative PCR. Based upon clinical resolution and PCR conversion to HD negative, a single oral dose of azithromycin is efficacious for the treatment of HD-CU. These results have implications for the treatment of individual patients and for the use of antibiotics in public health strategies to control CU in the tropics. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  13. Effect of azithromycin on the LPS-induced production and secretion of phospholipase A2 in lung cells.

    Science.gov (United States)

    Kitsiouli, Eirini; Antoniou, Georgia; Gotzou, Helen; Karagiannopoulos, Michalis; Basagiannis, Dimitris; Christoforidis, Savvas; Nakos, George; Lekka, Marilena E

    2015-07-01

    Azithromycin is a member of macrolides, utilized in the treatment of infections. Independently, these antibiotics also possess anti-inflammatory and immunomodulatory properties. Phospholipase A2 isotypes, which are implicated in the pathophysiology of inflammatory lung disorders, are produced by alveolar macrophages and other lung cells during inflammatory response and can promote lung injury by destructing lung surfactant. The aim of the study was to investigate whether in lung cells azithromycin can inhibit secretory and cytosolic phospholipases A2, (sPLA2) and (cPLA2), respectively, which are induced by an inflammatory trigger. In this respect, we studied the lipopolysaccharide (LPS)-mediated production or secretion of sPLA2 and cPLA2 from A549 cells, a cancer bronchial epithelial cell line, and alveolar macrophages, isolated from bronchoalveolar lavage fluid of ARDS and control patients without cardiopulmonary disease or sepsis. Pre-treatment of cells with azithromycin caused a dose-dependent decrease in the LPS-induced sPLA2-IIA levels in A549 cells. This inhibition was rather due to reduced PLA2G2A mRNA expression and secretion of sPLA2-IIA protein levels, as observed by western blotting and indirect immunofluorescence by confocal microscopy, respectively, than to the inhibition of the enzymic activity per se. On the contrary, azithromycin had no effect on the LPS-induced production or secretion of sPLA2-IIA from alveolar macrophages. The levels of LPS-induced c-PLA2 were not significantly affected by azithromycin in either cell type. We conclude that azithromycin exerts anti-inflammatory properties on lung epithelial cells through the inhibition of both the expression and secretion of LPS-induced sPLA2-IIA, while it does not affect alveolar macrophages. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Cluster of Neisseria gonorrhoeae Isolates With High-level Azithromycin Resistance and Decreased Ceftriaxone Susceptibility, Hawaii, 2016.

    Science.gov (United States)

    Katz, Alan R; Komeya, Alan Y; Kirkcaldy, Robert D; Whelen, A Christian; Soge, Olusegun O; Papp, John R; Kersh, Ellen N; Wasserman, Glenn M; O'Connor, Norman P; O'Brien, Pamela S; Sato, Douglas T; Maningas, Eloisa V; Kunimoto, Gail Y; Tomas, Juval E

    2017-09-15

    The Centers for Disease Control and Prevention (CDC) currently recommends dual therapy with ceftriaxone and azithromycin for gonorrhea to ensure effective treatment and slow emergence of antimicrobial resistance. Since 2013, the prevalence of reduced azithromycin susceptibility increased in the United States; however, these strains were highly susceptible to cephalosporins. We identified a cluster of Neisseria gonorrhoeae isolates with high-level azithromycin resistance, several of which also demonstrated decreased ceftriaxone susceptibility. Eight N. gonorrhoeae isolates collected from 7 patients on Oahu, Hawaii, seen 21 April 2016 through 10 May 2016 underwent routine Etest antimicrobial susceptibility testing by the Hawaii Department of Health. All demonstrated elevated azithromycin minimum inhibitory concentrations (MICs) >256 μg/mL and elevated ceftriaxone MICs (≥0.125 μg/mL). Isolates were sent to the University of Washington and CDC for confirmatory agar dilution testing; sequence data were sent to CDC for analysis. All patients were interviewed and treated, and when possible, partners were interviewed, tested, and treated. All isolates had azithromycin MICs >16 µg/mL and 5 had ceftriaxone MICs = 0.125 µg/mL by agar dilution. All isolates were β-lactamase positive and were resistant to penicillin, tetracycline, and ciprofloxacin. Genomic analysis revealed genetic relatedness. No patients reported recent travel or antibiotic use, and no male patients reported male sex partners. All patients were successfully treated. This cluster of genetically related gonococcal isolates with decreased ceftriaxone susceptibility and high-level azithromycin resistance may bring the threat of treatment failure in the United States with the current recommended dual therapy one step closer. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  15. Trends in antimicrobial susceptibility for azithromycin and ceftriaxone in Neisseria gonorrhoeae isolates in Amsterdam, the Netherlands, between 2012 and 2015.

    Science.gov (United States)

    Wind, Carolien M; Schim van der Loeff, Maarten F; van Dam, Alje P; de Vries, Henry Jc; van der Helm, Jannie J

    2017-01-05

    Resistance of Neisseria gonorrhoeae to azithromycin and ceftriaxone has been increasing in the past years. This is of concern since the combination of these antimicrobials is recommended as the first-line treatment option in most guidelines. To analyse trends in antimicrobial resistance, we retrospectively selected all consultations with a positive N. gonorrhoeae culture at the sexually transmitted infection clinic, Amsterdam, the Netherlands, from January 2012 through September 2015. Minimum inhibitory concentrations (MICs) for azithromycin and ceftriaxone were analysed per year, and determinants associated with decreased susceptibility to azithromycin (MIC > 0.25 mg/L) or ceftriaxone (MIC > 0.032 mg/L) were assessed. Between 2012 and 2015 azithromycin resistance (MIC > 0.5 mg/L) was around 1.2%, the percentage of isolates with intermediate MICs (> 0.25 and ≤ 0.5 mg/L) increased from 3.7% in 2012, to 8.6% in 2015. Determinants associated with decreased azithromycin susceptibility were, for men who have sex with men (MSM), infections diagnosed in the year 2014, two infected sites, and HIV status (HIV; associated with less decreased susceptibility); for heterosexuals this was having ≥ 10 sex partners (in previous six months). Although no ceftriaxone resistance (MIC > 0.125 mg/L) was observed during the study period, the proportion of isolates with decreased ceftriaxone susceptibility increased from 3.6% in 2012, to 8.4% in 2015. Determinants associated with decreased ceftriaxone susceptibility were, for MSM, infections diagnosed in 2014, and pharyngeal infections; and for heterosexuals, infections diagnosed in 2014 or 2015, being of female sex, and having ≥ 10 sex partners. Continued decrease of azithromycin and ceftriaxone susceptibility will threaten future treatment of gonorrhoea. Therefore, new treatment strategies are warranted. This article is copyright of The Authors, 2017.

  16. 12 CFR 7.2009 - Quorum of the board of directors; proxies not permissible.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Quorum of the board of directors; proxies not... BANK ACTIVITIES AND OPERATIONS Corporate Practices § 7.2009 Quorum of the board of directors; proxies... office. A national bank director may not vote by proxy. ...

  17. A broad range quorum sensing inhibitor working through sRNA inhibition

    DEFF Research Database (Denmark)

    Jakobsen, Tim H.; Warming, Anders N.; Vejborg, Rebecca M.

    2017-01-01

    that the repressing effect of ajoene on quorum sensing occurs by inhibition of small regulatory RNAs (sRNA) in P. aeruginosa as well as in Staphylococcus aureus, another important human pathogen that employs quorum sensing to control virulence gene expression. Using various reporter constructs, we found that ajoene...

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  19. Pseudomonas aeruginosa mutations in lasl and rhll quorum sensing systems result in milder chronic lung infection

    DEFF Research Database (Denmark)

    Wu, H.; Song, Z.J.; Givskov, Michael Christian

    2001-01-01

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

  20. Inactivation of bacterial quorum sensing signals N-acyl homoserine lactones is widespread in yeasts.

    Science.gov (United States)

    Leguina, Ana Carolina Del V; Nieto, Carolina; Pajot, Hipólito M; Bertini, Elisa V; Mac Cormack, Walter; Castellanos de Figueroa, Lucía I; Nieto-Peñalver, Carlos G

    2018-01-01

    The inactivation of quorum sensing signals, a phenomenon known as quorum quenching, has been described in diverse microorganisms, though it remains almost unexplored in yeasts. Beyond the well-known properties of these microorganisms for the industry or as eukaryotic models, the role of yeasts in soil or in the inner tissues of a plant is largely unknown. In this report, the wider survey of quorum quenching activities in yeasts isolated from Antarctic soil and the inner tissues of sugarcane, a tropical crop, is presented. Results show that, independently of their niche, quorum quenching activities are broadly present in unicellular fungi. Although yeasts showing a broad range of quorum quenching activity are present in the two niches, at the same time specific AHL inactivation profiles can also be found. Furthermore, yeasts from both sampling sites show quorum quenching activities compatible with lactonase-like and acylase-like inactivations of AHLs. Interestingly, the characterization of Rhodotorula mucilaginosa 7Apo1 showed that the presence of a particular AHL does not interfere with the quenching of a second molecule. Evidence suggests that yeasts could play a role in the modulation of the quorum sensing activity of bacteria. The relationship among phylogeny, sampling sites and yeast quorum quenching activities of the isolates is analyzed. Copyright © 2017 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    2011-01-01

    Background Biofilms are microbial communities encased in a layer of extracellular polymeric substances (EPS). The EPS matrix provides several functional purposes for the biofilm, such as protecting bacteria from environmental stresses, and providing mechanical stability. Quorum sensing is a cell-cell communication mechanism used by several bacterial taxa to coordinate gene expression and behaviour in groups, based on population densities. Model We mathematically model quorum sensing and EPS production in a growing biofilm under various environmental conditions, to study how a developing biofilm impacts quorum sensing, and conversely, how a biofilm is affected by quorum sensing-regulated EPS production. We investigate circumstances when using quorum-sensing regulated EPS production is a beneficial strategy for biofilm cells. Results We find that biofilms that use quorum sensing to induce increased EPS production do not obtain the high cell populations of low-EPS producers, but can rapidly increase their volume to parallel high-EPS producers. Quorum sensing-induced EPS production allows a biofilm to switch behaviours, from a colonization mode (with an optimized growth rate), to a protection mode. Conclusions A biofilm will benefit from using quorum sensing-induced EPS production if bacteria cells have the objective of acquiring a thick, protective layer of EPS, or if they wish to clog their environment with biomass as a means of securing nutrient supply and outcompeting other colonies in the channel, of their own or a different species. PMID:21477365

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

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  4. The organophosphate malathion disturbs gut microbiome development and the quorum-Sensing system.

    Science.gov (United States)

    Gao, Bei; Chi, Liang; Tu, Pengcheng; Bian, Xiaoming; Thomas, Jesse; Ru, Hongyu; Lu, Kun

    2018-02-01

    The gut microbiome has tremendous potential to impact health and disease. Various environmental toxicants, including insecticides, have been shown to alter gut microbiome community structures. However, the mechanism that compositionally and functionally regulates gut microbiota remains unclear. Quorum sensing is known to modulate intra- and interspecies gene expression and coordinate population responses. It is unknown whether quorum sensing is disrupted when environmental toxicants cause perturbations in the gut microbiome community structure. To reveal the response of the quorum-sensing system to environmental exposure, we use a combination of Illumina-based 16S rRNA gene amplicon and shotgun metagenome sequencing to examine the impacts of a widely used organophosphate insecticide, malathion, on the gut microbiome trajectory, quorum sensing system and behaviors related to quorum sensing, such as motility and pathogenicity. Our results demonstrated that malathion perturbed the gut microbiome development, quorum sensing and quorum sensing related behaviors. These findings may provide a novel mechanistic understanding of the role of quorum-sensing in the gut microbiome toxicity of malathion. Copyright © 2017. Published by Elsevier B.V.

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  6. Pseudomonas aeruginosa mutations in lasl and rhll quorum sensing systems result in milder chronic lung infection

    DEFF Research Database (Denmark)

    Wu, H.; Song, Z.J.; Givskov, Michael Christian

    2001-01-01

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

  7. Overall Low Extended-Spectrum Cephalosporin Resistance but high Azithromycin Resistance in Neisseria gonorrhoeae in 24 European Countries, 2015.

    Science.gov (United States)

    Cole, Michelle J; Spiteri, Gianfranco; Jacobsson, Susanne; Woodford, Neil; Tripodo, Francesco; Amato-Gauci, Andrew J; Unemo, Magnus

    2017-09-11

    Surveillance of Neisseria gonorrhoeae antimicrobial susceptibility in Europe is performed through the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP), which additionally provides data to inform the European gonorrhoea treatment guideline; currently recommending ceftriaxone 500 mg plus azithromycin 2 g as first-line therapy. We present antimicrobial susceptibility data from 24 European countries in 2015, linked to epidemiological data of patients, and compare the results to Euro-GASP data from previous years. Antimicrobial susceptibility testing by MIC gradient strips or agar dilution methodology was performed on 2134 N. gonorrhoeae isolates and interpreted using EUCAST breakpoints. Patient variables associated with resistance were established using logistic regression to estimate odds ratios (ORs). In 2015, 1.7% of isolates were cefixime resistant compared to 2.0% in 2014. Ceftriaxone resistance was detected in only one (0.05%) isolate in 2015, compared with five (0.2%) in 2014. Azithromycin resistance was detected in 7.1% of isolates in 2015 (7.9% in 2014), and five (0.2%) isolates displayed high-level azithromycin resistance (MIC ≥ 256 mg/L) compared with one (0.05%) in 2014. Ciprofloxacin resistance remained high (49.4%, vs. 50.7% in 2014). Cefixime resistance significantly increased among heterosexual males (4.1% vs. 1.7% in 2014), which was mainly attributable to data from two countries with high cefixime resistance (~11%), however rates among men-who-have-sex-with-men (MSM) and females continued to decline to 0.5% and 1%, respectively. Azithromycin resistance in MSM and heterosexual males was higher (both 8.1%) than in females (4.9% vs. 2.2% in 2014). The association between azithromycin resistance and previous gonorrhoea infection, observed in 2014, continued in 2015 (OR 2.1, CI 1.2-3.5, p resistance and low overall resistance to ceftriaxone and cefixime. The low cephalosporin resistance may be attributable to the effectiveness

  8. Topical azithromycin for the prevention of Lyme borreliosis: a randomised, placebo-controlled, phase 3 efficacy trial.

    Science.gov (United States)

    Schwameis, Michael; Kündig, Thomas; Huber, Gustave; von Bidder, Luzi; Meinel, Lorenz; Weisser, Roland; Aberer, Elisabeth; Härter, Georg; Weinke, Thomas; Jelinek, Tomas; Fätkenheuer, Gerd; Wollina, Uwe; Burchard, Gerd-Dieter; Aschoff, Roland; Nischik, Ruth; Sattler, Gerhard; Popp, Georg; Lotte, Wolfgang; Wiechert, Dirk; Eder, Gerald; Maus, Olga; Staubach-Renz, Petra; Gräfe, Andrea; Geigenberger, Veronika; Naudts, Ingomar; Sebastian, Michael; Reider, Norbert; Weber, Ridwan; Heckmann, Marc; Reisinger, Emil C; Klein, Georg; Wantzen, Johannes; Jilma, Bernd

    2017-03-01

    Lyme borreliosis develops in 1-5% of individuals bitten by ticks, but with a diagnostic gap affecting up to 30% of patients, a broadly applicable pharmacological prevention strategy is needed. Topical azithromycin effectively eradicated Borrelia burgdorferi sensu lato from the skin in preclinical studies. We assessed its efficacy in human beings. In this randomised, double-blind, placebo-controlled, multicentre trial done in 28 study sites in Germany and Austria, adults were equally assigned to receive topical 10% azithromycin or placebo twice daily for 3 consecutive days, within 72 h of a tick bite being confirmed. Randomisation numbers, which were stratified by study site, were accessed in study centres via an interactive voice-response system, by pharmacists not involved in the study. The primary outcome was the number of treatment failures, defined as erythema migrans, seroconversion, or both, in participants who were seronegative at baseline, had no further tick bites during the study, and had serology results available at 8 weeks (intention-to-treat [ITT] population). This study is registered with EudraCT, number 2011-000117-39. Between July 7, 2011, and Dec 3, 2012, 1371 participants were randomly assigned to treatment, of whom 995 were included in the ITT population. The trial was stopped early because an improvement in the primary endpoint in the group receiving azithromycin was not reached. At 8 weeks, 11 (2%) of 505 in the azithromycin group and 11 (2%) of 490 in the placebo group had treatment failure (odds ratio 0·97, 95% CI 0·42-2·26, p=0·47). Topical azithromycin was well tolerated. Similar numbers of patients had adverse events in the two groups (175 [26%] of 505 vs 177 [26%] of 490, p=0·87), and most adverse events were mild. Topical azithromycin was well tolerated and had a good safety profile. Inclusion of asymptomatic seroconversion into the primary efficacy analysis led to no prevention effect with topical azithromycin. Adequately powered

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

    Science.gov (United States)

    Rutherford, Steven T.; Bassler, Bonnie L.

    2012-01-01

    Quorum sensing is a process of cell–cell communication that allows bacteria to share information about cell density and adjust gene expression accordingly. This process enables bacteria to express energetically expensive processes as a collective only when the impact of those processes on the environment or on a host will be maximized. Among the many traits controlled by quorum sensing is the expression of virulence factors by pathogenic bacteria. Here we review the quorum-sensing circuits of Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, and Vibrio cholerae. We outline these canonical quorum-sensing mechanisms and how each uniquely controls virulence factor production. Additionally, we examine recent efforts to inhibit quorum sensing in these pathogens with the goal of designing novel antimicrobial therapeutics. PMID:23125205

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

    Science.gov (United States)

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

    2015-01-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  12. [Wastewater treatment based on biofilm regulation by Lux type quorum sensing system-a review].

    Science.gov (United States)

    Zhao, Chang; Wang, Ning; Wang, Wenzhao; Xu, Qiyong

    2017-09-25

    Studies on biofilm regulation based on Lux type quorum sensing system in wastewater treatment have attracted much attention. The intervention of quorum sensing system includes both mechanisms of positive and negative control. The positive invigorating effect improves the efficiency of biofilm wastewater treatment, promotes the production of extracellular polymeric substance (EPS) and soluble microbial products (SMP), and increases the yield of biofilm. The negative weakening effect of quorum sensing can decompose the signal molecules needed in the process of biofilm formation, interrupts the gene expression process of biofilm formation, and inhibits the formation of biofilm on MBR membrane surface effectively. The further study of the structure and mechanism of N-acyl homoserine lactone (AHLs), the immobilization technology and application of quorum quenching bacteria, the synergistic effect verification of different biofouling control methods and the application feasibility of quorum sensing system based technology in more wastewater treatment fields are the next important researches to explore.

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

    DEFF Research Database (Denmark)

    Høyland-Kroghsbo, Nina Molin

    in the bacterial cell-cell communication field is why E. coli harbors SdiA, an orphan quorum sensing receptor that is activated in response to AHL quorum sensing molecules produced by other Gram-negative species. The overall aim of this PhD thesis was to investigate to what degree AHL quorum sensing signals...... are exploited by E. coli to increase its chances of surviving potential environmental threats. This thesis uncovers the first quorum sensing-regulated bacteriophage defense mechanism, which serves to protect E. coli against infection by the bacteriophage viruses λ and χ. Investigating the regulatory mechanism...... underlying the quorum sensing regulated defense mechanism, led to the discovery that AHL activates expression of cnu, encoding an Hha-family protein that interacts with the global regulatory protein H-NS, and potentially modifies its functions. Inspired by the discovery that AHL protects E. coli from...

  14. Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Jensen, Peter Østrup; Rasmussen, Thomas B

    2005-01-01

    to otherwise lethal doses of antibiotics, and protects against the bactericidal activity of polymorphonuclear leukocytes (PMNs). It has been previously demonstrated that QS is inhibited by garlic extract. In this study, the synergistic effects of garlic and tobramycin, and PMNs activities have been evaluated...

  15. Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Jensen, P. Ø.; Rasmussen, Thomas Bovbjerg

    2005-01-01

    to otherwise lethal doses of antibiotics, and protects against the bactericidal activity of polymorphonuclear leukocytes (PMNs). It has been previously demonstrated that QS is inhibited by garlic extract. In this study, the synergistic effects of garlic and tobramycin, and PMNs activities have been evaluated....... P. aeruginosa was grown in vitro in continuous-culture once-through flow chambers with and without garlic extract. The garlic-treated biofilms were susceptible to both tobramycin and PMN grazing. Furthermore, the PMNs showed an increase in respiratory burst activation, when incubated with the garlic......-treated biofilm. Garlic extract was administered as treatment for a mouse pulmonary infection model. Mice were treated with garlic extract or placebo for 7 days, with the initial 2 days being prophylactic before P. aeruginosa was instilled in the left lung of the mice. Bacteriology, mortality, histopathology...

  16. Coumarin: a novel player in microbial quorum sensing and biofilm formation inhibition.

    Science.gov (United States)

    Reen, F Jerry; Gutiérrez-Barranquero, José A; Parages, María L; O Gara, Fergal

    2018-03-01

    Antibiotic resistance is a growing threat worldwide, causing serious problems in the treatment of microbial infections. The discovery and development of new drugs is urgently needed to overcome this problem which has greatly undermined the clinical effectiveness of conventional antibiotics. An intricate cell-cell communication system termed quorum sensing (QS) and the coordinated multicellular behaviour of biofilm formation have both been identified as promising targets for the treatment and clinical management of microbial infections. QS systems allow bacteria to adapt rapidly to harsh conditions, and are known to promote the formation of antibiotic tolerant biofilm communities. It is well known that biofilm is a recalcitrant mode of growth and it also increases bacterial resistance to conventional antibiotics. The pharmacological properties of coumarins have been well described, and these have included several that possess antimicrobial properties. More recently, reports have highlighted the potential role of coumarins as alternative therapeutic strategies based on their ability to block the QS signalling systems and to inhibit the formation of biofilms in clinically relevant pathogens. In addition to human infections, coumarins have also been found to be effective in controlling plant pathogens, infections in aquaculture, food spoilage and in reducing biofouling caused by eukaryotic organisms. Thus, the coumarin class of small molecule natural product are emerging as a promising strategy to combat bacterial infections in the new era of antimicrobial resistance.

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

    Directory of Open Access Journals (Sweden)

    Melissa Starkey

    2014-08-01

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

  18. Clinical Efficacy of a Single Two Gram Dose of Azithromycin Extended Release for Male Patients with Urethritis.

    Science.gov (United States)

    Takahashi, Satoshi; Kiyota, Hiroshi; Ito, Shin; Iwasawa, Akihiko; Hiyama, Yoshiki; Uehara, Teruhisa; Ichihara, Koji; Hashimoto, Jiro; Masumori, Naoya; Sunaoshi, Kenichi; Takeda, Koichi; Suzuki, Nobukazu; Hosobe, Takahide; Goto, Hirokazu; Suzuki, Hidenori; Onodera, Shoichi

    2014-04-02

    To clarify the clinical efficacy of a single oral 2 g dose of azithromycin extended-release for heterosexual male patients with urethritis, and the current antimicrobial sensitivity of Neisseria gonorrhoeae to azithromycin, a prospective clinical trial was conducted from 2011-2013. In patients with gonococcal urethritis, the eradication rate was 90.9% (30 of 33). The susceptibility rates of isolated Neisseria gonorrhoeae strains to ceftriaxone, spectinomycin, cefixime and azithromycin were 100%, 100%, 95.3% (41/43) and 37.2% (16/43), respectively. In the patients with nongonococcal urethritis, the eradication rate was 90.0% (45 of 50). The microbiological eradication rates for the pathogens were 90.9% (30/33) for Neisseria gonorrhoeae, 91.5% (43/47) for Chlamydia trachomatis, 71.4% (5/7) for Mycoplasma genitalium, and 100% (13/13) for Ureaplasma urealyticum. The main adverse event was diarrhea and its manifestation rate was 35.2% (32 of 120). The symptom of diarrhea was mostly temporary and resolved spontaneously. The conclusion was that the treatment regimen with a single oral 2 g dose of azithromycin extended-release would be effective for patients with urethritis. However, the antimicrobial susceptibilities of Neisseria gonorrhoeae and Mycoplasma genitalium should be carefully monitored because of possible treatment failure.

  19. Clinical Efficacy of a Single Two Gram Dose of Azithromycin Extended Release for Male Patients with Urethritis

    Directory of Open Access Journals (Sweden)

    Satoshi Takahashi

    2014-04-01

    Full Text Available To clarify the clinical efficacy of a single oral 2 g dose of azithromycin extended-release for heterosexual male patients with urethritis, and the current antimicrobial sensitivity of Neisseria gonorrhoeae to azithromycin, a prospective clinical trial was conducted from 2011–2013. In patients with gonococcal urethritis, the eradication rate was 90.9% (30 of 33. The susceptibility rates of isolated Neisseria gonorrhoeae strains to ceftriaxone, spectinomycin, cefixime and azithromycin were 100%, 100%, 95.3% (41/43 and 37.2% (16/43, respectively. In the patients with nongonococcal urethritis, the eradication rate was 90.0% (45 of 50. The microbiological eradication rates for the pathogens were 90.9% (30/33 for Neisseria gonorrhoeae, 91.5% (43/47 for Chlamydia trachomatis, 71.4% (5/7 for Mycoplasma genitalium, and 100% (13/13 for Ureaplasma urealyticum. The main adverse event was diarrhea and its manifestation rate was 35.2% (32 of 120. The symptom of diarrhea was mostly temporary and resolved spontaneously. The conclusion was that the treatment regimen with a single oral 2 g dose of azithromycin extended-release would be effective for patients with urethritis. However, the antimicrobial susceptibilities of Neisseria gonorrhoeae and Mycoplasma genitalium should be carefully monitored because of possible treatment failure.

  20. A prospective, randomized trial of pyrimethamine and azithromycin vs pyrimethamine and sulfadiazine for the treatment of ocular toxoplasmosis

    NARCIS (Netherlands)

    Bosch-Driessen, Lotje H.; Verbraak, Frank D.; Suttorp-Schulten, Maria S. A.; van Ruyven, Rutger L. J.; Klok, Anne Marie; Hoyng, Carel B.; Rothova, Aniki

    2002-01-01

    To compare the effects of two treatment regimens, one of which included azithromycin, for the treatment of sight-threatening (near optic disk or fovea) ocular toxoplasmosis. Prospective, randomized open-labeled multicenter study, masked in part with regard to evaluation. PARTICIPANTS TOTAL

  1. A prospective, randomized trial of pyrimethamine and azithromycin vs pyrimethamine and sulfadiazine for the treatment of ocular toxoplasmosis.

    NARCIS (Netherlands)

    Bosch-Driessen, L.H.; Verbraak, F.D.; Suttorp-Schulten, M.S.; Ruyven, R.L. van; Klok, A.M.; Hoyng, C.B.; Rothova, A.

    2002-01-01

    OBJECTIVE: To compare the effects of two treatment regimens, one of which included azithromycin, for the treatment of sight-threatening (near optic disk or fovea) ocular toxoplasmosis. DESIGN: Prospective, randomized open-labeled multicenter study, masked in part with regard to evaluation.

  2. Exploiting translational stalling peptides in an effort to extend azithromycin interaction within the prokaryotic ribosome nascent peptide exit tunnel.

    Science.gov (United States)

    Washington, Arren Z; Tapadar, Subhasish; George, Alex; Oyelere, Adegboyega K

    2015-08-15

    The ribosome is the primary protein synthesis machine in the cell and is a target for treatment of a variety of diseases including bacterial infection and cancer. The ribosomal peptide exit tunnel, the route of egress for the nascent peptide, is an inviting site for drug design. Toward a rational engagement of the nascent peptide components for the design of small molecule inhibitors of ribosome function, we designed and disclosed herein a set of N-10 indole functionalized azithromycin analogs. The indole moiety of these compounds is designed to mimic the translation stalling interaction of SecM W155 side-chain with the prokaryotic (Escherichia coli) ribosome A751 residue. Many of these N-10 functionalized compounds have enhanced translation inhibition activities against E. coli ribosome relative to azithromycin while a subset inhibited the growth of representative susceptible bacteria strains to about the same extent as azithromycin. Moreover, the inclusion of bovine serum in the bacterial growth media enhanced the anti-bacterial potency of the N-10 functionalized azithromycin analogs by as high as 10-fold. Published by Elsevier Ltd.

  3. Trends in antimicrobial susceptibility for azithromycin and ceftriaxone in Neisseria gonorrhoeae isolates in Amsterdam, the Netherlands, between 2012 and 2015

    NARCIS (Netherlands)

    Wind, Carolien M.; Schim van der Loeff, Maarten F.; van Dam, Alje P.; de Vries, Henry Jc; van der Helm, Jannie J.

    2017-01-01

    Resistance of Neisseria gonorrhoeae to azithromycin and ceftriaxone has been increasing in the past years. This is of concern since the combination of these antimicrobials is recommended as the first-line treatment option in most guidelines. To analyse trends in antimicrobial resistance, we

  4. Assessment of efficacy of topical azithromycin 1.5 per cent ophthalmic solution for the treatment of meibomian gland dysfunction.

    Science.gov (United States)

    Balci, Ozlem; Gulkilik, Gokhan

    2018-01-01

    The aim was to evaluate the clinical efficacy of topical azithromycin 1.5 per cent ophthalmic solution in treatment of the clinical signs and symptoms associated with meibomian gland dysfunction (MGD). In this retrospective study, 35 patients with MGD were treated with topical azithromycin 1.5 per cent ophthalmic solution for 30 days. Topical azithromycin 1.5 per cent ophthalmic solution was prescribed twice daily for two days and then once daily for a total of 30 days. Daily lid hygiene with dilute baby shampoo was instructed for all patients. Patient total symptom score, meibomian gland grading score, Schirmer score with anaesthetic, tear film break-up time (TFBUT) and corneal fluorescein staining score were evaluated at baseline and after one and three months. Patient total symptom score, meibomian gland grading score, Schirmer score with anaesthetic, TFBUT and corneal staining score reduced significantly from the baseline to the first month (p 0.05, for each). These results demonstrate that topical azithromycin 1.5 per cent ophthalmic solution appears effective in the short-term treatment of the clinical signs and symptoms associated with MGD. © 2017 Optometry Australia.

  5. Prospective bacterial quorum sensing inhibitors from Indian medicinal plant extracts.

    Science.gov (United States)

    Tiwary, B K; Ghosh, R; Moktan, S; Ranjan, V K; Dey, P; Choudhury, D; Dutta, S; Deb, D; Das, A P; Chakraborty, R

    2017-07-01

    As virulence of many pathogenic bacteria is regulated by the phenomenon of quorum sensing (QS), the present study aimed to find the QS-inhibiting (QS-I) property (if any) in 61 Indian medicinal plants. The presence of QS-I compound in the leaf extract was evaluated by its ability to inhibit production of pigment in Chromobacterium violaceum MTCC 2656 (violacein) and Pseudomonas aeruginosa MTCC 2297 (pyocyanin) or swarming of P. aeruginosa MTCC 2297. Extracts of three plants, Astilbe rivularis, Fragaria nubicola and Osbeckia nepalensis, have shown a dose-dependent inhibition of violacein production with no negative effect on bacterial growth. Inhibition of pyocyanin pigment production and swarming motility in P. aeruginosa MTCC 2297 was also shown. Based on the results obtained by gas chromatography-mass spectroscopy (GC-MS) and thin-layer chromatography-direct bioautography (TLC-DB), it was concluded that triterpenes and flavonoid compounds found in the three plant extracts could have QS-I activity. A novel alternative prospect to prevent bacterial infections without inhibiting the growth is to apply chemicals that inhibit quorum sensing mechanism of the pathogens. Antiquorum property of 61 medicinal plants was evaluated by the ability of their leaf extract(s) to inhibit production of pigment (violacein in Chromobacterium violaceum MTCC 2656, pyocyanin in Pseudomonas aeruginosa MTCC 2297) or swarming in P. aeruginosa MTCC 2297. The most prospective plants (for the development of quorum sensing inhibitor), showing inhibition of violacein production without affecting bacterial growth, were Astilbe rivularis, Fragaria nubicola and Osbeckia nepalensis. © 2017 The Society for Applied Microbiology.

  6. Quorum Sensing and LuxR Solos in Photorhabdus.

    Science.gov (United States)

    Brameyer, Sophie; Heermann, Ralf

    2017-01-01

    Bacterial communication via small diffusible molecules to mediate group-coordinated behaviour is commonly referred to as 'quorum sensing'. The prototypical quorum sensing system of Gram-negative bacteria consists of a LuxI-type autoinducer synthase that produces acyl-homoserine lactones (AHLs) as signals and a LuxR-type receptor that detects the AHLs to control expression of specific genes. However, many bacteria possess LuxR homologs but lack a cognate LuxI-type AHL-synthase. Those LuxR-type receptors are designated as 'LuxR orphans' or 'solos'. Entomopathogenic bacteria of the genus Photorhabdus all harbour a large number of LuxR solos, more than any other bacteria examined so far. Two novel quorum sensing systems were found to regulate cell clumping in Photorhabdus and therefore affect pathogenicity. In Photorhabdus luminescens and Photorhabdus temperata the LuxR solo PluR senses α-pyrones named 'photopyrones' instead of AHLs, which are produced by the pyrone synthase PpyS. In contrast, Photorhabdus asymbiotica, a closely related insect and human pathogen, has the PluR homolog PauR, which senses dialkylresorcinols produced by the DarABC pathway to regulate pathogenicity. All three Photorhabdus species harbour at least one LuxR solo with an intact AHL-binding motif, which might also allow sensing of exogenous AHLs. However, the majority of the LuxR solos in all Photorhabdus species have a PAS4 signal-binding domain. These receptors are assumed to detect eukaryotic compounds and are proposed to be involved in host sensing. Overall, because of the large number of LuxR solos they encode, bacteria of the genus Photorhabdus are ideal candidates to study and to identify novel bacterial communication networks.

  7. Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial.

    Science.gov (United States)

    Brusselle, Guy G; Vanderstichele, Christine; Jordens, Paul; Deman, René; Slabbynck, Hans; Ringoet, Veerle; Verleden, Geert; Demedts, Ingel K; Verhamme, Katia; Delporte, Anja; Demeyere, Bénédicte; Claeys, Geert; Boelens, Jerina; Padalko, Elizaveta; Verschakelen, Johny; Van Maele, Georges; Deschepper, Ellen; Joos, Guy F P

    2013-04-01

    Patients with severe asthma are at increased risk of exacerbations and lower respiratory tract infections (LRTI). Severe asthma is heterogeneous, encompassing eosinophilic and non-eosinophilic (mainly neutrophilic) phenotypes. Patients with neutropilic airway diseases may benefit from macrolides. We performed a randomised double-blind placebo-controlled trial in subjects with exacerbation-prone severe asthma. Subjects received low-dose azithromycin (n=55) or placebo (n=54) as add-on treatment to combination therapy of inhaled corticosteroids and long-acting β2 agonists for 6 months. The primary outcome was the rate of severe exacerbations and LRTI requiring treatment with antibiotics during the 26-week treatment phase. Secondary efficacy outcomes included lung function and scores on the Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ). The rate of primary endpoints (PEPs) during 6 months was not significantly different between the two treatment groups: 0.75 PEPs (95% CI 0.55 to 1.01) per subject in the azithromycin group versus 0.81 PEPs (95% CI 0.61 to 1.09) in the placebo group (p=0.682). In a predefined subgroup analysis according to the inflammatory phenotype, azithromycin was associated with a significantly lower PEP rate than placebo in subjects with non-eosinophilic severe asthma (blood eosinophilia ≤200/µl): 0.44 PEPs (95% CI 0.25 to 0.78) versus 1.03 PEPs (95% CI 0.72 to 1.48) (p=0.013). Azithromycin significantly improved the AQLQ score but there were no significant between-group differences in the ACQ score or lung function. Azithromycin was well tolerated, but was associated with increased oropharyngeal carriage of macrolide-resistant streptococci. Azithromycin did not reduce the rate of severe exacerbations and LRTI in patients with severe asthma. However, the significant reduction in the PEP rate in azithromycin-treated patients with non-eosinophilic severe asthma warrants further study. CLINICALTRIALS.GOV NUMBER

  8. Measurement of tissue azithromycin levels in self-collected vaginal swabs post treatment using liquid chromatography and tandem mass spectrometry (LC-MS/MS).

    Science.gov (United States)

    Vodstrcil, Lenka A; Rupasinghe, Thusitha W T; Kong, Fabian Y S; Tull, Dedreia; Worthington, Karen; Chen, Marcus Y; Huston, Wilhelmina M; Timms, Peter; McConville, Malcolm J; Fairley, Christopher K; Bradshaw, Catriona S; Tabrizi, Sepehr N; Hocking, Jane S

    2017-01-01

    Azithromycin is recommended for the treatment of uncomplicated urogenital chlamydia infection although the standard 1gram dose sometimes fails to eradicate the infection (treatment failure). One hypothesis proposed for treatment failure has been insufficient levels of the antibiotic at the site of infection. We developed an assay using liquid chromatography and tandem mass spectrometry (LC-MS/MS) to measure azithromycin concentration in high-vaginal swabs and monitor how concentration changes over time following routine azithromycin treatment. Azithromycin concentrations were measured in two groups of women either within the first 24h of taking a 1g dose (N = 11) or over 9 days (N = 10). Azithromycin concentrations were normalised to an internal standard (leucine enkephalin), and the bulk lipid species phosphatidylcholine [PC(34:1)], using an Agilent 6490 triple quadrupole instrument in positive ionisation mode. The abundances of azithromycin, PC(34:1), and leu-enkephalin were determined by multiple reaction monitoring and absolute levels of azithromycin estimated using standard curves prepared on vaginal specimens. Vaginal azithromycin concentrations of women were rapidly obtained after 5h post-treatment (mean concentration = 1031mcg/mg of lipid, range = 173-2693mcg/mg). In women followed for 9 days, peak concentrations were highest after day 2 (mean concentration = 2206mcg/mg, range = 721-5791mcg/mg), and remained high for at least 9 days with a mean concentration of 384mcg/mg (range = 139-1024mcg/mg) on day 9. Our study confirmed that a single 1g dose of azithromycin is rapidly absorbed and remains in the vagina at relatively high levels for at least a week, suggesting that poor antibiotic absorption is unlikely to be an explanation for treatment failure.

  9. Effect of Azithromycin on Airflow Decline-Free Survival After Allogeneic Hematopoietic Stem Cell Transplant: The ALLOZITHRO Randomized Clinical Trial.

    Science.gov (United States)

    Bergeron, Anne; Chevret, Sylvie; Granata, Angela; Chevallier, Patrice; Vincent, Laure; Huynh, Anne; Tabrizi, Reza; Labussiere-Wallet, Hélène; Bernard, Marc; Chantepie, Sylvain; Bay, Jacques-Olivier; Thiebaut-Bertrand, Anne; Thepot, Sylvain; Contentin, Nathalie; Fornecker, Luc-Matthieu; Maillard, Natacha; Risso, Karine; Berceanu, Ana; Blaise, Didier; Peffault de La Tour, Regis; Chien, Jason W; Coiteux, Valérie; Socié, Gérard

    2017-08-08

    Bronchiolitis obliterans syndrome has been associated with increased morbidity and mortality after allogeneic hematopoietic stem cell transplant (HSCT). Previous studies have suggested that azithromycin may reduce the incidence of post-lung transplant bronchiolitis obliterans syndrome. To evaluate if the early administration of azithromycin can improve airflow decline-free survival after allogeneic HSCT. The ALLOZITHRO parallel-group trial conducted in 19 French academic transplant centers and involving participants who were at least 16 years old, had undergone allogeneic HSCT for a hematological malignancy, and had available pretransplant pulmonary function test results. Enrollment was from February 2014 to August 2015 with follow-up through April 26, 2017. Patients were randomly assigned to receive 3 times a week either 250 mg of azithromycin (n = 243) or placebo (n = 237) for 2 years, starting at the time of the conditioning regimen. The primary efficacy end point was airflow decline-free survival at 2 years after randomization. Main secondary end points were overall survival and bronchiolitis obliterans syndrome at 2 years. Thirteen months after enrollment, the independent data and safety monitoring board detected an unanticipated imbalance across blinded groups in the number of hematological relapses, and the treatment was stopped December 26, 2016. Among 480 randomized participants, 465 (97%) were included in the modified intention-to-treat analysis (mean age, 52 [SD, 14] years; 75 women [35%]). At the time of data cutoff, 104 patients (22%; 54 azithromycin vs 50 placebo) had experienced an airflow decline; 138 patients (30%) died (78 azithromycin vs 60 placebo). Two-year airflow decline-free survival was 32.8% (95% CI, 25.9%-41.7%) with azithromycin and 41.3% (95% CI, 34.1%-50.1%) with placebo (unadjusted hazard ratio [HR], 1.3; 95% CI, 1.02-1.70; P = .03). Of the 22 patients (5%) who experienced bronchiolitis obliterans syndrome, 15 (6%) were in

  10. Quasisynchronization in Quorum Sensing Systems with Parameter Mismatches

    Directory of Open Access Journals (Sweden)

    Jianbao Zhang

    2014-01-01

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

  11. Quorum Sensing and Expression of Virulence in Pectobacteria

    Directory of Open Access Journals (Sweden)

    Andres Mäe

    2012-03-01

    Full Text Available 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.

  12. Efficacy and safety of azithromycin 1.5% eye drops in paediatric population with purulent bacterial conjunctivitis.

    Science.gov (United States)

    Bremond-Gignac, Dominique; Nezzar, Hachemi; Bianchi, Paolo Emilio; Messaoud, Riadh; Lazreg, Sihem; Voinea, Liliana; Speeg-Schatz, Claude; Hartani, Dahbia; Kaercher, Thomas; Kocyla-Karczmarewicz, Beata; Murta, Joaquim; Delval, Laurent; Renault, Didier; Chiambaretta, Frédéric

    2014-06-01

    To determine the efficacy and safety of azithromycin 1.5% eye drops in a paediatric population with purulent bacterial conjunctivitis. This was a multicentre, international, randomised, investigator-masked study in 286 children with purulent discharge and bulbar conjunctival injection. Patients received either azithromycin 1.5% eye drops (twice daily for 3 days) or tobramycin 0.3% eye drops (every 2 h for 2 days, then four times daily for 5 days). Clinical signs were evaluated on day (D) 0, 3 and 7, and cultures on D0 and D7. The primary variable was the clinical cure (absence of bulbar conjunctival injection and discharge) on D3 in the worse eye for patients with positive cultures on D0. 286 patients (mean age 3.2 years; range 1 day-17 years) were included; 203 had positive cultures on D0. Azithromycin was superior to tobramycin in clinical cure rate on D3 (47.1% vs 28.7%, p=0.013) and was non-inferior to tobramycin on D7 (89.2% vs 78.2%, respectively). Azithromycin treatment eradicated causative pathogens, including resistant species, with a similar resolution rate to tobramycin (89.8% vs 87.2%, respectively). These results were confirmed in a subgroup of patients younger than 24 months old. Azithromycin 1.5% eye drops provided a more rapid clinical cure than tobramycin 0.3% eye drops in the treatment of purulent bacterial conjunctivitis in children, with a more convenient twice-a-day dosing regimen. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  13. Influence of chronic azithromycin treatment on the composition of the oropharyngeal microbial community in patients with severe asthma.

    Science.gov (United States)

    Lopes Dos Santos Santiago, Guido; Brusselle, Guy; Dauwe, Kenny; Deschaght, Pieter; Verhofstede, Chris; Vaneechoutte, Dries; Deschepper, Ellen; Jordens, Paul; Joos, Guy; Vaneechoutte, Mario

    2017-05-10

    This study of the oropharyngeal microbiome complements the previously published AZIthromycin in Severe ASThma (AZISAST) clinical trial, where the use of azithromycin was assessed in subjects with exacerbation-prone severe asthma. Here, we determined the composition of the oropharyngeal microbial community by means of deep sequencing of the amplified 16S rRNA gene in oropharyngeal swabs from patients with exacerbation-prone severe asthma, at baseline and during and after 6 months treatment with azithromycin or placebo. A total of 1429 OTUs were observed, of which only 59 were represented by more than 0.02% of the reads. Firmicutes, Bacteroidetes, Fusobacteria, Proteobacteria and Actinobacteria were the most abundant phyla and Streptococcus and Prevotella were the most abundant genera in all the samples. Thirteen species only accounted for two thirds of the reads and two species only, i.e. Prevotella melaninogenica and Streptococcus mitis/pneumoniae, accounted for one fourth of the reads. We found that the overall composition of the oropharyngeal microbiome in patients with severe asthma is comparable to that of the healthy population, confirming the results of previous studies. Long term treatment (6 months) with azithromycin increased the species Streptococcus salivarius approximately 5-fold and decreased the species Leptotrichia wadei approximately 5-fold. This was confirmed by Boruta feature selection, which also indicated a significant decrease of L. buccalis/L. hofstadtii and of Fusobacterium nucleatum. Four of the 8 treated patients regained their initial microbial composition within one month after cessation of treatment. Despite large diversity of the oropharyngeal microbiome, only a few species predominate. We confirm the absence of significant differences between the oropharyngeal microbiomes of people with and without severe asthma. Possibly, long term azithromycin treatment may have long term effects on the composition of the oropharygeal microbiome in

  14. Impact of Azithromycin on Pregnancy Prolongation in Women at Risk of Preterm Labor: A Time-to-Event Analysis.

    Science.gov (United States)

    Goyer, Isabelle; Ferland, Gabrielle; Ruo, Ni; Morin, Caroline; Brochet, Marie-Sophie; Morin, Lucie; Ferreira, Ema

    2016-09-13

    Since 2006, the empiric use of azithromycin in women at risk of premature birth has become prevalent in our institution without any evidence of its efficacy. Although antibiotics can prolong pregnancy in preterm prolonged rupture of membranes, no published data are available for women with intact membranes. To describe the purpose of adding azithromycin to the usual treatments (cerclage, tocolysis, rest, etc.) to prolong pregnancy in women with intact membranes who are at risk of or already in preterm labour. A retrospective observational cohort study was done at a Mother-Child University Hospital Centre. Patients admitted to obstetric ward who received azithromycin between January 1 st , 2006 and August 1 st , 2010 were included. A total of 127 exposed women were matched to 127 controls through medical records and pharmacy software. A time-to-event analysis was done to compare gestational age at the time of the recorded composite event (delivery, or rupture of membranes, or second intervention to prolong pregnancy). To compare proportions of composite event at different time points, χ 2 tests were used. Patients who received azithromycin had a more severe condition at presentation. Once adjusted for confounding factors, prolongation of pregnancy (HR =1.049; CI 95%: 0.774-1.421 [p=0.758]) and gestational age at the event (HR=1.200; CI 95%: 0.894-1.609 [p=0.225]) did not differ between the groups. The proportions of women with an event ≥7 days post-diagnosis or ≥37 gestational weeks were similar. Azithromycin was added to medical therapy in a more at-risk population and no clear benefit was measured.

  15. Molecular basis for the substrate specificity of quorum signal synthases.

    Science.gov (United States)

    Dong, Shi-Hui; Frane, Nicole D; Christensen, Quin H; Greenberg, E Peter; Nagarajan, Rajesh; Nair, Satish K

    2017-08-22

    In several Proteobacteria , LuxI-type enzymes catalyze the biosynthesis of acyl-homoserine lactones (AHL) signals using S -adenosyl-l-methionine and either cellular acyl carrier protein (ACP)-coupled fatty acids or CoA-aryl/acyl moieties as progenitors. Little is known about the molecular mechanism of signal biosynthesis, the basis for substrate specificity, or the rationale for donor specificity for any LuxI member. Here, we present several cocrystal structures of BjaI, a CoA-dependent LuxI homolog that represent views of enzyme complexes that exist along the reaction coordinate of signal synthesis. Complementary biophysical, structure-function, and kinetic analysis define the features that facilitate the unusual acyl conjugation with S -adenosylmethionine (SAM). We also identify the determinant that establishes specificity for the acyl donor and identify residues that are critical for acyl/aryl specificity. These results highlight how a prevalent scaffold has evolved to catalyze quorum signal synthesis and provide a framework for the design of small-molecule antagonists of quorum signaling.

  16. Prediction by promoter logic in bacterial quorum sensing.

    Directory of Open Access Journals (Sweden)

    Navneet Rai

    2012-01-01

    Full Text Available 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.

  17. Quorum Regulated Resistance of Vibrio cholerae against Environmental Bacteriophages.

    Science.gov (United States)

    Hoque, M Mozammel; Naser, Iftekhar Bin; Bari, S M Nayeemul; Zhu, Jun; Mekalanos, John J; Faruque, Shah M

    2016-11-28

    Predation by bacteriophages can significantly influence the population structure of bacterial communities. Vibrio cholerae the causative agent of cholera epidemics interacts with numerous phages in the aquatic ecosystem, and in the intestine of cholera patients. Seasonal epidemics of cholera reportedly collapse due to predation of the pathogen by phages. However, it is not clear how sufficient number of the bacteria survive to seed the environment in the subsequent epidemic season. We found that bacterial cell density-dependent gene expression termed "quorum sensing" which is regulated by signal molecules called autoinducers (AIs) can protect V. cholerae against predatory phages. V. cholerae mutant strains carrying inactivated AI synthase genes were significantly more susceptible to multiple phages compared to the parent bacteria. Likewise when mixed cultures of phage and bacteria were supplemented with exogenous autoinducers CAI-1 or AI-2 produced by recombinant strains carrying cloned AI synthase genes, increased survival of V. cholerae and a decrease in phage titer was observed. Mutational analyses suggested that the observed effects of autoinducers are mediated in part through the quorum sensing-dependent production of haemaglutinin protease, and partly through downregulation of phage receptors. These results have implication in developing strategies for phage mediated control of cholera.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-02-27

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

  19. Prediction by promoter logic in bacterial quorum sensing.

    Science.gov (United States)

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

    2012-01-01

    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.

  20. Quorum Quenching in Culturable Phyllosphere Bacteria from Tobacco

    Directory of Open Access Journals (Sweden)

    Guoqiang Zhuang

    2013-07-01

    Full Text Available Many Gram-negative plant pathogenic bacteria employ a N-acylhomoserine lactone (AHL-based quorum sensing (QS system to regulate their virulence traits. A sustainable biocontrol strategy has been developed using quorum quenching (QQ bacteria to interfere with QS and protect plants from pathogens. Here, the prevalence and the diversity of QQ strains inhabiting tobacco leaf surfaces were explored. A total of 1177 leaf-associated isolates were screened for their ability to disrupt AHL-mediated QS, using the biosensor Chromobacterium violaceum CV026. One hundred and sixty-eight strains (14% are capable of interfering with AHL activity. Among these, 106 strains (63% of the culturable quenchers can enzymatically degrade AHL molecules, while the remaining strains might use other QS inhibitors to interrupt the chemical communication. Moreover, almost 79% of the QQ strains capable of inactivating AHLs enzymatically have lactonase activity. Further phylogenetic analysis based on 16S rDNA revealed that the leaf-associated QQ bacteria can be classified as Bacillus sp., Acinetobacter sp., Lysinibacillus sp., Serratia sp., Pseudomonas sp., and Myroides sp. The naturally occurring diversity of bacterial quenchers might provide opportunities to use them as effective biocontrol reagents for suppressing plant pathogen in situ.

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

    Science.gov (United States)

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

    2011-01-01

    Words such as language and behavior are frequently used to depict "quorum sensing" (QS) in the literature. Simplifying the concept, language and cross-talk between bacteria, and between bacteria and animal or plants hosts determine the behavior (e.g., beneficial or pathogenic effects). Genomics and transcriptomics were the principal approaches used to study the multiple mechanisms of QS. Nevertheless, sequencing of genomes paved the way for another approach which consists on comparative and functional proteomics. This review aims at describing how the proteomic dictionary translates: (i) the languages (N-acyl-L-homoserine lactones, AHL; autoinducing peptide, AIP; autoinducer-2, AI-2) used by bacteria to communicate; (ii) signals of QS which induce various phenotypes (e.g., virulence, biofilm maturation); (iii) cross-talk between lactic acid bacteria within various food ecosystems (e.g. sourdough and fermented milk); (iv) probiotic messages at intra- and inter-species and interkingdom levels; and (v) words for quorum quenching (QQ). Proteomics is an indispensible discipline to elucidate the mechanisms of regulation of the multitude of language signals which diffuse through different microbial communities. Copyright © 2010 Elsevier B.V. All rights reserved.

  2. [Screening and identification of marine fungi against bacterial quorum sensing].

    Science.gov (United States)

    Yin, Shouliang; Chang, Yajing; Deng, Suping; Wang, Qingchi; Yu, Wengong; Gong, Qianhong

    2011-09-01

    The discovery of quorum sensing (QS) system and its critical role in bacterial virulence have revealed a new way to attack pathogenic bacterium. The pathogenecity of QS deletion mutants decreases significantly. Targeting bacterial QS system is a promising therapeutic approach to control infections and anti-microbial resistance. To obtain natural QS inhibitors from marine organisms, marine fungi (69 strains) were isolated from marine mollusca, and their extracts were screened using improved QSIS2 (Quorum Sensing Inhibitor Selector 2) assay and Chromobacterium violaceum CV026. To improve the efficiency of QSIS2 screening, 2,3,5-triphenyltetrazolium chloride (TTC) staining method was used. Extract from strain QY013 was found to have QS inhibitory activity. Further experiment indicated that pyocyanin in Pseudomonas aeruginosa PAOI and violacein in C. violaceum CV026 were reduced by QY013 extract, without affecting bacterial growth. Morphological and 18S rDNA sequence analysis revealed that strain QY013 was most closely related to Penicillium species. The above results suggest that active constituents from QY013 may be used as novel antimicrobial agents against bacterial infection.

  3. Effect of azithromycin on enhancement of methane production from waste activated sludge.

    Science.gov (United States)

    Nguyen, Minh Tuan; Maeda, Toshinari; Mohd Yusoff, Mohd Zulkhairi; Ogawa, Hiroaki I

    2014-07-01

    In the methane production from waste activated sludge (WAS), complex bacterial interactions in WAS have been known as a major contribution to methane production. Therefore, the influence of bacterial community changes toward methane production from WAS was investigated by an application of antibiotics as a simple means for it. In this study, azithromycin (Azm) as an antibiotic was mainly used to observe the effect on microbial changes that influence methane production from WAS. The results showed that at the end of fermentation, Azm enhanced methane production about twofold compared to control. Azm fostered the growth of acid-producing bacterial communities, which synthesized more precursors for methane formation. DGGE result showed that the hydrolysis as well as acetogenesis stage was improved by the dominant of B1, B2 and B3 strains, which are Clostridium species. In the presence of Azm, the total population of archaeal group was increased, resulting in higher methane productivity achievement.

  4. Effects of antibiotics on quorum sensing in pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Skindersø, Mette Elena; Alhede, Morten; Phipps, Richard Kerry

    2008-01-01

    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...

  5. Well-known quorum sensing inhibitors do not affect bacterial quorum sensing-regulated bean sprout spoilage.

    Science.gov (United States)

    Rasch, M; Rasmussen, T B; Andersen, J B; Persson, T; Nielsen, J; Givskov, M; Gram, L

    2007-03-01

    To investigate the potential of quorum sensing inhibitors (QSI) as food preservative agents in a food product, where bacterial spoilage is controlled by quorum sensing (QS). The effects of well-known QSI were tested on spoilage phenotypes and on QS-regulated genes of a bean sprout spoiling bacterial isolate (Pectobacterium A2JM) in laboratory substrates and in a bean sprout model system. The acylated homoserine lactones (AHL) analogues PenS-AHL and HepS-AHL decreased the specific protease activity of Pectobacterium A2JM in broth but did not reduce the expression of a QS-regulated secretion protein, and were without effect on soft rot of bean sprouts. The QSI ProS-AHL, furanone C-30, patulin, penicillic acid and 4-nitropyridine-N-oxide did not have any effect on protease activity, on gene expression or bean sprout appearance at nongrowth inhibitory concentrations. Extracts from garlic and bean sprouts induced the QS system of Pectobacterium in bean sprouts and a broth system, respectively. Among the several well-known QSI compounds, only PenS-AHL and HepS-AHL, inhibited QS-regulated protease activity of Pectobacterium A2JM in broth cultures, but had no effect on bean sprout spoilage. The QSI compounds must be selected in the specific system in which they are to function and they cannot easily be transferred from one QS system to another.

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

    Science.gov (United States)

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

    2013-12-01

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

  7. Peptides as Quorum Sensing Molecules: Measurement Techniques and Obtained LevelsIn vitroandIn vivo.

    Science.gov (United States)

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

    2017-01-01

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

  8. Quorum Sensing Gene Regulation by LuxR/HapR Master Regulators in Vibrios.

    Science.gov (United States)

    Ball, Alyssa S; Chaparian, Ryan R; van Kessel, Julia C

    2017-10-01

    The coordination of group behaviors in bacteria is accomplished via the cell-cell signaling process called quorum sensing. Vibrios have historically been models for studying bacterial communication due to the diverse and remarkable behaviors controlled by quorum sensing in these bacteria, including bioluminescence, type III and type VI secretion, biofilm formation, and motility. Here, we discuss the Vibrio LuxR/HapR family of proteins, the master global transcription factors that direct downstream gene expression in response to changes in cell density. These proteins are structurally similar to TetR transcription factors but exhibit distinct biochemical and genetic features from TetR that determine their regulatory influence on the quorum sensing gene network. We review here the gene groups regulated by LuxR/HapR and quorum sensing and explore the targets that are common and unique among Vibrio species. Copyright © 2017 American Society for Microbiology.

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

    Science.gov (United States)

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

    2015-04-08

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

  10. Quorum sensing inhibition in Pseudomonas aeruginosa biofilms: new insights through network mining.

    Science.gov (United States)

    Pérez-Pérez, Martín; Jorge, Paula; Pérez Rodríguez, Gael; Pereira, Maria Olívia; Lourenço, Anália

    2017-02-01

    Quorum sensing plays a pivotal role in Pseudomonas aeruginosa's virulence. This paper reviews experimental results on antimicrobial strategies based on quorum sensing inhibition and discusses current targets in the regulatory network that determines P. aeruginosa biofilm formation and virulence. A bioinformatics framework combining literature mining with information from biomedical ontologies and curated databases was used to create a knowledge network of potential anti-quorum sensing agents for P. aeruginosa. A total of 110 scientific articles, corresponding to 1,004 annotations, were so far included in the network and are analysed in this work. Information on the most studied agents, QS targets and methods is detailed. This knowledge network offers a unique view of existing strategies for quorum sensing inhibition and their main regulatory targets and may be used to readily access otherwise scattered information and to help generate new testable hypotheses. This knowledge network is publicly available at http://pcquorum.org/ .

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

    Digital Repository Service at National Institute of Oceanography (India)

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

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

  12. Linear peptidomimetics as potent antagonists of Staphylococcus aureus agr quorum sensing

    DEFF Research Database (Denmark)

    Karathanasi, Georgia; Bojer, Martin Saxtorph; Baldry, Mara

    2018-01-01

    Staphylococcus aureus is an important pathogen causing infections in humans and animals. Increasing problems with antimicrobial resistance has prompted the development of alternative treatment strategies, including antivirulence approaches targeting virulence regulation such as the agr quorum...

  13. Remarkable increase of Neisseria gonorrhoeae with decreased susceptibility of azithromycin and increase in the failure of azithromycin therapy in male gonococcal urethritis in Sendai in 2015.

    Science.gov (United States)

    Yasuda, Mitsuru; Ito, Shin; Hatazaki, Kyoko; Deguchi, Takashi

    2016-12-01

    The antimicrobial resistance of Neisseria gonorrhoeae is a serious problem worldwide. In this study, we examined the susceptibility of N. gonorrhoeae isolated from male gonococcal urethritis in Sendai in 2014 and 2015. Furthermore, of all cases, we investigated the clinical efficacy of a single 2-g dose of extended-release azithromycin (AZM-SR) in the treatment of male gonococcal urethritis retrospectively. Sixty N. gonorrhoeae strains in 2014 and 54 strains in 2015 were isolated from male gonococcal urethritis and stored each year. The MIC of AZM was ≥1 mg/L in 4 strains (6.7%) in 2014 and in 13 strains (24.1%) in 2015 and the number of strains having ≥1 mg/L MIC increased significantly (P = 0.016). Microbiological efficacy was evaluated in 32 and 29 of these patients, and the rates of treatment success were 93.8% and 79.3%, respectively. All of the treatment failures were caused by strains having a MIC of AZM of ≥0.5 mg/L. In particular, the increase in the isolates having a MIC of AZM of ≥1 mg/L was remarkable. Therefore, it was thought that the increase in these strains was the reason for the increase in treatment failures in 2015. Because no other drug is effective, it is currently necessary to use AZM-SR to treat gonococcal infections caused by ceftriaxone-resistant strains or patients allergic to ceftriaxone. To prevent a further increase in resistance to AZM, we should not use AZM-SR to treat normal cases of gonococcal infection. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  14. Steady-State Therapy with Azithromycin or Low-Dose Prednisolone in Paediatric Cystic Fibrosis Patients: Inflammatory Markers and Disease Progression.

    Science.gov (United States)

    Shmarina, Galina; Pukhalsky, Alexander; Avakian, Lucine; Semykin, Sergey; Pukhalskaya, Daria; Alioshkin, Vladimir

    2017-01-01

    Anti-inflammatory therapy is a logical approach to slowing the inevitable lung function deterioration in cystic fibrosis (CF) patients. This study's aim was to evaluate inflammatory markers and disease progression in paediatric CF patients chronically treated with azithromycin or low-dose prednisolone. The study included 204 patients with CF and 100 healthy controls; 102 CF patients were treated with basic therapy only (without anti-inflammatory treatment; WAT), and 102 individuals received basic therapy along with azithromycin (n = 59) or low-dose prednisolone (n = 43). The median duration of therapy was 24 months (range 12-82) with azithromycin and 31 months (range 12-180) with prednisolone. A cross-sectional analysis of plasma and sputum biomarkers was performed. Compared with the healthy controls, the WAT group showed elevated IFN-γ, IL-10 (total), and TGFβ1 concentrations, and decreased TNFα (total) and adrenocorticotropic hormone (ACTH) levels (all p azithromycin/prednisolone patients were significantly higher than those in WAT patients and similar to those of healthy children. In contrast, IL-10 (total) levels were significantly decreased in azithromycin/prednisolone-treated patients compared with WAT patients. Children from the azithromycin group demonstrated ACTH levels similar to those of healthy controls. Azithromycin-treated patients showed a significantly reduced rate of CF-related liver disease and a significantly increased incidence of glucose metabolism disturbances. Steady-state anti-inflammatory treatments may have a sustained immunomodulatory action at systemic and local levels in CF patients. Further investigations are needed to assess the effects of supportive azithromycin therapy on the hypothalamic-pituitary-adrenal axis and the incidence of non-pulmonary CF complications. © 2017 S. Karger AG, Basel.

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

    Science.gov (United States)

    Van Delden, Christian; Pesci, Everett C.; Pearson, James P.; Iglewski, Barbara H.

    1998-01-01

    The las quorum-sensing system of Pseudomonas aeruginosa controls the expression of elastase and rhamnolipid. 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 compensation by the rhl system. These data show that P. aeruginosa can restore elastase and rhamnolipid production in the absence of a functional las quorum-sensing system. PMID:9712807

  16. Transition to quorum sensing in an Agrobacterium population: A stochastic model.

    Directory of Open Access Journals (Sweden)

    Andrew B Goryachev

    2005-09-01

    Full Text Available Understanding of the intracellular molecular machinery that is responsible for the complex collective behavior of multicellular populations is an exigent problem of modern biology. Quorum sensing, which allows bacteria to activate genetic programs cooperatively, provides an instructive and tractable example illuminating the causal relationships between the molecular organization of gene networks and the complex phenotypes they control. In this work we--to our knowledge for the first time--present a detailed model of the population-wide transition to quorum sensing using the example of Agrobacterium tumefaciens. We construct a model describing the Ti plasmid quorum-sensing gene network and demonstrate that it behaves as an "on-off" gene expression switch that is robust to molecular noise and that activates the plasmid conjugation program in response to the increase in autoinducer concentration. This intracellular model is then incorporated into an agent-based stochastic population model that also describes bacterial motion, cell division, and chemical communication. Simulating the transition to quorum sensing in a liquid medium and biofilm, we explain the experimentally observed gradual manifestation of the quorum-sensing phenotype by showing that the transition of individual model cells into the "on" state is spread stochastically over a broad range of autoinducer concentrations. At the same time, the population-averaged values of critical autoinducer concentration and the threshold population density are shown to be robust to variability between individual cells, predictable and specific to particular growth conditions. Our modeling approach connects intracellular and population scales of the quorum-sensing phenomenon and provides plausible answers to the long-standing questions regarding the ecological and evolutionary significance of the phenomenon. Thus, we demonstrate that the transition to quorum sensing requires a much higher threshold

  17. The small nucleoid protein Fis is involved in Vibrio cholerae quorum sensing.

    Science.gov (United States)

    Lenz, Derrick H; Bassler, Bonnie L

    2007-02-01

    Quorum sensing is a process of cell-cell communication that bacteria use to relay information to one another about the cell density and species composition of the bacterial community. Quorum sensing involves the production, secretion and population-wide detection of small signalling molecules called autoinducers. This process allows bacteria to synchronize group behaviours and act as multicellular units. The human pathogen, Vibrio cholerae, uses quorum sensing to co-ordinate such complex behaviours as pathogenicity and biofilm formation. The quorum-sensing circuit of V. cholerae consists of two autoinducer/sensor systems, CAI-1/CqsS and AI-2/LuxPQ, and the VarS/A-CsrA/BCD growth-phase regulatory system. Genetic analysis suggests that an additional regulatory arm involved in quorum sensing exists in V. cholerae. All of these systems channel information into the histidine phosphotransfer protein, LuxU, and/or the response regulator, LuxO. LuxO, when phosphorylated, activates the expression of four genes encoding the Qrr (quorum regulatory RNAs) small RNAs (sRNAs). The Qrr sRNAs destabilize the hapR transcript encoding the master regulator of quorum sensing, HapR. Here we identify the nucleoid protein Fis as playing a major role in the V. cholerae quorum-sensing circuit. Fis fulfils the predictions required to be the putative additional component that inputs information into the cascade: its expression is regulated in a growth phase-dependent manner; it requires LuxO but acts independently of LuxU, and it regulates all four qrr genes and, in turn, HapR by directly binding to the qrr gene promoters and modulating their expression.

  18. Pseudomonas aeruginosa with lasI quorum-sensing deficiency during corneal infection

    DEFF Research Database (Denmark)

    Zhu, H.; Bandara, R.; Conibear, T.C.

    2004-01-01

    in lasI, lasR, or rhlR were investigated in the study. METHODS: The possession of the quorum-sensing genes lasI, lasR, rhlI, rhlR, and the quorum-sensing controlled genes lasB, aprA, and rhlAB in the clinical isolates were determined by polymerase chain reaction and Southern blot hybridization...

  19. Identification of Quorum Quenching Bacteria and Its Biocontrol Potential Against Soft Rot Disease Bacteria, Dickeya Dadantii

    OpenAIRE

    Khoiri, Syaiful; Damayanti, Tri Asmira; Giyanto, Giyanto

    2017-01-01

    Dickeya dadantii is one of newly found bacteria causing soft rot on orchids in Indonesia. Infected plants showed severe rot rapidly only in few days. An effort to control the bacteria was conducted by utilizing selected quorum quenching (QQ) inducer bacteria which produce AHL-lactonase by aiiA gene. The aims of this research were to screen and identify of quorum quenching bacteria, and also assayed their biocontrol potential ability against D. dadantii in laboratory. The screening of QQ bacte...

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

    DEFF Research Database (Denmark)

    Kjelleberg, S.; Molin, Søren

    2002-01-01

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

  1. Synthesis and antibacterial activity of novel 4″-O-(1-aralkyl-1,2,3-triazol-4-methyl-carbamoyl) azithromycin analogs.

    Science.gov (United States)

    Wang, Yinhu; Cong, Chao; Chai, Wern Chern; Dong, Ruiqian; Jia, Li; Song, Di; Zhou, Ziteng; Ma, Shutao

    2017-08-15

    Three novel structural series of 4″-O-(1-aralkyl-1,2,3-triazol-4-methyl-carbamoyl) azithromycin analogs were designed, synthesized and evaluated for their in vitro antibacterial activity. All the target compounds exhibited excellent activity against erythromycin-susceptible Streptococcus pyogenes, and significantly improved activity against three phenotypes of erythromycin-resistant Streptococcus pneumoniae compared with clarithromycin and azithromycin. Among the three series of azithromycin analogs, the novel series of 11,4″-disubstituted azithromycin analogs 9a-k exhibited the most effective and balanced activity against susceptible and resistant bacteria. Among them, compound 9j showed the most potent activity against Staphylococcus aureus ATCC25923 (0.008µg/mL) and Streptococcus pyogenes R2 (1µg/mL). Besides, all the 11,4″-disubstituted azithromycin analogs 9a-k except 9f shared the identical activity with the MIC value azithromycin, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2017-01-01

    Quorum sensing is a process of cell-cell communication that bacteria use to regulate collective behaviors. Quorum sensing depends on the production, detection, and group-wide response to extracellular signal molecules called autoinducers. In many bacterial species, quorum sensing controls virulence factor production. Thus, disrupting quorum sensing is considered a promising strategy to combat bacterial pathogenicity. Several members of a family of naturally produced plant metabolites called flavonoids inhibit Pseudomonas aeruginosa biofilm formation by an unknown mechanism. Here, we explore this family of molecules further, and we demonstrate that flavonoids specifically inhibit quorum sensing via antagonism of the autoinducer-binding receptors, LasR and RhlR. Structure-activity relationship analyses demonstrate that the presence of two hydroxyl moieties in the flavone A-ring backbone are essential for potent inhibition of LasR/RhlR. Biochemical analyses reveal that the flavonoids function non-competitively to prevent LasR/RhlR DNA binding. Administration of the flavonoids to P. aeruginosa alters transcription of quorum sensing-controlled target promoters and suppresses virulence factor production, confirming their potential as anti-infectives that do not function by traditional bacteriocidal or bacteriostatic mechanisms. PMID:28119451

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

    Directory of Open Access Journals (Sweden)

    Vincent eLeung

    2015-10-01

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

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

    Science.gov (United States)

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

    2010-07-01

    Quorum sensing is one of several mechanisms that bacterial cells use to interact with each other and coordinate certain physiological processes in response to cell density. This mechanism is mediated by extracellular signaling molecules; once a critical threshold concentration has been reached, a target sensor kinase or response regulator is activated (or repressed), facilitating the expression of quorum sensing-dependent genes. Gram-positive bacteria mostly use oligo-peptides as signaling molecules. These cells have a special kind of quorum-sensing systems in which the receptor protein interacts directly with its cognate signaling peptide. The receptors are either Rap phosphatases or transcriptional regulators and integrate the protein family RNPP, from Rap, Npr, PlcR, and PrgX. These quorum-sensing systems control several microbial processes, like sporulation, virulence, biofilm formation, conjugation, and production of extracellular enzymes. Insights of the mechanism of protein-signaling peptide binding as well as the molecular interaction among receptor protein, signaling peptide, and target DNA have changed some earlier perceptions. In spite of the increased knowledge and the potential biotechnological applications of these quorum-sensing systems, few examples on engineering for biotechnological applications have been published. Real applications will arise only when researchers working in applied microbiology and biotechnology are aware of the importance of quorum-sensing systems for health and bioprocess applications.

  5. Flavonoids SuppressPseudomonas aeruginosaVirulence through Allosteric Inhibition of Quorum-sensing Receptors.

    Science.gov (United States)

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

    2017-03-10

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

  6. Inhibition of quorum sensing-controlled virulence factors and biofilm formation in Pseudomonas fluorescens by cinnamaldehyde.

    Science.gov (United States)

    Li, Tingting; Wang, Dangfeng; Liu, Nan; Ma, Yan; Ding, Ting; Mei, Yongchao; Li, Jianrong

    2018-03-23

    Pseudomonas fluorescens, an important food spoiling bacteria, uses quorum sensing to control biofilm formation and motility. To date, only a few compounds targeting the LuxR-based quorum sensing system of P. fluorescens have been identified. In the present study, the quorum sensing inhibitory effect of cinnamaldehyde at sublethal concentrations was investigated in terms of inhibition of the extracellular protease, biofilm formation, and swimming and swarming motility. The total volatile basic nitrogen value was also measured to evaluate the effect of cinnamaldehyde on quality preservation of turbot fillets stored at 4 ± 1 °C for 15 days. The results showed that cinnamaldehyde significantly inhibited quorum sensing-dependent factors in P. fluorescens and extended the storage life of turbot. Unexpectedly, cinnamaldehyde did not interfere with production of AHLs (N-acylhomoserine lactones) by P. fluorescens, as shown by measurement of AHL production using GC-MS. Molecular docking analysis revealed that cinnamaldehyde can interact with the LuxR-type protein of P. fluorescens, which could constitute the molecular basis of the quorum sensing inhibition observed. These findings strongly suggest that cinnamaldehyde is a quorum sensing inhibitor with great potential for the preservation of aquatic products to guarantee food safety. Copyright © 2018 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2016-01-01

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

  8. Recent Advances in Ligand and Structure Based Screening of Potent Quorum Sensing Inhibitors Against Antibiotic Resistance Induced Bacterial Virulence.

    Science.gov (United States)

    Nandi, Sisir

    2016-01-01

    Antibiotic resistance is a growing threat in the treatment of bacterial diseases. Bacterial invasion and its virulence can cause damage to the host cells via quorum sensing mechanism which is responsible for the intercellular communication among bacteria that regulates expression of many genes. Quorum sensing (QS) differentially expresses specific sets of genes which may produce resistance. Researchers have been devoted to develop more potent compounds against bacterial resistant quorum sensing inhibitors. A number of anti-quorum sensing approaches have been documented to screen potent inhibitors against quorum sensing induced bacterial virulence. Experimental screening of a large chemical compound library against a quorum sensing biological target is an established technology for lead identification but it is expensive, laborious and time consuming. Therefore, computer-aided high throughput ligand and structure based virtual screening are most effective pharmacoinformatic tools prior to experiment in this context. Ligand based screening includes quantitative structure-activity relationship (QSAR) and pharmacophore generation whereas techniques of structure based virtual screening include molecular docking. The study in this direction can increase the findings of hit rates and decrease cost of drug design and development by producing potent natural as well as synthetic anti-quorum sensing compounds. Most recent patent coverage on ligand and structure based design of novel bioactive quorum sensing inhibitors has been presented here. The paper has also critically reviewed the screening and design of potent quorum sensing inhibitor leads that would help in patenting novel leads active against bacterial virulence and minimizing antibiotic resistance among bacterial pathogens.

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

    Directory of Open Access Journals (Sweden)

    Kok-Gan Chan

    2013-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Jindong Zan

    2014-01-01

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

  11. Bulk input queues with quorum and multiple vacations

    Directory of Open Access Journals (Sweden)

    Dshalalow Jewgeni H.

    1996-01-01

    Full Text Available The authors study a single-server queueing system with bulk arrivals and batch service in accordance to the general quorum discipline: a batch taken for service is not less than r and not greater than R ( ≥ r . The server takes vacations each time the queue level falls below r ( ≥ 1 in accordance with the multiple vacation discipline. The input to the system is assumed to be a compound Poisson process. The analysis of the system is based on the theory of first excess processes developed by the first author. A preliminary analysis of such processes enabled the authors to obtain all major characteristics for the queueing process in an analytically tractable form. Some examples and applications are given.

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jia-Yi Tan

    2014-04-01

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

  14. A survey on the effects of Azithromycin in the treatment of gingival overgrowth induced by Cyclosporin in renal transplant patients

    Directory of Open Access Journals (Sweden)

    Kadkhoda Z.

    2004-07-01

    Full Text Available Statement of Problem: Gingival overgrowth is a side effect commonly induced by Cyclosporin treatment. The effects of Azithromycin, a macrolidic antibiotic, has been focused on gingival enlargement treatment induced by cyclosporine in numerous articles. Purpose: The goal of the present study was to survey the effects of systemic Azithromycin in the treatment of gingival overgrowth induced by cyclosporine among renal transplant patients. Materials and Methods: In this clinical trial study, 18 renal transplant patients (6 females and 12 males with gingival overgrowth were studied. Samples were randomly divided into two groups: case group were treated by systemic Azithromycin and controls were treated by systemic placebo. Periodontal parameters including bleeding on probing (BOP, clinical crown length (CL, periodontal pocket depth (PPD, gingival overgrowth (GOI and stent-IDP (vertical distant between a stent or plate with teeth occlusal planes at least from three of the most anterior contact points to mesial papillae before treatment, two and six weeks after treatment were measured. To analyze the data, Wilcoxon and Mann-Whitney tests were used. Results: Most of the measured indices, among case and control groups, were significantly improved, after two weeks (P<0.05. No statistically significant differences were found between two groups except for BOP index (P<0.05. In other words, more BOP improvement was observed in the case group after six weeks comparing to the control group. Conclusion: Considering the findings of this study, one can assume that the reported effects of Azithromycine on gingival overgrowth, induced by cyclosporine is somehow exaggerated and the effects attributed this medicine is probably inflammation reduction.

  15. Evaluation of the improvement of quality of life with Azithromycin in the treatment of eosinophilic nasal polyposis.

    Science.gov (United States)

    Oliveira, Isamara Simas de; Crosara, Paulo Fernando Tormin Borges; Cassali, Geovanni Dantas; Reis, Diego Carlos dos; Resende, Camilo Brandão de; Nunes, Flavio Barbosa; Guimarães, Roberto Eustáquio Santos

    2016-01-01

    The Sino-Nasal Outcome Test 22 (SNOT-22) is an important tool in assessing the quality of life (QoL) of patients with chronic rhinosinusitis with a validated version in Brazil. The eosinophilic nasal polyposis (ENP) represents most of the cases of nasal polyposis (85-90%) and belongs to the group of chronic rhinosinusitis. It is a chronic inflammatory disease that impacts the QoL of patients, not only causing localized symptoms, but also resulting in a general malaise. The standard treatments (corticosteroids and nasal endoscopic surgery) lead to partial control of symptoms, but relapses are frequent. Macrolide acting as an immunomodulator is a promising tool for more effective control of this disease. Studies are still lacking to assess the real impact on the QoL in patients treated with macrolides. To evaluate the improvement of QL, evaluated using SNOT-22, in patients with PNSE treated with immunomodulatory dose azithromycin. This is a paired experimental study in patients with ENP. Comparison of pre-treatment and post-treatment with azithromycin was performed. Patients completed the SNOT-22 questionnaire before the start of treatment and returned for evaluation after eight weeks of treatment. Azithromycin was prescribed at a dose of 500 mg, orally, three times a week, for 8 weeks. SNOT-22 score decreased 20.3 points on average. There was a significant decrease in the SNOT-22 (difference greater than 14 points) in 19 patients (57.6%). There was no significant difference in improvement in SNOT in subgroups with or without asthma/aspirin intolerance. Azithromycin resulted in significant improvement of QoL, assessed by SNOT-22, in the studied population. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  16. Mass drug administration of azithromycin for trachoma reduces the prevalence of genital Chlamydia trachomatis infection in the Solomon Islands.

    Science.gov (United States)

    Marks, M; Bottomley, C; Tome, H; Pitakaka, R; Butcher, R; Sokana, O; Kako, H; Solomon, A W; Mabey, D C

    2016-06-01

    Chlamydia trachomatis is the most common bacterial sexually transmitted infection and is frequently asymptomatic; ocular C. trachomatis strains cause trachoma. Mass drug administration (MDA) of azithromycin for trachoma might also reduce the prevalence of genital C. trachomatis. In a survey conducted in the Solomon Islands in 2014, prior to MDA, the prevalence of genital C. trachomatis was 20.3% (95% CI 15.9% to 25.4%). We conducted a survey to establish the impact of MDA with azithromycin on genital C. trachomatis. Women attending three community outpatient clinics, predominantly for antenatal care, 10 months after MDA with azithromycin given for trachoma elimination, were enrolled in this survey. Self-taken high vaginal swabs were for C. trachomatis and Neisseria gonorrhoeae using the BD Probetec strand displacement assay. 298 women were enrolled. C. trachomatis infection was diagnosed in 43 women (14.4%, 95% CI 10.6% to 18.9%) and N. gonorrhoeae in 9 (3%, 95% CI 1.4% to 5.7%). The age-adjusted OR for C. trachomatis infection was consistent with a significant decrease in the prevalence of C. trachomatis following MDA (OR 0.58, 95% CI 0.37 to 0.94, p=0.027). There was no change in the prevalence of N. gonorrhoeae between following MDA (OR 0.51, 95% CI 0.22 to 1.22, p=0.13). This study demonstrated a 40% reduction in the age-adjusted prevalence of genital C. trachomatis infection following azithromycin MDA for trachoma elimination. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  17. Evaluation of the improvement of quality of life with Azithromycin in the treatment of eosinophilic nasal polyposis

    Directory of Open Access Journals (Sweden)

    Isamara Simas de Oliveira

    2016-04-01

    Full Text Available ABSTRACT INTRODUCTION: The Sino-Nasal Outcome Test 22 (SNOT-22 is an important tool in assessing the quality of life (QoL of patients with chronic rhinosinusitis with a validated version in Brazil. The eosinophilic nasal polyposis (ENP represents most of the cases of nasal polyposis (85-90% and belongs to the group of chronic rhinosinusitis. It is a chronic inflammatory disease that impacts the QoL of patients, not only causing localized symptoms, but also resulting in a general malaise. The standard treatments (corticosteroids and nasal endoscopic surgery lead to partial control of symptoms, but relapses are frequent. Macrolide acting as an immunomodulator is a promising tool for more effective control of this disease. Studies are still lacking to assess the real impact on the QoL in patients treated with macrolides. OBJECTIVE: To evaluate the improvement of QL, evaluated using SNOT-22, in patients with PNSE treated with immunomodulatory dose azithromycin. METHODS: This is a paired experimental study in patients with ENP. Comparison of pre-treatment and post-treatment with azithromycin was performed. Patients completed the SNOT-22 questionnaire before the start of treatment and returned for evaluation after eight weeks of treatment. Azithromycin was prescribed at a dose of 500 mg, orally, three times a week, for 8 weeks. RESULTS: SNOT-22 score decreased 20.3 points on average. There was a significant decrease in the SNOT-22 (difference greater than 14 points in 19 patients (57.6%. There was no significant difference in improvement in SNOT in subgroups with or without asthma/aspirin intolerance. CONCLUSION: Azithromycin resulted in significant improvement of QoL, assessed by SNOT-22, in the studied population.

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

    Directory of Open Access Journals (Sweden)

    Stéphane Perchat

    2016-08-01

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

  19. Clinical evaluation of piroxicam-FDDF and azithromycin in the prevention of complications associated with impacted lower third molar extraction.

    Science.gov (United States)

    Graziani, F; Corsi, L; Fornai, M; Antonioli, L; Tonelli, M; Cei, S; Colucci, R; Blandizzi, C; Gabriele, M; Del Tacca, M

    2005-12-01

    Combined treatments with non-steroidal anti-inflammatory drugs and antibiotics may offer significant benefits in the prevention of pain and infections associated with oral surgery. In this study, piroxicam and azithromycin were administered to patients undergoing dental extraction to examine the efficacy of piroxicam in the prevention of post-operative pain and inflammatory complications, either in the absence or in the presence of a concomitant antibiotic treatment. Thirty patients were randomly assigned to three groups and treated for 3 days, before impacted lower third molar removal, as follows: (1) sublingual piroxicam-FDDF (fast dissolving dosage formulation) 20 mg/day; (2) oral azithromycin 500 mg/day; (3) piroxicam-FDDF 20 mg/day plus azithromycin 500 mg/day. Oral acetaminophen (500 mg tablets) was allowed as rescue analgesic medication. Pain intensity was evaluated on a 100-mm visual-analogue scale after dental extraction (day 1), and at days 2, 3, 7 after surgery. Edema and trismus were estimated at days 2 and 7. At days 1 and 2, pain intensity was significantly lower in patients treated with piroxicam-FDDF, either alone (p antibiotic may reduce the influence of piroxicam on post-operative inflammation, without affecting its beneficial effect on surgical pain.

  20. Early Administration of Azithromycin and Prevention of Severe Lower Respiratory Tract Illnesses in Preschool Children With a History of Such Illnesses: A Randomized Clinical Trial.

    Science.gov (United States)

    Bacharier, Leonard B; Guilbert, Theresa W; Mauger, David T; Boehmer, Susan; Beigelman, Avraham; Fitzpatrick, Anne M; Jackson, Daniel J; Baxi, Sachin N; Benson, Mindy; Burnham, Carey-Ann D; Cabana, Michael; Castro, Mario; Chmiel, James F; Covar, Ronina; Daines, Michael; Gaffin, Jonathan M; Gentile, Deborah Ann; Holguin, Fernando; Israel, Elliot; Kelly, H William; Lazarus, Stephen C; Lemanske, Robert F; Ly, Ngoc; Meade, Kelley; Morgan, Wayne; Moy, James; Olin, Tod; Peters, Stephen P; Phipatanakul, Wanda; Pongracic, Jacqueline A; Raissy, Hengameh H; Ross, Kristie; Sheehan, William J; Sorkness, Christine; Szefler, Stanley J; Teague, W Gerald; Thyne, Shannon; Martinez, Fernando D

    2015-11-17

    Many preschool children develop recurrent, severe episodes of lower respiratory tract illness (LRTI). Although viral infections are often present, bacteria may also contribute to illness pathogenesis. Strategies that effectively attenuate such episodes are needed. To evaluate if early administration of azithromycin, started prior to the onset of severe LRTI symptoms, in preschool children with recurrent severe LRTIs can prevent the progression of these episodes. A randomized, double-blind, placebo-controlled, parallel-group trial conducted across 9 academic US medical centers in the National Heart, Lung, and Blood Institute's AsthmaNet network, with enrollment starting in April 2011 and follow-up complete by December 2014. Participants were 607 children aged 12 through 71 months with histories of recurrent, severe LRTIs and minimal day-to-day impairment. Participants were randomly assigned to receive azithromycin (12 mg/kg/d for 5 days; n = 307) or matching placebo (n = 300), started early during each predefined RTI (child's signs or symptoms prior to development of LRTI), based on individualized action plans, over a 12- through 18-month period. The primary outcome measure was the number of RTIs not progressing to a severe LRTI, measured at the level of the RTI, that would in clinical practice trigger the prescription of oral corticosteroids. Presence of azithromycin-resistant organisms in oropharyngeal samples, along with adverse events, were among the secondary outcome measures. A total of 937 treated RTIs (azithromycin group, 473; placebo group, 464) were experienced by 443 children (azithromycin group, 223; placebo group, 220), including 92 severe LRTIs (azithromycin group, 35; placebo group, 57). Azithromycin significantly reduced the risk of progressing to severe LRTI relative to placebo (hazard ratio, 0.64 [95% CI, 0.41-0.98], P = .04; absolute risk for first RTI: 0.05 for azithromycin, 0.08 for placebo; risk difference, 0.03 [95% CI, 0

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

    Science.gov (United States)

    Scholz, Rebecca L; Greenberg, E Peter

    2017-07-25

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

  2. Protective Effects of Carvedilol and Vitamin C against Azithromycin-Induced Cardiotoxicity in Rats via Decreasing ROS, IL1-β, and TNF-α Production and Inhibiting NF-κB and Caspase-3 Expression.

    Science.gov (United States)

    El-Shitany, Nagla A; El-Desoky, Karema

    2016-01-01

    The Food and Drug Administration recently warned of the fatal cardiovascular risks of azithromycin in humans. In addition, a recently published study documented azithromycin-induced cardiotoxicity in rats. This study aimed to justify the exact cardiovascular events accompanying azithromycin administration in rats, focusing on electrocardiographic, biochemical, and histopathological changes. In addition, the underlying mechanisms were studied regarding reactive oxygen species production, cytokine release, and apoptotic cell-death. Finally, the supposed protective effects of both carvedilol and vitamin C were assessed. Four groups of rats were used: (1) control, (2) azithromycin, (3) azithromycin + carvedilol, and (4) azithromycin + vitamin C. Azithromycin resulted in marked atrophy of cardiac muscle fibers and electrocardiographic segment alteration. It increased the heart rate, lactate dehydrogenase, creatine phosphokinase, malondialdehyde, nitric oxide, interleukin-1 beta (IL1-β), tumor necrosis factor alpha (TNF-α), nuclear factor kappa beta (NF-κB), and caspase-3. It decreased reduced glutathione, glutathione peroxidase, and superoxide dismutase. Carvedilol and vitamin C prevented most of the azithromycin-induced electrocardiographic and histopathological changes. Carvedilol and vitamin C decreased lactate dehydrogenase, malondialdehyde, IL1-β, TNF-α, NF-κB, and caspase-3. Both agents increased glutathione peroxidase. This study shows that both carvedilol and vitamin C protect against azithromycin-induced cardiotoxicity through antioxidant, immunomodulatory, and antiapoptotic mechanisms.

  3. The effect of azithromycin in adults with stable neutrophilic COPD: a double blind randomised, placebo controlled trial.

    Directory of Open Access Journals (Sweden)

    Jodie L Simpson

    Full Text Available Chronic Obstructive Pulmonary Disease (COPD is a progressive airway disease characterised by neutrophilic airway inflammation or bronchitis. Neutrophilic bronchitis is associated with both bacterial colonisation and lung function decline and is common in exacerbations of COPD. Despite current available therapies to control inflammation, neutrophilic bronchitis remains common. This study tested the hypothesis that azithromycin treatment, as an add-on to standard medication, would significantly reduce airway neutrophil and neutrophils chemokine (CXCL8 levels, as well as bacterial load. We conducted a randomised, double-blind, placebo-controlled study in COPD participants with stable neutrophilic bronchitis.Eligible participants (n = 30 were randomised to azithromycin 250 mg daily or placebo for 12 weeks in addition to their standard respiratory medications. Sputum was induced at screening, randomisation and monthly for a 12 week treatment period and processed for differential cell counts, CXCL8 and neutrophil elastase assessment. Quantitative bacteriology was assessed in sputum samples at randomisation and the end of treatment visit. Severe exacerbations where symptoms increased requiring unscheduled treatment were recorded during the 12 week treatment period and for 14 weeks following treatment. A sub-group of participants underwent chest computed tomography scans (n = 15.Nine participants with neutrophilic bronchitis had a potentially pathogenic bacteria isolated and the median total bacterial load of all participants was 5.22×107 cfu/mL. Azithromycin treatment resulted in a non-significant reduction in sputum neutrophil proportion, CXCL8 levels and bacterial load. The mean severe exacerbation rate was 0.33 per person per 26 weeks in the azithromycin group compared to 0.93 exacerbations per person in the placebo group (incidence rate ratio (95%CI: 0.37 (0.11,1.21, p = 0.062. For participants who underwent chest CT scans, no

  4. Azithromycin-Induced, Biopsy-Proven Acute Interstitial Nephritis in an Adult Successfully Treated with Low-Dose Corticosteroids.

    Science.gov (United States)

    Woodruff, Ashley E; Meaney, Calvin J; Hansen, Elizabeth A; Prescott, Gina M

    2015-11-01

    Acute interstitial nephritis (AIN) is a form of acute kidney injury (AKI) characterized by a rapid deterioration of renal function, inflammatory infiltration of interstitial tissues, and renal edema. Drug-induced AIN is the most common etiology of AIN, but AIN can also have infectious, autoimmune, or idiopathic causes. β-Lactam antibacterials, nonsteroidal antiinflammatory drugs, and proton pump inhibitors are recognized as leading causes of AIN; however, many other drugs have been identified as causes. We describe the case of a 59-year-old white male who developed AIN that required hemodialysis following azithromycin treatment. He presented to the hospital with complaints of nausea, vomiting, malaise, and fever over the past 3 days, along with no urine output in the preceding 24 hours. Two weeks earlier, he had completed a 5-day course of azithromycin 500 mg on day 1 followed by 250 mg/day on days 2-5 (total dose 1.5 g) for an upper respiratory tract infection. On admission, the patient's serum creatinine (S(cr)) concentration was 7.4 mg/dl (baseline = 1.3 mg/dl). He reported a similar episode of kidney failure 2 years earlier after taking azithromycin; however, at that time it was believed the AKI was likely due to benazepril use in the setting of acute infection, and a kidney biopsy was not performed. His S(cr) concentration peaked at 11.4 mg/dl, and three sessions of hemodialysis were required. A kidney biopsy was performed that revealed AIN. Low-dose prednisone 0.3 mg/kg (30 mg)/day, tapered over the next 3 months, was administered, and his renal function improved to near baseline prior to discharge; 6 months later, his Scr concentration was 1.4 mg/dl. Despite lower than recommended dosing, this patient responded well to prednisone and did not experience long-term sequelae from renal injury. Use of the Naranjo Adverse Drug Reaction Probability Scale indicated a definite relationship (score of 10) between azithromycin exposure and the manifestation of AIN. To

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

    Science.gov (United States)

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

    2014-08-01

    Quorum sensing, a group behaviour coordinated by a diffusible pheromone signal and a cognate receptor, is typical of bacteria that form symbioses with plants and animals. LuxIR-type N-acyl L-homoserine (AHL) quorum sensing is common in Gram-negative Proteobacteria, and many members of this group have additional quorum-sensing networks. The bioluminescent symbiont Vibrio fischeri encodes two AHL signal synthases: AinS and LuxI. AinS-dependent quorum sensing converges with LuxI-dependent quorum sensing at the LuxR regulatory element. Both AinS- and LuxI-mediated signalling are required for efficient and persistent colonization of the squid host, Euprymna scolopes. The basis of the mutualism is symbiont bioluminescence, which is regulated by both LuxI- and AinS-dependent quorum sensing, and is essential for maintaining a colonization of the host. Here, we used chemical and genetic approaches to probe the dynamics of LuxI- and AinS-mediated regulation of bioluminescence during symbiosis. We demonstrate that both native AHLs and non-native AHL analogues can be used to non-invasively and specifically modulate induction of symbiotic bioluminescence via LuxI-dependent quorum sensing. Our data suggest that the first day of colonization, during which symbiont bioluminescence is induced by LuxIR, is a critical period that determines the stability of the V. fischeri population once symbiosis is established. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

  6. A Case-Control Study of Molecular Epidemiology in Relation to Azithromycin Resistance in Neisseria gonorrhoeae Isolates Collected in Amsterdam, the Netherlands, between 2008 and 2015.

    Science.gov (United States)

    Wind, Carolien M; Bruisten, Sylvia M; Schim van der Loeff, Maarten F; Dierdorp, Mirjam; de Vries, Henry J C; van Dam, Alje P

    2017-06-01

    Neisseria gonorrhoeae resistance to ceftriaxone and azithromycin is increasing, which threatens the recommended dual therapy. We used molecular epidemiology to identify N. gonorrhoeae clusters and associations with azithromycin resistance in Amsterdam, the Netherlands. N. gonorrhoeae isolates ( n = 143) were selected from patients visiting the Amsterdam STI Outpatient Clinic from January 2008 through September 2015. We included all 69 azithromycin-resistant isolates (MIC ≥ 2.0 mg/liter) and 74 frequency-matched susceptible controls (MIC ≤ 0.25 mg/liter). The methods used were 23S rRNA and mtrR sequencing, N. gonorrhoeae multiantigen sequence typing (NG-MAST), N. gonorrhoeae multilocus variable-number tandem-repeat analysis (NG-MLVA), and a specific PCR to detect mosaic penA genes. A hierarchical cluster analysis of NG-MLVA related to resistance and epidemiological characteristics was performed. Azithromycin-resistant isolates had C2611T mutations in 23S rRNA ( n = 62, 89.9%, P azithromycin resistance was found. Twenty-four isolates, including 10 azithromycin-resistant isolates, showed reduced susceptibility to extended-spectrum cephalosporins. Of these, five contained a penA mosaic gene. Four of the five NG-MLVA clusters contained resistant and susceptible isolates. Two clusters consisting mainly of resistant isolates included strains from men who have sex with men and from heterosexual males and females. The co-occurrence of resistant and susceptible strains in NG-MLVA clusters and the frequent occurrence of resistant strains outside of clusters suggest that azithromycin resistance develops independently from the background genome. Copyright © 2017 American Society for Microbiology.

  7. Preparation and characterization of azithromycin--Aerosil 200 solid dispersions with enhanced physical stability.

    Science.gov (United States)

    Li, Xuechao; Peng, Huanhuan; Tian, Bin; Gou, Jingxin; Yao, Qing; Tao, Xiaoguang; He, Haibing; Zhang, Yu; Tang, Xing; Cai, Cuifang

    2015-01-01

    The main purpose of this study was to investigate the feasibility of azithromycin (AZI)--Aerosil 200 solid dispersions specifically with high stability under accelerated condition (40 °C/75% RH). Ball milling (BM) and hot-melt extrusion (HME) were used to prepare AZI solid dispersions. The physical properties of solid dispersions were evaluated by differential scanning calorimetry (DSC), scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA). For solid dispersions prepared with both methods, no crystalline of AZI was detected (except for AZI: Aerosil 200=75:25) by DSC or PXRD, indicating the amorphous state of AZI in solid dispersions. The FT-IR results demonstrated the loss of crystallization water and the formation of hydrogen bonds between Aerosil 200 and AZI during the preparation of solid dispersions. After 4 weeks storage under accelerated condition, the degree of crystallinity of AZI increased in solid dispersions prepared by BM, whereas for solid dispersions containing AZI, Aerosil 200 and glyceryl behenate (GB) prepared by HME, no crystalline of AZI was identified. This high stability can be attributed to the hydrophobic properties of GB and the presence of hydrogen bonds. Based on the above results, it is inferred the protection of hydrogen bonds between AZI and Aerosil 200 formed during preparation process effectively inhibited the recrystallization of AZI and improved the physical stability of amorphous AZI in the presence of Aerosil 200. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. The therapeutic efficacy of azithromycin and nitazoxanide in the acute pig model of Cryptosporidium hominis.

    Science.gov (United States)

    Lee, Sangun; Harwood, Melanie; Girouard, Don; Meyers, Marvin J; Campbell, Mary A; Beamer, Gillian; Tzipori, Saul

    2017-01-01

    Recent reports highlighting the global significance of cryptosporidiosis among children, have renewed efforts to develop control measures. We have optimized the gnotobiotic piglet model of acute diarrhea to evaluate azithromycin (AZR), nitazoxanide (NTZ), or treatment with both against Cryptosporidium hominis, the species responsible for most human cases. Piglets, animals reproducibly clinically susceptible to C. hominis, when inoculated with 106 oocysts, developed acute diarrhea with oocyst excretion in feces within 3 days. Ten day-treatment with recommended doses for children, commencing at onset of diarrhea, showed that treatment with AZR or NTZ relieved symptoms early in the treatment compared with untreated animals. Piglets treated with AZR exhibited no reduction of oocyst excretion whereas treatment with NTZ significantly reduced oocyst shedding early, increasing however after 5 days. While treatment with AZR+NTZ led to considerable symptomatic improvement, it had a modest effect on reducing mucosal injury, and did not completely eliminate oocyst excretion. Doubling the dose of AZR and/or NTZ did not improve the clinical outcome, confirming clinical observations that NTZ is only partially effective in reducing duration of diarrhea in children. This investigation confirms the gnotobiotic piglet as a useful tool for drug evaluation for the treatment of cryptosporidiosis in children.

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

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    DEFF Research Database (Denmark)

    Wu, H; Song, Z; Givskov, Michael

    2001-01-01

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

  11. High azithromycin concentration in lungs by way of bovine serum albumin microspheres as targeted drug delivery: lung targeting efficiency in albino mice.

    Science.gov (United States)

    Ramaiah, Balakeshwa; Nagaraja, Sree Harsha; Kapanigowda, Usha Ganganahalli; Boggarapu, Prakash Rao; Subramanian, Rajarajan

    2016-05-05

    Following administration, the antibiotic travels freely through the body and also accumulates in other parts apart from the infection site. High dosage and repeated ingestion of antibiotics in the treatment of pneumonia leads to undesirable effects and inappropriate disposition of the drug. By way of targeted lung delivery, this study was intended to eliminate inappropriate azithromycin disposition and to achieve higher azithromycin concentration to treat deeper airway infections. The Azithromycin Albumin Microspheres (AAM) was prepared by emulsion polymerization technique. The optimized AAM was subjected to in vitro release study, release kinetics, XRD and stability studies. Further, in vivo pharmacokinetics and tissue distribution of azithromycin released from AAM and azithromycin solution in albino mice was investigated to prove suitability of moving forward the next steps in the clinic. The mean particle size of the optimized AAM was 10.02 μm, an optimal size to get deposited in the lungs by mechanical entrapment. The maximum encapsulation efficiency of 82.3 % was observed in this study. The release kinetic was significant and best fitted for Korsmeyer-Peppas model (R(2) = 0.9962, n = 0.41). The XRD and stability study showed favorable results. Azithromycin concentration in mice lungs (40.62 μg g(-1), 30 min) of AAM was appreciably higher than other tissues and plasma. In comparison with control, azithromycin concentration in lungs was 30.15 μg g(-1) after 30 min. The azithromycin AUC (929.94 μg h mL(-1)) and intake rate (re) (8.88) for lung were higher and statistically significant in AAM group. Compared with spleen and liver, the targeting efficacy (te) in mice lung increased by a factor of 40.15 and ~14.10 respectively. Subsequently by a factor of 8.94, the ratio of peak concentration (Ce) in lung was higher in AAM treated mice. The AAM lung tissue histopathology did not show any degenerative changes. High azithromycin concentration in

  12. Effects of Azithromycin on Gene Expression Profiles of Proinflammatory and Anti-inflammatory Mediators in the Eyelid Margin and Conjunctiva of Patients With Meibomian Gland Disease

    Science.gov (United States)

    Zhang, Lili; Su, Zhitao; Zhang, Zongduan; Lin, Jing; Li, De-Quan; Pflugfelder, Stephen C.

    2017-01-01

    IMPORTANCE Topical application of azithromycin suppresses expression of proinflammatory mediators while restoring transforming growth factor β1 (TGF-β1) levels as evaluated by eyelid margin and conjunctival impression cytology. OBJECTIVE To explore the effects of azithromycin therapy on expression of proinflammatory and anti-inflammatory mediators in meibomian gland disease (MGD). DESIGN, SETTING, AND PARTICIPANTS Case-control study performed in a clinic setting from August 17, 2010, to December 31, 2010. Sixteen patients with posterior blepharitis and conjunctival inflammation due to MGD were treated with azithromycin, 1%, drops for 4 weeks. Impression cytology of the lower eyelid margin and tarsal conjunctiva to measure cytokine expression by quantitative real-time polymerase chain reaction as well as tear collection to measure matrix metalloproteinase 9 (MMP-9) activity were performed once in 8 asymptomatic healthy control participants and 5 times in the 16 symptomatic patients (every 2 weeks for 8 weeks), before, during, and after azithromycin treatment. EXPOSURE Azithromycin, 1%, drops for 4 weeks. MAIN OUTCOMES AND MEASURES Cytokine expression in the eyelid margin and conjunctiva, and MMP-9 activity in tears. RESULTS Compared with a 1-time measurement of 8 healthy participants, among 16 symptomatic patients, the mean (SD; 95% CI) fold change of expression of proinflammatory mediators interleukin 1β (IL-1β), IL-8, and MMP-9 increased to 13.26 (4.33; 11.14–15.38; P Azithromycin, 1%, caused a change in the expression pattern of these mediators toward normal levels during 4 weeks of treatment. Levels of IL-1β, IL-8, and MMP-9 mRNA remained suppressed, although they rebounded toward pretreatment values 4 weeks after azithromycin withdrawal. Expression of TGF-β1 increased during treatment and remained at levels similar to the healthy controls after drug withdrawal. Change in tear MMP-9 activity was similar to the pattern of MMP-9 transcripts. CONCLUSIONS

  13. Implications of endophyte-plant crosstalk in light of quorum responses for plant biotechnology.

    Science.gov (United States)

    Kusari, Parijat; Kusari, Souvik; Spiteller, Michael; Kayser, Oliver

    2015-07-01

    Quorum sensing, the cell-to-cell communication system mediated by autoinducers, is responsible for regulation of virulence factors, infections, invasion, colonization, biofilm formation, and antibiotic resistance within bacterial populations. Concomitantly, quorum quenching is a process that involves attenuation of virulence factors by inhibiting or degrading quorum signaling autoinducers. Survival of endophytic microorganisms, commonly known as endophytes, in planta is a continuous mêlée with invading pathogens and pests. In order to survive in their microhabitats inside plants, endophytes have co-evolved to not only utilize an arsenal of biologically active defense compounds but also impede communication between invading pathogens. Such antivirulence strategies prevent pathogens from communicating with or recognizing each other and thus, colonizing plants. The quenching phenomena often involves microbial crosstalk within single or mixed population(s) vis-à-vis gene expression, and production/modulation of quenching enzymes coupled to various antagonistic and synergistic interactions. This concept is particularly interesting because it can be biotechnologically translated in the future to quorum inhibiting antivirulence therapies without triggering resistance in bacteria, which is currently a major problem worldwide that cannot be tackled only with antimicrobial therapies. In this mini-review, we highlight the quorum quenching capacity of endophytes with respect to attenuation of virulence factors and aiding in plant defense response. Further, benefits and potential challenges of using such systems in biotechnology are discussed.

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

    Directory of Open Access Journals (Sweden)

    Evelina Papaioannou

    2013-09-01

    Full Text Available Bacteria, although considered for decades to be antisocial organisms whose sole purpose is to find nutrients and multiply are, in fact, highly communicative organisms. Referred to as quorum sensing, cell-to-cell communication mechanisms have been adopted by bacteria in order to co-ordinate their gene expression. By behaving as a community rather than as individuals, bacteria can simultaneously switch on their virulence factor production and establish successful infections in eukaryotes. Understanding pathogen-host interactions requires the use of infection models. As the use of rodents is limited, for ethical considerations and the high costs associated with their use, alternative models based on invertebrates have been developed. Invertebrate models have the benefits of low handling costs, limited space requirements and rapid generation of results. This review presents examples of such models available for studying the pathogenicity of the Gram-negative bacterium Pseudomonas aeruginosa. Quorum sensing interference, known as quorum quenching, suggests a promising disease-control strategy since quorum-quenching mechanisms appear to play important roles in microbe-microbe and host-pathogen interactions. Examples of natural and synthetic quorum sensing inhibitors and their potential as antimicrobials in Pseudomonas-related infections are discussed in the second part of this review.

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

    Directory of Open Access Journals (Sweden)

    Zhengwei Huang

    2012-05-01

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

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

    Science.gov (United States)

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

    2015-09-30

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

  17. Repurposing metformin as a quorum sensing inhibitor inPseudomonas aeruginosa.

    Science.gov (United States)

    Abbas, Hisham A; Elsherbini, Ahmed M; Shaldam, Moutaz A

    2017-09-01

    Quorum sensing is a mechanism of intercellular communication that controls the production of virulence factors in Pseudomonas aeruginosa . Inhibition of quorum sensing can disarm the virulence factors without exerting stress on bacterial growth that leads to emergence of antibiotic resistance. Finding a new quorum sensing inhibitor and determining its inhibitory activities against virulence factors of Pseudomonas aeruginosa PAO1 strain. Quorum sensing was evaluated by estimation of violacein production by Chromobacterium violaceum CV026. Molecular docking was used to investigate the possible binding of metformin to LasR and rhlR receptors. The inhibition of pyocyanin, hemolysin, protease, elastase in addition to swimming and twitching motilities, biofilm formation and resistance to oxidative stress by metformin was also assessed. Metformin significantly reduced the production of violacein pigment. Significant inhibition of pyocyanin, hemolysin, protease and elastase was achieved. Metformin markedly decreased biofilm formation, swimming and twitching motilities and increased the sensitivity to oxidative stress. In the molecular docking study, metformin could bind to LasR by hydrogen bonding and electrostatic interaction and to rhlR by hydrogen bonding only. Metformin can act as a quorum sensing inhibitor and virulence inhibiting agent that may be useful in the treatment of Pseudomonas aeruginosa infection.

  18. Glyceryl trinitrate is a novel inhibitor of quorum sensing inPseudomonas aeruginosa.

    Science.gov (United States)

    Abbas, Hisham A; Shaldam, Moutaz A

    2016-12-01

    Targeting quorum sensing is an alternative approach to antibiotics.Targeting quorum sensing-regulated virulence will disarm the pathogen without exerting pressure on its growth. As a result, emergence of resistance is avoided and the immune system can easily eradicate bacteria. Investigation of the possible inhibition of quorum sensing-regulated virulence of Pseudomonas aeruginosa by glyceryltrinitrate. The quorum sensing inhibiting activity of glyceryl trinitrate was assessed by inhibition of violacein production in Chromobacterium violaceum ATCC 12472. Its ability to inhibit pyocyanin, protease, biofilm and tolerance to oxidative stress was evaluated. Docking study was performed to study the interference of glyceryl trinitrate with the binding of autoinducers with LasR and rhlR receptors. Glyceryl trinitrate exerted a significant biofilm inhibiting and eradicating activities. It decreased the production of quorum-sensing dependent violacein production. It significantly inhibited the production of pyocyanin and protease and diminished the tolerance against oxidative stress. Molecular docking study showed that glyceryl trinitrate interferes with the binding of autoinducers to their receptors. It could bind to Las Rand rhlr receptors with binding energy of -93.47 and -77.23, respectively. Glyceryl trinitrate can be an antivirulence agent in the treatment of Pseudomonas aeruginosa topical infections such as burn infections.

  19. Production of quorum-sensing signals by bacteria in the coral mucus layer

    Science.gov (United States)

    Li, Jie; Kuang, Weiqi; Long, Lijuan; Zhang, Si

    2017-12-01

    Quorum sensing is an integral part of bacterial communication and interaction, but has not been well characterized in coral mucus microbiota. In this study, of 61 coral mucus isolates, five alphaproteobacteria and one Vibrio species were found to produce N-acyl homoserine lactone (AHL), a quorum-sensing signal in bacteria. Eight gammaproteobacteria isolates were found to produce autoinducer-2 (AI-2) quorum-sensing signals along with two actinobacteria of the genus Rothia. Coral mucus is rich in the antioxidant dimethylsulfoniopropionate (DMSP), the concentration of which has been found to increase under heat stress. Neither AHL nor AI-2 activity was induced by DMSP in those coral mucus isolates that did not initially produce quorum-sensing signals. However, the AI-2 activities of one Rothia isolate (SCSIO 13017) from coral mucus and of Vibrio shilonii (DSM 13774 isolated from a bleached coral) were found to increase in response to 5 μM DMSP but decreased in response to 50 μM DMSP for the first time. These findings suggest that the production of quorum-sensing signals in the coral mucus microbiota may play a role in structuring the surface microbial community as they respond to environmental stress.

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

    Directory of Open Access Journals (Sweden)

    Ines Mandic-Mulec

    2003-01-01

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

  1. Ultrasound guided supraclavicular block.

    LENUS (Irish Health Repository)

    Hanumanthaiah, Deepak

    2013-09-01

    Ultrasound guided regional anaesthesia is becoming increasingly popular. The supraclavicular block has been transformed by ultrasound guidance into a potentially safe superficial block. We reviewed the techniques of performing supraclavicular block with special focus on ultrasound guidance.

  2. Azithromycin treatment is able to control the infection by two genotypes of Toxoplasma gondii in human trophoblast BeWo cells.

    Science.gov (United States)

    Ribeiro, Mayara; Franco, Priscila Silva; Lopes-Maria, Janice Buiate; Angeloni, Mariana Bodini; Barbosa, Bellisa de Freitas; Gomes, Angelica de Oliveira; Castro, Andressa Silva; Silva, Rafaela José da; Oliveira, Fernanda Chaves de; Milian, Iliana Claudia Balga; Martins-Filho, Olindo Assis; Ietta, Francesca; Mineo, José Roberto; Ferro, Eloisa Amália Vieira

    2017-10-01

    Trophoblast infection by Toxoplasma gondii plays a pivotal role in the vertical transmission of toxoplasmosis. Here, we investigate whether the antibiotic therapy with azithromycin, spiramycin and sulfadiazine/pyrimethamine are effective to control trophoblast infection by two Brazilian T. gondii genotypes, TgChBrUD1 or TgChBrUD2. Two antibiotic protocols were evaluated, as follow: i) pre-treatment of T. gondii-tachyzoites with selected antibiotics prior trophoblast infection and ii) post-treatment of infected trophoblasts. The infection index/replication and the impact of the antibiotic therapy on the cytokine milieu were characterized. It was observed that TgChBrUD2 infection induced lower infection index/replication as compared to TgChBrUD1. Regardless the therapeutic protocol, azithromycin was more effective to control the trophoblast infection with both genotypes when compared to conventional antibiotics. Azithromycin induced higher IL-12 production in TgChBrUD1-infected cells that may synergize the anti-parasitic effect. In contrast, the effectiveness of azithromycin to control the TgChBrUD2-infection was not associated with the IL-12 production. BeWo-trophoblasts display distinct susceptibility to T. gondii genotypes and the azithromycin treatment showed to be more effective than conventional antibiotics to control the T. gondii infection/replication regardless the parasite genotype. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Kimberly Aebli

    2016-05-01

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

  4. Ecological feedback in quorum-sensing microbial populations can induce heterogeneous production of autoinducers.

    Science.gov (United States)

    Bauer, Matthias; Knebel, Johannes; Lechner, Matthias; Pickl, Peter; Frey, Erwin

    2017-07-25

    Autoinducers are small signaling molecules that mediate intercellular communication in microbial populations and trigger coordinated gene expression via 'quorum sensing'. Elucidating the mechanisms that control autoinducer production is, thus, pertinent to understanding collective microbial behavior, such as virulence and bioluminescence. Recent experiments have shown a heterogeneous promoter activity of autoinducer synthase genes, suggesting that some of the isogenic cells in a population might produce autoinducers, whereas others might not. However, the mechanism underlying this phenotypic heterogeneity in quorum-sensing microbial populations has remained elusive. In our theoretical model, cells synthesize and secrete autoinducers into the environment, up-regulate their production in this self-shaped environment, and non-producers replicate faster than producers. We show that the coupling between ecological and population dynamics through quorum sensing can induce phenotypic heterogeneity in microbial populations, suggesting an alternative mechanism to stochastic gene expression in bistable gene regulatory circuits.

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

    Science.gov (United States)

    Barron, Addie; Hagen, Steve; Son, Minjun

    2015-03-01

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

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

    Science.gov (United States)

    Bressloff, Paul C.

    2016-06-01

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

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

    Science.gov (United States)

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

    2016-02-23

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

  8. Molecular Mechanism of Quorum-Sensing in Enterococcus faecalis: Its Role in Virulence and Therapeutic Approaches.

    Science.gov (United States)

    Ali, Liaqat; Goraya, Mohsan Ullah; Arafat, Yasir; Ajmal, Muhammad; Chen, Ji-Long; Yu, Daojin

    2017-05-03

    Quorum-sensing systems control major virulence determinants in Enterococcus faecalis , which causes nosocomial infections. The E . faecalis quorum-sensing systems include several virulence factors that are regulated by the cytolysin operon, which encodes the cytolysin toxin. In addition, the E . faecalis Fsr regulator system controls the expression of gelatinase, serine protease, and enterocin O16. The cytolysin and Fsr virulence factor systems are linked to enterococcal diseases that affect the health of humans and other host models. Therefore, there is substantial interest in understanding and targeting these regulatory pathways to develop novel therapies for enterococcal infection control. Quorum-sensing inhibitors could be potential therapeutic agents for attenuating the pathogenic effects of E . faecalis . Here, we discuss the regulation of cytolysin, the LuxS system, and the Fsr system, their role in E . faecalis -mediated infections, and possible therapeutic approaches to prevent E . faecalis infection.

  9. Linear peptidomimetics as potent antagonists of Staphylococcus aureus agr quorum sensing

    DEFF Research Database (Denmark)

    Karathanasi, Georgia; Bojer, Martin Saxtorph; Baldry, Mara

    2018-01-01

    Staphylococcus aureus is an important pathogen causing infections in humans and animals. Increasing problems with antimicrobial resistance has prompted the development of alternative treatment strategies, including antivirulence approaches targeting virulence regulation such as the agr quorum sen......, these peptidomimetics may be valuable starting scaffolds for the development of new inhibitors of staphylococcal quorum sensing and virulence gene expression.......Staphylococcus aureus is an important pathogen causing infections in humans and animals. Increasing problems with antimicrobial resistance has prompted the development of alternative treatment strategies, including antivirulence approaches targeting virulence regulation such as the agr quorum...... sensing system. agr is naturally induced by cyclic auto-inducing peptides (AIPs) binding to the AgrC receptor and cyclic peptide inhibitors have been identified competing with AIP binding to AgrC. Here, we disclose that small, linear peptidomimetics can act as specific and potent inhibitors of the S...

  10. Quorum-Sensing Signal-Response Systems in Gram-Negative Bacteria

    Science.gov (United States)

    Papenfort, Kai; Bassler, Bonnie

    2016-01-01

    Abstract / Preface Bacteria use quorum sensing to orchestrate gene expression programmes that underlie collective behaviours. Quorum sensing relies on the production, release, detection and group-level response to extracellular signalling molecules, which are called autoinducers. Recent work has discovered new autoinducers in Gram-negative bacteria, shown how these molecules are recognized by cognate receptors, revealed new regulatory components that are embedded in canonical signalling circuits and identified novel regulatory network designs. In this Review we examine how, together, these features of quorum sensing signal–response systems combine to control collective behaviours in Gram-negative bacteria and we discuss the implications for host–microbial associations and antibacterial therapy. PMID:27510864

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

    Science.gov (United States)

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

    2006-01-01

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

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

    Science.gov (United States)

    Lang, Julien; Faure, Denis

    2014-01-01

    In Agrobacterium tumefaciens, horizontal transfer and vegetative replication of oncogenic Ti plasmids involve a cell-to-cell communication process called quorum-sensing (QS). The determinants of the QS-system belong to the LuxR/LuxI class. The LuxI-like protein TraI synthesizes N-acyl-homoserine lactone molecules which act as diffusible QS-signals. Beyond a threshold concentration, these molecules bind and activate the LuxR-like transcriptional regulator TraR, thereby initiating the QS-regulatory pathway. For the last 20 years, A. tumefaciens has stood as a prominent model in the understanding of the LuxR/LuxI type of QS systems. A number of studies also unveiled features which are unique to A. tumefaciens QS, some of them being directly related to the phytopathogenic lifestyle of the bacteria. In this review, we will present the current knowledge of QS in A. tumefaciens at both the genetic and molecular levels. We will also describe how interactions with plant host modulate the QS pathway of A. tumefaciens, and discuss what could be the advantages for the agrobacteria to use such a tightly regulated QS-system to disseminate the Ti plasmids. PMID:24550924

  13. Memory decay and loss of criticality in quorum percolation

    Science.gov (United States)

    Renault, Renaud; Monceau, Pascal; Bottani, Samuel

    2013-12-01

    In this paper, we present the effects of memory decay on a bootstrap percolation model applied to random directed graphs (quorum percolation). The addition of decay was motivated by its natural occurrence in physical systems previously described by percolation theory, such as cultured neuronal networks, where decay originates from ionic leakage through the membrane of neurons and/or synaptic depression. Surprisingly, this feature alone appears to change the critical behavior of the percolation transition, where discontinuities are replaced by steep but finite slopes. Using different numerical approaches, we show evidence for this qualitative change even for very small decay values. In experiments where the steepest slopes can not be resolved and still appear as discontinuities, decay produces nonetheless a quantitative difference on the location of the apparent critical point. We discuss how this shift impacts network connectivity previously estimated without considering decay. In addition to this particular example, we believe that other percolation models are worth reinvestigating, taking into account similar sorts of memory decay.

  14. Quorum-sensing and cheating in bacterial biofilms

    Science.gov (United States)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Denis eFaure

    2014-01-01

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

  16. Bacterial biofilms and quorum sensing: fidelity in bioremediation technology.

    Science.gov (United States)

    Mangwani, Neelam; Kumari, Supriya; Das, Surajit

    Increased contamination of the environment with toxic pollutants has paved the way for efficient strategies which can be implemented for environmental restoration. The major problem with conventional methods used for cleaning of pollutants is inefficiency and high economic costs. Bioremediation is a growing technology having advanced potential of cleaning pollutants. Biofilm formed by various micro-organisms potentially provide a suitable microenvironment for efficient bioremediation processes. High cell density and stress resistance properties of the biofilm environment provide opportunities for efficient metabolism of number of hydrophobic and toxic compounds. Bacterial biofilm formation is often regulated by quorum sensing (QS) which is a population density-based cell-cell communication process via signaling molecules. Numerous signaling molecules such as acyl homoserine lactones, peptides, autoinducer-2, diffusion signaling factors, and α-hydroxyketones have been studied in bacteria. Genetic alteration of QS machinery can be useful to modulate vital characters valuable for environmental applications such as biofilm formation, biosurfactant production, exopolysaccharide synthesis, horizontal gene transfer, catabolic gene expression, motility, and chemotaxis. These qualities are imperative for bacteria during degradation or detoxification of any pollutant. QS signals can be used for the fabrication of engineered biofilms with enhanced degradation kinetics. This review discusses the connection between QS and biofilm formation by bacteria in relation to bioremediation technology.

  17. Quantifying the strength of quorum sensing crosstalk within microbial communities.

    Directory of Open Access Journals (Sweden)

    Kalinga Pavan T Silva

    2017-10-01

    Full Text Available In multispecies microbial communities, the exchange of signals such as acyl-homoserine lactones (AHL enables communication within and between species of Gram-negative bacteria. This process, commonly known as quorum sensing, aids in the regulation of genes crucial for the survival of species within heterogeneous populations of microbes. Although signal exchange was studied extensively in well-mixed environments, less is known about the consequences of crosstalk in spatially distributed mixtures of species. Here, signaling dynamics were measured in a spatially distributed system containing multiple strains utilizing homologous signaling systems. Crosstalk between strains containing the lux, las and rhl AHL-receptor circuits was quantified. In a distributed population of microbes, the impact of community composition on spatio-temporal dynamics was characterized and compared to simulation results using a modified reaction-diffusion model. After introducing a single term to account for crosstalk between each pair of signals, the model was able to reproduce the activation patterns observed in experiments. We quantified the robustness of signal propagation in the presence of interacting signals, finding that signaling dynamics are largely robust to interference. The ability of several wild isolates to participate in AHL-mediated signaling was investigated, revealing distinct signatures of crosstalk for each species. Our results present a route to characterize crosstalk between species and predict systems-level signaling dynamics in multispecies communities.

  18. Specificity and complexity in bacterial quorum-sensing systems

    Science.gov (United States)

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

    2016-01-01

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

  19. Resilience of bacterial quorum sensing against fluid flow

    Science.gov (United States)

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

    2016-09-01

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

  20. Bacterial quorum sensing and nitrogen cycling in rhizosphere soil

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-10-01

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

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

    Science.gov (United States)

    Dallidis, Stylianos E; Karafyllidis, Ioannis G

    2014-09-01

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

  2. Anti-Quorum Sensing Potential of Potato Rhizospheric Bacteria

    Directory of Open Access Journals (Sweden)

    Adeleh Sobhanipour

    2017-01-01

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

  3. Logic of two antagonizing intra-species quorum sensing systems in bacteria.

    Science.gov (United States)

    Prajapat, Mahendra Kumar; Saini, Supreet

    2018-03-01

    Bacteria release signaling molecules into the surrounding environment and sense them when present in their proximity. Using this strategy, a cell estimates the number of neighbors in its surrounding. Upon sensing a critical number of individuals, bacteria coordinate a number of cellular processes. This density-dependent control of gene expression and physiology is called quorum sensing (QS). Quorum sensing controls a wide variety of functions in bacteria, including those related to motility, growth, virulence etc. Quorum sensing has been widely observed in bacteria while the individuals of the same species or different species compete and cooperate each other. Interestingly, many species possess more than one QS system (intra-species) and these QS systems interact each other to perform quorum sensing. Thus, several logical arrangements can be possible based on the interaction among intra-species QS systems - parallel, series, antagonizing, and agonizing. In this work, we perform simulations to understand the logic of interaction between two antagonizing intra-species QS systems. In such an interaction, one QS system gets fully expressed and the other only gets partially expressed. This is found to be dictated by the interplay between autoinducer's diffusivity and antagonizing strength. In addition, we speculate an important role of the intracellular regulators (eg. LuxR) in maintaining the uniform response among the individual cells from the different localities. We also expect the interplay between the autoinducer's diffusivity and distribution of cells in fine tuning the collective response. Interestingly, in a localized niche with a heterogeneous cell distribution, the cells are expected to perform a global quorum sensing via fully expressed QS system and a local quorum sensing via partially expressed QS system. Copyright © 2018 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2016-06-01

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

  5. Microbiological and Clinical Effects of Sitafloxacin and Azithromycin in Periodontitis Patients Receiving Supportive Periodontal Therapy.

    Science.gov (United States)

    Nakajima, Takako; Okui, Takafumi; Ito, Harue; Nakajima, Mayuka; Honda, Tomoyuki; Shimada, Yasuko; Tabeta, Koichi; Akazawa, Kohei; Yamazaki, Kazuhisa

    2016-01-04

    Sitafloxacin (STFX) is a newly developed quinolone that has robust antimicrobial activity against periodontopathic bacteria. We previously reported that oral administration of STFX during supportive periodontal therapy was as effective as conventional mechanical debridement under local anesthesia microbiologically and clinically for 3 months. The aim of the present study was to examine the short-term and long-term microbiological and clinical effects of systemic STFX and azithromycin (AZM) on active periodontal pockets during supportive periodontal therapy. Fifty-one patients receiving supportive periodontal therapy were randomly allocated to the STFX group (200 mg/day of STFX for 5 days) or the AZM group (500 mg/day of AZM for 3 days). The microbiological and clinical parameters were examined until 12 months after the systemic administration of each drug. The concentration of each drug in periodontal pockets and the antimicrobial susceptibility of clinical isolates were also analyzed. The proportions of red complex bacteria, i.e., Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, which are the representative periodontopathic bacteria, were significantly reduced at 1 month and remained lower at 12 months than those at baseline in both the STFX and AZM groups. Clinical parameters were significantly improved over the 12-month period in both groups. An increase in the MIC of AZM against clinical isolates was observed in the AZM group. These results indicate that monotherapy with systemic STFX and AZM might be an alternative treatment during supportive periodontal therapy in patients for whom invasive mechanical treatment is inappropriate. (This study has been registered with the University Hospital Medical Information Network-Clinical Trials Registry [UMIN-CTR] under registration number UMIN000007834.). Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  6. Azithromycin Synergistically Enhances Anti-Proliferative Activity of Vincristine in Cervical and Gastric Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Xuezhang; Zhang, Yuyan; Li, Yong; Hao, Xiujing; Liu, Xiaoming, E-mail: erc1080@gmail.com; Wang, Yujiong, E-mail: erc1080@gmail.com [Key Laboratory of the Ministry of Education for the Conservation and Utilization of Special Biological Resources of Western China, Yinchuan 750021, Ningxia (China); College of Life Science, Ningxia University, Yinchuan 750021, Ningxia (China)

    2012-12-04

    In this study, the anti-proliferative and anticancer activity of azithromycin (AZM) was examined. In the presence of AZM, cell growth was inhibited more effectively in Hela and SGC-7901 cancer cells, relative to transformed BHK-21 cells. The respective 50% inhibition of cell growth (IC{sub 50}) values for Hela, SGC-7901 and BHK-21 were 15.66, 26.05 and 91.00 µg/mL at 72 h post incubation, indicative of a selective cytotoxicity against cancer cells. Cell apoptosis analysis using Hoechst nuclear staining and annexin V-FITC binding assay further demonstrated that AZM was capable of inducing apoptosis in both cancer cells and transformed cells. The apoptosis induced by AZM was partly through a caspase-dependent mechanism with an up-regulation of apoptotic protein cleavage PARP and caspase-3 products, as well as a down-regulation of anti-apoptotic proteins, Mcl-1, bcl-2 and bcl-X1. More importantly, a combination of AZM and a low dose of the common anti-cancer chemotherapeutic agent vincristine (VCR), produced a selectively synergistic effect on apoptosis of Hela and SGC-7901 cells, but not BHK-21 cells. In the presence of 12.50 μg/mL of VCR, the respective IC{sub 50} values of Hela, SGC-7901 and BHK-21 cells to AZM were reduced to 9.47 µg/mL, 8.43 µg/mL and 40.15 µg/mL at 72 h after the incubation, suggesting that the cytotoxicity of AZM had a selective anti-cancer effect on cancer over transformed cells in vitro. These results imply that AZM may be a potential anticancer agent for use in chemotherapy regimens, and it may minimize side effects via reduction of dosage and enhancing the effectiveness common chemotherapeutic drugs.

  7. IncA/C plasmids conferring high azithromycin resistance in vibrio cholerae.

    Science.gov (United States)

    Wang, Ruibai; Liu, Haican; Zhao, Xiuqin; Li, Jie; Wan, Kanglin

    2018-01-01

    Azithromycin (AZM) is a clinically important antibiotic against Vibrio cholerae, especially for inhibiting V. cholerae colonisation of the intestine and for the treatment of severe cholera in children and pregnant women. An IncA/C plasmid was isolated from two high minimum inhibitory concentration (MIC) AZM-resistant V. cholerae strains of the two mainly pathogenic serogroups (O1 and O139) isolated in China. In the 172 predicted open reading frames (ORFs), 16 genes were related to antibiotic resistance, of which 5 were well-defined genes associated with macrolide resistance. The five macrolide resistance genes distributed in two clusters, mphR-mrx-mph(K) and mel-mph2, flanked by insertion sequence elements and involving two kinds of resistance mechanism. Deletion of the complete region of the two clusters deceased the AZM MIC from ≥64 µg/mL to ≤0.5 µg/mL. This IncA/C plasmid shows great ability to accumulate antibiotic resistance genes. In addition to 11 resistance genes to other antibiotics, 5 macrolide resistance genes with different function were gathered repeatedly through transposition on one plasmid. This genotype could not be simply explained by antibiotic stress applied on the host from the environment or treatment. These phosphorylases and transmembrane transporters might be involved in the transport and metabolism of other non-antibiotic substances, enabling this kind of plasmid to propagate better in the host. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  8. Azithromycin Synergistically Enhances Anti-Proliferative Activity of Vincristine in Cervical and Gastric Cancer Cells

    International Nuclear Information System (INIS)

    Zhou, Xuezhang; Zhang, Yuyan; Li, Yong; Hao, Xiujing; Liu, Xiaoming; Wang, Yujiong

    2012-01-01

    In this study, the anti-proliferative and anticancer activity of azithromycin (AZM) was examined. In the presence of AZM, cell growth was inhibited more effectively in Hela and SGC-7901 cancer cells, relative to transformed BHK-21 cells. The respective 50% inhibition of cell growth (IC 50 ) values for Hela, SGC-7901 and BHK-21 were 15.66, 26.05 and 91.00 µg/mL at 72 h post incubation, indicative of a selective cytotoxicity against cancer cells. Cell apoptosis analysis using Hoechst nuclear staining and annexin V-FITC binding assay further demonstrated that AZM was capable of inducing apoptosis in both cancer cells and transformed cells. The apoptosis induced by AZM was partly through a caspase-dependent mechanism with an up-regulation of apoptotic protein cleavage PARP and caspase-3 products, as well as a down-regulation of anti-apoptotic proteins, Mcl-1, bcl-2 and bcl-X1. More importantly, a combination of AZM and a low dose of the common anti-cancer chemotherapeutic agent vincristine (VCR), produced a selectively synergistic effect on apoptosis of Hela and SGC-7901 cells, but not BHK-21 cells. In the presence of 12.50 μg/mL of VCR, the respective IC 50 values of Hela, SGC-7901 and BHK-21 cells to AZM were reduced to 9.47 µg/mL, 8.43 µg/mL and 40.15 µg/mL at 72 h after the incubation, suggesting that the cytotoxicity of AZM had a selective anti-cancer effect on cancer over transformed cells in vitro. These results imply that AZM may be a potential anticancer agent for use in chemotherapy regimens, and it may minimize side effects via reduction of dosage and enhancing the effectiveness common chemotherapeutic drugs

  9. Comparative evaluation of 2 g single dose versus conventional dose azithromycin in uncomplicated skin and skin structure infections.

    Science.gov (United States)

    Dey, Sudipta Kumar; Das, Amal Kanti; Sen, Sumit; Hazra, Avijit

    2015-01-01

    Uncomplicated skin and skin structure infections (uSSSIs) are a common clinical problem. Majority are caused by staphylococci and streptococci. Different oral antibiotics are used for uSSSI, with comparable efficacy but varying treatment duration, cost, and adverse event profile. Azithromycin is used in uSSSI in adults conventionally in a dose of 500 mg once for 5 days. The extensive tissue distribution of the drug and its long elimination half-life prompted us to explore whether a single 2 g dose of the drug would produce a response in uSSSI comparable to conventional dosing. We conducted a parallel group, open-label, randomized, controlled trial (CTRI/2015/07/005969) with subjects of either sex, ≥12 years of age, presenting with uSSSI to the dermatology outpatient department. One group (n = 146) received 2 g single supervised dose while the other (n = 146) received conventional dose of 500 mg once daily for 5 days. Subjects were followed up on day 4 and day 8. Complete clinical cure implied complete healing of lesions, without residual signs or symptoms, within 7 days. High cure rate was observed in both arms (97.97% and 98.63%, respectively) along with noticeable improvement in symptom profile from baseline but without statistically significant difference between groups. However, excellent adherence (defined as no tablets missed) was better in single dosing arm (98.65% vs. 86.30%). Tolerability was also comparable between groups with the majority of adverse events encountered being gastrointestinal in nature and mild. Single 2 g azithromycin dose achieved the same result as conventional azithromycin dosing in uSSSI with comparable tolerability but with the advantage of assured adherence. This dose can, therefore, be recommended as an alternative and administration supervised if feasible.

  10. A longitudinal trial comparing chloroquine as monotherapy or in combination with artesunate, azithromycin or atovaquone-proguanil to treat malaria.

    Directory of Open Access Journals (Sweden)

    Miriam K Laufer

    Full Text Available The predominance of chloroquine-susceptible falciparum malaria in Malawi more than a decade after chloroquine's withdrawal permits contemplation of re-introducing chloroquine for targeted uses. We aimed to compare the ability of different partner drugs to preserve chloroquine efficacy and prevent the re-emergence of resistance.Children with uncomplicated malaria were enrolled at a government health center in Blantyre, Malawi. Participants were randomized to receive chloroquine alone or combined with artesunate, azithromycin or atovaquone-proguanil for all episodes of uncomplicated malaria for one year. The primary outcome was incidence of clinical malaria. Secondary endpoints included treatment efficacy, and incidence of the chloroquine resistance marker pfcrt T76 and of anemia. Of the 640 children enrolled, 628 were included in the intention-to-treat analysis. Malaria incidence (95% confidence interval was 0.59 (.46-.74, .61 (.49-.76, .63 (.50-.79 and .68 (.54-.86 episodes/person-year for group randomized to receive chloroquine alone or in combination with artesunate, azithromycin or atovaquone-proguanil respectively and the differences were not statistically significant. Treatment efficacy for first episodes was 100% for chloroquine monotherapy and 97.9% for subsequent episodes of malaria. Similar results were seen in each of the chloroquine combination groups. The incidence of pfcrt T76 in pure form was 0%; mixed infections with both K76 and T76 were found in two out of 911 infections. Young children treated with chloroquine-azithromycin had higher hemoglobin concentrations at the study's end than did those in the chloroquine monotherapy group.Sustained chloroquine efficacy with repeated treatment supports the eventual re-introduction of chloroquine combinations for targeted uses such as intermittent preventive treatment.ClinicalTrials.gov NCT00379821.

  11. Homogeneous bilateral block shifts

    Indian Academy of Sciences (India)

    Douglas class were classified in [3]; they are unilateral block shifts of arbitrary block size (i.e. dim H(n) can be anything). However, no examples of irreducible homogeneous bilateral block shifts of block size larger than 1 were known until now.

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

    DEFF Research Database (Denmark)

    Hentzer, Morten; Givskov, Michael Christian

    2003-01-01

    Traditional treatment of infectious diseases is based on compounds that aim to kill or inhibit bacterial growth. A major concern with this approach is the frequently observed development of resistance to antimicrobial compounds. The discovery of bacterial-communication systems (quorum-sensing sys......Traditional treatment of infectious diseases is based on compounds that aim to kill or inhibit bacterial growth. A major concern with this approach is the frequently observed development of resistance to antimicrobial compounds. The discovery of bacterial-communication systems (quorum...

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

    DEFF Research Database (Denmark)

    Claussen, Anetta

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

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

    DEFF Research Database (Denmark)

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

    2002-01-01

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

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

    Science.gov (United States)

    Sakaguchi, Hidetsugu; Maeyama, Satomi

    2013-02-01

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

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

    DEFF Research Database (Denmark)

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

    2003-01-01

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

  17. Prevalence of Active and Latent Yaws in the Solomon Islands 18 Months after Azithromycin Mass Drug Administration for Trachoma.

    Science.gov (United States)

    Marks, Michael; Sokana, Oliver; Nachamkin, Eli; Puiahi, Elliot; Kilua, Georgina; Pillay, Allan; Bottomley, Christian; Solomon, Anthony W; Mabey, David C

    2016-08-01

    Both yaws and trachoma are endemic in the Pacific. Mass treatment with azithromycin is the mainstay of the WHO strategy for both the eradication of yaws and the elimination of trachoma as a public health problem, but the dose recommended for trachoma is lower than that for yaws. In countries where both diseases are endemic, there is a potential for synergy between yaws and trachoma control programs if mass treatment with the lower dose of azithromycin was shown to be effective for the treatment of yaws. In an earlier study, we demonstrated a profound reduction in the clinical and serological prevalence of yaws following a single round of mass treatment with azithromycin 20 mg/kg undertaken for the purposes of trachoma elimination. This survey was conducted 18 months following a single round of azithromycin mass treatment in the same communities in which we had conducted our previous six-month follow-up survey. We examined children aged 1-14 years and took blood and lesion samples for yaws diagnosis using the Treponema pallidum particle agglutination assay (TPPA) and the non-treponemal Rapid Plasma Reagin (RPR) test. A total of 1,284 children were enrolled in the study. Amongst children aged 5-14 years, 223 had a positive TPPA (27.5%, 95% CI 13.6-47.7%). The TPPA seroprevalence amongst this age group did not differ significantly from either our pre-mass treatment survey or our initial follow-up survey. Thirty-five children had positive TPPA and positive RPR (4.3%, 95% CI 2.1-8.7%), and this did not differ significantly from our initial post-mass drug administration (MDA) follow-up survey (4.3% versus 3.5%, p = 0.43) but remained significantly lower than our initial pre-MDA survey (4.3% vs 21.7%, p threshold, and strategies to improve coverage at all stages of yaws eradication efforts should be investigated.

  18. A Phase III clinical study to evaluate the efficacy of combined azithromycin and dexamethasone in the treatment of blepharoconjunctivitis

    Directory of Open Access Journals (Sweden)

    Hosseini K

    2013-11-01

    Full Text Available Kamran Hosseini,1,2 Judith Hutcheson,1 Richard L Lindstrom3–5 1Clinical Affairs, 2Regulatory Affairs, InSite Vision Incorporated, Alameda, CA, USA; 3Minnesota Eye Consultants, Bloomington, MN, USA; 4University of Minnesota Department of Ophthalmology, Minneapolis, MN, USA; 5University of California, Irvine Gavin Herbert Eye Institute, Irvine, CA, USA Purpose: The purpose of this study was to evaluate the clinical and antimicrobial efficacy and safety of ISV-502 (1.0% azithromycin and 0.1% dexamethasone compared to 1.0% azithromycin or 0.1% dexamethasone in the treatment of subjects with blepharoconjunctivitis. Patients and methods: Patients with verified blepharoconjunctivitis were randomized to receive ISV-502 (Group 1; n=140, 1.0% azithromycin alone (Group 2; n=141, or 0.1% dexamethasone alone (Group 3; n=136. Bacterial cultures were obtained from the conjunctiva and eyelid. Treatment was instilled in both eyes twice daily at 12-hour intervals for 14 days. The primary endpoint was complete resolution of clinical signs and symptoms at Day 15. The secondary endpoint was complete bacterial eradication at Day 15 among subjects with positive bacterial cultures at baseline. Results: Significantly more Group 1 subjects met the primary endpoint (27.1% than those in Group 2 (15.6%; P=0.028, but not compared to Group 3 (23.5%; P=0.581. Significantly more Group 1 patients (60% had complete bacterial eradication at Day 15 compared with Group 3 (40.2%; P=0.007, but there was no difference compared with Group 2 (66.3%; P=0.306. Adverse events were reported in about 25% of the subjects, with an equal distribution among treatment arms; the most common adverse event was irritation at the instillation site. Visual acuity and intraocular pressure differences were not statistically significant, but did show age and sex differences between groups. Conclusion: ISV-502 is effective in the treatment of blepharoconjunctivitis as evaluated by clinical cure and

  19. Azithromycin vs. Placebo for the Clinical Outcome in Campylobacter concisus Diarrhoea in Adults: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

    Science.gov (United States)

    Nielsen, Hans Linde; Kirk, Karina Frahm; Bodilsen, Jacob; Ejlertsen, Tove; Nielsen, Henrik

    2016-01-01

    Campylobacter concisus has been associated with prolonged mild diarrhoea, but investigations regarding the efficacy of antimicrobial treatment have not been reported previously. We initiated a phase 3, single-centre, randomized, double-blinded, placebo-controlled study comparing the efficacy of 500 mg once-daily dose of azithromycin with a 500 mg once-daily dose of placebo for three days, for the treatment of C. concisus diarrhoea in adult patients with a follow-up period of ten days. If symptoms persisted at day ten, the patient was offered cross-over study treatment of three days and another ten-day follow-up period. The primary efficacy endpoint was the clinical response, defined as time to cessation of diarrhoea (azithromycin (n = 12) or placebo (n = 12). Both groups presented symptoms of mild, prolonged diarrhoea with a mean duration of 18 days (95% CI: 16-19). One person in the azithromycin group and four from the placebo group chose to continue with crossover medication after the initial ten-day period. In the azithromycin group, there was a mean of seven days (95% CI: 5-9) to clinical cure and for the placebo group it was ten days (95% CI: 6-14) (OR-3 (95% CI: -7-1). We observed no differences in all examined outcomes between azithromycin treatment and placebo. However, due to unforeseen recruitment difficulties we did not reach our estimated sample size of 100 patients and statistical power to conclude on an effect of azithromycin treatment was not obtained. Clinicaltrials.gov identifier: NCT01531218.

  20. A randomized controlled pilot trial of azithromycin or artesunate added to sulfadoxine-pyrimethamine as treatment for malaria in pregnant women.

    Directory of Open Access Journals (Sweden)

    Linda Kalilani

    2007-11-01

    Full Text Available New anti-malarial regimens are urgently needed in sub-Saharan Africa because of the increase in drug resistance. We investigated the safety and efficacy of azithromycin or artesunate combined with sulfadoxine-pyrimethamine used for treatment of malaria in pregnant women in Blantyre, Malawi.This was a randomized open-label clinical trial, conducted at two rural health centers in Blantyre district, Malawi. A total of 141 pregnant women with uncomplicated Plasmodium falciparum malaria were recruited and randomly allocated to 3 treatment groups: sulfadoxine-pyrimethamine (SP; 3 tablets, 500 mg sulfadoxine and 25 mg pyrimethamine per tablet; SP plus azithromycin (1 g/dayx2 days; or SP plus artesunate (200 mg/dayx3 days. Women received two doses administered at least 4 weeks apart. Heteroduplex tracking assays were performed to distinguish recrudescence from new infections. Main outcome measures were incidence of adverse outcomes, parasite and fever clearance times and recrudescence rates. All treatment regimens were well tolerated. Two women vomited soon after ingesting azithromycin. The parasite clearance time was significantly faster in the SP-artesunate group. Recrudescent episodes of malaria were less frequent with SP-azithromycin [Hazard Ratio 0.19 (95% confidence interval 0.06 to 0.63] and SP-artesunate [Hazard Ratio 0.25 (95% confidence interval 0.10 to 0.65] compared with SP monotherapy. With one exception (an abortion in the SP-azithromycin group, all adverse pregnancy outcomes could be attributed to known infectious or obstetrical causes. Because of the small sample size, the effect on birth outcomes, maternal malaria or maternal anemia could not be evaluated.Both SP-artesunate and SP-azithromycin appeared to be safe, well tolerated and efficacious for the treatment of malaria during pregnancy. A larger study is needed to determine their safety and efficacy in preventing poor birth outcomes.ClinialTrials.gov NCT00287300.

  1. A Single Dose Oral Azithromycin versus Intramuscular Benzathine Penicillin for the Treatment of Yaws-A Randomized Non Inferiority Trial in Ghana.

    Science.gov (United States)

    Kwakye-Maclean, Cynthia; Agana, Nsiire; Gyapong, John; Nortey, Priscilia; Adu-Sarkodie, Yaw; Aryee, Esther; Asiedu, Kingsley; Ballard, Roland; Binka, Fred

    2017-01-01

    Yaws is a treponemal infection that was almost eradicated fifty years ago; however, the disease has re-emerged in a number of countries including Ghana. A single-dose of intramuscular benzathine penicillin has been the mainstay of treatment for yaws. However, intramuscular injections are painful and pose safety and logistical constraints in the poor areas where yaws occurs. A single center randomized control trial (RCT) carried out in Papua New Guinea in 2012 demonstrated the efficacy of a single-dose of oral azithromycin for the treatment of yaws. In this study, we also compared the efficacy of a single oral dose of azithromycin as an alternative to intramuscular benzathine penicillin for the treatment of the disease in another geographic setting. We conducted an open-label, randomized non-inferiority trial in three neighboring yaws-endemic districts in Southern Ghana. Children aged 1-15 years with yaws lesions were assigned to receive either 30mg/kg of oral azithromycin or 50,000 units/kg of intramuscular benzathine penicillin. The primary end point was clinical cure rate, defined as a complete or partial resolution of lesions 3 weeks after treatment. The secondary endpoint was serological cure, defined as at least a 4-fold decline in baseline RPR titre 6 months after treatment. Non- inferiority of azithromycin treatment was determined if the upper bound limit of a 2 sided 95% CI was less than 10%. The mean age of participants was 9.5 years (S.D.3.1, range: 1-15 years), 247(70%) were males. The clinical cure rates were 98.2% (95% CI: 96.2-100) in the azithromycin group and 96.9% (95% CI: 94.1-99.6) in the benzathine penicillin group. The serological cure rates at 6 months were 57.4% (95% CI: 49.9-64.9) in the azithromycin group and 49.1% (95% CI: 41.2-56.9) in the benzathine penicillin group, thus achieving the specified criteria for non-inferiority. A single oral dose of azithromycin, at a dosage of 30mg/kg, was non-inferior to a single dose of intramuscular

  2. Clinical effect of azithromycin as an adjunct to non-surgical treatment of chronic periodontitis: a meta-analysis of randomized controlled clinical trials.

    Science.gov (United States)

    Zhang, Z; Zheng, Y; Bian, X

    2016-06-01

    The results of recent published studies focusing on the effect of azithromycin as an adjunct to scaling and root planing (SRP) in the treatment of chronic periodontitis are inconsistent. We conducted a meta-analysis of randomized controlled clinical trials to examine the effect of azithromycin combined with SRP on periodontal clinical parameters as compared to SRP alone. An electronic search was carried out on Pubmed, Embase and the Cochrane Central Register of Controlled Trials from their earliest records through December 28, 2014 to identify studies that met pre-stated inclusion criteria. Reference lists of retrieved articles were also reviewed. Data were extracted independently by two authors. Either a fixed- or random-effects model was used to calculate the overall effect sizes of azithromycin on probing depth, attachment level (AL) and bleeding on probing (BOP). Heterogeneity was evaluated using the Q test and I(2) statistic. Publication bias was evaluated by Begg's test and Egger's test. A total of 14 trials were included in the meta-analysis. Compared with SRP alone, locally delivered azithromycin plus SRP statistically significantly reduced probing depth by 0.99 mm (95% CI 0.42-1.57) and increased AL by 1.12 mm (95% CI 0.31-1.92). In addition, systemically administered azithromycin plus SRP statistically significantly reduced probing depth by 0.21 mm (95% CI 0.12-0.29), BOP by 4.50% (95% CI 1.45-7.56) and increased AL by 0.23 mm (95% CI 0.07-0.39). Sensitivity analysis yielded similar results. No evidence of publication bias was observed. The additional benefit of systemic azithromycin was shown at the initially deep probing depth sites, but not at shallow or moderate sites. The overall effect sizes of systemic azithromycin showed a tendency to decrease with time, and meta-regression analysis suggested a negative relation between the length of follow-up and net change in probing depth (r = -0.05, p = 0.02). This meta-analysis provides further

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

    Science.gov (United States)

    Corral-Lugo, Andrés; Daddaoua, Abdelali; Ortega, Alvaro; Espinosa-Urgel, Manuel; Krell, Tino

    2016-01-05

    Quorum sensing is a bacterial communication mechanism that controls genes, enabling bacteria to live as communities, such as biofilms. Homoserine lactone (HSL) molecules function as quorum-sensing signals for Gram-negative bacteria. Plants also produce previously unidentified compounds that affect quorum sensing. We identified rosmarinic acid as a plant-derived compound that functioned as an HSL mimic. In vitro assays showed that rosmarinic acid bound to the quorum-sensing regulator RhlR of Pseudomonas aeruginosa PAO1 and competed with the bacterial ligand N-butanoyl-homoserine lactone (C4-HSL). Furthermore, rosmarinic acid stimulated a greater increase in RhlR-mediated transcription in vitro than that of C4-HSL. In P. aeruginosa, rosmarinic acid induced quorum sensing-dependent gene expression and increased biofilm formation and the production of the virulence factors pyocyanin and elastase. Because P. aeruginosa PAO1 infection induces rosmarinic acid secretion from plant roots, our results indicate that rosmarinic acid secretion is a plant defense mechanism to stimulate a premature quorum-sensing response. P. aeruginosa is a ubiquitous pathogen that infects plants and animals; therefore, identification of rosmarinic acid as an inducer of premature quorum-sensing responses may be useful in agriculture and inform human therapeutic strategies. Copyright © 2016, American Association for the Advancement of Science.

  4. Quorum Sensing in the Context of Food Microbiology

    Science.gov (United States)

    Skandamis, Panagiotis N.

    2012-01-01

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

  5. Leaders of neuronal cultures in a quorum percolation model

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Eckmann

    2010-09-01

    Full Text Available We present a theoretical framework using quorum-percolation for describing the initiation of activity in a neural culture. The cultures are modeled as random graphs, whose nodes are neurons with $kin$ inputs and $kout$ outputs, and whose input degrees $kin=k$ obey given distribution functions $p_k$. We examine the firing activity of the population of neurons according to their input degree ($k$ classes and calculate for each class its firing probability $Phi_k(t$ as a function of $t$. The probability of a node to fire is found to be determined by its in-degree $k$, and the first-to-fire neurons are those that have a high $k$. A small minority of high-$k$ classes may be called ``Leaders,'' as they form an inter-connected subnetwork that consistently fires much before the rest of the culture. Once initiated, the activity spreads from the Leaders to the less connected majority of the culture. We then use the distribution of in-degree of the Leaders to study the growth rate of the number of neurons active in a burst, which was experimentally measured to be initially exponential. We find that this kind of growth rate is best described by a population that has an in-degree distribution that is a Gaussian centered around $k=75$ with width $sigma=31$ for the majority of the neurons, but also has a power law tail with exponent $-2$ for ten percent of the population. Neurons in the tail may have as many as $k=4,700$ inputs. We explore and discuss the correspondence between the degree distribution and a dynamic neuronal threshold, showing that from the functional point of view, structure and elementary dynamics are interchangeable. We discuss possible geometric origins of this distribution, and comment on the importance of size, or of having a large number of neurons, in the culture.

  6. Flexible dynamics of two quorum-sensing coupled repressilators

    Science.gov (United States)

    Hellen, Edward H.; Volkov, Evgeny

    2017-02-01

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

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

    Science.gov (United States)

    Naik, Varsha; Mahajan, Girish

    2013-10-01

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

  8. The effects of Lactobacillus reuteri probiotics combined with azithromycin on peri-implantitis: A randomized placebo-controlled study.

    Science.gov (United States)

    Tada, Hiroaki; Masaki, Chihiro; Tsuka, Shintaro; Mukaibo, Taro; Kondo, Yusuke; Hosokawa, Ryuji

    2018-01-01

    The aim of this randomized placebo-controlled clinical study was to investigate the effects of a probiotic tablet containing Lactobacillus reuteri in peri-implantitis patients. Subjects comprised 30 patients with mild to moderate peri-implantitis. A baseline clinical examination and microbiological assessment were conducted, followed by an antibiotics treatment (azithromycin, 500mg, once a day for 3 days). Subjects were divided into probiotic and placebo groups. The clinical examination and bacterial sampling were performed 0, 4, 12 and 24 weeks after the intake of probiotics. The clinical examination included probing pocket depth (PPD), bleeding on probing (BOP), the modified plaque index (mPI), and modified bleeding index (mBI). The number of bacteria was assessed using the PCR-invader method. The Wilcoxon rank-sum test and Wilcoxon signed-rank test with Bonferroni corrections were used for data analyses. Although the number of bacteria decreased after the administration of azithromycin in both groups, they increased again thereafter. No significant difference was observed in bacterial numbers between the two groups. Although PPD in the probiotics group was significantly lower at 4 and 24 weeks than at 0 weeks (pprobiotics group than in the placebo group (pprobiotics prevent inflammation by affecting host responses rather than improving microbial flora in peri-implant sulci in peri-implantitis patients. Copyright © 2017 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

  9. Expression comparison of azithromycin and clarithromycin in triple-therapy regimens for eradication of Helicobacter pylori in hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Jamshid Vafaeimanesh

    2014-01-01

    Full Text Available To compare a triple-therapy regimen based on change of antibiotic (azithromycin and clarithromycin for the eradication of Helicobacter pylori in hemodialysis (HD patients, we studied in a prospective, randomized, double-blinded clinical trial 39 patients who had dyspepsia and showed two positive results from the diagnostic tests of H. pylori infection including anti-H. pylori serology and stool antigen (HpSAg and urease breath test (UBT. The patients were divided into two groups: Group-A received omeprazol 20 mg, amoxycilin 500 mg and clarithromycin 500 mg twice a day and Group-B received omeprazol 20 mg, amoxicillin 500 mg and azithromycin 250 mg twice a day. The adverse events and compliance with triple therapy were reviewed at one visit per week. Both groups were prescribed their medications for 14 days. Of the 39 patients, only 37 patients completed the treatment schedule (20 men and 19 women, with the mean being 59 years. Two patients died due to myocardial infarction before the start of treatment and were out of the study. The eradication rate of H. pylori, evaluated by negative results of UBT, was 82.4% in Group-A and 80% in Group-B (P-value = 1.0. The results of our study showed no significant difference of azitromycin versus claritromycin in the eradication of H. pylori infection in HD patients.

  10. Resolution of spontaneous hemoabdomen secondary to peliosis hepatis following surgery and azithromycin treatment in a Bartonella species infected dog.

    Science.gov (United States)

    Berkowitz, Steven T; Gannon, Kristi M; Carberry, Carol A; Cortes, Yonaira

    2016-11-01

    To describe a case of hemoperitonium in a dog with Bartonellosis and peliosis hepatis (PH) lesions that resolved following antimicrobial therapy. A 3-year-11-month-old 22.5 kg female spayed mixed breed dog presented for progressive lethargy and vomiting. An abdominal ultrasonographic examination revealed moderate ascites, which when sampled was nonclotting hemorrhagic fluid. An exploratory laparotomy revealed a large volume of nonclotted blood in the dog's abdomen and blood-filled vesicular lesions dispersed diffusely along multiple lobes of the liver. Biopsies revealed lesions indicative of PH. Serology testing for Bartonella species was positive. Treatment with azithromycin resulted in Bartonella serology negative status and no further evidence of hemoperitonium at recheck examination 12 months after initial presentation. This is the first reported case of PH and hemoperitoneum in a Bartonella species serology positive dog wherein treatment with azithromycin resulted in serology negative status. There have been no subsequent episodes of hemoperitoneum in the 12 months since treatment. © Veterinary Emergency and Critical Care Society 2016.

  11. Rational design and synthesis of new quorum-sensing inhibitors derived from acylated homoserine lactones and natural products from garlic

    DEFF Research Database (Denmark)

    Persson, T.; Rasmussen, Thomas Bovbjerg; Skindersoe, M.

    2005-01-01

    with similarity both to sulfides 10a-s and to bioactive structures from garlic. Design and biological screening of all compounds presented in this work targeted inhibition of quorum-sensing comprising competitive inhibition of transcriptional regulators LuxR and LasR. The design was based on critical interactions...... within the binding-site and structural motifs in molecular components isolated from garlic, 7 and 8, shown to be quorum-sensing inhibitors but not antibiotics. A potent quorum-sensing inhibitor N-(heptylsulfanylacetyl)-L-homoserine lactone (10c) was identified. Together with data collected for the other...

  12. Prevalence of Active and Latent Yaws in the Solomon Islands 18 Months after Azithromycin Mass Drug Administration for Trachoma.

    Directory of Open Access Journals (Sweden)

    Michael Marks

    2016-08-01

    Full Text Available Both yaws and trachoma are endemic in the Pacific. Mass treatment with azithromycin is the mainstay of the WHO strategy for both the eradication of yaws and the elimination of trachoma as a public health problem, but the dose recommended for trachoma is lower than that for yaws. In countries where both diseases are endemic, there is a potential for synergy between yaws and trachoma control programs if mass treatment with the lower dose of azithromycin was shown to be effective for the treatment of yaws. In an earlier study, we demonstrated a profound reduction in the clinical and serological prevalence of yaws following a single round of mass treatment with azithromycin 20 mg/kg undertaken for the purposes of trachoma elimination.This survey was conducted 18 months following a single round of azithromycin mass treatment in the same communities in which we had conducted our previous six-month follow-up survey. We examined children aged 1-14 years and took blood and lesion samples for yaws diagnosis using the Treponema pallidum particle agglutination assay (TPPA and the non-treponemal Rapid Plasma Reagin (RPR test.A total of 1,284 children were enrolled in the study. Amongst children aged 5-14 years, 223 had a positive TPPA (27.5%, 95% CI 13.6-47.7%. The TPPA seroprevalence amongst this age group did not differ significantly from either our pre-mass treatment survey or our initial follow-up survey. Thirty-five children had positive TPPA and positive RPR (4.3%, 95% CI 2.1-8.7%, and this did not differ significantly from our initial post-mass drug administration (MDA follow-up survey (4.3% versus 3.5%, p = 0.43 but remained significantly lower than our initial pre-MDA survey (4.3% vs 21.7%, p <0.0001. Village-level MDA coverage was strongly associated with dual-seropositivity (p = 0.005. Amongst children aged 1-4 years, 16 had a positive TPPA (3.5%, 95% CI 1.6-7.1%. This did not differ significantly from the seroprevalence in this age group that had

  13. Non-participation during azithromycin mass treatment for trachoma in The Gambia: heterogeneity and risk factors.

    Directory of Open Access Journals (Sweden)

    Tansy Edwards

    2014-08-01

    Full Text Available There is concern that untreated individuals in mass drug administration (MDA programs for neglected tropical diseases can reduce the impact of elimination efforts by maintaining a source of transmission and re-infection.Treatment receipt was recorded against the community census during three MDAs with azithromycin for trachoma in The Gambia, a hypo-endemic setting. Predictors of non-participation were investigated in 1-9 year olds using random effects logistic regression of cross-sectional data for each MDA. Two types of non-participators were identified: present during MDA but not treated (PNT and eligible for treatment but absent during MDA (EBA. PNT and EBA children were compared to treated children separately. Multivariable models were developed using baseline data and validated using year one and two data, with a priori adjustment for previous treatment status. Analyses included approximately 10000 children at baseline and 5000 children subsequently. There was strong evidence of spatial heterogeneity, and persistent non-participation within households and individuals. By year two, non-participation increased significantly to 10.4% overall from 6.2% at baseline, with more, smaller geographical clusters of non-participating households. Multivariable models suggested household level predictors of non-participation (increased time to water and household head non-participation for both PNT and EBA; increased household size for PNT status only; non-inclusion in a previous trachoma examination survey and younger age for EBA only. Enhanced coverage efforts did not decrease non-participation. Few infected children were detected at year three and only one infected child was EBA previously. Infected children were in communities close to untreated endemic areas with higher rates of EBA non-participation during MDA.In hypo-endemic settings, with good coverage and no association between non-participation and infection, efforts to improve participation

  14. Quantitative thin-layer chromatographic method of analysis of azithromycin in pure and capsule forms.

    Science.gov (United States)

    Khedr, Alaa; Sheha, Mahmoud

    2003-01-01

    A validated stability-indicating thin-layer chromatographic (TLC) method of the analysis of azithromycin (AZT) in bulk and capsule forms is developed. Both AZT potential impurity and degradation products can be selectively and accurately estimated in both raw material and product onto one precoated silica-gel TLC plate 60F254. The development system used is n-hexane-ethyl acetate-diethylamine (75:25:10, v/v/v). The separated bands are detected as brown to brownish red spots after spraying with modified Dragendorff's solution. The Rf values of AZT, azaerythromycin A, and the three degradation products are 0.54, 0.35, 0.40, 0.20, and 0.12, respectively. The optical densities of the separated spots are found to be linear in proportion to the amount used. The stress testing of AZT shows that azaerythromycin A is the major impurity and degradation product, accompanied by three other unknown degradation products. The stability of AZT is studied under accelerated conditions in order to provide a rapid indication of differences that might result from a change in the manufacturing process or source of the sample. The forced degradation conditions include the effect of heat, moisture, light, acid-base hydrolysis, sonication, and oxidation. The compatibility of AZT with the excipients used is also studied in the presence and absence of moisture. The amounts of AZT and azaerythromycin A are calculated from the corresponding linear calibration curve; however, the amounts of any other generated or detected unknown impurities are calculated as if it were AZT. This method shows enough selectivity, sensitivity, accuracy, precision, linearity-range, and robustness to satisfy Federal Drug Administration/International Conference of Harmonization regulatory requirements. The method developed can also be used for the purity testing of AZT raw material and capsules, content uniformity testing, dissolution testing, and stability testing of AZT capsules. The potential impurity profiles of

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

    DEFF Research Database (Denmark)

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

    2003-01-01

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

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

    DEFF Research Database (Denmark)

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

    2004-01-01

    Serratia liquefaciens MG1 contains an N-acylhomoserine lactone-mediated quorum-sensing system that is known to regulate swarming motility colonization. In this study, we describe for S. liquefaciens MG1 the development of a novel biofilm consisting of cell aggregates and differentiated cell types...

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  18. Quorum-Quenching Acylase Reduces the Virulence of Pseudomonas aeruginosa in a Caenorhabditis elegans Infection Model

    NARCIS (Netherlands)

    Papaioannou, Evelina; Wahjudi, Mariana; Nadal-Jimenez, Pol; Koch, Gudrun; Setroikromo, Rita; Quax, Wim J.

    2009-01-01

    The Pseudomonas aeruginosa PAO1 gene pvdQ encodes an acyl-homoserine lactone (AHL) acylase capable of degrading N-(3-oxododecanoyl)-L-homoserine lactone by cleaving the AHL amide. PvdQ has been proven to function as a quorum quencher in vitro in a number of phenotypic assays. To address the question

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

    Science.gov (United States)

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

    2016-08-01

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

  20. NprR, a moonlighting quorum sensor shifting from a phosphatase activity to a transcriptional activator

    Directory of Open Access Journals (Sweden)

    Stéphane Perchat

    2016-11-01

    Full Text Available Regulation of biological functions requires factors (proteins, peptides or chemicals able to sense and translate environmental conditions or any circumstances in order to modulate the transcription of a gene, the stability of a transcript or the activity of a protein. Quorum sensing is a regulation mechanism connecting cell density to the physiological state of a single cell. In bacteria, quorum sensing coordinates virulence, cell fate and commitment to sporulation and other adaptation properties. The critical role of such regulatory systems was demonstrated in pathogenicity and adaptation of bacteria from the Bacillus cereus group (i.e. B. cereus and Bacillus thuringiensis. Furthermore, using insects as a model of infection, it was shown that sequential activation of several quorum sensing systems allowed bacteria to switch from a virulence state to a necrotrophic lifestyle, allowing their survival in the host cadaver, and ultimately to the commitment into sporulation. The chronological development of these physiological states is directed by quorum sensors forming the RNPP family. Among them, NprR combines two distinct functions connecting sporulation to necrotrophism in B. thuringiensis. In the absence of its cognate signaling peptide (NprX, NprR negatively controls sporulation by acting as a phosphatase. In the presence of NprX, it acts as a transcription factor regulating a set of genes involved in the survival of the bacteria in the insect cadaver.

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

    DEFF Research Database (Denmark)

    Christensen, Allan Beck; Riedel, Kathrin; Eberl, Leo

    2003-01-01

    N-Acyl-L-homoserine-lactone-producing Serratia species are frequently encountered in spoiling foods of vegetable and protein origin. The role of quorum sensing in the food spoiling properties of these bacteria is currently being investigated. A set of luxR luxI homologous genes encoding a putative...... quorum sensor was identified in the N-(3-oxo-hexanoyl)-L-homoserine lactone (3-oxo-C6-HSL)-producing Serratia proteamaculans strain B5a. The 3-oxo-C6-HSL synthase SprI showed 79% similarity with Esal from Pantoea stewartii and the putative regulatory protein SprR was 86% similar to the SpnR of Serratia...... marcescens. Proteome analysis suggested that the presence of at least 39 intracellular proteins was affected by the 3-oxo-C6-HSL-based quorum sensing system. The lipB-encoded secretion system was identified as one target gene of the quorum sensing system. LipB was required for the production of extracellular...

  2. Rhodotorula mucilaginosa, a quorum quenching yeast exhibiting lactonase activity isolated from a tropical shoreline.

    Science.gov (United States)

    Ghani, Norshazliza Ab; Sulaiman, Joanita; Ismail, Zahidah; Chan, Xin-Yue; Yin, Wai-Fong; Chan, Kok-Gan

    2014-04-09

    Two microbial isolates from a Malaysian shoreline were found to be capable of degrading N-acylhomoserine lactones. Both Matrix Assisted Laser Desorption Ionization-Time of Flight-Mass Spectrometry and 18S rDNA phylogenetic analyses confirmed that these isolates are Rhodotorula mucilaginosa. Quorum quenching activities were detected by a series of bioassays and rapid resolution liquid chromatography analysis. The isolates were able to degrade various quorum sensing molecules namely N-hexanoyl-L-homoserine lactone (C6-HSL), N-(3-oxo-hexanoyl)-L-homoserine lactone (3-oxo-C6-HSL) and N-(3-hydroxyhexanoyl)-L-homoserine lactone (3-hydroxy-C6-HSL). Using a relactonisation assay to verify the quorum quenching mechanism, it is confirmed that Rh. mucilaginosa degrades the quorum sensing molecules via lactonase activity. To the best of our knowledge, this is the first documentation of the fact that Rh. mucilaginosa has activity against a broad range of AHLs namely C6-HSL, 3-oxo-C6-HSL and 3-hydroxy-C6-HSL.

  3. Handling Neighbor Discovery and Rendezvous Consistency with Weighted Quorum-Based Approach

    Directory of Open Access Journals (Sweden)

    Chung-Ming Own

    2015-09-01

    Full Text Available Neighbor discovery and the power of sensors play an important role in the formation of Wireless Sensor Networks (WSNs and mobile networks. Many asynchronous protocols based on wake-up time scheduling have been proposed to enable neighbor discovery among neighboring nodes for the energy saving, especially in the difficulty of clock synchronization. However, existing researches are divided two parts with the neighbor-discovery methods, one is the quorum-based protocols and the other is co-primality based protocols. Their distinction is on the arrangements of time slots, the former uses the quorums in the matrix, the latter adopts the numerical analysis. In our study, we propose the weighted heuristic quorum system (WQS, which is based on the quorum algorithm to eliminate redundant paths of active slots. We demonstrate the specification of our system: fewer active slots are required, the referring rate is balanced, and remaining power is considered particularly when a device maintains rendezvous with discovered neighbors. The evaluation results showed that our proposed method can effectively reschedule the active slots and save the computing time of the network system.

  4. Effect of certain natural products and organic solvents on quorum sensing in Chromobacterium violaceum.

    Science.gov (United States)

    Chaudhari, Vimla; Gosai, Haren; Raval, Shreya; Kothari, Vijay

    2014-09-01

    To investigate the effect of seed extracts of Pongamia pinnata, Pyrus pyrifolia, and Manilkara hexandra, bacterial pigment prodigiosin, and three organic solvents (ethanol, methanol, and dimethylsulfoxide), on quorum sensing (QS) in Chromobacterium violaceum (C. violaceum). C. violaceum was challenged with plant extracts prepared by microwave assisted extraction method, prodigiosin, and organic solvents. Effect of these test substances on C. violaceum growth, and quorum sensing regulated pigment (violacein) production was studied by broth dilution assay. High performance liquid chromatography was also applied to generate chromatographic fingerprint of the active extracts. Effect of sub-minimum inhibitory concentration level of the antibiotic streptomycin on quorum sensing regulated pigment production was also studied. Pongamia pinnata seed extracts and prodigiosin were found to possess anti-QS, and Manilkara hexandra and Pyrus pyrifolia seed extracts to possess QS-enhancing effect in C. violaceum. Dimethylsulfoxide was found to enhance violacein production, whereas ethanol and methanol reduced violacein production in C. violaceum. Streptomycin at sub-minimum inhibitory concentration level was able to significantly arrest QS-regulated pigment production in C. violaceum and Serratia marcescens. Prodigiosin and the seed extracts used in this study could affect quorum sensing in C. violaceum to a notable extent. Results of this study also emphasize the importance of inclusion of appropriate solvent controls (negative controls) in bioassays designed for screening of antimicrobial and/or anti-QS compounds. Antipathogenic potential of low concentrations of streptomycin was also demonstrated. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  5. Detection of Possible AI-2-mediated Quorum Sensing System in Commensal Intestinal Bacteria

    Czech Academy of Sciences Publication Activity Database

    Lukáš, Filip; Gorenc, G.; Kopečný, Jan

    2008-01-01

    Roč. 53, č. 3 (2008), s. 221-224 ISSN 0015-5632 R&D Projects: GA ČR GA303/06/0974 Institutional research plan: CEZ:AV0Z50450515 Keywords : quorum sensing system Subject RIV: EE - Microbiology, Virology Impact factor: 1.172, year: 2008

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

    DEFF Research Database (Denmark)

    Valiente, E.; Bruhn, Jesper Bartholin; Nielsen, Kristian Fog

    2009-01-01

    Vibrio vulnificus is an aquatic pathogenic bacterium that can cause vibriosis in humans and fish. The species is subdivided into three biotypes with the fish-virulent strains belonging to biotype 2. The quorum sensing (QS) phenomenon mediated by furanosyl borate diester or autoinducer 2 (AI-2) has...

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

    Science.gov (United States)

    The bacterium Pseudomonas syringae is a plant-pathogen, which through quorum sensing (QS), controls virulence. In this paper, by means of mathematical modeling, we investigate QS of this bacterium when living on leaf surfaces. We extend an existing stochastic model for the formation of Pseudomonas s...

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

    Directory of Open Access Journals (Sweden)

    Zhaoshou Wang

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

  9. Quorum sensing - A novel target for the treatment of biofilm infections

    DEFF Research Database (Denmark)

    Hentzer, Morten; Eberl, L.; Nielsen, J.

    2003-01-01

    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...

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Wolf-Rainer Abraham

    2016-01-01

    Full Text Available Most bacteria attach to surfaces where they form a biofilm, cells embedded in a complex matrix of polymers. Cells in biofilms are much better protected against noxious agents than free-living cells. As a consequence it is very difficult to control pathogens with antibiotics in biofilm infections and novel targets are urgently needed. One approach aims at the communication between cells to form and to maintain a biofilm, a process called quorum-sensing. Water soluble small-sized molecules mediate this process and a number of antagonists of these compounds have been found. In this review natural compounds and synthetic drugs which do not interfere with the classical quorum-sensing compounds are discussed. For some of these compounds the targets are still not known, but others interfere with the formation of exopolysaccharides, virulence factors, or cell wall synthesis or they start an internal program of biofilm dispersal. Some of their targets are more conserved among pathogens than the receptors for quorum sensing autoinducers mediating quorum-sensing, enabling a broader application of the drug. The broad spectrum of mechanisms, the diversity of bioactive compounds, their activity against several targets, and the conservation of some targets among bacterial pathogens are promising aspects for several clinical applications of this type of biofilm-controlling compound in the future.

  12. A common evolutionary pathway for maintaining quorum sensing in Pseudomonas aeruginosa.

    Science.gov (United States)

    Lai, Bai-Min; Yan, Hui-Cong; Wang, Mei-Zhen; Li, Na; Shen, Dong-Sheng

    2018-02-01

    In the bacterium Pseudomonas aeruginosa, the synthesis and secretion of extracellular protease is a typical cooperative behavior regulated by quorum sensing. However, this type of cooperative behavior is easily exploited by other individuals who do not synthesize public goods, which is known as the "tragedy of the commons". Here P. aeruginosa was inoculated into casein media with different nitrogen salts added. In casein broth, protease (a type of public good) is necessary for bacterial growth. After 30 days of sequential transfer, some groups propagated stably and avoided "tragedy of the commons". The evolved cooperators who continued to synthesize protease were isolated from these stable groups. By comparing the characteristics of quorum sensing in these cooperators, an identical evolutionary pattern was found. A variety of cooperative behaviors regulated by quorum sensing, such as the synthesis and secretion of protease and signals, were significantly reduced during the process of evolution. Such reductions improved the efficiency of cooperation, helping to prevent cheating. In addition, the production of pyocyanin, which is regulated by the RhlIR system, increased during the process of evolution, possibly due to its role in stabilizing the cooperation. This study contributes towards our understanding of the evolution of quorum sensing of P. aeruginosa.

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

    NARCIS (Netherlands)

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

    2013-01-01

    Bacteria, although considered for decades to be antisocial organisms whose sole purpose is to find nutrients and multiply are, in fact, highly communicative organisms. Referred to as quorum sensing, cell-to-cell communication mechanisms have been adopted by bacteria in order to co-ordinate their

  14. Quorum sensing integrates environmental cues, cell density and cell history to control bacterial competence

    NARCIS (Netherlands)

    Moreno-Gámez, Stefany; Sorg, Robin A; Domenech, Arnau; Kjos, Morten; Weissing, Franz J; van Doorn, G Sander; Veening, Jan-Willem

    2017-01-01

    Streptococcus pneumoniae becomes competent for genetic transformation when exposed to an autoinducer peptide known as competence-stimulating peptide (CSP). This peptide was originally described as a quorum-sensing signal, enabling individual cells to regulate competence in response to population

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

    DEFF Research Database (Denmark)

    Nielsen, Anita; Månsson, Maria; Bojer, Martin S.

    2014-01-01

    that a cyclodepsipeptide termed Solonamide B isolated from the marine bacterium, Photobacterium halotolerans strongly reduces expression of RNAIII, the effector molecule of the agr quorum sensing system. Here we show that Solonamide B interferes with the binding of S. aureus autoinducing peptides (AIPs) to sensor...

  16. Surface-Attached Molecules Control Staphylococcus aureus Quorum Sensing and Biofilm Development

    Science.gov (United States)

    Kim, Minyoung Kevin; Zhao, Aishan; Wang, Ashley; Brown, Zachary Z.; Muir, Tom W.; Stone, Howard A.; Bassler, Bonnie L.

    2017-01-01

    Bacteria use a process called quorum sensing to communicate and orchestrate collective behaviors including virulence factor secretion and biofilm formation. Quorum sensing relies on production, release, accumulation, and population-wide detection of signal molecules called autoinducers. Here, we develop concepts to coat surfaces with quorum-sensing-manipulation molecules as a method to control collective behaviors. We probe this strategy using Staphylococcus aureus. Pro- and anti-quorum-sensing molecules can be covalently attached to surfaces using click chemistry, where they retain their abilities to influence bacterial behaviors. We investigate key features of the compounds, linkers, and surfaces necessary to appropriately position molecules to interact with cognate receptors, and the ability of modified surfaces to resist long-term storage, repeated infections, host plasma components, and flow-generated stresses. Our studies highlight how this surface approach can be used to make colonization-resistant materials against S. aureus and other pathogens and how the approach can be adapted to promote beneficial behaviors of bacteria on surfaces. PMID:28530651

  17. Melnikov method to a bacteria-immunity model with bacterial quorum sensing mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Zhonghua [School of Sciences, Xi' an University of Science and Technology, Xi' an 710054 (China)], E-mail: wwwzhonghua@sohu.com; Peng Jigen [Research Center for Applied Mathematics, Xi' an Jiaotong University, Xi' an 710049 (China); Zhang Juan [Department of Mathematics, North China Electric Power University, Beijing 102206 (China)

    2009-04-15

    A bacteria-immunity model with bacterial quorum sensing is formulated, which describes the competition between bacteria and immune cells. After periodic perturbation and a series of coordinate transformations, the model is brought into a standard form, and which is amenable to Melnikov method. By the method, the existences of chaotic motion and homoclinic bifurcations are proved.

  18. Quorum sensing integrates environmental cues, cell density and cell history to control bacterial competence.

    Science.gov (United States)

    Moreno-Gámez, Stefany; Sorg, Robin A; Domenech, Arnau; Kjos, Morten; Weissing, Franz J; van Doorn, G Sander; Veening, Jan-Willem

    2017-10-11

    Streptococcus pneumoniae becomes competent for genetic transformation when exposed to an autoinducer peptide known as competence-stimulating peptide (CSP). This peptide was originally described as a quorum-sensing signal, enabling individual cells to regulate competence in response to population density. However, recent studies suggest that CSP may instead serve as a probe for sensing environmental cues, such as antibiotic stress or environmental diffusion. Here, we show that competence induction can be simultaneously influenced by cell density, external pH, antibiotic-induced stress, and cell history. Our experimental data is explained by a mathematical model where the environment and cell history modify the rate at which cells produce or sense CSP. Taken together, model and experiments indicate that autoinducer concentration can function as an indicator of cell density across environmental conditions, while also incorporating information on environmental factors or cell history, allowing cells to integrate cues such as antibiotic stress into their quorum-sensing response. This unifying perspective may apply to other debated quorum-sensing systems.Peptide CSP regulates natural competence in pneumococci and has been proposed as a quorum-sensing signal or a probe for sensing environmental cues. Here, the authors show that CSP levels can indeed act as an indicator of cell density and also incorporate information on environmental factors or cell history.

  19. Kinetic Model for Signal Binding to the Quorum Sensing Regulator LasR

    DEFF Research Database (Denmark)

    Claussen, Anetta; Jakobsen, Tim Holm; Bjarnsholt, Thomas

    2013-01-01

    of the active LasR quorum-sensing regulator was studied in an Escherichia coli background as a function of signal molecule concentration. The functional activity of the regulator was monitored via a GFP reporter fusion to lasB expressed from the native lasB promoter. The new data shows that the active form...

  20. Ligand Binding Kinetics of the Quorum Sensing Regulator PqsR

    DEFF Research Database (Denmark)

    Welch, Martin; Hodgkinson, James T.; Gross, Jeremy

    2013-01-01

    The Pseudomonas aeruginosa quinolone signal (PQS) is a quorum sensing molecule that plays an important role in regulating the virulence of this organism. We have purified the ligand binding domain of the receptor PqsRLBD for PQS and have used Förster resonance energy transfer fluorimetry...

  1. Protoanemonin: a natural quorum sensing inhibitor that selectively activates iron starvation response

    NARCIS (Netherlands)

    Fazzini, R.A.; Skindersoe, M.; Bielecki, M.; Puchalka, J.; Givskov, M.; Martins Dos Santos, V.A.P.

    2013-01-01

    Many Gram-negative bacteria employ cell-to-cell communication mediated by N-acyl homoserine lactones (quorum sensing) to control expression of a wide range of genes including, but not limited to, genes encoding virulence factors. Outside the laboratory, the bacteria live in complex communities where

  2. Switches induced by quorum sensing in a model of enzyme-loaded microparticles.

    Science.gov (United States)

    Bánsági, Tamás; Taylor, Annette F

    2017-03-01

    Quorum sensing refers to the ability of bacteria and other single-celled organisms to respond to changes in cell density or number with population-wide changes in behaviour. Here, simulations were performed to investigate quorum sensing in groups of diffusively coupled enzyme microparticles using a well-characterized autocatalytic reaction which raises the pH of the medium: hydrolysis of urea by urease. The enzyme urease is found in both plants and microorganisms, and has been widely exploited in engineering processes. We demonstrate how increases in group size can be used to achieve a sigmoidal switch in pH at high enzyme loading, oscillations in pH at intermediate enzyme loading and a bistable, hysteretic switch at low enzyme loading. Thus, quorum sensing can be exploited to obtain different types of response in the same system, depending on the enzyme concentration. The implications for microorganisms in colonies are discussed, and the results could help in the design of synthetic quorum sensing for biotechnology applications such as drug delivery. © 2018 The Author(s).

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

    Science.gov (United States)

    Kavanaugh, Jeffrey S; Horswill, Alexander R

    2016-06-10

    Staphylococci are commensal bacteria that colonize the epithelial surfaces of humans and many other mammals. These bacteria can also attach to implanted medical devices and develop surface-associated biofilm communities that resist clearance by host defenses and available chemotherapies. These communities are often associated with persistent staphylococcal infections that place a tremendous burden on the healthcare system. Understanding the regulatory program that controls staphylococcal biofilm development, as well as the environmental conditions that modulate this program, has been a focal point of research in recent years. A central regulator controlling biofilm development is a peptide quorum-sensing system, also called the accessory gene regulator or agr system. In the opportunistic pathogen Staphylococcus aureus, the agr system controls production of exo-toxins and exo-enzymes essential for causing infections, and simultaneously, it modulates the ability of this pathogen to attach to surfaces and develop a biofilm, or to disperse from the biofilm state. In this review, we explore advances on the interconnections between the agr quorum-sensing system and biofilm mechanisms, and topics covered include recent findings on how different environmental conditions influence quorum sensing, the impact on biofilm development, and ongoing questions and challenges in the field. As our understanding of the quorum sensing and biofilm interconnection advances, there are growing opportunities to take advantage of this knowledge and develop therapeutic approaches to control staphylococcal infections. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. In vitro screens for quorum sensing inhibitors and in vivo confirmation of their effect

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; van Gennip, Maria; Jakobsen, Tim H

    2010-01-01

    This article will introduce the reader to protocols intended for (i) identification of quorum sensing (QS) inhibitors (QSIs), (ii) characterization of these compounds in vitro and (iii) evaluation of these compounds in animal models. Traditional antimicrobial drugs are designed against planktonic...

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

    DEFF Research Database (Denmark)

    Rasmussen, Thomas Bovbjerg; Manefield, M.; Andersen, Jens Bo

    2000-01-01

    Halogenated furanones produced by the benthic marine macroalga Delisea pulchra inhibit swarming motility of Serratia liquefaciens MG1. This study demonstrates that exogenously added furanones control transcription of the quorum sensing regulated gene swrA in competition with the cognate signal...

  6. Development of Quorum-Based Anti-Virulence Therapeutics Targeting Gram-Negative Bacterial Pathogens

    Directory of Open Access Journals (Sweden)

    Wen Shan Yew

    2013-08-01

    Full Text Available Quorum sensing is a cell density-dependent signaling phenomenon used by bacteria for coordination of population-wide phenotypes, such as expression of virulence genes, antibiotic resistance and biofilm formation. Lately, disruption of bacterial communication has emerged as an anti-virulence strategy with enormous therapeutic potential given the increasing incidences of drug resistance in pathogenic bacteria. The quorum quenching therapeutic approach promises a lower risk of resistance development, since interference with virulence generally does not affect the growth and fitness of the bacteria and, hence, does not exert an associated selection pressure for drug-resistant strains. With better understanding of bacterial communication networks and mechanisms, many quorum quenching methods have been developed against various clinically significant bacterial pathogens. In particular, Gram-negative bacteria are an important group of pathogens, because, collectively, they are responsible for the majority of hospital-acquired infections. Here, we discuss the current understanding of existing quorum sensing mechanisms and present important inhibitory strategies that have been developed against this group of pathogenic bacteria.

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

    Science.gov (United States)

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

    2015-06-16

    Selection for phage resistance is a key driver of bacterial diversity and evolution, and phage-host interactions may therefore have strong influence on the genetic and functional dynamics of bacterial communities. In this study, we found that an important, but so far largely overlooked, determinant of the outcome of phage-bacterial encounters in the fish pathogen Vibrio anguillarum is bacterial cell-cell communication, known as quorum sensing. Specifically, V. anguillarum PF430-3 cells locked in the low-cell-density state (ΔvanT mutant) express high levels of the phage receptor OmpK, resulting in a high susceptibility to phage KVP40, but achieve protection from infection by enhanced biofilm formation. By contrast, cells locked in the high-cell-density state (ΔvanΟ mutant) are almost completely unsusceptible due to quorum-sensing-mediated downregulation of OmpK expression. The phenotypes of the two quorum-sensing mutant strains are accurately reflected in the behavior of wild-type V. anguillarum, which (i) displays increased OmpK expression in aggregated cells compared to free-living variants in the same culture, (ii) displays a clear inverse correlation between ompK mRNA levels and the concentration of N-acylhomoserine lactone quorum-sensing signals in the culture medium, and (iii) survives mainly by one of these two defense mechanisms, rather than by genetic mutation to phage resistance. Taken together, our results demonstrate that V. anguillarum employs quorum-sensing information to choose between two complementary antiphage defense strategies. Further, the prevalence of nonmutational defense mechanisms in strain PF430-3 suggests highly flexible adaptations to KVP40 phage infection pressure, possibly allowing the long-term coexistence of phage and host. Comprehensive knowledge on bacterial antiphage strategies and their regulation is essential for understanding the role of phages as drivers of bacterial evolution and diversity. In an applied context

  8. Anti-bacterial activity of intermittent preventive treatment of malaria in pregnancy: comparative in vitro study of sulphadoxine-pyrimethamine, mefloquine, and azithromycin

    Directory of Open Access Journals (Sweden)

    Mombo-Ngoma Ghyslain

    2010-10-01

    Full Text Available Abstract Background Intermittent preventive treatment of malaria with sulphadoxine-pyrimethamine (SP is recommended for the prevention of malaria in pregnancy in sub-Saharan Africa. Increasing drug resistance necessitates the urgent evaluation of alternative drugs. Currently, the most promising candidates in clinical development are mefloquine and azithromycin. Besides the anti-malarial activity, SP is also a potent antibiotic and incurs significant anti-microbial activity when given as IPTp - though systematic clinical evaluation of this action is still lacking. Methods In this study, the intrinsic anti-bacterial activity of mefloquine and azithromycin was assessed in comparison to sulphadoxine-pyrimethamine against bacterial pathogens with clinical importance in pregnancy in a standard microdilution assay. Results SP was highly active against Staphylococcus aureus and Streptococcus pneumoniae. All tested Gram-positive bacteria, except Enterococcus faecalis, were sensitive to azithromycin. Additionally, azithromycin was active against Neisseria gonorrhoeae. Mefloquine showed good activity against pneumococci but lower in vitro action against all other tested pathogens. Conclusion These data indicate important differences in the spectrum of anti-bacterial activity for the evaluated anti-malarial drugs. Given the large scale use of IPTp in Africa, the need for prospective clinical trials evaluating the impact of antibiotic activity of anti-malarials on maternal and foetal health and on the risk of promoting specific drug resistance of bacterial pathogens is discussed.

  9. Azithromycin and cough-specific health status in patients with chronic obstructive pulmonary disease and chronic cough : a randomised controlled trial

    NARCIS (Netherlands)

    Berkhof, Farida F.; Doornewaard-ten Hertog, Nynke E.; Uil, Steven M.; Kerstjens, Huib A. M.; van den Berg, Jan W. K.

    2013-01-01

    Background: Macrolides reduce exacerbations in patients with COPD. Their effects on health status has not been assessed as primary outcome and is less clear. This study assessed the effects of prophylactic azithromycin on cough-specific health status in COPD-patients with chronic productive cough.

  10. Quantitative determination of azithromycin in plasma, blood and isolated neutrophils by liquid chromatography using pre-column derivatization with 9-fluorenylmethyloxycarbonyl-chloride and fluorescence detection

    NARCIS (Netherlands)

    Wilms, Erik; Trumpie, Henk; Veenendaal, Wim; Touw, Daan

    2005-01-01

    In this study, a high-performance liquid chromatographic method with pre-column derivatization and fluorescence detection was optimised and validated for the quantification of azithromycin (AZM) in plasma. Clarithromycin (CLM) was used as an internal standard. Pre-column derivatization was done with

  11. Efficacy, safety and tolerability of 3 day azithromycin versus 10 day co-amoxiclav in the treatment of children with acute lower respiratory tract infections

    NARCIS (Netherlands)

    A. Ferwerda (Annemarie); H.A. Moll (Henriëtte); W.C.J. Hop (Wim); J.M. Kouwenberg (Jan); C.V. Tjon Pian Gi

    2001-01-01

    textabstractTo compare the efficacy, safety and tolerability of a 3 day course of azithromycin with a 10 day course of co-amoxiclav in the treatment of children with acute lower respiratory tract infection (LRTI), 118 patients with community-acquired LRTI were

  12. Affecting Pseudomonas aeruginosa phenotypic plasticity by quorum sensing dysregulation hampers pathogenicity in murine chronic lung infection.

    Directory of Open Access Journals (Sweden)

    Roslen Bondí

    Full Text Available In Pseudomonas aeruginosa quorum sensing (QS activates the production of virulence factors, playing a critical role in pathogenesis. Multiple negative regulators modulate the timing and the extent of the QS response either in the pre-quorum or post-quorum phases of growth. This regulation likely increases P. aeruginosa phenotypic plasticity and population fitness, facilitating colonization of challenging environments such as higher organisms. Accordingly, in addition to the factors required for QS signals synthesis and response, also QS regulators have been proposed as targets for anti-virulence therapies. However, while it is known that P. aeruginosa mutants impaired in QS are attenuated in their pathogenic potential, the effect of mutations causing a dysregulated timing and/or magnitude of the QS response has been poorly investigated so far in animal models of infection. In order to investigate the impact of QS dysregulation on P. aeruginosa pathogenesis in a murine model of lung infection, the QteE and RsaL proteins have been selected as representatives of negative regulators controlling P. aeruginosa QS in the pre- and post-quorum periods, respectively. Results showed that the qteE mutation does not affect P. aeruginosa lethality and ability to establish chronic infection in mice, despite causing a premature QS response and enhanced virulence factors production in test tube cultures compared to the wild type. Conversely, the post-quorum dysregulation caused by the rsaL mutation hampers the establishment of P. aeruginosa chronic lung infection in mice without affecting the mortality rate. On the whole, this study contributes to a better understanding of the impact of QS regulation on P. aeruginosa phenotypic plasticity during the infection process. Possible fallouts of these findings in the anti-virulence therapy field are also discussed.

  13. A medicinal herb Cassia alata attenuates quorum sensing in Chromobacterium violaceum and Pseudomonas aeruginosa.

    Science.gov (United States)

    Rekha, P D; Vasavi, H S; Vipin, C; Saptami, K; Arun, A B

    2017-03-01

    Quorum sensing (QS) has been shown to play a crucial role in the pathogenesis in many bacteria, and attenuation of QS is one of the targets of antimicrobial therapy with particular interest in combating drug resistance. This study reports the QS inhibitory activity of metabolites from Cassia alata L. (Ca. alata), an important medicinal herb widely used in the treatment of microbial infections. For investigating the QS inhibition (QSI), the potential of Ca. alata L., initially, metabolites of the leaves extracted using ethanol was tested against biosensor strain Chromobacterium violaceum CV026 and C. violaceum wild-type strains. Furthermore, a purified fraction rich in flavonoids (F-AF) was used for establishing QSI activity by studying the inhibition of violacein production in C. violaceum, and QS controlled virulence and biofilm formation in Pseudomonas aeruginosa PAO1. The study results showed 50% inhibition of violacein production in C. violaceum at 0·05 mg ml -1 concentration of F-AF. In P. aeruginosa PAO1, it inhibited the tested virulence factors and biofilm formation significantly. The F-AF contained major flavonoids namely, quercetin, quercetrin and kaempferol displaying QSI activity individually against the test organisms. Present study demonstrates the quorum sensing inhibitory activity of metabolites from Cassia alata, an important medicinal herb which is commonly used worldwide in the treatment of infections caused by microorganisms. An extract prepared from the leaves of the plant showed activity against quorum sensing in Chromobacterium violaceum and was also effective against attenuating the quorum sensing controlled virulence factors in Pseudomonas aeruginosa. Activity is attributed to the rich flavonoid composition of the plant. Results of the present investigation throw an insight into the possibility of developing drug formulations using the isolated compounds against infections caused by quorum sensing-mediated pathogenicity of bacteria

  14. Bacterial quorum sensing and the role of algae in bacterial diseases control in aquaculture

    Directory of Open Access Journals (Sweden)

    . Wiyoto

    2010-07-01

    Full Text Available Bacterial disease is one of the most common diseases in aquaculture practices which have a significant impact. Several researches noted that pathogenicity of a certain bacteria can be determined by its quorum sensing activity. Quorum sensing is a communication process of a certain bacteria with the same or different species of bacteria which involves the releasing and capturing of signal molecule to and from the environment. This activity will activate a certain target gene which further resulted in the expression of a phenotype by the bacteria. With regard to this characteristic, one of the methods to control bacterial diseases is by quorum sensing disruption. Several species of algae, both micro and macro, have been found to be able to intervense bacterial quorum sensing and thus can be used as an alternative in bacterial disease control.    Key words: quorum sensing, bacterial disease, aquaculture, algae  Abstrak Penyakit bakteri adalah salah satu penyakit yang paling umum dalam akuakultur dengan dampak yang cukup signifikan. Beberapa penelitian menunjukkan bahwa tingkat patogenitas suatu bakteri salah satunya ditentukan oleh aktivitas kuorum sensing bakteri. Kuorum sensing bakteri merupakan suatu proses komunikasi yang dilakukan oleh bakteri dengan bakteri lainnya baik yang sejenis maupun berlainan jenis yang berupa pelepasan dan penangkapan molekul sinyal menuju dan dari lingkungan sekitar bakteri tersebut. Aktivitas inilah yang akan menentukan ekspresi suatu gen target seperti patogenitas, sehingga salah satu metode yang dapat digunakan dalam mengendalikan penyakit yang disebabkan oleh bakteri adalah dengan mengganggu aktivitas kuorum sensing bakteri. Beberapa jenis alga, baik mikro maupun makro, diketahui dapat mengintervensi aktivitas kuorum sensing, dan dapat menjadi salah satu alternatif bagi pengendalian penyakit bakterial. Kata-kata kunci: kuorum sensing, penyakit bakterial, akuakultur, alga

  15. Homogeneous bilateral block shifts

    Indian Academy of Sciences (India)

    A new 3-parameter family of homogeneous 2-by-2 block shifts is described. These are the first examples of irreducible homogeneous bilateral block shifts of block size larger than 1. Author Affiliations. Adam Korányi1. Department of Mathematics, The Graduate Center, City University of New York, New York, NY 10016, USA ...

  16. Intra-Species Bacterial Quorum Sensing Studied at Single Cell Level in a Double Droplet Trapping System

    Directory of Open Access Journals (Sweden)

    Wilhelm T. S. Huck

    2013-05-01

    Full Text Available In this paper, we investigated the intra-species bacterial quorum sensing at the single cell level using a double droplet trapping system. Escherichia coli transformed to express the quorum sensing receptor protein, LasR, were encapsulated in microdroplets that were positioned adjacent to microdroplets containing the autoinducer, N-(3-oxododecanoyl-L-homoserine lactone (OdDHL. Functional activation of the LasR protein by diffusion of the OdDHL across the droplet interface was measured by monitoring the expression of green fluorescent protein (GFP from a LasR-dependent promoter. A threshold concentration of OdDHL was found to induce production of quorum-sensing associated GFP by E. coli. Additionally, we demonstrated that LasR-dependent activation of GFP expression was also initiated when the adjacent droplets contained single E. coli transformed with the OdDHL synthase gene, LasI, representing a simple quorum sensing circuit between two droplets.

  17. How Much Surface Coating of Hydrophobic Azithromycin Is Sufficient to Prevent Moisture-Induced Decrease in Aerosolisation of Hygroscopic Amorphous Colistin Powder?

    Science.gov (United States)

    Zhou, Qi Tony; Loh, Zhi Hui; Yu, Jiaqi; Sun, Si-Ping; Gengenbach, Thomas; Denman, John A; Li, Jian; Chan, Hak-Kim

    2016-09-01

    Aerosolisation performance of hygroscopic particles of colistin could be compromised at elevated humidity due to increased capillary forces. Co-spray drying colistin with a hydrophobic drug is known to provide a protective coating on the composite particle surfaces against moisture-induced reduction in aerosolisation performance; however, the effects of component ratio on surface coating quality and powder aerosolisation at elevated relative humidities are unknown. In this study, we have systematically examined the effects of mass ratio of hydrophobic azithromycin on surface coating quality and aerosolisation performance of the co-spray dried composite particles. Four combination formulations with varying drug ratios were prepared by co-spray drying drug solutions. Both of the drugs in each combination formulation had similar in vitro deposition profiles, suggesting that each composite particle comprises two drugs in the designed mass ratio, which is supported by X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) data. XPS and ToF-SIMS measurements also revealed that 50% by weight (or 35% by molecular fraction) of azithromycin in the formulation provided a near complete coating of 96.5% (molar fraction) on the composite particle surface, which is sufficient to prevent moisture-induced reduction in fine particle fraction (FPF)recovered and FPFemitted. Higher azithromycin content did not increase coating coverage, while contents of azithromycin lower than 20% w/w did not totally prevent the negative effects of humidity on aerosolisation performance. This study has highlighted that a critical amount of azithromycin is required to sufficiently coat the colistin particles for short-term protection against moisture.

  18. How much surface coating of hydrophobic azithromycin is sufficient to prevent moisture-induced decrease in aerosolisation of hygroscopic colistin powder?

    Science.gov (United States)

    Zhou, Qi (Tony); Loh, Zhi Hui; Yu, Jiaqi; Sun, Si-ping; Gengenbach, Thomas; Denman, John A.; Li, Jian; Chan, Hak-Kim

    2017-01-01

    Aerosolisation performance of hygroscopic particles of colistin could be compromised at elevated humidity due to increased capillary forces. Co-spray drying colistin with a hydrophobic drug is known to provide a protective coating on the composite particle surfaces against moisture-induced reduction in aerosolisation performance; however, the effects of component ratio on surface coating quality and powder aerosolisation at elevated relative humidities are unknown. In this study, we have systematically examined the effects of mass ratio of hydrophobic azithromycin on surface coating quality and aerosolisation performance of the co-spray dried composite particles. Four combination formulations with varying drug ratios were prepared by co-spray drying drug solutions. Both of the drugs in each combination formulation had similar in vitro deposition profiles, suggesting that each composite particle comprise two drugs in the designed mass ratio, which is supported by XPS and ToF-SIMS data. XPS and ToF-SIMS measurements also revealed that 50 % by weight (or 35 % by molecular fraction) of azithromycin in the formulation provided a near-complete coating of 96.5 % (molar fraction) on the composite particle surface, which is sufficient to prevent moisture-induced reduction in FPFrecovered and FPFemitted. Higher azithromycin content did not increase coating coverage, while contents of azithromycin lower than 20 %w/w did not totally prevent the negative effects of humidity on aerosolisation performance. This study has highlighted that a critical amount of azithromycin is required to sufficiently coat the colistin particles for short-term protection against moisture. PMID:27255350

  19. Effect of budesonide inhalation combined with azithromycin on pulmonary function, serum inflammatory factors and immune function of children with mycoplasma pneumonia

    Directory of Open Access Journals (Sweden)

    Yi-Lin Tan

    2016-11-01

    Full Text Available Objective: To observe the effect of budesonide inhalation combined with azithromycin on pulmonary function ,serum inflammatory factors and immune function of children with mycoplasma pneumonia. Methods: A total of 128 cases of children with MPP were selected from June 2014 to May 2016 and were randomly divided into observation group (68 cases and control group (60 cases.The control group were treated with azithromycin while the observation group were given both budesonide aerosol inhalation and azithromycin therapy. After two weeks, observe two groups of lung function index (FVC, FEV1, PEV and PEF25, the serum levels of inflammatory factors (TNF-α, IL-2, IL-6, INF-γ and the immune function (IgM, IgG, IgA. Results: After treatment, the level of FEV1, FVC, PEV and PEF25 of the two group were increased compared with before (P<0.05, and the FEV1, FVC, PEV and PEF25 of observation group after treatment were respectively significantly higher than the control group (P<0.05. TNFα, IL-2, IL-6 and INF-γ in both groups were decreased compared with before (P<0.05, and the TNFα, IL-2, IL-6 and INF-γ of observation group after treatment were significantly lower than the control group (P<0.05. IgM and IgA were decreased while the IgG was increased (P<0.05, the observation group was significantly lower than control group (P<0.05. Conclusion: Budesonide aerosol inhalation in combination with azithromycin can significantly improve lung function, inhibit inflammation and regulate immune function strongly than that of azithromycin alone in treatment of children MPP.

  20. Oral azithromycin in extended dosage schedule for chronic, subclinical Chlamydia pneumoniae infection causing coronary artery disease: a probable cure in sight? Results of a controlled preliminary trial

    Directory of Open Access Journals (Sweden)

    Dogra J

    2012-06-01

    Full Text Available Jaideep DograPoly Clinic, Central Government Health Scheme, Jaipur, Rajasthan, IndiaPurpose: Two mega trials have raised the question as to whether the hypothesis that infection plays a role in atherosclerosis is still relevant. This controlled preliminary trial investigated an extended dose of azithromycin in the treatment of Chlamydia pneumoniae infection causing coronary artery disease (CAD.Patients and methods: Forty patients with documentary evidence of CAD were screened for immunoglobulin G titers against C. pneumoniae and grouped into either the study group (patients with positive titer, n = 32 or control group (patients with negative titer, n = 8. Cases who met inclusion criteria could not have had coronary artery bypass graft surgery or percutaneous coronary intervention in the preceding 6 months. Informed consent was obtained from every patient. Baseline blood samples were analyzed for red blood cell indices, serum creatinine, and liver function tests, and repeated every 2 months. A primary event was defined as the first occurrence of death by any cause, recurrent myocardial infarction, coronary revascularization procedure, or hospitalization for angina. Patients in the study group received 500 mg of oral azithromycin once daily for 5 days, which was then repeated after a gap of 10 days (total of 24 courses in the 1-year trial period. The control group did not have azithromycin added to their standard CAD treatment.Results: In the study group, 30 patients completed the trial. Two patients had to undergo percutaneous coronary intervention in the initial first quarter of the 1-year trial period. In the control group, one patient died during the trial, one had to undergo coronary artery bypass graft surgery, and one had percutaneous coronary intervention.Conclusion: The patients tolerated the therapy well and there was a positive correlation between azithromycin and secondary prevention of CAD.Keywords: azithromycin, Chlamydia pneumoniae