Development of molecularly imprinted polymers to block quorum sensing and inhibit bacterial biofilm formation.

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Ma, Luyao; Feng, Shaolong; de la Fuente-Nunez, Cesar; Hancock, Robert E W; Lu, Xiaonan

2018-05-16

Bacterial biofilms are responsible for most clinical infections and show increased antimicrobial resistance. In this study, molecularly imprinted polymers (MIPs) were developed to specifically capture prototypical quorum sensing autoinducers [i.e., N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12AHL)], interrupt quorum sensing, and subsequently inhibit biofilm formation of Pseudomonas aeruginosa, an important human nosocomial pathogen. The synthesis of MIPs was optimized by considering the amount and type of the functional monomers itaconic acid (IA) and 2-hydroxyethyl methacrylate (HEMA). IA-based MIPs showed high adsorption affinity towards 3-oxo-C12AHL with an imprinting factor of 1.68. Compared to IA-based MIPs, the adsorption capacity of HEMA-based MIPs was improved 5-fold. HEMA-based MIPs significantly reduced biofilm formation (by ~65%), while biofilm suppression by IA-based MIPs was neutralized due to increased bacterial attachment. The developed MIPs represent promising alternative biofilm intervention agents that can be applied to surfaces relevant to clinical settings and food processing equipment.

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

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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

Childhood mortality in a cohort treated with mass azithromycin for trachoma.

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

2011-04-01

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. 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. 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]). 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. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

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

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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.

Quorum Quenching Revisited—From Signal Decays to Signalling Confusion

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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.

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

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Kato, Kazuya; Iwasaki, Yoshiaki; Onodera, Kazuhiko; Higuchi, Mineko; Kato, Kimitaka; Kato, Yurina; Tsutsui, Masato; Taniguchi, Masahiko; Furukawa, Hiroyuki

2016-01-01

Rhabdomyolysis associated with the use of pregabalin or azithromycin has been demonstrated to be a rare but potentially life-threatening adverse event. Here, we report an extremely rare case of rhabdomyolysis with purpura in a patient who had used pregabalin and azithromycin. We present the case of a 75-year-old woman with a history of fibromyalgia who was admitted with mild limb weakness and lower abdominal purpura. She was prescribed pregabalin (75mg, twice daily) for almost 3 months to treat chronic back pain. Her medical history revealed that 3days before admission, she began experiencing acute bronchitis and was treated with a single dose of azithromycin (500mg). She had developed rapid onset severe myalgia, mild whole body edema, muscle weakness leading to gait instability, abdominal purpura and tender purpura on the lower extremities. Laboratory values included a white blood cell count of 25,400/mL and a creatinine phosphokinase (CPK) concentration of 1250 IU/L. Based on these findings and the patient's clinical history, a diagnosis of pregabalin- and azithromycin-induced rhabdomyolysis was made. The long-term use of pregabalin and the initiation azithromycin therapy followed by a rapid onset of rhabdomyolysis is indicative of a drug interaction between pregabalin and azithromycin. 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. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Global Analysis of the Burkholderia thailandensis Quorum Sensing-Controlled Regulon

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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

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

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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.

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...... and the complement system. Moreover, we show that AZM may affect the polymerization of P. aeruginosa alginate by the incomplete precipitation of polymerized alginate and high levels of readily dialyzable uronic acids. In addition, we find that mucoid bacteria in the stationary growth phase became sensitive to AZM......, whereas cells in the exponential phase did not. Interestingly, AZM-treated P. aeruginosa lasI mutants appeared to be particularly resistant to serum, whereas bacteria with a functional QS system did not. We show in a CF mouse model of chronic P. aeruginosa lung infection that AZM treatment results...

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

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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

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

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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.

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

Limited Azithromycin Localization to Rabbit Meibomian Glands Revealed by LC-MS-Based Bioanalysis and DESI Imaging.

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Asano, Nagayoshi; Wiseman, Justin Michael; Tsuji, Fumio; Kawazu, Kouichi

2017-01-01

Meibomian gland dysfunction (MGD) is the leading cause of dry eye, and although it affects approximately 4% of the population, treatment options remain limited. Topical azithromycin is one of the most promising pharmacological agents because of its multiple mechanisms of action and long sustainability. Azithromycin is frequently used as an off-label medication in the U.S. However, although azithromycin is presumed to act directly on meibomian gland cells, the mechanisms of action that contribute to its clinical efficacy remain unclear because no studies using a pharmacokinetic approach have been performed. Therefore, we aimed to clarify whether topical azithromycin reaches the meibomian glands sufficiently to generate a biological effect. We measured azithromycin concentrations in rabbit meibomian glands collected using a recently developed method. Moreover, we also visualized the azithromycin micro-distribution using desorption electrospray ionization (DESI) imaging. Azithromycin concentration in the meibomian glands reached only 0.8 µg/g tissue following a single application of a 1% azithromycin ophthalmic solution and was 1000-fold lower than the concentration in conjunctival epithelium. Similarly, no signal was observed in the meibomian glands on DESI images. Our results clearly demonstrated that topical azithromycin had limited access to the meibomian glands and was predominantly distributed in ocular surface tissues such as the palpebral conjunctiva and lid margins. These findings provide new insight into the clinical responses to topical azithromycin therapy and will aid in the further development of effective drugs with more suitable pharmacokinetic properties.

Quorum decision-making in foraging fish shoals.

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Ashley J W Ward

Full Text Available Quorum responses provide a means for group-living animals to integrate and filter disparate social information to produce accurate and coherent group decisions. A quorum response may be defined as a steep increase in the probability of group members performing a given behaviour once a threshold minimum number of their group mates already performing that behaviour is exceeded. In a previous study we reported the use of a quorum response in group decision-making of threespine sticklebacks (Gasterosteus aculeatus under a simulated predation threat. Here we examine the use of quorum responses by shoals of sticklebacks in first locating and then leaving a foraging patch. We show that a quorum rule explains movement decisions by threespine sticklebacks toward and then away from a food patch. Following both to and from a food patch occurred when a threshold number of initiators was exceeded, with the threshold being determined by the group size.

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

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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.

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...

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

Benefits of additional courses of systemic azithromycin in periodontal disease case report.

Science.gov (United States)

Schmidt, Edgard F; Bretz, Walter A

2007-01-01

The strong association of subgingival anaerobic bacteria, such as Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia, with destructive periodontal disease has been well documented in the literature. Several double-blind studies have also shown the beneficial use of systemic antimicrobials that are active against these microorganisms in conjunction with conventional periodontal treatment, especially when periodontal abscesses and/or suppuration upon probing are present. Four cases with periodontal abscesses were treated with scaling/root planing in conjunction with systemic azithromycin. Partial improvement led to retreatment with two additional courses of azithromycin. Bone formation was noted on periapical radiographs after the patients took additional courses of azithromycin. In view of the benefits of using additional courses of azithromycin in the treatment of destructive periodontal disease, we conclude that the single course of systemic antimicrobials currently used in periodontal therapy may be insufficient to reach necessary therapeutic levels in infected sites.

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

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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.

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

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

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......-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 phagocytosis by PMNs, as well as leading to an improved outcome of pulmonary infections....

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

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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.

Quorum sensing and bacterial pathogenicity: From molecules to disease

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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.

Quorum signaling and sensing by nontypeable Haemophilus influenzae.

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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.

Quorum signaling and sensing by nontypeable Haemophilus influenzae

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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.

Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors

DEFF Research Database (Denmark)

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

2003-01-01

Traditional treatment of infectious diseases is based on compounds that kill or inhibit growth of bacteria. A major concern with this approach is the frequent development of resistance to antibiotics. The discovery of communication systems (quorum sensing systems) regulating bacterial virulence has...... of natural furanone compounds can act as a potent antagonist of bacterial quorum sensing. We employed GeneChip((R)) microarray technology to identify furanone target genes and to map the quorum sensing regulon. The transcriptome analysis showed that the furanone drug specifically targeted quorum sensing...

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

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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.

Sustained transmission of high-level azithromycin-resistant Neisseria gonorrhoeae in England: an observational study.

Science.gov (United States)

Fifer, Helen; Cole, Michelle; Hughes, Gwenda; Padfield, Simon; Smolarchuk, Christa; Woodford, Neil; Wensley, Adrian; Mustafa, Nazim; Schaefer, Ulf; Myers, Richard; Templeton, Kate; Shepherd, Jill; Underwood, Anthony

2018-05-01

Between Nov 3, 2014, and Feb 24, 2017, 70 cases of high-level azithromycin-resistant (HL-AziR; minimum inhibitory concentration [MIC] ≥256 mg/L) Neisseria gonorrhoeae were reported from across England. Whole-genome sequencing was done to investigate this outbreak to determine whether the ongoing outbreak represented clonal spread of an HL-AziR N gonorrhoeae strain identified in Leeds. We also wanted to elucidate the molecular mechanisms of azithromycin resistance in N gonorrhoeae in the UK. In this observational study, whole-genome sequencing was done on the HL-AziR N gonorrhoeae isolates from England. As comparators, 110 isolates from the UK and Ireland with a range of azithromycin MICs were also sequenced, including eight isolates from Scotland with azithromycin MICs ranging from 0·12 mg/L to 1·00 mg/L that were N gonorrhoeae multi-antigen sequence type 9768 (ST9768), which was the sequence type initially responsible for the outbreak. The presence of mutations or genes associated with azithromycin resistance was also investigated. 37 of the 60 HL-AziR isolates from England belonged to ST9768, and were genetically similar (mean 4·3 single-nucleotide polymorphisms). A 2059A→G mutation was detected in three or all four alleles of the 23S rRNA gene. Five susceptible ST9768 isolates had one mutated 23S rRNA allele and one low-level resistant ST9768 isolate had two mutated alleles. Sustained transmission of a successful HL-AziR clone was seen across England. Mutation 2059A→G was found in isolates with lower azithromycin MICs. Azithromycin exposure might have provided the selection pressure for one or two mutated copies of the 23S rRNA gene to recombine with wild-type copies, leading to three or four mutated copies and the HL-AziR phenotype. HL-AziR could emerge in isolates with low azithromycin MICs and eliminate the effectiveness of azithromycin as part of dual therapy for the treatment of gonorrhoea. Public Health England. Copyright © 2018 Elsevier Ltd. All

Pseudomonas aeruginosa tolerance to tobramycin, hydrogen peroxide and polymorphonuclear leukocytes is quorum-sensing dependent

DEFF Research Database (Denmark)

Bjarnsholt, Thomas; Jensen, P.O.; Burmolle, M.

2005-01-01

to otherwise lethal doses of antibiotics and are protected from bactericidal activity of polymorphonuclear leukocytes (PMNs). P. aeruginosa controls the expression of many of its virulence factors by means of a cell-cell communication system termed quorum sensing (QS). In the present report it is demonstrated...... that biofilm bacteria in which QS is blocked either by mutation or by administration of QS inhibitory drugs are sensitive to treatment with tobramycin and H2O2, and are readily phagocytosed by PMNs, in contrast to bacteria with functional QS systems. In contrast to the wild-type, QS-deficient biofilms led...... to an immediate respiratory-burst activation of the PMNs in vitro. In vivo QS-deficient mutants provoked a higher degree of inflammation. It is suggested that quorum signals and QS-inhibitory drugs play direct and opposite roles in this process. Consequently, the faster and highly efficient clearance of QS-deficient...

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.

[Susceptibility to azithromycin and other antibiotics in recent isolates of Salmonella, Shigella and Yersinia].

Science.gov (United States)

Martín-Pozo, Angeles; Arana, David M; Fuentes, Miriam; Alós, Juan-Ignacio

2014-01-01

Azithromycin represents an alternative option to treat bacterial diarrhea when the antibiotic therapy is indicated. Little is known regarding the susceptibility to azithromycin in enteropathogens in Spain. The MICs of azithromycin were determined by E-test against Salmonella non-typhi (SNT), Shigella and Yersinia isolates collected over the last three years (2010-2012). In addition, the susceptibility to other antibiotics usually used to treat gastrointestinal diseases was determined in these isolates by using a microdilution method. A total of 139 strains of SNT, Shigella and Yersinia were studied. All of them, except one strain, had a MIC≤16mg/L of azithromycin. In the adult population, 14.7% and 40.6% of SNT and Shigella isolates, respectively, were resistant to at least 2 of following antibiotics: amoxicillin, trimethoprim-sulfamethoxazole and ciprofloxacin. In the pediatric population, 10% of SNT clinical isolates and 28.6% (2/7) of Shigella isolates were resistant to amoxicillin and trimethoprim-sulfamethoxazole. In our experience, azithromycin would be a useful antibiotic alternative to treat bacterial diarrhea. Copyright © 2013 Elsevier España, S.L. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

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.

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

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: ...

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.

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.

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...

Quorum quenching properties of Actinobacteria isolated from Malaysian tropical soils.

Science.gov (United States)

Devaraj, Kavimalar; Tan, Geok Yuan Annie; Chan, Kok-Gan

2017-08-01

In this study, a total of 147 soil actinobacterial strains were screened for their ability to inhibit response of Chromobacterium violaceum CV026 to short chain N-acyl homoserine lactone (AHL) which is a quorum sensing molecule. Of these, three actinobacterial strains showed positive for violacein inhibition. We further tested these strains for the inhibition of Pseudomonas aeruginosa PAO1 quorum sensing-regulated phenotypes, namely, swarming and pyocyanin production. The three strains were found to inhibit at least one of the quorum sensing-regulated phenotypes of PAO1. Phylogenetic analysis of the 16S rRNA gene sequences indicated that these strains belong to the genera Micromonospora, Rhodococcus and Streptomyces. This is the first report presenting quorum quenching activity by a species of the genus Micromonospora. Our data suggest that Actinobacteria may be a rich source of active compounds that can act against bacterial quorum sensing system.

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.

Case report: failure under azithromycin treatment in a case of bacteremia due to Salmonella enterica Paratyphi A.

Science.gov (United States)

Kobayashi, Tetsuro; Hayakawa, Kayoko; Mawatari, Momoko; Mezaki, Kazuhisa; Takeshita, Nozomi; Kutsuna, Satoshi; Fujiya, Yoshihiro; Kanagawa, Shuzo; Ohmagari, Norio; Kato, Yasuyuki; Morita, Masatomo

2014-07-20

Limited information is available regarding the clinical efficacy of azithromycin for the treatment of enteric fever due to fluoroquinolone-resistant Salmonella Typhi and Salmonella Paratyphi among travelers returning to their home countries. We report a case of a 52-year-old Japanese man who returned from India, who developed a fever of 39°C with no accompanying symptoms 10 days after returning to Japan from a 1-month business trip to Delhi, India. His blood culture results were positive for Salmonella Paratyphi A. He was treated with 14 days of ceftriaxone, after which he remained afebrile for 18 days before his body temperature again rose to 39°C with no apparent symptoms. He was then empirically given 500 mg of azithromycin, but experienced clinical and microbiological failure of azithromycin treatment for enteric fever due to Salmonella Paratyphi A. However, the minimum inhibitory concentration (MIC) of azithromycin was not elevated (8 mg/L). He was again given ceftriaxone for 14 days with no signs of recurrence during the follow-up. There are limited data available for the treatment of enteric fever using azithromycin in travelers from developed countries who are not immune to the disease, and thus, careful follow-up is necessary. In our case, the low azithromycin dose might have contributed the treatment failure. Additional clinical data are needed to determine the rate of success, MIC, and contributing factors for success and/or failure of azithromycin treatment for both Salmonella Typhi and Salmonella Paratyphi infections.

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

Quorum Systems

DEFF Research Database (Denmark)

Wattenhofer, Roger; Förster, Klaus-Tycho

2016-01-01

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

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.

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...

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

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.

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.

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...

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

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.

Azithromycin-chloroquine and the intermittent preventive treatment of malaria in pregnancy

Directory of Open Access Journals (Sweden)

Greenwood Brian

2008-12-01

Full Text Available Abstract In the high malaria-transmission settings of sub-Saharan Africa, malaria in pregnancy is an important cause of maternal, perinatal and neonatal morbidity. Intermittent preventive treatment of malaria in pregnancy (IPTp with sulphadoxine-pyrimethamine (SP reduces the incidence of low birth-weight, pre-term delivery, intrauterine growth-retardation and maternal anaemia. However, the public health benefits of IPTp are declining due to SP resistance. The combination of azithromycin and chloroquine is a potential alternative to SP for IPTp. This review summarizes key in vitro and in vivo evidence of azithromycin and chloroquine activity against Plasmodium falciparum and Plasmodium vivax, as well as the anticipated secondary benefits that may result from their combined use in IPTp, including the cure and prevention of many sexually transmitted diseases. Drug costs and the necessity for external financing are discussed along with a range of issues related to drug resistance and surveillance. Several scientific and programmatic questions of interest to policymakers and programme managers are also presented that would need to be addressed before azithromycin-chloroquine could be adopted for use in IPTp.

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 ...

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...

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...

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

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

Directory of Open Access Journals (Sweden)

Kok-Gan Chan

2013-05-01

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

Quorum sensing negatively regulates chitinase in Vibrio harveyi.

Science.gov (United States)

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

2010-02-01

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

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

DEFF Research Database (Denmark)

Jakobsen, Tim Holm; Bragason, Steinn Kristinn; Phipps, Richard Kerry

2012-01-01

of traditional antibiotics to treat infections caused by bacterial biofilms and multidrug-resistant bacteria. Several QSIs of natural origin have been identified, and in this study, several common food products and plants were extracted and screened for QSI activity in an attempt to isolate and characterize...... to transcend problems with selective pressures for antibiotic resistance, is to interrupt bacterial communication, also known as quorum sensing (QS), by means of signal antagonists, the so-called QS inhibitors (QSIs). Furthermore, QSI agents offer a potential solution to the deficiencies associated with use......-diode array detector-mass spectrometry (LC-DAD-MS) and nuclear magnetic resonance (NMR) spectroscopy as iberin—an isothiocyanate produced by many members of the Brassicaceae family. Real-time PCR (RT-PCR) and DNA microarray studies showed that iberin specifically blocks expression of QS-regulated genes in P...

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.

The Effects of Chinese Herbal Medicines on the Quorum Sensing-Regulated Virulence in Pseudomonas aeruginosa PAO1

OpenAIRE

Yee Meng Chong; Kah Yan How; Wai Fong Yin; Kok Gan Chan

2018-01-01

The quorum sensing (QS) system has been used by many opportunistic pathogenic bacteria to coordinate their virulence determinants in relation to cell-population density. As antibiotic-resistant bacteria are on the rise, interference with QS has been regarded as a novel way to control bacterial infections. As such, many plant-based natural products have been widely explored for their therapeutic roles. These natural products may contain anti-QS compounds that could block QS signals generation ...

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

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...... 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...... initiation of treatment, showing a reduction in episode duration of 83% if treatment was initiated before day 6 of the episode compared with 36% if initiated on or after day 6 (pevents between the azithromycin (18 [23%] of 78 episodes included in final...

Topical azithromycin and oral doxycycline therapy of meibomian gland dysfunction: a comparative clinical and spectroscopic pilot study.

Science.gov (United States)

Foulks, Gary N; Borchman, Douglas; Yappert, Marta; Kakar, Shelley

2013-01-01

Meibomian gland dysfunction (MGD) is a common clinical problem that is often associated with evaporative dry eye disease. Alterations of the lipids of the meibomian glands have been identified in several studies of MGD. This prospective, observational, open-label clinical trial documents the improvement in both clinical signs and symptoms of disease as well as spectroscopic characteristics of the meibomian gland lipids after therapy with topical azithromycin ophthalmic solution and oral doxycycline treatment. Subjects with symptomatic MGD were recruited. Signs of MGD were evaluated with a slit lamp. Symptoms of MGD were measured by the response of subjects to a questionnaire. Meibum lipid-lipid interaction strength, conformation, and phase transition parameters, and meibum protein content were measured using Fourier transform infrared spectroscopy and principal component analysis. Terpenoids, short-chain CH3 moieties, lipid oxidation, wax, cholesterylesters and glycerides were measured with a proton nuclear magnetic resonance (H-NMR) spectrometer. Topical therapy with azithromycin and oral therapy with doxycycline relieved signs and symptoms and restored the lipid properties of the meibomian gland secretion toward normal. Compared with 4 weeks of azithromycin treatment reported in our previous study, oral doxycycline treatment was slightly less effective in improving foreign body sensation and the signs of plugging and secretion. In subjects with clinical evidence of MGD, changes in ordering of the lipids and phase transition temperature were brought closer to normal with azithromycin treatment than doxycycline treatment. Treatment with doxycycline but not azithromycin restored the Fourier transform infrared spectroscopy-principal component analysis scores and relative area of the H-NMR resonance at 1.26 ppm. Both doxycycline and azithromycin treatment restored the levels of the relative areas of the H-NMR resonance at 5.2 and 7.9 ppm to normal levels. The levels

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

DEFF Research Database (Denmark)

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

2015-01-01

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

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

Science.gov (United States)

Belda, Walter; Di Chiacchio, Nilton G; Di Chiacchio, Nilton; Romiti, Ricardo; Criado, Paulo R; Velho, Paulo Eduardo N Ferreira

2009-06-01

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.

Azithromycin-induced rash in a patient of infectious mononucleosis - a case report with review of literature.

Science.gov (United States)

Banerjee, Indranil; Mondal, Somnath; Sen, Sukanta; Tripathi, Santanu Kumar; Banerjee, Gautam

2014-08-01

Antibiotic induced skin rash in setting of infectious mononucleosis is often encountered in clinical practice. However, macrolides like azithromycin are considered relatively safe and till date only two cases of azithromycin induced rash in setting of infectious mononucleosis have been reported. The following report illustrates the case of a 23-year-old man suffering from infectious mononucleosis who exhibited a generalized cutaneous rash following treatment with azithromycin. Using the Naranjo ADR probability scale, this case of acute onset rash following azithromycin administration was found to be in 'probable' category. The mechanism of antibiotic-induced rash in patients suffering from infectious mononucleosis is incompletely understood. It has been suggested that the rash could result from virus mediated immunomodulation or due to altered drug metabolism. The report calls for cautious use of antibiotics in the setting of suspected viral infections like infectious mononucleosis as injudicious use might increase the risk of deleterious skin reactions and increase the cost of healthcare.

Fremmedlegemeinfektioner--nyt om biofilm og quorum sensing

DEFF Research Database (Denmark)

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

2007-01-01

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

Searching the ASRS Database Using QUORUM Keyword Search, Phrase Search, Phrase Generation, and Phrase Discovery

Science.gov (United States)

McGreevy, Michael W.; Connors, Mary M. (Technical Monitor)

2001-01-01

To support Search Requests and Quick Responses at the Aviation Safety Reporting System (ASRS), four new QUORUM methods have been developed: keyword search, phrase search, phrase generation, and phrase discovery. These methods build upon the core QUORUM methods of text analysis, modeling, and relevance-ranking. QUORUM keyword search retrieves ASRS incident narratives that contain one or more user-specified keywords in typical or selected contexts, and ranks the narratives on their relevance to the keywords in context. QUORUM phrase search retrieves narratives that contain one or more user-specified phrases, and ranks the narratives on their relevance to the phrases. QUORUM phrase generation produces a list of phrases from the ASRS database that contain a user-specified word or phrase. QUORUM phrase discovery finds phrases that are related to topics of interest. Phrase generation and phrase discovery are particularly useful for finding query phrases for input to QUORUM phrase search. The presentation of the new QUORUM methods includes: a brief review of the underlying core QUORUM methods; an overview of the new methods; numerous, concrete examples of ASRS database searches using the new methods; discussion of related methods; and, in the appendices, detailed descriptions of the new methods.

Natamycin and Azithromycin are Synergistic in vitro against Ocular Pathogenic Aspergillus flavus species complex and Fusarium solani species complex Isolates.

Science.gov (United States)

Guo, Haoyi; Zhou, Lutan; He, Yi; Gao, Chuanwen; Han, Lei; Xu, Yan

2018-05-07

The interaction of natamycin-azithromycin combination against 60 ocular fungal isolates was tested in vitro The combination produced 100% synergistic interactions when natamycin added azithromycin at 20, 40, 50 μg/ml against Aspergillus flavus species complex (AFSC) isolates and added azithromycin at 50 μg/ml against Fusarium solani species complex isolates. The combination with 50 μg/ml azithromycin enhanced natamycin's effect against AFSC isolates by reducing natamycin MICs from MIC 90 64μg/ml to MIC 90 0.031μg/ml. No antagonism was observed. Copyright © 2018 American Society for Microbiology.

Nonsurgical therapy of chronic periodontitis with adjunctive systemic azithromycin or amoxicillin/metronidazole.

Science.gov (United States)

Jentsch, Holger F R; Buchmann, Andreas; Friedrich, Abel; Eick, Sigrun

2016-09-01

The objective of the present study is to compare the effect of systemic adjunctive use of azithromycin with amoxicillin/metronidazole to scaling and root planing (SRP) in a clinical study. Data from 60 individuals with chronic periodontitis were evaluated after full-mouth SRP. Antibiotics were given from the first day of SRP, in the test group (n = 29), azithromycin for 3 days and, in the control group (n = 31), amoxicillin/metronidazole for7 days. Probing depth (PD), attachment level (AL), and bleeding on probing (BOP) were recorded at baseline and after 3 and 12 months. Gingival crevicular fluid was analyzed for matrix metalloprotease (MMP)-8 and interleukin (IL)-1beta levels. Subgingival plaque was taken for assessment of the major bacteria associated with periodontitis. In both groups, PD, AL, and BOP were significantly reduced (p chronic periodontitis; however, a randomized placebo-controlled multicenter study is needed. Application of azithromycin as a single antibiotic for 3 days might be considered as an additional adjunctive antibiotic to SRP in selected patients.

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

OpenAIRE

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

2013-01-01

Quorum sensing is a system of stimuli and responses in relation to bacterial cell population density that regulates gene expression, including virulence determinants. Consequently, quorum sensing has been an attractive target for the development of novel anti-infective measures that do not rely on the use of antibiotics. Anti-quorum sensing has been a promising strategy to combat bacterial infections as it is unlikely to develop multidrug resistant pathogens since it does not impose any selec...

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.

Fremmedlegemeinfektioner--nyt om biofilm og quorum sensing

DEFF Research Database (Denmark)

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

2007-01-01

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

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

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

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.

Quorum sensing: an under-explored phenomenon in the phylum Actinobacteria

Directory of Open Access Journals (Sweden)

Ashish Vasant Polkade

2016-02-01

Full Text Available 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.

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.

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. Targ...

Quorum sensing regulates the osmotic stress response in Vibrio harveyi.

Science.gov (United States)

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

2015-01-01

Bacteria use a chemical communication process called quorum sensing to monitor cell density and to alter behavior in response to fluctuations in population numbers. Previous studies with Vibrio harveyi have shown that LuxR, the master quorum-sensing regulator, activates and represses >600 genes. These include six genes that encode homologs of the Escherichia coli Bet and ProU systems for synthesis and transport, respectively, of glycine betaine, an osmoprotectant used during osmotic stress. Here we show that LuxR activates expression of the glycine betaine operon betIBA-proXWV, which enhances growth recovery under osmotic stress conditions. BetI, an autorepressor of the V. harveyi betIBA-proXWV operon, activates the expression of genes encoding regulatory small RNAs that control quorum-sensing transitions. Connecting quorum-sensing and glycine betaine pathways presumably enables V. harveyi to tune its execution of collective behaviors to its tolerance to stress. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Azithromycin-Induced Rash in a Patient of Infectious Mononucleosis – A Case Report with Review of Literature

Science.gov (United States)

Mondal, Somnath; Sen, Sukanta; Tripathi, Santanu Kumar; Banerjee, Gautam

2014-01-01

Antibiotic induced skin rash in setting of infectious mononucleosis is often encountered in clinical practice. However, macrolides like azithromycin are considered relatively safe and till date only two cases of azithromycin induced rash in setting of infectious mononucleosis have been reported. The following report illustrates the case of a 23-year-old man suffering from infectious mononucleosis who exhibited a generalized cutaneous rash following treatment with azithromycin. Using the Naranjo ADR probability scale, this case of acute onset rash following azithromycin administration was found to be in ‘probable’ category. The mechanism of antibiotic-induced rash in patients suffering from infectious mononucleosis is incompletely understood. It has been suggested that the rash could result from virus mediated immunomodulation or due to altered drug metabolism. The report calls for cautious use of antibiotics in the setting of suspected viral infections like infectious mononucleosis as injudicious use might increase the risk of deleterious skin reactions and increase the cost of healthcare. PMID:25302218

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.

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 resis...... 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....

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.

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.

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

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

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Lenka A Vodstrcil

Full Text Available 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.

Azithromycin and erythromycin ameliorate the extent of colonic damage induced by acetic acid in rats

International Nuclear Information System (INIS)

Mahgoub, Afaf; El-Medany, Azza; Mustafa, Ali; Arafah, Maha; Moursi, Mahmoud

2005-01-01

Ulcerative colitis is a common inflammatory bowel disease (IBD) of unknown etiology. Recent studies have revealed the role of some microorganisms in the initiation and perpetuation of IBD. The role of antibiotics in the possible modulation of colon inflammation is still uncertain. In this study, we evaluated the effects of two macrolides, namely azithromycin and erythromycin, at different doses on the extent and severity of ulcerative colitis caused by intracolonic administration of 3% acetic acid in rats. The lesions and the inflammatory response were assessed by histology and measurement of myeloperoxidase (MPO) activity, nitric oxide synthetase (NOS) and tumor necrosis factor alpha (TNFα) in colonic tissues. Inflammation following acetic acid instillation was characterized by oedema, diffuse inflammatory cell infiltration and necrosis. Increase in MPO, NOS and TNFα was detected in the colonic tissues. Administration of either azithromycin or erythromycin at different dosage (10, 20 and 40 mg/kg orally, daily for 5 consecutive days) significantly (P < 0.05) reduced the colonic damage, MPO and NOS activities as well as TNFα level. This reduction was highly significant with azithromycin when given at a dose of 40 mg/kg. It is concluded that azithromycin and erythromycin may have a beneficial therapeutic role in ulcerative colitis

Pseudomonas aeruginosa with lasI quorum-sensing deficiency during corneal infection

DEFF Research Database (Denmark)

Zhu, H.; Bandara, R.; Conibear, T.C.

2004-01-01

To understand the importance of Pseudomonas aeruginosa quorum-sensing systems in the development of corneal infection, the genotypic characteristics and pathogenesis of seven ocular isolates with low-protease and acyl homoserine lactone (AHL) activity and quorum-sensing mutants of PAO1 deficient...

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.

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

KAUST Repository

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

2016-01-01

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

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.

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.

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...

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 ...

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.

Safety and efficacy of topical azithromycin ophthalmic solution 1.0% in the treatment of contact lens-related dry eye.

Science.gov (United States)

Nichols, Jason J; Bickle, Katherine M; Zink, Richard C; Schiewe, Michael D; Haque, Reza M; Nichols, Kelly K

2012-03-01

The purpose of this pilot study was to evaluate the safety and efficacy of azithromycin ophthalmic solution 1% in patients with contact lens-related dry eye (CLDE). This was a 4-week, single-center, open-label clinical trial in patients diagnosed with CLDE using the Contact Lens Dry Eye Questionnaire (CLDEQ). Fifty patients were enrolled in this study. The patients were randomized to 1 of 2 treatment groups: azithromycin ophthalmic solution administered bid on days 1 and 2 and on days 3 to 29±1 or Visine for Contacts rewetting drops administered qid on days 1 to 29±1. The patient diaries were used daily to collect data on comfortable and total contact lens wear time and ocular dryness throughout the treatment period. Tear osmolarity, fluorescein corneal staining, and visual acuity were also assessed during clinic visits. Fifty patients were enrolled, and 44 completed the study. One patient discontinued in the azithromycin group, and five patients discontinued in the rewetting drops group because of adverse events. A statistically significant increase in mean comfortable contact lens wear time from baseline was observed for the subjects treated with azithromycin ophthalmic solution as compared with the subjects treated with rewetting drops at week 4 (P=0.004; primary endpoint), in addition to weeks 2 and 3. The improvement in the mean comfortable wear time for the patients in the azithromycin treatment group exceeded 2 hrs throughout the treatment period (weeks 1-4). No significant differences were observed between the groups for total wear time, low contrast visual acuity, or tear osmolarity. Subject-rated ocular dryness (PM time assessments) was significantly improved from baseline in the subjects treated with azithromycin ophthalmic solution as compared with those treated with rewetting drops at weeks 2 and 3 endpoints (P=0.015 for each week). Additionally, a statistical difference was observed in favor of the azithromycin treatment group at week 2 for the

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

Science.gov (United States)

Ho, Jessica S.; Geske, Grant D.; Blackwell, Helen E.; Ruby, Edward G.

2014-01-01

SUMMARY Quorum sensing, a group behavior coordinated by a diffusible pheromone signal and a cognate receptor, is typical of bacteria that form symbioses with plants and animals. LuxIR-type acyl homoserine-lactone (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 signaling 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 analogs can be used to non-invasively and specifically modulate induction of symbiotic bioluminescence via LuxI-dependent quorum sensing. Our data suggest that the first day of colonization, during which symbiont bioluminescence is induced by LuxIR, is a critical period that determines the stability of the V. fischeri population once symbiosis is established. PMID:24191970

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.

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.

The activity of azithromycin against Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis in the golden hamster model

OpenAIRE

Sinagra,Ángel; Luna,Concepción; Abraham,David; Iannella,Maria del Carmen; Riarte,Adelina; Krolewiecki,Alejandro J.

2007-01-01

New therapeutic alternatives against leishmaniasis remain a priority. The activity of azithromycin against Leishmania (Leishmania) major has been previously demonstrated. Different responses among species of Leishmania make species-specific drug screening necessary. The activity of azithromycin against Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis was evaluated in golden hamsters infected through footpad injections of metacyclic promastigotes, and compared with unt...

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

Directory of Open Access Journals (Sweden)

Giantommaso Scarascia

2016-12-01

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

Designer cells programming quorum-sensing interference with microbes.

Science.gov (United States)

Sedlmayer, Ferdinand; Hell, Dennis; Müller, Marius; Ausländer, David; Fussenegger, Martin

2018-05-08

Quorum sensing is a promising target for next-generation anti-infectives designed to address evolving bacterial drug resistance. The autoinducer-2 (AI-2) is a key quorum-sensing signal molecule which regulates bacterial group behaviors and is recognized by many Gram-negative and Gram-positive bacteria. Here we report a synthetic mammalian cell-based microbial-control device that detects microbial chemotactic formyl peptides through a formyl peptide sensor (FPS) and responds by releasing AI-2. The microbial-control device was designed by rewiring an artificial receptor-based signaling cascade to a modular biosynthetic AI-2 production platform. Mammalian cells equipped with the microbial-control gene circuit detect formyl peptides secreted from various microbes with high sensitivity and respond with robust AI-2 production, resulting in control of quorum sensing-related behavior of pathogenic Vibrio harveyi and attenuation of biofilm formation by the human pathogen Candida albicans. The ability to manipulate mixed microbial populations through fine-tuning of AI-2 levels may provide opportunities for future anti-infective strategies.

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

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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.

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

Science.gov (United States)

Defoirdt, Tom; Sorgeloos, Patrick

2012-12-01

Quorum sensing, bacterial cell-to-cell communication, has been linked to the virulence of pathogenic bacteria. Indeed, in vitro experiments have shown that many bacterial pathogens regulate the expression of virulence genes by this cell-to-cell communication process. Moreover, signal molecules have been detected in samples retrieved from infected hosts and quorum sensing disruption has been reported to result in reduced virulence in different host-pathogen systems. However, data on in vivo quorum sensing activity of pathogens during infection of a host are currently lacking. We previously reported that quorum sensing regulates the virulence of Vibrio harveyi in a standardised model system with gnotobiotic brine shrimp (Artemia franciscana) larvae. Here, we monitored quorum sensing activity in Vibrio harveyi during infection of the shrimp, using bioluminescence as a read-out. We found that wild-type Vibrio harveyi shows a strong increase in quorum sensing activity early during infection. In this respect, the bacteria behave remarkably similar in different larvae, despite the fact that only half of them survive the infection. Interestingly, when expressed per bacterial cell, Vibrio harveyi showed around 200-fold higher maximal quorum sensing-regulated bioluminescence when associated with larvae than in the culture water. Finally, the in vivo quorum sensing activity of mutants defective in the production of one of the three signal molecules is consistent with their virulence, with no detectable in vivo quorum sensing activity in AI-2- and CAI-1-deficient mutants. These results indicate that AI-2 and CAI-1 are the dominant signals during infection of brine shrimp.

Handling Neighbor Discovery and Rendezvous Consistency with Weighted Quorum-Based Approach.

Science.gov (United States)

Own, Chung-Ming; Meng, Zhaopeng; Liu, Kehan

2015-09-03

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.

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.

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.

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......-spectrum compounds transcending the Gram negative-positive borderline....

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.

Tetracycline and Azithromycin Resistance Investigation on Shigella spp. Isolated from the Stool of Children with Diarrhea in Tehran, Iran

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Shadi Shahsavan

2016-10-01

Full Text Available Background & objectives: Shigella spp. are gram negative bacteria that can cause shigellosis in human. It is important in young children as well as elderly and immunocompromised people. Threatening complications can occur in severe cases with multidrug resistance species. It has been observed that Shigella spp. have become resistant to antibiotics like other bacteria. Investigation of resistance to azithromycin, tetracycline and pattern of resistance are the objectives of this study. Methods: Fifty isolates of Shigella spp. which have been collected from three hospitals in Tehran were studied. Isolates identified and confirmed as Shigella spp. by biochemical, serological and molecular methods (ipaH, wbgz, rfc genes. Antimicrobial susceptibility test was performed for ampicillin, azithromycin, ciprofloxacin, doxycycline, levofloxacin, minocycline, nalidixic acid, norfloxacin, streptomycin, trimethoprim-sulfamethoxazole and tetracycline by disc agar diffusion method. Minimal inhibition concentrations were performed for azithromycin and tetracycline. Results: From a total of 50 Shigella spp. isolates, 16% of them were Shigella flexneri and 84% Shigella sonnei. The majority of isolates were multidrug resistant. The most resistance was seen to doxycycline, streptomycin, trimethoprim-sulfamethoxazole and tetracycline. Resistance to azithromycin was 6%  and all of the isolates were susceptible to norfloxacin and levofloxacin. Nine patterns of resistance were revealed to these isolates. Conclusion: High resistance to tetracycline was observed and resistance to azithromycin as an alternative treatment choice was also considerable.

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

Science.gov (United States)

Schwartz, Noah; Drucker, Nick; Campbell, Kenyth

2012-01-01

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

Preparation and evaluation of azithromycin binary solid dispersions using various polyethylene glycols for the improvement of the drug solubility and dissolution rate

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Ehsan Adeli

Full Text Available ABSTRACT Azithromycin is a water-insoluble drug, with a very low bioavailability. In order to increase the solubility and dissolution rate, and consequently increase the bioavailability of poorly-soluble drugs (such as azithromycin, various techniques can be applied. One of such techniques is "solid dispersion". This technique is frequently used to improve the dissolution rate of poorly water-soluble compounds. Owing to its low solubility and dissolution rate, azithromycin does not have a suitable bioavailability. Therefore, the main purpose of this investigation was to increase the solubility and dissolution rate of azithromycin by preparing its solid dispersion, using different Polyethylene glycols (PEG. Preparations of solid dispersions and physical mixtures of azithromycin were made using PEG 4000, 6000, 8000, 12000 and 20000 in various ratios, based on the solvent evaporation method. From the studied drug release profile, it was discovered that the dissolution rate of the physical mixture, as the well as the solid dispersions, were higher than those of the drug alone. There was no chemical incompatibility between the drug and polymer from the observed Infrared (IR spectra. Drug-polymer interactions were also investigated using Differential Scanning Calorimetry (DSC, Powder X-Ray Diffraction (PXRD and Scanning Election Microscopy (SEM. In conclusion, the dissolution rate and solubility of azithromycin were found to improve significantly, using hydrophilic carriers, especially PEG 6000.

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

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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.

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

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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.

Design, Synthesis and Biological Evaluation of Quorum Sensing Modulators

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Hansen, Mette Reimert

to intercept the communication system by synthetic non-native ligands and thereby lower the pathogenesis and antibiotic tolerance of a bacterial biofilm. To identify new ligands with quorum sensing modulating activities, three types of AHL analogs were synthesized using different synthetic strategies....... Overall, 17 compounds were identified as quorum sensing activators with EC50 values in the low micromolar range. Two build/couple/pair strategies for the synthesis of structurally diverse small molecules are presented. In the first strategy, the Petasis 3-component reaction (Petasis 3-CR) of hydrazides...

Noise and crosstalk in two quorum-sensing inputs of Vibrio fischeri

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Weiss Joel T

2011-09-01

Full Text Available Abstract Background One of the puzzles in bacterial quorum sensing is understanding how an organism integrates the information gained from multiple input signals. The marine bacterium Vibrio fischeri regulates its bioluminescence through a quorum sensing mechanism that receives input from three pheromone signals, including two acyl homoserine lactone (HSL signals. While the role of the 3-oxo-C6 homoserine lactone (3OC6HSL signal in activating the lux genes has been extensively studied and modeled, the role of the C8 homoserine lactone (C8HSL is less obvious, as it can either activate luminescence or block its activation. It remains unclear how crosstalk between C8HSL and 3OC6HSL affects the information that the bacterium obtains through quorum sensing. Results We have used microfluidic methods to measure the response of individual V.fischeri cells to combinations of C8HSL and 3OC6HSL. By measuring the fluorescence of individual V.fischeri cells containing a chromosomal gfp-reporter for the lux genes, we study how combinations of exogenous HSLs affect both the population average and the cell-to-cell variability of lux activation levels. At the level of a population average, the crosstalk between the C8HSL and 3OC6HSL inputs is well-described by a competitive inhibition model. At the level of individual cells, the heterogeneity in the lux response depends only on the average degree of activation, so that the noise in the output is not reduced by the presence of the second HSL signal. Overall we find that the mutual information between the signal inputs and the lux output is less than one bit. A nonlinear correlation between fluorescence and bioluminescence outputs from lux leads to different noise properties for these reporters. Conclusions The lux genes in V.fischeri do not appear to distinguish between the two HSL inputs, and even with two signal inputs the regulation of lux is extremely noisy. Hence the role of crosstalk from the C8HSL input

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

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

2009-01-01

the quorum regulatory RNAs 1-4 (Qrr1-4). The four Qrr sRNAs are functionally redundant. That is, expression of any one of them is sufficient for wild-type quorum-sensing behaviour. Here, we show that the combined action of two feedback loops, one involving the sRNA-activator LuxO and one involving the sRNA......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......-target HapR, promotes gene dosage compensation between the four qrr genes. Gene dosage compensation adjusts the total Qrr1-4 sRNA pool and provides the molecular mechanism underlying sRNA redundancy. The dosage compensation mechanism is exquisitely sensitive to small perturbations in Qrr levels. Precisely...

Development of Quorum-Based Anti-Virulence Therapeutics Targeting Gram-Negative Bacterial Pathogens

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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.

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

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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.

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

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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.

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

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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.

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

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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.

Cryptococcus neoformans sexual reproduction is controlled by a quorum sensing peptide.

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Tian, Xiuyun; He, Guang-Jun; Hu, Pengjie; Chen, Lei; Tao, Changyu; Cui, Ying-Lu; Shen, Lan; Ke, Weixin; Xu, Haijiao; Zhao, Youbao; Xu, Qijiang; Bai, Fengyan; Wu, Bian; Yang, Ence; Lin, Xiaorong; Wang, Linqi

2018-06-01

Bacterial quorum sensing is a well-characterized communication system that governs a large variety of collective behaviours. By comparison, quorum sensing regulation in eukaryotic microbes remains poorly understood, especially its functional role in eukaryote-specific behaviours, such as sexual reproduction. Cryptococcus neoformans is a prevalent fungal pathogen that has two defined sexual cycles (bisexual and unisexual) and is a model organism for studying sexual reproduction in fungi. Here, we show that the quorum sensing peptide Qsp1 serves as an important signalling molecule for both forms of sexual reproduction. Qsp1 orchestrates various differentiation and molecular processes, including meiosis, the hallmark of sexual reproduction. It activates bisexual mating, at least in part through the control of pheromone, a signal necessary for bisexual activation. Notably, Qsp1 also plays a major role in the intercellular regulation of unisexual initiation and coordination, in which pheromone is not strictly required. Through a multi-layered genetic screening approach, we identified the atypical zinc finger regulator Cqs2 as an important component of the Qsp1 signalling cascade during both bisexual and unisexual reproduction. The absence of Cqs2 eliminates the Qsp1-stimulated mating response. Together, these findings extend the range of behaviours governed by quorum sensing to sexual development and meiosis.

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

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Younis, Khansa Mohammed; Usup, Gires; Ahmad, Asmat

2016-03-01

Quorum-sensing regulates bacterial biofilm formation and virulence factors, thereby making it an interesting target for attenuating pathogens. In this study, we investigated anti-biofilm and anti-quorum-sensing compounds from secondary metabolites of halophiles marine streptomyces against urinary catheter biofilm forming Proteus mirabilis without effect on growth viability. A total of 40 actinomycetes were isolated from samples collected from different places in Iraq including marine sediments and soil samples. Fifteen isolates identified as streptomyces and their supernatant screened as anti-quorum-sensing by inhibiting quorum-sensing regulated prodigiosin biosynthesis of Serratia marcescens strain Smj-11 as a reporter strain. Isolate Sediment Lake Iraq (sdLi) showed potential anti-quorum-sensing activity. Out of 35 clinical isolates obtained from Urinary catheter used by patient at the Universiti Kebangsaan Malaysia Medical Center, 22 isolates were characterized and identified as Proteus mirabilis. Isolate Urinary Catheter B4 (UCB4) showed the highest biofilm formation with highest resistance to used antibiotic and was chosen for further studies. Ethyl acetate secondary metabolites extract was produced from sdLi isolate. First, we determined the Minimum Inhibitory Concentration (MIC) of sdLi crude extract against UCB4 isolate, and all further experiments used concentrations below the MIC. Tests of subinhibitory concentrations of sdLi crude extract showed good inhibition against UCB4 isolate biofilm formation on urinary catheter and cover glass using Scanning electron microscopy and light microscopy respectively. The influence of sub-MIC of sdLi crude extract was also found to attenuate the quorum sensing (QS)-dependent factors such as hemolysin activity, urease activity, pH value, and motility of UCB4 isolate. Evidence is presented that these nontoxic secondary metabolites may act as antagonists of bacterial quorum sensing by competing with quorum-sensing signals

Azithromycin in the extremely low birth weight infant for the prevention of Bronchopulmonary Dysplasia: a pilot study

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Anstead Michael I

2007-06-01

Full Text Available Abstract Background Azithromycin reduces the severity of illness in patients with inflammatory lung disease such as cystic fibrosis and diffuse panbronchiolitis. Bronchopulmonary dysplasia (BPD is a pulmonary disorder which causes significant morbidity and mortality in premature infants. BPD is pathologically characterized by inflammation, fibrosis and impaired alveolar development. The purpose of this study was to obtain pilot data on the effectiveness and safety of prophylactic azithromycin in reducing the incidence and severity of BPD in an extremely low birth weight (≤ 1000 grams population. Methods Infants ≤ 1000 g birth weight admitted to the University of Kentucky Neonatal Intensive Care Unit (level III, regional referral center from 9/1/02-6/30/03 were eligible for this pilot study. The pilot study was double-blinded, randomized, and placebo-controlled. Infants were randomized to treatment or placebo within 12 hours of beginning mechanical ventilation (IMV and within 72 hours of birth. The treatment group received azithromycin 10 mg/kg/day for 7 days followed by 5 mg/kg/day for the duration of the study. Azithromycin or placebo was continued until the infant no longer required IMV or supplemental oxygen, to a maximum of 6 weeks. Primary endpoints were incidence of BPD as defined by oxygen requirement at 36 weeks gestation, post-natal steroid use, days of IMV, and mortality. Data was analyzed by intention to treat using Chi-square and ANOVA. Results A total of 43 extremely premature infants were enrolled in this pilot study. Mean gestational age and birth weight were similar between groups. Mortality, incidence of BPD, days of IMV, and other morbidities were not significantly different between groups. Post-natal steroid use was significantly less in the treatment group [31% (6/19] vs. placebo group [62% (10/16] (p = 0.05. Duration of mechanical ventilation was significantly less in treatment survivors, with a median of 13 days (1–47

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

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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.

Rhodotorula mucilaginosa, a quorum quenching yeast exhibiting lactonase activity isolated from a tropical shoreline.

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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.

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

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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.

Clinical effect of azithromycin as an adjunct to non-surgical treatment of chronic periodontitis: a meta-analysis of randomized controlled clinical trials.

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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

Quorum sensing influences Vibrio harveyi growth rates in a manner not fully accounted for by the marker effect of bioluminescence.

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Nackerdien, Zeena E; Keynan, Alexander; Bassler, Bonnie L; Lederberg, Joshua; Thaler, David S

2008-02-27

The light-emitting Vibrios provide excellent material for studying the interaction of cellular communication with growth rate because bioluminescence is a convenient marker for quorum sensing. However, the use of bioluminescence as a marker is complicated because bioluminescence itself may affect growth rate, e.g. by diverting energy. The marker effect was explored via growth rate studies in isogenic Vibrio harveyi (Vh) strains altered in quorum sensing on the one hand, and bioluminescence on the other. By hypothesis, growth rate is energy limited: mutants deficient in quorum sensing grow faster because wild type quorum sensing unleashes bioluminescence and bioluminescence diverts energy. Findings reported here confirm a role for bioluminescence in limiting Vh growth rate, at least under the conditions tested. However, the results argue that the bioluminescence is insufficient to explain the relationship of growth rate and quorum sensing in Vh. A Vh mutant null for all genes encoding the bioluminescence pathway grew faster than wild type but not as fast as null mutants in quorum sensing. Vh quorum sensing mutants showed altered growth rates that do not always rank with their relative increase or decrease in bioluminescence. In addition, the cell-free culture fluids of a rapidly growing Vibrio parahaemolyticus (Vp) strain increased the growth rate of wild type Vh without significantly altering Vh's bioluminescence. The same cell-free culture fluid increased the bioluminescence of Vh quorum mutants. The effect of quorum sensing on Vh growth rate can be either positive or negative and includes both bioluminescence-dependent and independent components. Bioluminescence tends to slow growth rate but not enough to account for the effects of quorum sensing on growth rate.

Quorum sensing influences Vibrio harveyi growth rates in a manner not fully accounted for by the marker effect of bioluminescence.

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Zeena E Nackerdien

2008-02-01

Full Text Available The light-emitting Vibrios provide excellent material for studying the interaction of cellular communication with growth rate because bioluminescence is a convenient marker for quorum sensing. However, the use of bioluminescence as a marker is complicated because bioluminescence itself may affect growth rate, e.g. by diverting energy.The marker effect was explored via growth rate studies in isogenic Vibrio harveyi (Vh strains altered in quorum sensing on the one hand, and bioluminescence on the other. By hypothesis, growth rate is energy limited: mutants deficient in quorum sensing grow faster because wild type quorum sensing unleashes bioluminescence and bioluminescence diverts energy. Findings reported here confirm a role for bioluminescence in limiting Vh growth rate, at least under the conditions tested. However, the results argue that the bioluminescence is insufficient to explain the relationship of growth rate and quorum sensing in Vh. A Vh mutant null for all genes encoding the bioluminescence pathway grew faster than wild type but not as fast as null mutants in quorum sensing. Vh quorum sensing mutants showed altered growth rates that do not always rank with their relative increase or decrease in bioluminescence. In addition, the cell-free culture fluids of a rapidly growing Vibrio parahaemolyticus (Vp strain increased the growth rate of wild type Vh without significantly altering Vh's bioluminescence. The same cell-free culture fluid increased the bioluminescence of Vh quorum mutants.The effect of quorum sensing on Vh growth rate can be either positive or negative and includes both bioluminescence-dependent and independent components. Bioluminescence tends to slow growth rate but not enough to account for the effects of quorum sensing on growth rate.

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

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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.

Stability and thermophysical properties of azithromycin dihydrate

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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.

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%.

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...

Comparison effect of azithromycin gel 2% with clindamycin gel 1% in patients with acne

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Fatemeh Mokhtari

2016-01-01

Conclusion: Azithromycin gel has medical impact at least similar to Clindamycin Gel in treatment of mild to moderate acne vulgaris, and it may be consider as suitable drug for resistant acne to conventional topical therapy.

Macrolide resistance mechanisms in Enterobacteriaceae: Focus on azithromycin.

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Gomes, Cláudia; Martínez-Puchol, Sandra; Palma, Noemí; Horna, Gertrudis; Ruiz-Roldán, Lidia; Pons, Maria J; Ruiz, Joaquim

2017-02-01

From its introduction in 1952 onwards, the clinical use of macrolides has been steadily increasing, both in human and veterinary medicine. Although initially designed to the treatment of Gram-positive microorganisms, this antimicrobial family has also been used to treat specific Gram-negative bacteria. Some of them, as azithromycin, are considered in the armamentarium against Enterobacteriaceae infections. However, the facility that this bacterial genus has to gain or develop mechanisms of antibiotic resistance may compromise the future usefulness of these antibiotics to fight against Enterobacteriaceae infections. The present review is focused on the mechanisms of macrolide resistance, currently described in Enterobacteriaceae.

Synthesis of Cefixime and Azithromycin Nanoparticles: An Attempt to Enhance Their Antimicrobial Activity and Dissolution Rate

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Farhat Ali Khan

2016-01-01

Full Text Available In this study cefixime and azithromycin nanoparticles were prepared by antisolvent precipitation with syringe pump (APSP and evaporator precipitation nanosuspension (EPN methods. The nanoparticles were characterized by XRD, FTIR, SEM, and TGA. X-ray diffraction pattern of cefixime samples showed the amorphous form, while azithromycin samples showed crystalline form. The FTIR spectra of parental drugs and synthesized nanoparticles have no major structural changes detected. The SEM images showed that nanoparticles of both drugs have submicron sized and nanosized particles. TGA analyses showed that above 30°C the decomposition of cefixime samples starts and their weight gradually decreases up to 600°C, while, in case of azithromycin, 30°C to 250°C, very small changes occur in weight; from above 250°C decomposition of the sample took place to a greater extent. The antibacterial activities of raw drugs and prepared samples of nanoparticles were determined against Staphylococcus aureus, Shigella, E. coli, and Salmonella typhi by agar well diffusion method. Every time the nanoparticles samples showed better results than parental drugs. The dissolution rates of raw drugs and prepared nanoparticles were also determined. The results were always better for the synthesized nanoparticles than parental drug.

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

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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.

Modulation of Quorum Sensing in a Gram-Positive Pathogen by Linear Molecularly Imprinted Polymers with Anti-infective Properties.

Science.gov (United States)

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 W; Yesilkaya, Hasan

2017-12-22

We describe the development, characterization, and biological testing of a new type of linear molecularly imprinted polymer (LMIP) designed to act as an anti-infective by blocking the quorum sensing (QS) mechanism and so abrogating the virulence of the pathogen Streptococcus pneumoniae. The LMIP is prepared (polymerized) in presence of a template molecule, but unlike in traditional molecular imprinting approaches, no cross-linker is used. This results in soluble low-molecular-weight oligomers that can act as a therapeutic agent in vitro and in vivo. The LMIP was characterized by mass spectrometry to determine its monomer composition. Fragments identified were then aligned along the peptide template by computer modeling to predict the possible monomer sequence of the LMIP. These findings provide a proof of principle that LMIPs can be used to block QS, thus setting the stage for the development of LMIPs a novel drug-discovery platform and class of materials to target Gram-positive pathogens. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Humans use social information to adjust their quorum thresholds adaptively in a simulated predator detection experiment

NARCIS (Netherlands)

Kurvers, R.H.J.M.; Wolf, M.; Krause, J.

2014-01-01

Quorum sensing is used in many biological systems to increase decision accuracy. In quorum sensing, the probability that an individual adopts a behavior is a nonlinear function of the number of other individuals adopting this behavior. From an optimal decision-making perspective, individuals should

Deciphering Physiological Functions of AHL Quorum Quenching Acylases

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Putri D. Utari

2017-06-01

Full Text Available 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. Enzymatic degradation of AHLs can be beneficial in attenuating bacterial virulence, which can be exploited as a novel approach to fight infection of human pathogens, phytopathogens or aquaculture-related contaminations. Numerous acylases from both prokaryotic and eukaryotic sources have been characterized and tested for the interference of quorum sensing-regulated functions. The existence of AHL-acylases in a multitude of organisms from various ecological niches, raises the question of what the physiological roles of AHL-acylases actually are. In this review, we attempt to bring together recent studies to extend our understanding of the biological functions of these enzymes in nature.

Rational Design of an Ultrasensitive Quorum-Sensing Switch.

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Zeng, Weiqian; Du, Pei; Lou, Qiuli; Wu, Lili; Zhang, Haoqian M; Lou, Chunbo; Wang, Hongli; Ouyang, Qi

2017-08-18

One of the purposes of synthetic biology is to develop rational methods that accelerate the design of genetic circuits, saving time and effort spent on experiments and providing reliably predictable circuit performance. We applied a reverse engineering approach to design an ultrasensitive transcriptional quorum-sensing switch. We want to explore how systems biology can guide synthetic biology in the choice of specific DNA sequences and their regulatory relations to achieve a targeted function. The workflow comprises network enumeration that achieves the target function robustly, experimental restriction of the obtained candidate networks, global parameter optimization via mathematical analysis, selection and engineering of parts based on these calculations, and finally, circuit construction based on the principles of standardization and modularization. The performance of realized quorum-sensing switches was in good qualitative agreement with the computational predictions. This study provides practical principles for the rational design of genetic circuits with targeted functions.

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

Science.gov (United States)

Feng, Lihui; Rutherford, Steven T; Papenfort, Kai; Bagert, John D; van Kessel, Julia C; Tirrell, David A; Wingreen, Ned S; Bassler, Bonnie L

2015-01-15

Quorum sensing is a cell-cell communication process that bacteria use to transition between individual and social lifestyles. In vibrios, homologous small RNAs called the Qrr sRNAs function at the center of quorum-sensing pathways. The Qrr sRNAs regulate multiple mRNA targets including those encoding the quorum-sensing regulatory components luxR, luxO, luxM, and aphA. We show that a representative Qrr, Qrr3, uses four distinct mechanisms to control its particular targets: the Qrr3 sRNA represses luxR through catalytic degradation, represses luxM through coupled degradation, represses luxO through sequestration, and activates aphA by revealing the ribosome binding site while the sRNA itself is degraded. Qrr3 forms different base-pairing interactions with each mRNA target, and the particular pairing strategy determines which regulatory mechanism occurs. Combined mathematical modeling and experiments show that the specific Qrr regulatory mechanism employed governs the potency, dynamics, and competition of target mRNA regulation, which in turn, defines the overall quorum-sensing response. Copyright © 2015 Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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

2015-02-01

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

Quorum Quenching Agents: Resources for Antivirulence Therapy

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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.

Antioxidant and Anti-quorum Sensing Potential of Acer monspessulanum subsp. monspessulanum Extracts.

Science.gov (United States)

Ceylan, Ozgur; Sahin, Mehtap Donmez; Akdamar, Gultekin

2016-10-01

In this study, anti-quorum sensing, and antioxidant activities, and chemical composition of Acer monspessulanum subsp. monspessulanum extracts were evaluated. Determination of the antioxidant activity was revealed by DPPH radical scavenging activity, the total phenolic content assay, and the β -carotene/linoleic acid assay. The detection of phenolic compounds was determined using RP-HPLC. Anti-quorum sensing activity and violacein inhibition activity were determined using Chromobacterium violaceum CV026 and C. violaceum ATCC 112 472, respectively. The determination of anti-swarming activity was carried out with Pseudomonas aeruginosa PA01. In DPPH and total phenolic content assays, the water extract exhibited good antioxidant activity. In the β -carotene-linoleic acid assay, ethyl acetate and ethanol extracts exhibited good lipid peroxidation inhibition activity, demonstrating 96.95 ± 0.03 % and 95.35 ± 0.00 % at 2.5 mg/mL concentrations, respectively. The predominant phenolic compounds of the extracts were determined as rutin, naringin, catechin hydrate, quercetin, and protocatechuic acid. Ethyl acetate and ethanol extracts were found to contain a high level of violacein inhibition and anti-quorum sensing activity. The ethanol extract also showed weak anti-swarming activity. In this first study that used Acer monspessulanum subsp. monspessulanum extracts, it was revealed that the water extract has antioxidant activity and the ethanol and ethyl acetate extracts have anti-quorum sensing activity depending on the phenolic compounds that it contained. Georg Thieme Verlag KG Stuttgart · New York.

A New Class of Quorum Quenching Molecules from Staphylococcus Species Affects Communication and Growth of Gram-Negative Bacteria

Science.gov (United States)

Chu, Ya-Yun; Nega, Mulugeta; Wölfle, Martina; Plener, Laure; Grond, Stephanie; Jung, Kirsten; Götz, Friedrich

2013-01-01

The knowledge that many pathogens rely on cell-to-cell communication mechanisms known as quorum sensing, opens a new disease control strategy: quorum quenching. Here we report on one of the rare examples where Gram-positive bacteria, the ‘Staphylococcus intermedius group’ of zoonotic pathogens, excrete two compounds in millimolar concentrations that suppress the quorum sensing signaling and inhibit the growth of a broad spectrum of Gram-negative beta- and gamma-proteobacteria. These compounds were isolated from Staphylococcus delphini. They represent a new class of quorum quenchers with the chemical formula N-[2-(1H-indol-3-yl)ethyl]-urea and N-(2-phenethyl)-urea, which we named yayurea A and B, respectively. In vitro studies with the N-acyl homoserine lactone (AHL) responding receptor LuxN of V. harveyi indicated that both compounds caused opposite effects on phosphorylation to those caused by AHL. This explains the quorum quenching activity. Staphylococcal strains producing yayurea A and B clearly benefit from an increased competitiveness in a mixed community. PMID:24098134

Pharmacokinetics, microbial response, and pulmonary outcomes of multidose intravenous azithromycin in preterm infants at risk for Ureaplasma respiratory colonization.

Science.gov (United States)

Merchan, L Marcela; Hassan, Hazem E; Terrin, Michael L; Waites, Ken B; Kaufman, David A; Ambalavanan, Namasivayam; Donohue, Pamela; Dulkerian, Susan J; Schelonka, Robert; Magder, Laurence S; Shukla, Sagar; Eddington, Natalie D; Viscardi, Rose M

2015-01-01

The study objectives were to refine the population pharmacokinetics (PK) model, determine microbial clearance, and assess short-term pulmonary outcomes of multiple-dose azithromycin treatment in preterm infants at risk for Ureaplasma respiratory colonization. Fifteen subjects (7 of whom were Ureaplasma positive) received intravenous azithromycin at 20 mg/kg of body weight every 24 h for 3 doses. Azithromycin concentrations were determined in plasma samples obtained up to 168 h post-first dose by using a validated liquid chromatography-tandem mass spectrometry method. Respiratory samples were obtained predose and at three time points post-last dose for Ureaplasma culture, PCR, antibiotic susceptibility testing, and cytokine concentration determinations. Pharmacokinetic data from these 15 subjects as well as 25 additional subjects (who received either a single 10-mg/kg dose [n = 12] or a single 20-mg/kg dose [n = 13]) were analyzed by using a nonlinear mixed-effect population modeling (NONMEM) approach. Pulmonary outcomes were assessed at 36 weeks post-menstrual age and 6 months adjusted age. A 2-compartment model with all PK parameters allometrically scaled on body weight best described the azithromycin pharmacokinetics in preterm neonates. The population pharmacokinetics parameter estimates for clearance, central volume of distribution, intercompartmental clearance, and peripheral volume of distribution were 0.15 liters/h · kg(0.75), 1.88 liters · kg, 1.79 liters/h · kg(0.75), and 13 liters · kg, respectively. The estimated area under the concentration-time curve over 24 h (AUC24)/MIC90 value was ∼ 4 h. All posttreatment cultures were negative, and there were no drug-related adverse events. One Ureaplasma-positive infant died at 4 months of age, but no survivors were hospitalized for respiratory etiologies during the first 6 months (adjusted age). Thus, a 3-day course of 20 mg/kg/day intravenous azithromycin shows preliminary efficacy in eradicating

Comparative efficacy of low-dose versus standard-dose azithromycin for patients with yaws: a randomised non-inferiority trial in Ghana and Papua New Guinea

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Michael Marks, PhD

2018-04-01

Full Text Available Summary: Background: A dose of 30 mg/kg of azithromycin is recommended for treatment of yaws, a disease targeted for global eradication. Treatment with 20 mg/kg of azithromycin is recommended for the elimination of trachoma as a public health problem. In some settings, these diseases are co-endemic. We aimed to determine the efficacy of 20 mg/kg of azithromycin compared with 30 mg/kg azithromycin for the treatment of active and latent yaws. Methods: We did a non-inferiority, open-label, randomised controlled trial in children aged 6–15 years who were recruited from schools in Ghana and schools and the community in Papua New Guinea. Participants were enrolled based on the presence of a clinical lesion that was consistent with infectious primary or secondary yaws and a positive rapid diagnostic test for treponemal and non-treponemal antibodies. Participants were randomly assigned (1:1 to receive either standard-dose (30 mg/kg or low-dose (20 mg/kg azithromycin by a computer-generated random number sequence. Health-care workers assessing clinical outcomes in the field were not blinded to the patient's treatment, but investigators involved in statistical or laboratory analyses and the participants were blinded to treatment group. We followed up participants at 4 weeks and 6 months. The primary outcome was cure at 6 months, defined as lesion healing at 4 weeks in patients with active yaws and at least a four-fold decrease in rapid plasma reagin titre from baseline to 6 months in patients with active and latent yaws. Active yaws was defined as a skin lesion that was positive for Treponema pallidum ssp pertenue in PCR testing. We used a non-inferiority margin of 10%. This trial was registered with ClinicalTrials.gov, number NCT02344628. Findings: Between June 12, 2015, and July 2, 2016, 583 (65·1% of 895 children screened were enrolled; 292 patients were assigned a low dose of azithromycin and 291 patients were assigned a standard dose of

Bacterial bioluminescence onset and quenching: a dynamical model for a quorum sensing-mediated property

OpenAIRE

Side, Domenico Delle; Nassisi, Vincenzo; Pennetta, Cecilia; Alifano, Pietro; Di Salvo, Marco; Talà, Adelfia; Chechkin, Aleksei; Seno, Flavio; Trovato, Antonio

2017-01-01

We present an effective dynamical model for the onset of bacterial bioluminescence, one of the most studied quorum sensing-mediated traits. Our model is built upon simple equations that describe the growth of the bacterial colony, the production and accumulation of autoinducer signal molecules, their sensing within bacterial cells, and the ensuing quorum activation mechanism that triggers bioluminescent emission. The model is directly tested to quantitatively reproduce the experimental distri...

Identification of Quorum Sensing Signal Molecule of Lactobacillus delbrueckii subsp. bulgaricus.

Science.gov (United States)

Pang, Xiaoyang; Liu, Cuiping; Lyu, Pengcheng; Zhang, Shuwen; Liu, Lu; Lu, Jing; Ma, Changlu; Lv, Jiaping

2016-12-14

Many bacteria in nature use quorum sensing (QS) to regulate gene expression. The quorum sensing system plays critical roles in the adaptation of bacteria to the surrounding environment. Previous studies have shown that during high-density fermentation, the autolysis of lactic acid bacteria was regulated by the QS system, and the two-component system (TCS, LBUL_RS00115/LBUL_RS00110) is involved in the autolysis of Lactobacillus delbrueckii subsp. bulgaricus. However, the QS signal molecule, which regulates this pathway, has not been identified. In this study, we compared the genome of Lactobacillus bulgaricus ATCC BAA-365 with the locus of seven lactobacillus QS systems; the position of the QS signal molecule of Lactobacillus bulgaricus ATCC BAA-365 was predicted by bioinformatics tool. Its function was identified by in vitro experiments. Construction of TCS mutant by gene knockout of LBUL_RS00115 confirmed that the signal molecule regulates the density of the flora by the TCS (LBUL_RS00115/LBUL_RS00110). This study indicated that quorum quenching and inhibition based on the signal molecule might serve as an approach to reduce the rate of autolysis of LAB and increase the number of live bacteria in fermentation.

Efficacy of Doxycycline, Azithromycin, or Trovafloxacin for Treatment of Experimental Rocky Mountain Spotted Fever in Dogs

Science.gov (United States)

Breitschwerdt, E. B.; Papich, M. G.; Hegarty, B. C.; Gilger, B.; Hancock, S. I.; Davidson, M. G.

1999-01-01

Dogs were experimentally inoculated with Rickettsia rickettsii (canine origin) in order to compare the efficacies of azithromycin and trovafloxacin to that of the current antibiotic standard, doxycycline, for the treatment of Rocky Mountain spotted fever. Clinicopathologic parameters, isolation of rickettsiae in tissue culture, and PCR amplification of rickettsial DNA were used to evaluate the response to therapy or duration of illness (untreated infection control group) in the four groups. Concentrations of the three antibiotics in plasma and blood cells were measured by high-performance liquid chromatography. Doxycycline and trovafloxacin treatments resulted in more-rapid defervescence, whereas all three antibiotics caused rapid improvement in attitudinal scores, blood platelet numbers, and the albumin/total-protein ratio. Based upon detection of retinal vascular lesions by fluorescein angiography, trovafloxacin and doxycycline substantially decreased rickettsia-induced vascular injury to the eye, whereas the number of ocular lesions in the azithromycin group did not differ from that in the infection control group. As assessed by tissue culture isolation, doxycycline resulted in the earliest apparent clearance of viable circulating rickettsiae; however, rickettsial DNA could still be detected in the blood of some dogs from all four groups on day 21 postinfection, despite our inability to isolate viable rickettsiae at that point. As administered in this study, trovafloxacin was as efficacious as doxycycline but azithromycin proved less efficacious, possibly due to the short duration of administration. PMID:10103185

Anti-bacterial activity of intermittent preventive treatment of malaria in pregnancy: comparative in vitro study of sulphadoxine-pyrimethamine, mefloquine, and azithromycin

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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.

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

African Journals Online (AJOL)

Fr. Ikenga

However, the day the consolidated motions were heard, only the ..... Was reduction in quorums of election petition tribunals meant to reduce financial ..... with or breach of the Act, and where having regard to any statement taken or to be.

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.

Virulence Inhibitors from Brazilian Peppertree Block Quorum Sensing and Abate Dermonecrosis in Skin Infection Models

Science.gov (United States)

Muhs, Amelia; Lyles, James T.; Parlet, Corey P.; Nelson, Kate; Kavanaugh, Jeffery S.; Horswill, Alexander R.; Quave, Cassandra L.

2017-01-01

Widespread antibiotic resistance is on the rise and current therapies are becoming increasingly limited in both scope and efficacy. Methicillin-resistant Staphylococcus aureus (MRSA) represents a major contributor to this trend. Quorum sensing controlled virulence factors include secreted toxins responsible for extensive damage to host tissues and evasion of the immune system response; they are major contributors to morbidity and mortality. Investigation of botanical folk medicines for wounds and infections led us to study Schinus terebinthifolia (Brazilian Peppertree) as a potential source of virulence inhibitors. Here, we report the inhibitory activity of a flavone rich extract “430D-F5” against all S. aureus accessory gene regulator (agr) alleles in the absence of growth inhibition. Evidence for this activity is supported by its agr-quenching activity (IC50 2–32 μg mL−1) in transcriptional reporters, direct protein outputs (α-hemolysin and δ-toxin), and an in vivo skin challenge model. Importantly, 430D-F5 was well tolerated by human keratinocytes in cell culture and mouse skin in vivo; it also demonstrated significant reduction in dermonecrosis following skin challenge with a virulent strain of MRSA. This study provides an explanation for the anti-infective activity of peppertree remedies and yields insight into the potential utility of non-biocide virulence inhibitors in treating skin infections. PMID:28186134

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 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...

Cell-Free and In Vivo Characterization of Lux, Las, and Rpa Quorum Activation Systems in E. coli.

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Halleran, Andrew D; Murray, Richard M

2018-02-16

Synthetic biologists have turned toward quorum systems as a path for building sophisticated microbial consortia that exhibit group decision making. Currently, however, even the most complex consortium circuits rely on only one or two quorum sensing systems, greatly restricting the available design space. High-throughput characterization of available quorum sensing systems is useful for finding compatible sets of systems that are suitable for a defined circuit architecture. Recently, cell-free systems have gained popularity as a test-bed for rapid prototyping of genetic circuitry. We take advantage of the transcription-translation cell-free system to characterize three commonly used Lux-type quorum activators, Lux, Las, and Rpa. We then compare the cell-free characterization to results obtained in vivo. We find significant genetic crosstalk in both the Las and Rpa systems and substantial signal crosstalk in Lux activation. We show that cell-free characterization predicts crosstalk observed in vivo.

[Clinical effect of Saccharomyces boulardii powder combined with azithromycin sequential therapy in treatment of children with diarrhea secondary to Mycoplasma pneumoniae pneumonia].

Science.gov (United States)

Chen, Qi-Fen; Zhang, Yi-Wei

2018-02-01

To investigate the clinical effect of Saccharomyces boulardii powder combined with azithromycin sequential therapy in the treatment of children with diarrhea secondary to Mycoplasma pneumoniae pneumonia. A total of 88 children with diarrhea secondary to Mycoplasma pneumoniae pneumonia between June 2015 and March 2017 were divided into control group and study group using a random number table, with 44 children in each group. The children in the control group were given routine treatment combined with azithromycin sequential therapy, and those in the study group were given oral Saccharomyces boulardii powder in addition to the treatment in the control group until the end of azithromycin sequential therapy. After the treatment ended, the two groups were compared in terms of time to improvement of clinical symptoms, length of hospital stay, clinical outcome, defecation frequency before and after treatment, condition of intestinal dysbacteriosis, and incidence of adverse events. Compared with the control group, the study group had significantly shorter time to improvement of clinical symptoms and length of hospital stay (P0.05). In the treatment of children with diarrhea secondary to Mycoplasma pneumoniae pneumonia, Saccharomyces boulardii powder combined with azithromycin sequential therapy can improve clinical symptoms, shorten the length of hospital stay, reduce defecation frequency and the incidence of intestinal dysbacteriosis, and improve clinical outcomes, and does not increase the risk of adverse events.

Clinical evaluation of piroxicam-FDDF and azithromycin in the prevention of complications associated with impacted lower third molar extraction.

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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.

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

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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.

Polycystic Ovarian Syndrome-associated Confluent and Reticulated Papillomatosis: Report of a Patient Successfully Treated with Azithromycin.

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Fite, Laura Paul; Cohen, Philip R

2017-09-01

Polycystic ovarian syndrome is a common endocrine disorder with a variety of dermatologic manifestations among young women. Confluent and reticulated papillomatosis is a rare dermatosis of unknown etiology that is seldom reported in patients with polycystic ovarian syndrome. We describe the case of a young woman with obesity, confluent and reticulated papillomatosis, and concurrent acanthosis nigricans. Her history, physical examination, and laboratory evaluation led to the diagnosis of polycystic ovarian syndrome. The proposed etiologies and the various of treatment options for confluent and reticulated papillomatosis are discussed. In our case, the patient had a dramatic response to treatment with azithromycin. The etiology of confluent and reticulated papillomatosis remains to be established. Additionally, the mechanism behind the success of treatment with antibiotics is unclear; however, in this patient, azithromycin was a safe and effective option for the treatment of confluent and reticulated papillomatosis.

Quorum-Quenching Human Designer Cells for Closed-Loop Control of Pseudomonas aeruginosa Biofilms.

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Sedlmayer, Ferdinand; Jaeger, Tina; Jenal, Urs; Fussenegger, Martin

2017-08-09

Current antibiotics gradually lose their efficacy against chronic Pseudomonas aeruginosa infections due to development of increased resistance mediated by biofilm formation, as well as the large arsenal of microbial virulence factors that are coordinated by the cell density-dependent phenomenon of quorum sensing. Here, we address this issue by using synthetic biology principles to rationally engineer quorum-quencher cells with closed-loop control to autonomously dampen virulence and interfere with biofilm integrity. Pathogen-derived signals dynamically activate a synthetic mammalian autoinducer sensor driving downstream expression of next-generation anti-infectives. Engineered cells were able to sensitively score autoinducer levels from P. aeruginosa clinical isolates and mount a 2-fold defense consisting of an autoinducer-inactivating enzyme to silence bacterial quorum sensing and a bipartite antibiofilm effector to dissolve the biofilm matrix. The self-guided cellular device fully cleared autoinducers, potentiated bacterial antibiotic susceptibility, substantially reduced biofilms, and alleviated cytotoxicity to lung epithelial cells. We believe this strategy of dividing otherwise coordinated pathogens and breaking up their shielded stronghold represents a blueprint for cellular anti-infectives in the postantibiotic era.

Effect of Candida albicans and Candida dubliniensis planktonic/biofilm quorum sensing molecules on yeast morphogenesis

OpenAIRE

Henriques, Mariana; Martins, Margarida Isabel Barros Coelho; Azeredo, Joana; Oliveira, Rosário

2006-01-01

One of the aims of this work was to study the effect of farnesol, a quorum sensing molecule for Candida albicans, on morphologic inhibition of Candida dubliniensis. The second goal of this work was to confirm if Candida dubliniensis also excreted quorum sensing molecules, on both planktonic and biofilm forms. The results clearly demonstrate that Candida dubliniensis undergoes morphological alterations triggered by farnesol. It was also found that supernatants of Candida dubliniensis and Ca...

A 3-day regimen with azithromycin 1.5% eyedrops for the treatment of purulent bacterial conjunctivitis in children: efficacy on clinical signs and impact on the burden of illness

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Bremond-Gignac D

2015-04-01

Full Text Available Dominique Bremond-Gignac,1,2 Riadh Messaoud,3 Sihem Lazreg,4 Claude Speeg-Schatz,5 Didier Renault,6 Frédéric Chiambaretta7,8 On behalf of the Azithromycin Pediatric Study Group 1Ophthalmology Department, Centre St Victor, University Hospital of Amiens, Picardie Jules Verne University, Amiens, France; 2CNRS FR3636, Paris V University, France; 3Ophthalmology Department, Tahar Sfar University Hospital, Mahdia, Tunisia; 4Dar El Beida, Blida, Algeria; 5Ophthalmology Department, University Hospital of Strasbourg, Strasbourg, France; 6Laboratoires THÉA, Clermont-Ferrand, France; 7Ophthalmology Department, University Hospital of Clermont-Ferrand, Gabriel Montpied Hospital, Clermont-Ferrand, France; 8EA 7281 R2D2, Auvergne University, Clermont-Ferrand, France Purpose: To compare the efficacy of azithromycin 1.5% versus tobramycin 0.3% eyedrops on clinical ocular signs and symptoms of bacterial conjunctivitis in children and to assess the parents’ satisfaction regarding the dosing regimen.Patients and methods: An international, multicenter, randomized, investigator-masked, controlled clinical trial conducted in children (1 day to 18 years old with bulbar conjunctival hyperemia and purulent discharge. Azithromycin 1.5% was administered as 1 drop twice daily for 3 days, and tobramycin 0.3% as 1 drop every 2 hours for 2 days, then 4 times daily for 5 days.Results: A total of 286 patients (mean age: 3.2 years were enrolled. In children with bacteriologically positive cultures (N=203, azithromycin produced a significantly greater improvement in conjunctival discharge (P<0.01 and a trend (P=0.054 toward improvement in conjunctival hyperemia at day 7 than did tobramycin. Complete resolution of conjunctival discharge was significantly more frequent at day 3 on azithromycin than tobramycin (P=0.005. More parents found azithromycin easier to use (in terms of treatment duration, total number of instillations, instilling drops during the day, and difficulty in

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....... For a disk-shaped biofilm the geometric factor is the horizontal dimension multiplied by the height, and the square of the height of the biofilm if there is significant flow above the biofilm. A remarkably simple factorized expression for the size is obtained, which separates the all-or-none ignition caused...

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

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Afonso R.M. Almeida

2012-05-01

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

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...

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...

Allele-dependent differences in quorum-sensing dynamics result in variant expression of virulence genes in Staphylococcus aureus.

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Geisinger, Edward; Chen, John; Novick, Richard P

2012-06-01

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

Effect of Yanhuning in combined with azithromycin on the inflammatory cytokines and immunological function in children with mycoplasma pneumonia

Institute of Scientific and Technical Information of China (English)

Guo Hui; Ge Liang

2017-01-01

Objective: To explore the effect of Yanhuning in combined with azithromycin on the inflammatory cytokines and immunological function in children with mycoplasma pneumonia. Methods: A total of 130 children with mycoplasma pneumonia were included in the study and randomized into the treatment group (n=65) and the control group (n=65). The patients in the control group were given azithromycin. On the above basis, the patients in the treatment group were given Yanhuning. The patients in the two groups were continuously treated for 7 d. The levels of serum inflammatory cytokines and immunological function indicators before and after treatment in the two groups were detected and compared. Results: When compared with before treatment, the serum IL-2 level after treatment in the two groups was significantly elevated, while IL-4, IL-10, IL-13, IL-6, TNF-α, and IFN-γ levels were significantly reduced; moreover, the improvement in the treatment group was significantly superior to that in the control group. When compared with before treatment, CD3+, CD4+, and CD4+/CD8+ after treatment in the two groups were significantly elevated, and those in the treatment group were significantly higher than those in the control group, while CD8+ was significantly reduced, but the comparison between the two groups was not statistically significant. When compared with before treatment, RBC-C3bR after treatment in the two groups was significantly elevated, while RBC-ICR was significantly reduced; moreover, the improvement in the treatment group was significantly superior to that in the control group. Conclusions: Yanhuning in combined with azithromycin in the treatment of mycoplasma pneumonia in children can significantly enhance the immunological function, and reduce the inflammatory reaction, with an effect significantly superior to that by single application of azithromycin.

Azithromycin in DuraSite® for the treatment of blepharitis

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Jodi Luchs

2010-06-01

Full Text Available Jodi LuchsDepartment of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, NY, USAAbstract: Blepharitis is a common inflammatory disease of the eyelid. Posterior blepharitis affects the posterior lamella of the eyelid and involves inflammation of the meibomian glands, whereas anterior blepharitis affects the anterior lamella of the eyelid and the eyelashes; either version can be inflammatory or infectious in nature. Each of these conditions can incite or propagate the other; anterior blepharitis, if not treated, can lead to meibomian gland disease, and vice versa. Blepharitis is typically chronic, and can be associated with a variety of systemic diseases such as dermatitis, as well as ocular diseases such as dry eye, conjunctivitis, or keratitis. The standard treatment regimen historically consists of lid hygiene with warm compresses and eyelid scrubs, although these treatment modalities may have limited efficacy for many patients, especially those with more severe disease. Adjunctive treatment includes systemic and topical antibiotics, topical corticosteroids, and tear replacement therapy. Topical antibiotics are recommended to decrease the bacterial load, and topical corticosteroids may help in cases of severe inflammation. Azithromycin ophthalmic solution 1% in DuraSite® (AzaSite®; Inspire Pharmaceuticals, Durham, North Carolina, USA has been proposed as a novel treatment for posterior blepharitis, based on its well-known anti-infective profile, its antiinflammatory properties, its excellent tissue penetration, and its regulatory approval for the treatment of bacterial conjunctivitis. This review focuses on an off-label indication for topical azithromycin 1% in DuraSite for the treatment of blepharitis.Keywords: lid margin disease, meibomian gland disease

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 effic...

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...

A survey on the effects of Azithromycin in the treatment of gingival overgrowth induced by Cyclosporin in renal transplant patients

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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.

A meta-analysis comparing the safety and efficacy of azithromycin over the alternate drugs used for treatment of uncomplicated enteric fever

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N A Trivedi

2012-01-01

Full Text Available Background: Drug-resistant typhoid fever is a major clinical problem globally. Emergence of multidrug-resistant (MDR S. Typhi has complicated therapy by limiting treatment options. Objectives: A meta-analysis was planned to determine the strength of evidence supporting use of azithromycin over the alternate drugs available for treatment of uncomplicated typhoid fever. Materials and Methods: Studies were identified using electronic database such as MEDLINE and other data at the National Library of Medicine assessed using PUBMED search engine as well as Cochrane Clinical Trial Register. Randomized control trials (RCTs comparing azithromycin with chloramphenicol, fluoroquinolones and cephalosporins in culture-proven enteric fever were included. Data was extracted and methodological quality was assessed. Risk ratio (RR with 95% confidence intervals was estimated for the dichotomous outcomes and mean difference (MD with 95% confidence was estimated for continuous data. Primary outcomes studied were clinical failure (CF, microbiological failure, and relapse. Results: A total of seven RCTs involving 773 patients met with our inclusion criteria. In comparison to older fluoroquinolones, azithromycin is marginally better in reducing the chance of CF with RR 0.46 (95% CI 0.25-0.82, while in comparison to ceftriaxone, it significantly reduced the chance of relapse with RR 0.1 (95% CI 0.01- 0.76. There were no serious adverse events reported in any of the trials. Conclusion: Azithromycin can be recommended as a second-line drug in MDR typhoid fever, however, large trials involving pediatric age group patients are recommended to arrive at a definite conclusion.

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...

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)

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

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...

Reducing virulence of the human pathogen Burkholderia by altering the substrate specificity of the quorum-quenching acylase PvdQ

NARCIS (Netherlands)

Koch, Gudrun; Nadal-Jimenez, Pol; Reis, Carlos R.; Muntendam, Remco; Bokhove, Marcel; Melillo, Elena; Dijkstra, Bauke W.; Cool, Robbert H.; Quax, Wim J.

2014-01-01

The use of enzymes to interfere with quorum sensing represents an attractive strategy to fight bacterial infections. We used PvdQ, an effective quorum-quenching enzyme from Pseudomonas aeruginosa, as a template to generate an acylase able to effectively hydrolyze C8-HSL, the major communication

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....

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...... characteristics and release profiles of microspheres. In conclusion, the overall improvement of microspheres in appearance, encapsulation efficiency and controlled drug release through the RSE method could be easily fulfilled under optimal preparation conditions....

In vitro activity of solithromycin and its metabolites, CEM-214 and N-acetyl-CEM-101, against 100 clinical Ureaplasma spp. isolates compared with azithromycin.

Science.gov (United States)

Furfaro, Lucy L; Spiller, O Brad; Keelan, Jeffrey A; Payne, Matthew S

2015-09-01

There is a strong association between vaginal and/or amniotic fluid Ureaplasma spp. colonisation and risk of preterm birth. The novel fluoroketolide antibiotic solithromycin (CEM-101) is active against Ureaplasma spp. in vitro. Evidence from ex vivo and in vivo models suggests that, unlike most macrolide antibiotics, solithromycin readily crosses the placenta. Solithromycin metabolism varies according to species; in pregnant sheep, the bioactive metabolites CEM-214 and N-acetyl-CEM-101 (NAc-CEM-101) have been shown to accumulate in the amniotic cavity following maternal solithromycin administration, potentially contributing to its antimicrobial effects. To determine the antimicrobial activity of these metabolites against Ureaplasma spp., the effects of solithromycin, CEM-214, NAc-CEM-101 and the comparator azithromycin were tested on a collection of 100 clinical Ureaplasma spp. isolates from the UK and Australia using a modified 96-well broth microdilution method. MIC90 values observed for the combined cohort were: solithromycin, 0.125 mg/L; CEM-214, 0.5mg/L; NAc-CEM-101, 0.5mg/L; and azithromycin, 2mg/L. Solithromycin showed 34-fold greater activity against Ureaplasma spp. isolates than azithromycin, whilst CEM-214 and NAc-CEM-101 possessed ca. 22% and 17% of the activity of solithromycin, respectively, significantly greater than that of azithromycin. One bacterial isolate showed resistance to azithromycin (MIC=16 mg/L) but had a much lower MIC for solithromycin (MIC=0.25mg/L). In conclusion, the metabolites of solithromycin had reduced, but still potent, activity against 100 clinical Ureaplasma spp. isolates in vitro. This may be important in some instances such as pregnancy, however studies to determine levels of the metabolites in these settings are required. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

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.

Quorum Quenching in Culturable Phyllosphere Bacteria from Tobacco

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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.

Prediction by promoter logic in bacterial quorum sensing.

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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.

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...

Evolution of the Quorum network and the mobilome (plasmids and bacteriophages) in clinical strains of Acinetobacter baumannii during a decade.

Science.gov (United States)

López, M; Rueda, A; Florido, J P; Blasco, L; Fernández-García, L; Trastoy, R; Fernández-Cuenca, F; Martínez-Martínez, L; Vila, J; Pascual, A; Bou, G; Tomas, M

2018-02-06

In this study, we compared eighteen clinical strains of A. baumannii belonging to the ST-2 clone and isolated from patients in the same intensive care unit (ICU) in 2000 (9 strains referred to collectively as Ab_GEIH-2000) and 2010 (9 strains referred to collectively as Ab_GEIH-2010), during the GEIH-REIPI project (Umbrella BioProject PRJNA422585). We observed two main molecular differences between the Ab_GEIH-2010 and the Ab_GEIH-2000 collections, acquired over the course of the decade long sampling interval and involving the mobilome: i) a plasmid harbouring genes for bla OXA 24/40 ß-lactamase and abKA/abkB proteins of a toxin-antitoxin system; and ii) two temperate bacteriophages, Ab105-1ϕ (63 proteins) and Ab105-2ϕ (93 proteins), containing important viral defence proteins. Moreover, all Ab_GEIH-2010 strains contained a Quorum functional network of Quorum Sensing (QS) and Quorum Quenching (QQ) mechanisms, including a new QQ enzyme, AidA, which acts as a bacterial defence mechanism against the exogenous 3-oxo-C12-HSL. Interestingly, the infective capacity of the bacteriophages isolated in this study (Ab105-1ϕ and Ab105-2ϕ) was higher in the Ab_GEIH-2010 strains (carrying a functional Quorum network) than in the Ab_GEIH-2000 strains (carrying a deficient Quorum network), in which the bacteriophages showed little or no infectivity. This is the first study about the evolution of the Quorum network and the mobilome in clinical strains of Acinetobacter baumannii during a decade.

Piper betle leaf extract affects the quorum sensing and hence virulence of Pseudomonas aeruginosa PAO1.

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Datta, Siraj; Jana, Debanjan; Maity, Tilak Raj; Samanta, Aveek; Banerjee, Rajarshi

2016-06-01

Quorum sensing (QS) plays an important role in virulence of Pseudomonas aeruginosa, blocking of QS ability are viewed as viable antimicrobial chemotherapy and which may prove to be a safe anti-virulent drug. Bioactive components from Piper betle have been reported to possess antimicrobial ability. This study envisages on the anti-QS properties of ethanolic extract of P. betle leaf (PbLE) using P. aeruginosa PAO1 as a model organism. A marked reduction in swarming, swimming, and twitching ability of the bacteria is demonstrated in presence of PbLE. The biofilm and pyocyanin production also shows a marked reduction in presence of PbLE, though it does not affect the bacterial growth. Thus, the studies hint on the possible effect of the bioactive components of PbLE on reducing the virulent ability of the bacteria; identification of bioactive compounds should be investigated further.

Outcome of Intravenous Azithromycin Therapy in Patients with Complicated Scrub Typhus Compared with That of Doxycycline Therapy Using Propensity-Matched Analysis

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Jang, Mi-Ok; Jang, Hee-Chang; Kim, Uh Jin; Ahn, Joon Hwan; Kang, Seung-Ji; Jung, Sook-In; Shin, Hee-Young

2014-01-01

There are no well-matched, controlled studies comparing azithromycin with doxycycline for the treatment of complicated scrub typhus. A retrospective propensity score-matched case-control study was performed for patients who presented with complicated scrub typhus and were treated with doxycycline or azithromycin between 2001 and 2011. Data on comorbidities, clinical manifestations, laboratory studies, treatments, and outcomes were extracted for analysis. The clinical characteristics and outcomes of the azithromycin-treated group (n = 73) were compared to those of the doxycycline-treated group (n = 108). Of 181 patients, 73 from each group were matched by propensity scores. There were no significant differences in baseline characteristics between the matched groups. The treatment success and survival rates were not significantly different (89% [65/73 patients] versus 96% [70/73 patients] and 96% [70/73 patients] versus 96% [70/73 patients], respectively [P > 0.05]). No difference was observed in the time to defervescence or length of hospital stay between the two groups (P > 0.05). In complicated scrub typhus patients (n = 181), multivariate analysis showed that only APACHE II score was an independent risk factor for mortality (95% confidence interval, 1.11 to 1.56; P scrub typhus. PMID:24366734

Quorum sensing-controlled biofilm development in Serratia liquefaciens MG1

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

2004-01-01

aggregates and differentiated cell chains. Signal-based complementation of this mutant resulted in a biofilm with the wild-type architecture. Two quorum-sensing-regulated genes (bsmA and bsmB) involved in biofilm development were identified, and we propose that these genes are engaged in fine...

Bacterial gangs: United and strong by means of quorum sensing

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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 simi...... similar molecules in humans, are called pheromones....

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 ...

Identity and effects of quorum sensing inhibitors produced by Penicillium species

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

2005-01-01

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

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

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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.

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

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Kok-Gan Chan

2012-03-01

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

Plakofuranolactone as a Quorum Quenching Agent from the Indonesian Sponge Plakortis cf. lita

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Valeria Costantino

2017-02-01

Full Text Available There is an urgent need for novel strategies to fight drug resistance and multi-drug resistance. As an alternative to the classic antibiotic therapy, attenuation of the bacteria virulence affecting their Quorum sensing (QS system is a promising approach. Quorum sensing (QS is a genetic regulation system that allows bacteria to communicate with each other and coordinate group behaviors. A new γ-lactone that is capable of inhibiting the LasI/R QS system, plakofuranolactone (1, was discovered in the extract of the marine sponge Plakortis cf. lita, and its structure, including absolute configuration, was determined by NMR spectroscopy, MS spectrometry, and quantum-mechanical prediction of optical rotation. The quorum quenching activity of plakofuranolactone was evaluated using reporter gene assays for long- and short-chain signals (E. coli pSB1075, E. coli pSB401, and C. violeaceum CV026 and was confirmed by measuring the total protease activity (a virulence factor which is under control of the LasI/R system of the wild-type P. aeruginosa PAO1. Further research will be pursued to assess the potential of plakofuranolactone as a new antivirulence lead compound and a chemical tool to increase the knowledge in this field.

A broad range quorum sensing inhibitor working through sRNA inhibition

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

2017-01-01

For the last decade, chemical control of bacterial virulence has received considerable attention. Ajoene, a sulfur-rich molecule from garlic has been shown to reduce expression of key quorum sensing regulated virulence factors in the opportunistic pathogen Pseudomonas aeruginosa. Here we show...

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

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H A Darshanee Ruwandeepika

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

Methanol Extract from Anogeissus leiocarpus (DC Guill. et Perr. (Combretaceae Stem Bark Quenches the Quorum Sensing of Pseudomonas aeruginosa PAO1

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Vincent Ouedraogo

2016-10-01

Full Text Available Background: Due to its extensive arsenal of virulence factors and inherent resistance to antibiotics, Pseudomonas aeruginosa is a threat particularly in immunocompromised patients. Considering the central role of quorum sensing in the production of virulence factors, inhibition of bacterial communication mechanism constitute an opportunity to attenuate pathogenicity of bacteria resistant to available antibiotics. Our study aimed to assess the anti-quorum sensing activity of Anogeissus leiocarpus, traditionally used in Burkina Faso, for the treatment of infected burn wounds. Methods: Investigations were carried out on methanol extract from A. leiocarpus stem bark. The reporter strains Chromobacterium violaceum CV026 and P. aeruginosa PAO1 derivatives were used to evidence any interference with the bacterial quorum sensing and expression of related genes. P. aeruginosa PAO1 was used to measure the impact on pyocyanin production. Results: At a sub-inhibitory concentration (100 µg/mL, A. leiocarpus methanol extract quenched the quorum sensing mechanism of P. aeruginosa PAO1 by down-streaming the rhlR gene, with a subsequent reduction of pyocyanin production. Moreover, the antioxidant polyphenols evidenced are able to reduce the oxidative stress induced by pyocyanin. Conclusion: The antioxidant and anti-quorum sensing activities of A. leiocarpus stem bark could justify its traditional use in the treatment of infected burn wounds.

Azithromycin to prevent bronchopulmonary dysplasia in ureaplasma-infected preterm infants: pharmacokinetics, safety, microbial response, and clinical outcomes with a 20-milligram-per-kilogram single intravenous dose.

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Viscardi, Rose M; Othman, Ahmed A; Hassan, Hazem E; Eddington, Natalie D; Abebe, Elias; Terrin, Michael L; Kaufman, David A; Waites, Ken B

2013-05-01

Ureaplasma respiratory tract colonization is associated with bronchopulmonary dysplasia (BPD) in preterm infants. Previously, we demonstrated that a single intravenous (i.v.) dose of azithromycin (10 mg/kg of body weight) is safe but inadequate to eradicate Ureaplasma spp. in preterm infants. We performed a nonrandomized, single-arm open-label study of the pharmacokinetics (PK) and safety of intravenous 20-mg/kg single-dose azithromycin in 13 mechanically ventilated neonates with a gestational age between 24 weeks 0 days and 28 weeks 6 days. Pharmacokinetic data from 25 neonates (12 dosed with 10 mg/kg i.v. and 13 dosed with 20 mg/kg i.v.) were analyzed using a population modeling approach. Using a two-compartment model with allometric scaling of parameters on body weight (WT), the population PK parameter estimates were as follows: clearance, 0.21 liter/h × WT(kg)(0.75) [WT(kg)(0.75) indicates that clearance was allometrically scaled on body weight (in kilograms) with a fixed exponent of 0.75]; intercompartmental clearance, 2.1 liters/h × WT(kg)(0.75); central volume of distribution (V), 1.97 liters × WT (kg); and peripheral V, 17.9 liters × WT (kg). There was no evidence of departure from dose proportionality in azithromycin exposure over the tested dose range. The calculated area under the concentration-time curve over 24 h in the steady state divided by the MIC90 (AUC24/MIC90) for the single dose of azithromycin (20 mg/kg) was 7.5 h. Simulations suggest that 20 mg/kg for 3 days will maintain azithromycin concentrations of >MIC50 of 1 μg/ml for this group of Ureaplasma isolates for ≥ 96 h after the first dose. Azithromycin was well tolerated with no drug-related adverse events. One of seven (14%) Ureaplasma-positive subjects and three of six (50%) Ureaplasma-negative subjects developed physiologic BPD. Ureaplasma was eradicated in all treated Ureaplasma-positive subjects. Simulations suggest that a multiple-dose regimen may be efficacious for microbial

Synthetic furanones inhibit quorum-sensing and enhance bacterial clearance in Pseudomonas aeruginosa lung infection in mice

DEFF Research Database (Denmark)

Wu, H.; Song, Z.; Hentzer, Morten

2004-01-01

Introduction: Antibiotics are used to treat bacterial infections by killing the bacteria or inhibiting their growth, but resistance to antibiotics can develop readily. The discovery that bacterial quorum-sensing regulates bacterial virulence as well as the formation of biofilms opens up new ways...... to control certain bacterial infections. Furanone compounds capable of inhibiting bacterial quorum-sensing systems have been isolated from the marine macro alga Delisea pulchra. Objectives: Two synthetic furanones were tested for their ability to attenuate bacterial virulence in the mouse models of chronic...

Targeting quorum sensing in Pseudomonas aeruginosa biofilms

DEFF Research Database (Denmark)

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

2013-01-01

Bacterial resistance to conventional antibiotics combined with an increasing acknowledgement of the role of biofilms in chronic infections has led to a growing interest in new antimicrobial strategies that target the biofilm mode of growth. In the aggregated biofilm mode, cell-to-cell communication...... 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...

Development of Topical Treatment for Pseudomonas aeruginosa Wound Infections by Quorum-Sensing Inhibitors Mediated by Poly(amidoamine) (PAMAM) Dendrimers

Science.gov (United States)

2013-01-01

dendrimers would provide added benefits as a delivery vehicle of QSI compounds to inhibit PA biofilms, by both increasing the transport of QSI as drug...Pseudomonas aeruginosa Wound Infections by Quorum-Sensing Inhibitors Mediated by Poly(amidoamine) (PAMAM) Dendrimers PRINCIPAL INVESTIGATOR...Development of Topical Treatment for Pseudomonas aeruginosa Wound Infections by Quorum-Sensing Inhibitors Mediated by Poly(amidoamine) (PAMAM) Dendrimers

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

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Adelfia Talà

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

Proteomics of the bacterial cross-talk by quorum sensing.

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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.

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

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

2008-07-01

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

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

Science.gov (United States)

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

2012-01-01

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

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).

Improved quorum sensing capacity by culturing Vibrio harveyi in microcapsules.

Science.gov (United States)

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

2016-04-01

Microcapsule entrapped low density cells with culture (ELDCwc), different from free cell culture, conferred stronger stress resistance and improved cell viability of microorganisms. In this paper, the quorum sensing (QS) system of Vibrio harveyi was used to investigate changes when cells were cultured in microcapsules. Cells in ELDCwc group grew into cell aggregates, which facilitated cell-cell communication and led to increased bioluminescence intensity. Moreover, the luxS-AI-2 system, a well-studied QS signal pathway, was detected as both luxS gene and the AI-2 signaling molecule, and the results were analyzed with respect to QS capacity of unit cell. The V. harveyi of ELDCwc also showed higher relative gene expression and stronger quorum sensing capacity when compared with free cells. In conclusion, the confined microcapsule space can promote the cell aggregates formation, reduce cell-cell communication distance and increase local concentration of signal molecule, which are beneficial to bacterial QS. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

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

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Ismail, Anisa S; Valastyan, Julie S; Bassler, Bonnie L

2016-04-13

Host-microbial symbioses are vital to health; nonetheless, little is known about the role crosskingdom signaling plays in these relationships. In a process called quorum sensing, bacteria communicate with one another using extracellular signal molecules called autoinducers. One autoinducer, AI-2, is proposed to promote interspecies bacterial communication, including in the mammalian gut. We show that mammalian epithelia produce an AI-2 mimic activity in response to bacteria or tight-junction disruption. This AI-2 mimic is detected by the bacterial AI-2 receptor, LuxP/LsrB, and can activate quorum-sensing-controlled gene expression, including in the enteric pathogen Salmonella typhimurium. AI-2 mimic activity is induced when epithelia are directly or indirectly exposed to bacteria, suggesting that a secreted bacterial component(s) stimulates its production. Mutagenesis revealed genes required for bacteria to both detect and stimulate production of the AI-2 mimic. These findings uncover a potential role for the mammalian AI-2 mimic in fostering crosskingdom signaling and host-bacterial symbioses. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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

2015-01-01

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

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

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Sigde Mamani

2016-09-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2010-03-29

The proposed research was motivated by an interest in understanding Y. pestis virulence mechanisms and bacteria cell-cell communication. It is expected that a greater understanding of virulence mechanisms will ultimately lead to biothreat countermeasures and novel therapeutics. Y. pestis is the etiological agent of plague, the most devastating disease in human history. Y. pestis infection has a high mortality rate and a short incubation before mortality. There is no widely available and effective vaccine for Y. pestis and multi-drug resistant strains are emerging. Y. pestis is a recognized biothreat agent based on the wide distribution of the bacteria in research laboratories around the world and on the knowledge that methods exist to produce and aerosolize large amounts of bacteria. We hypothesized that cell-cell communication via signaling molecules, or quorum sensing, by Y. pestis is important for the regulation of virulence factor gene expression during host invasion, though a causative link had never been established. Quorum sensing is a mode of intercellular communication which enables orchestration of gene expression for many bacteria as a function of population density and available evidence suggests there may be a link between quorum sensing and regulation of Y. pesits virulence. Several pathogenic bacteria have been shown to regulate expression of virulence factor genes, including genes encoding type III secretion, via quorum sensing. The Y. pestis genome encodes several cell-cell signaling pathways and the interaction of at least three of these are thought to be involved in one or more modes of host invasion. Furthermore, Y. pestis gene expression array studies carried out at LLNL have established a correlation between expression of known virulence factors and genes involved in processing of the AI-2 quorum sensing signal. This was a basic research project that was intended to provide new insights into bacterial intercellular communication and how it is

Imidazolines as Non-Classical Bioisosteres of N-Acyl homoserine lactones and Quorum Sensing Inhibitors

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Mabel Montenegro-Sustaita

2012-01-01

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

Luminescence, virulence and quorum sensing signal production by pathogenic Vibrio campbellii and Vibrio harveyi isolates.

Science.gov (United States)

Defoirdt, T; Verstraete, W; Bossier, P

2008-05-01

To study the relationship between luminescence, autoinducer production and virulence of pathogenic vibrios. Luminescence, quorum sensing signal production and virulence towards brine shrimp nauplii of 13 Vibrio campbellii and Vibrio harveyi strains were studied. Although only two of the tested strains were brightly luminescent, all of them were shown to produce the three different types of quorum sensing signals known to be produced by Vibrio harveyi. Cell-free culture fluids of all strains significantly induced bioluminescence in the cholerae autoinducer 1, autoinducer 2 and harveyi autoinducer 1 reporter strains JAF375, JMH597 and JMH612, respectively. There was no relation between luminescence and signal production and virulence towards brine shrimp. There is a large difference between different strains of Vibrio campbellii and Vibrio harveyi with respect to bioluminescence. However, this is not reflected in signal production and virulence towards gnotobiotic brine shrimp. Moreover, there seems to be no relation between quorum sensing signal production and virulence towards brine shrimp. The results presented here indicate that strains that are most brightly luminescent are not necessarily the most virulent ones and that the lower virulence of some of the strains is not due to a lack of autoinducer production.

A Phase III clinical study to evaluate the efficacy of combined azithromycin and dexamethasone in the treatment of blepharoconjunctivitis

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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

Regulation of Nicotine Tolerance by Quorum Sensing and High Efficiency of Quorum Quenching Under Nicotine Stress in Pseudomonas aeruginosa PAO1

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Huiming Tang

2018-03-01

Full Text Available Quorum sensing (QS regulates the behavior of bacterial populations and promotes their adaptation and survival under stress. As QS is responsible for the virulence of vast majority of bacteria, quorum quenching (QQ, the interruption of QS, has become an attractive therapeutic strategy. However, the role of QS in stress tolerance and the efficiency of QQ under stress in bacteria are seldom explored. In this study, we demonstrated that QS-regulated catalase (CAT expression and biofilm formation help Pseudomonas aeruginosa PAO1 resist nicotine stress. CAT activity and biofilm formation in wild type (WT and ΔrhlR strains are significantly higher than those in the ΔlasR strain. Supplementation of ΔlasI strain with 3OC12-HSL showed similar CAT activity and biofilm formation as those of the WT strain. LasIR circuit rather than RhlIR circuit is vital to nicotine tolerance. Acylase I significantly decreased the production of virulence factors, namely elastase, pyocyanin, and pyoverdine under nicotine stress compared to the levels observed in the absence of nicotine stress. Thus, QQ is more efficient under stress. To our knowledge, this is the first study to report that QS contributes to nicotine tolerance in P. aeruginosa. This work facilitates a better application of QQ for the treatment of bacterial infections, especially under stress.

Regulation of Nicotine Tolerance by Quorum Sensing and High Efficiency of Quorum Quenching Under Nicotine Stress in Pseudomonas aeruginosa PAO1.

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Tang, Huiming; Zhang, Yunyun; Ma, Yifan; Tang, Mengmeng; Shen, Dongsheng; Wang, Meizhen

2018-01-01

Quorum sensing (QS) regulates the behavior of bacterial populations and promotes their adaptation and survival under stress. As QS is responsible for the virulence of vast majority of bacteria, quorum quenching (QQ), the interruption of QS, has become an attractive therapeutic strategy. However, the role of QS in stress tolerance and the efficiency of QQ under stress in bacteria are seldom explored. In this study, we demonstrated that QS-regulated catalase (CAT) expression and biofilm formation help Pseudomonas aeruginosa PAO1 resist nicotine stress. CAT activity and biofilm formation in wild type (WT) and Δ rhlR strains are significantly higher than those in the Δ lasR strain. Supplementation of Δ lasI strain with 3OC12-HSL showed similar CAT activity and biofilm formation as those of the WT strain. LasIR circuit rather than RhlIR circuit is vital to nicotine tolerance. Acylase I significantly decreased the production of virulence factors, namely elastase, pyocyanin, and pyoverdine under nicotine stress compared to the levels observed in the absence of nicotine stress. Thus, QQ is more efficient under stress. To our knowledge, this is the first study to report that QS contributes to nicotine tolerance in P. aeruginosa . This work facilitates a better application of QQ for the treatment of bacterial infections, especially under stress.

Castanea sativa (European Chestnut Leaf Extracts Rich in Ursene and Oleanene Derivatives Block Staphylococcus aureus Virulence and Pathogenesis without Detectable Resistance.

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Cassandra L Quave

Full Text Available The Mediterranean is home to a rich history of medical traditions that have developed under the influence of diverse cultures over millennia. Today, many such traditions are still alive in the folk medical practices of local people. Investigation of botanical folk medicines used in the treatment of skin and soft tissue infections led us to study Castanea sativa (European Chestnut for its potential antibacterial activity. Here, we report the quorum sensing inhibitory activity of refined and chemically characterized European Chestnut leaf extracts, rich in oleanene and ursene derivatives (pentacyclic triterpenes, against all Staphylococcus aureus accessory gene regulator (agr alleles. We present layers of evidence of agr blocking activity (IC50 1.56-25 μg mL-1, as measured in toxin outputs, reporter assays hemolytic activity, cytotoxicity studies, and an in vivo abscess model. We demonstrate the extract's lack of cytotoxicity to human keratinocytes and murine skin, as well as lack of growth inhibitory activity against S. aureus and a panel of skin commensals. Lastly, we demonstrate that serial passaging of the extract does not result in acquisition of resistance to the quorum quenching composition. In conclusion, through disruption of quorum sensing in the absence of growth inhibition, this study provides insight into the role that non-biocide inhibitors of virulence may play in future antibiotic therapies.

Antipneumococcal activities of two novel macrolides, GW 773546 and GW 708408, compared with those of erythromycin, azithromycin, clarithromycin, clindamycin, and telithromycin.

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Matic, Vlatka; Kosowska, Klaudia; Bozdogan, Bulent; Kelly, Linda M; Smith, Kathy; Ednie, Lois M; Lin, Gengrong; Credito, Kim L; Clark, Catherine L; McGhee, Pamela; Pankuch, Glenn A; Jacobs, Michael R; Appelbaum, Peter C

2004-11-01

The MICs of GW 773546, GW 708408, and telithromycin for 164 macrolide-susceptible and 161 macrolide-resistant pneumococci were low. The MICs of GW 773546, GW 708408, and telithromycin for macrolide-resistant strains were similar, irrespective of the resistance genotypes of the strains. Clindamycin was active against all macrolide-resistant strains except those with erm(B) and one strain with a 23S rRNA mutation. GW 773546, GW 708408, and telithromycin at two times their MICs were bactericidal after 24 h for 7 to 8 of 12 strains. Serial passages of 12 strains in the presence of sub-MICs yielded 54 mutants, 29 of which had changes in the L4 or L22 protein or the 23S rRNA sequence. Among the macrolide-susceptible strains, resistant mutants developed most rapidly after passage in the presence of clindamycin, GW 773546, erythromycin, azithromycin, and clarithromycin and slowest after passage in the presence of GW 708408 and telithromycin. Selection of strains for which MICs were >/=0.5 microg/ml from susceptible parents occurred only with erythromycin, azithromycin, clarithromycin, and clindamycin; 36 resistant clones from susceptible parent strains had changes in the sequences of the L4 or L22 protein or 23S rRNA. No mef(E) strains yielded resistant clones after passage in the presence of erythromycin and azithromycin. Selection with GW 773546, GW 708408, telithromycin, and clindamycin in two mef(E) strains did not raise the erythromycin, azithromycin, and clarithromycin MICs more than twofold. There were no change in the ribosomal protein (L4 or L22) or 23S rRNA sequences for 15 of 18 mutants selected for macrolide resistance; 3 mutants had changes in the L22-protein sequence. GW 773546, GW 708408, and telithromycin selected clones for which MICs were 0.03 to >2.0 microg/ml. Single-step studies showed mutation frequencies 4.3 x 10(-3) for resistant strains. The postantibiotic effects of GW 773546, GW 708408, and telithromycin were 2.4 to 9.8 h.

Susceptibility of Neisseria gonorrhoeae to azithromycin and ceftriaxone in China: A retrospective study of national surveillance data from 2013 to 2016.

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Yue-Ping Yin

2018-02-01

Full Text Available Gonorrhea remains one of the most common sexually transmitted diseases worldwide. Successful treatment has been hampered by emerging resistance to each of the antibiotics recommended as first-line therapies. We retrospectively analyzed the susceptibility of gonorrhea to azithromycin and ceftriaxone using data from the China Gonococcal Resistance Surveillance Programme (China-GRSP in order to provide evidence for updating the treatment recommendations in China.In this study, we included 3,849 isolates collected from patients with a confirmed positive Neisseria gonorrhoeae (N. gonorrhoeae culture at clinic visits during the period of 1 January 2013 through 31 December 2016 in 7 provinces. Antimicrobial susceptibility testing of gonorrhea isolates using agar dilution was conducted to determine minimum inhibitory concentration (MIC. Resistance to azithromycin (RTA was defined as MIC ≥ 1.0 mg/l, and decreased susceptibility to ceftriaxone (DSC was defined as MIC ≥ 0.125 mg/l. The prevalence of isolates with RTA was 18.6% (710/3,827; 95% CI 17.4%-19.8%. The percentage of patients with DSC fluctuated between 9.7% and 12.2% over this period. The overall prevalence of isolates with both RTA and DSC was 2.3% (87/3,827; 95% CI 1.9%-2.8% and it increased from 1.9% in 2013 to 3.3% in 2016 (chi-squared test for trend, P = 0.03. Study limitations include the retrospective study design and potential biases in the sample, which may overrepresent men with symptomatic infection, coastal residents, and people reporting as heterosexual.To our knowledge, this is the first national study on susceptibility of N. gonorrhoeae to azithromycin and ceftriaxone in China. Our findings indicate high rates of RTA and DSC from 2013 to 2016. Although dual therapy with azithromycin and ceftriaxone has been recommended by WHO and many countries to treat gonorrhea, reevaluation of this therapy is needed prior to its introduction in China.

Effect of azithromycin combined with fat-soluble vitamin on serum inflammatory cytokines and chemokines as well as lung function in children with mycoplasma pneumonia

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Ming-Guang Yang1

2017-04-01

Full Text Available Objective: To study the effect of azithromycin combined with fat-soluble vitamin on serum inflammatory cytokines and chemokines as well as lung function in children with mycoplasma pneumonia. Methods: 56 children with mycoplasma pneumonia admitted in our hospital between May 2012 and May 2016 were collected, the treatment methods and laboratory test results were retrospectively analyzed, and then they were divided into the control group (n=26 who received azithromycin treatment alone and the observation group (n=30 who received fatsoluble vitamin combined with azithromycin treatment. Before treatment and after 1 week of treatment, enzyme-linked immunosorbent assay (ELISA was used to detect the serum levels of inflammatory cytokines and chemokines; lung function monitor for children was used to detect lung function index levels. Results: Before treatment, differences in serum inflammation index and chemokine contents as well as lung function indexes were not statistically significant between two groups of patients (P>0.05. After treatment, serum inflammation indexes IL-4 and IL-13 contents of observation group were lower than those of control group while IL- 10 and IL-12 contents were higher than those of control group (P<0.05; serum chemokines MCP-4, MDC and CysLTs contents of observation group were lower than those of control group (P<0.05; lung function indexes V-T, FEV1, PEF and MMEF25%-75% levels of observation group were higher than those of control group (P<0.05. Conclusion: Fat-soluble vitamin combined with azithromycin can reduce the systemic inflammatory response and optimize the lung function in children with mycoplasma pneumoniae infection.

Luminescence, virulence and quorum sensing signal production by pathogenic Vibrio campbellii and Vibrio harveyi isolates

OpenAIRE

Defoirdt, T.; Verstraete, W.; Bossier, P.

2008-01-01

Aims: To study the relationship between luminescence, autoinducer production and virulence of pathogenic vibrios.Methods and Results: Luminescence, quorum sensing signal production and virulence towards brine shrimp nauplii of 13 Vibrio campbellii and Vibrio harveyi strains were studied. Although only two of the tested strains were brightly luminescent, all of them were shown to produce the three different types of quorum sensing signals known to be produced by Vibrio harveyi. Cell-free cultu...

A quorum-sensing-induced bacteriophage defense mechanism

DEFF Research Database (Denmark)

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

2013-01-01

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

Comparison of Neisseria gonorrhoeae MICs Obtained by Etest and Agar Dilution for Ceftriaxone, Cefpodoxime, Cefixime and Azithromycin.

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Gose, Severin; Kong, Carol J; Lee, Yer; Samuel, Michael C; Bauer, Heidi M; Dixon, Paula; Soge, Olusegun O; Lei, John; Pandori, Mark

2013-10-24

We evaluated Neisseria gonorrhoeae Etest minimum inhibitory concentrations (MICs) relative to agar dilution MICs for 664 urethral isolates for ceftriaxone (CRO) and azithromycin (AZM), 351 isolates for cefpodoxime (CPD) and 315 isolates for cefixime (CFM). Etest accurately determined CPD, CFM and AZM MICs, but resulted in higher CRO MICs. © 2013. Published by Elsevier B.V. All rights reserved.

Azithromycin, fluoroquinolone and chloramphenicol resistance of non-chlamydia conjunctival bacteria in rural community of Ethiopia

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Bayeh Abera

2014-01-01

Full Text Available Aim: To determine profiles of non-chlamydia conjunctival bacteria and their antimicrobial susceptibility from adults who underwent trachomatous trichiasis surgery in rural areas of Ethiopia. Materials and Methods: A cross-sectional study was conducted in rural districts in West Gojjam administrative zone. Conjunctival swabs were collected during surgery and transported using Stuart transport broth (Oxoid, UK. Antibiotic susceptibility of conjunctival isolates was determined using the Kirby-Bauer disc-diffusion method. Results: Non-chlamydia pathogenic bacteria were recovered from conjunctiva of 438 (31% participants before treatment. The isolated conjunctival bacteria were Staphylococcus aureus, coagulase-negative Staphylococci, Streptococcus group (A, C, F and G, Enterococci, Streptococcus pneumoniae, Moraxella spp., Escherichia coli, Citrobacter spp., Proteus spp., Klebsiella spp., Pseudomonas spp. and Enterobacter spp. Overall, resistance rates of 57.8% to azithromycin and 68.5% to chloramphenicol were found. However, 86-94.4% sensitivity was demonstrated to ciprofloxacin and norfloxacin. Moderate sensitivity rates (61.8-78.4% were observed to ceftriaxone, tetracycline and cotrimoxazole. Conclusion: Fluoroquinolones that have activity against the majority of bacterial isolates were potent at in vitro. However, unacceptably high levels of resistance to azithromycin and chloramphenicol in rural community indicated a need for further study and antimicrobial resistance surveillance.

A study on the role that quorum sensing play in antibiotic-resistant plasmid conjugative transfer in Escherichia coli.

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Zhang, Yueheng; Ma, Qingping; Su, Bingmei; Chen, Rui; Lin, Juan; Lin, Zhifen; Wang, Dali; Yu, Yang

2018-03-01

Horizontal genes transfer (HGT) plays an important role in the dissemination of antibiotic resistance genes (ARGs) in the environment. However, the mechanisms of HGT of ARGs under the influence of antibiotics in sub-MIC remain rarely explored. Moreover, given its collective nature, HGT was considered to be relative to quorum sensing (QS) system. To investigate whether QS has any impact on horizontal gene transfer of ARGs, experiments were conducted to determine the conjugative efficiency of plasmid RP4 on Escherichia coli (E.coli) under the influences of tetracyclines (TCs), quorum sensing autoinducers (AIs) and quorum sensing inhibitors (QSIs). The results indicated that the sub-MIC TCs could facilitate the conjugative transfer of RP4, a process which could be enhanced by AIs but inhibited by QSIs. This study demonstrated the roles that QS played in the dissemination of ARGs, and provided theoretical insights into the mechanism of HGT of ARGs in the environment.

RpoS induces expression of the Vibrio anguillarum quorum-sensing regulator VanT.

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Weber, Barbara; Croxatto, Antony; Chen, Chang; Milton, Debra L

2008-03-01

In vibrios, regulation of the Vibrio harveyi-like LuxR transcriptional activators occurs post-transcriptionally via small regulatory RNAs (sRNAs) that destabilize the luxR mRNA at a low cell population, eliminating expression of LuxR. Expression of the sRNAs is modulated by the vibrio quorum-sensing phosphorelay systems. However, vanT mRNA, which encodes a LuxR homologue in Vibrio anguillarum, is abundant at low and high cell density, indicating that VanT expression may be regulated via additional mechanisms. In this study, Western analyses showed that VanT was expressed throughout growth with a peak of expression during late exponential growth. VanO induced partial destabilization of vanT mRNA via activation of at least one Qrr sRNA. Interestingly, the sigma factor RpoS significantly stabilized vanT mRNA and induced VanT expression during late exponential growth. This induction was in part due to RpoS repressing expression of Hfq, an RNA chaperone. RpoS is not part of the quorum-sensing regulatory cascade since RpoS did not regulate expression or activity of VanO, and RpoS was not regulated by VanO or VanT. VanT and RpoS were needed for survival following UV irradiation and for pigment and metalloprotease production, suggesting that RpoS works with the quorum-sensing systems to modulate expression of VanT, which regulates survival and stress responses.

In Vitro Synergism between Azithromycin or Terbinafine and Topical Antimicrobial Agents against Pythium insidiosum

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Itaqui, Sabrina R.; Verdi, Camila M.; Tondolo, Juliana S. M.; da Luz, Thaisa S.; Alves, Sydney H.; Santurio, Janio M.

2016-01-01

We describe here in vitro activity for the combination of azithromycin or terbinafine and benzalkonium, cetrimide, cetylpyridinium, mupirocin, triclosan, or potassium permanganate. With the exception of potassium permanganate, the remaining antimicrobial drugs were active and had an MIC90 between 2 and 32 μg∕ml. The greatest synergism was observed for the combination of terbinafine and cetrimide (71.4%). In vivo experimental evaluations will clarify the potential of these drugs for the topical treatment of lesions caused by Pythium insidiosum. PMID:27216049

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

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

2015-05-01

Chemosynthetic Epsilonproteobacteria from deep-sea hydrothermal vents colonize substrates exposed to steep thermal and redox gradients. In many bacteria, substrate attachment, biofilm formation, expression of virulence genes and host colonization are partly controlled via a cell density-dependent mechanism involving signal molecules, known as quorum sensing. Within the Epsilonproteobacteria, quorum sensing has been investigated only in human pathogens that use the luxS/autoinducer-2 (AI-2) mechanism to control the expression of some of these functions. In this study we showed that luxS is conserved in Epsilonproteobacteria and that pathogenic and mesophilic members of this class inherited this gene from a thermophilic ancestor. Furthermore, we provide evidence that the luxS gene is expressed--and a quorum-sensing signal is produced--during growth of Sulfurovum lithotrophicum and Caminibacter mediatlanticus, two Epsilonproteobacteria from deep-sea hydrothermal vents. Finally, we detected luxS transcripts in Epsilonproteobacteria-dominated biofilm communities collected from deep-sea hydrothermal vents. Taken together, our findings indicate that the epsiloproteobacterial lineage of the LuxS enzyme originated in high-temperature geothermal environments and that, in vent Epsilonproteobacteria, luxS expression is linked to the production of AI-2 signals, which are likely produced in situ at deep-sea vents. We conclude that the luxS gene is part of the ancestral epsilonproteobacterial genome and represents an evolutionary link that connects thermophiles to human pathogens.

Comparative Activity of Pradofloxacin, Enrofloxacin, and Azithromycin against Bartonella henselae Isolates Collected from Cats and a Human ▿

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Biswas, Silpak; Maggi, Ricardo G.; Papich, Mark G.; Keil, Daniel; Breitschwerdt, Edward B.

2010-01-01

Using Bartonella henselae isolates from cats and a human, the activity of pradofloxacin was compared with those of enrofloxacin and azithromycin. By Etest and disc diffusion assay, pradofloxacin showed greater antimicrobial activity than did other antibiotics. We conclude that pradofloxacin may prove useful for the treatment of B. henselae infections. PMID:20007401

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.

Signal Integration in Quorum Sensing Enables Cross-Species Induction of Virulence in Pectobacterium wasabiae.

Science.gov (United States)

Valente, Rita S; Nadal-Jimenez, Pol; Carvalho, André F P; Vieira, Filipe J D; Xavier, Karina B

2017-05-23

Bacterial communities can sense their neighbors, regulating group behaviors in response to cell density and environmental changes. The diversity of signaling networks in a single species has been postulated to allow custom responses to different stimuli; however, little is known about how multiple signals are integrated and the implications of this integration in different ecological contexts. In the plant pathogen Pectobacterium wasabiae (formerly Erwinia carotovora ), two signaling networks-the N-acyl homoserine lactone (AHL) quorum-sensing system and the Gac/Rsm signal transduction pathway-control the expression of secreted plant cell wall-degrading enzymes, its major virulence determinants. We show that the AHL system controls the Gac/Rsm system by affecting the expression of the regulatory RNA RsmB. This regulation is mediated by ExpR2, the quorum-sensing receptor that responds to the P. wasabiae cognate AHL but also to AHLs produced by other bacterial species. As a consequence, this level of regulation allows P. wasabiae to bypass the Gac-dependent regulation of RsmB in the presence of exogenous AHLs or AHL-producing bacteria. We provide in vivo evidence that this pivotal role of RsmB in signal transduction is important for the ability of P. wasabiae to induce virulence in response to other AHL-producing bacteria in multispecies plant lesions. Our results suggest that the signaling architecture in P. wasabiae was coopted to prime the bacteria to eavesdrop on other bacteria and quickly join the efforts of other species, which are already exploiting host resources. IMPORTANCE Quorum-sensing mechanisms enable bacteria to communicate through small signal molecules and coordinate group behaviors. Often, bacteria have various quorum-sensing receptors and integrate information with other signal transduction pathways, presumably allowing them to respond to different ecological contexts. The plant pathogen Pectobacterium wasabiae has two N-acyl homoserine lactone

Novel quorum-quenching agents promote methicillin-resistant Staphylococcus aureus (MRSA) wound healing and sensitize MRSA to β-lactam antibiotics.

Science.gov (United States)

Kuo, David; Yu, Guanping; Hoch, Wyatt; Gabay, Dean; Long, Lisa; Ghannoum, Mahmoud; Nagy, Nancy; Harding, Clifford V; Viswanathan, Rajesh; Shoham, Menachem

2015-03-01

The dwindling repertoire of antibiotics to treat methicillin-resistant Staphylococcus aureus (MRSA) calls for novel treatment options. Quorum-quenching agents offer an alternative or an adjuvant to antibiotic therapy. Three biaryl hydroxyketone compounds discovered previously (F1, F12, and F19; G. Yu, D. Kuo, M. Shoham, and R. Viswanathan, ACS Comb Sci 16:85-91, 2014) were tested for efficacy in MRSA-infected animal models. Topical therapy of compounds F1 and F12 in a MRSA murine wound infection model promotes wound healing compared to the untreated control. Compounds F1, F12, and F19 afford significant survival benefits in a MRSA insect larva model. Combination therapy of these quorum-quenching agents with cephalothin or nafcillin, antibiotics to which MRSA is resistant in monotherapy, revealed additional survival benefits. The quorum-quenching agents sensitize MRSA to the antibiotic by a synergistic mode of action that also is observed in vitro. An adjuvant of 1 μg/ml F1, F12, or F19 reduces the MIC of nafcillin and cephalothin about 50-fold to values comparable to those for vancomycin, the antibiotic often prescribed for MRSA infections. These findings suggest that it is possible to resurrect obsolete antibiotic therapies in combination with these novel quorum-quenching agents. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Quorum Quenching and Microbial Control through Phenolic Extract of Eugenia Uniflora Fruits.

Science.gov (United States)

Rodrigues, Adeline Conceição; Zola, Flávia Guimarães; Ávila Oliveira, Brígida D'; Sacramento, Nayara Thais Barbosa; da Silva, Elis Regina; Bertoldi, Michele Corrêa; Taylor, Jason Guy; Pinto, Uelinton Manoel

2016-10-01

We describe the characterization of the centesimal composition, mineral and phenolic content of Eugenia uniflora fruit and the determination of the antioxidant, antimicrobial and quorum quenching activities of the pulp phenolic extract. Centesimal composition was determined according to standard methods; trace elements were measured by total reflection X-ray fluorescence spectroscopy. The phenolic compounds were extracted by solid-phase chromatography and quantified by spectrophotometry. Antioxidant activity was determined by using 3 different methods. Antimicrobial activity was evaluated against a panel of foodborne microorganisms and antiquorum sensing activity in Chromobacterium violaceum was performed by measuring inhibition of quorum sensing dependent violacein production. The centesimal composition (per 100 g of pulp) was as follows: protein 3.68 ± 0.21 g, lipids 0.02 ± 0.03 g, carbohydrates 10.31 g and fiber 2.06 g. Trace elements (mg/g of pulp) were determined as: K 0.90, Ca 3.36, Fe 0.60, Zn 0.17, Cl 0.56, Cr 0.06, Ni 0.04, and Cu 0.07. The pulp is a source of phenolic compounds and presents antioxidant activity similar to other berries. The fruit phenolic extract inhibited all tested bacteria. We also found that the fruit phenolic extract at low subinhibitory concentrations inhibited up to 96% of violacein production in C. violaceum, likely due to the fruit's phenolic content. This study shows the contribution of E. uniflora phenolic compounds to the antioxidant, antimicrobial and the newly discovered quorum quenching activity, all of which could be used by the food and pharmaceutical industries to develop new functional products. © 2016 Institute of Food Technologists®.

Interference with the quorum sensing systems in a Vibrio harveyi strain alters the growth rate of gnotobiotically cultured rotifer Brachionus plicatilis.

Science.gov (United States)

Tinh, N T N; Linh, N D; Wood, T K; Dierckens, K; Sorgeloos, P; Bossier, P

2007-07-01

To evaluate the effect of Vibrio harveyi strains on the growth rate of the gnotobiotically cultured rotifer Brachionus plicatilis, and to establish whether quorum sensing is involved in the observed phenomena. Gnotobiotic B. plicatilis sensu strictu, obtained by hatching glutaraldehyde-treated amictic eggs, were used as test organisms. Challenge tests were performed with 11 V. harveyi strains and different quorum sensing mutants derived from the V. harveyi BB120 strain. Brominated furanone [(5Z)-4-bromo-5-(bromomethylene)-3-butyl-2(5H)-furanone] as a quorum sensing inhibitor was tested in Brachionus challenge tests. Some V. harveyi strains, such as strain BB120, had a significantly negative effect on the Brachionus growth rate. In the challenge test with MM77, an isogenic strain of BB120 in which the two autoinducers (HAI-1 and AI-2) are both inactivated, no negative effect was observed. The effect of single mutants was the same as that observed in the BB120 strain. This indicates that both systems are responsible for the growth-retarding (GR) effect of the BB120 strain towards Brachionus. Moreover, the addition of an exogenous source of HAI-1 or AI-2 could restore the GR effect in the HAI-1 and AI-2 nonproducing mutant MM77. The addition of brominated furanone at a concentration of 2.5 mg l(-1) could neutralize the GR effect of some strains such as BB120 and VH-014. Two quorum sensing systems in V. harveyi strain BB120 (namely HAI-1 and AI-2-mediated) are necessary for its GR effect on B. plicatilis. With some other V. harveyi strains, however, growth inhibition towards Brachionus does not seem to be related to quorum sensing. Interference with the quorum sensing system might help to counteract the GR effect of some V. harveyi strains on Brachionus. However, further studies are needed to demonstrate the positive effect of halogenated furanone in nongnotobiotic Brachionus cultures and eventually, in other segments of the aquaculture industry.

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...

A longitudinal trial comparing chloroquine as monotherapy or in combination with artesunate, azithromycin or atovaquone-proguanil to treat malaria.

Science.gov (United States)

Laufer, Miriam K; Thesing, Phillip C; Dzinjalamala, Fraction K; Nyirenda, Osward M; Masonga, Rhoda; Laurens, Matthew B; Stokes-Riner, Abbie; Taylor, Terrie E; Plowe, Christopher V

2012-01-01

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.

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...

Effect of the synthetic cannabinoid HU-210 on quorum sensing and on the production of quorum sensing-mediated virulence factors by Vibrio harveyi

OpenAIRE

Soni, Divya; Smoum, Reem; Breuer, Aviva; Mechoulam, Raphael; Steinberg, Doron

2015-01-01

Background Bacterial populations communicate through the cell density-dependent mechanism of quorum sensing (QS). Vibrio harveyi, one of the best studied model organisms for QS, was used to explore effects of the synthetic cannabinoid HU-210 on QS and different QS-regulated physiological processes in bacteria. Results Analysis of QS-regulated bioluminescence in wild-type and mutant strains of V. harveyi revealed that HU-210 affects the autoinducer-2 (AI-2) pathway, one of three known QS casca...

Identification of AI-2 Quorum Sensing Inhibitors in Vibrio harveyi Through Structure-Based Virtual Screening.

Science.gov (United States)

Jiang, Tianyu; Zhu, Peng; Du, Lupei; Li, Minyong

2018-01-01

Quorum sensing (QS) is a cell-to-cell communication system that regulates gene expression as a result of the production and perception of signal molecules called autoinducers (AIs). AI-2 is a QS autoinducer produced by both Gram-negative and Gram-positive bacteria, in which it regulates intraspecies and interspecies communication. The identification of QS inhibitors is considered a promising strategy for the development of anti-virulence drugs with reduced selective pressure for resistance. Here we describe a high-throughput virtual screening approach to identify AI-2 quorum sensing inhibitors on the basis of Vibrio harveyi LuxPQ crystal structure. Seven potent inhibitors with IC 50 values in the micromolar range were selected with no effect or low effect on V. harveyi growth rate.

Comparison effect of azithromycin gel 2% with clindamycin gel 1% in patients with acne.

Science.gov (United States)

Mokhtari, Fatemeh; Faghihi, Gita; Basiri, Akram; Farhadi, Sadaf; Nilforoushzadeh, Mohammadali; Behfar, Shadi

2016-01-01

Acne vulgaris is the most common skin disease. Local and systemic antimicrobial drugs are used for its treatment. But increasing resistance of Propionibacterium acnes to antibiotics has been reported. In a double-blind clinical trial, 40 patients with mild to moderate acne vulgaris were recruited. one side of the face was treated with Clindamycin Gel 1% and the other side with Azithromycin Topical Gel 2% BID for 8 weeks and then they were assessed. Average age was 21. 8 ± 7 years. 82.5% of them were female. Average number of papules, pustules and comedones was similarly reduced in both groups and, no significant difference was observed between the two groups (P > 0.05, repeated measurs ANOVA). The mean indexes of ASI and TLC also significantly decreased during treatment in both groups, no significant difference was observed between the two groups. (P > 0.05, repeated measurs ANOVA). Also, impact of both drugs on papules and pustules was 2-3 times greater than the effect on comedones. Average satisfaction score was not significant between the two groups (P = 0.6, repeated measurs ANOVA). finally, frequency distribution of complications was not significant between the two groups (P > 0.05, Fisher Exact test). Azithromycin gel has medical impact at least similar to Clindamycin Gel in treatment of mild to moderate acne vulgaris, and it may be consider as suitable drug for resistant acne to conventional topical therapy.

Regular Wounding in a Natural System: Bacteria Associated With Reproductive Organs of Bedbugs and Their Quorum Sensing Abilities

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Oliver Otti

2017-12-01

Full Text Available During wounding, tissues are disrupted so that bacteria can easily enter the host and trigger a host response. Both the host response and bacterial communication can occur through quorum sensing (QS and quorum sensing inhibition (QSI. Here, we characterize the effect of wounding on the host-associated bacterial community of the bed bug. This is a model system where the male is wounding the female during every mating. Whereas several aspects of the microbial involvement during wounding have been previously examined, it is not clear to what extent QS and QSI play a role. We find that the microbiome differs depending on mating and feeding status of female bedbugs and is specific to the location of isolation. Most organs of bedbugs harbor bacteria, which are capable of both QS and QSI signaling. By focusing on the prokaryotic quorum communication system, we provide a baseline for future research in this unique system. We advocate the bedbug system as suitable for studying the effects of bacteria on reproduction and for addressing prokaryote and eukaryote communication during wounding.

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......-controlled protein spots of the surface fraction, confirming the high specificity of the compound. Importantly, 20 novel QS-regulated proteins were identified, many of which are involved in iron utilization, suggesting a link between quorum sensing and the iron regulatory system. Two of these proteins, PhuR and Has......Ap, are components of the two distinct haem-uptake systems present in P. aeruginosa. In agreement with the finding that both proteins are positively regulated by the QS cascade, we show that the lasI rhlI double mutant grows poorly with haemoglobin as the only iron source when compared with the wild type...

Quorum system and random based asynchronous rendezvous protocol for cognitive radio ad hoc networks

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Sylwia Romaszko

2013-12-01

Full Text Available This paper proposes a rendezvous protocol for cognitive radio ad hoc networks, RAC2E-gQS, which utilizes (1 the asynchronous and randomness properties of the RAC2E protocol, and (2 channel mapping protocol, based on a grid Quorum System (gQS, and taking into account channel heterogeneity and asymmetric channel views. We show that the combination of the RAC2E protocol with the grid-quorum based channel mapping can yield a powerful RAC2E-gQS rendezvous protocol for asynchronous operation in a distributed environment assuring a rapid rendezvous between the cognitive radio nodes having available both symmetric and asymmetric channel views. We also propose an enhancement of the protocol, which uses a torus QS for a slot allocation, dealing with the worst case scenario, a large number of channels with opposite ranking lists.

Marine organisms as source of extracts to disrupt bacterial communication: bioguided isolation and identification of quorum sensing inhibitors from Ircinia felix

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Jairo Quintana

Full Text Available AbstractIn this study, 39 extracts from marine organisms were evaluated as quorum sensing inhibitors, collected in the Colombian Caribbean Sea and the Brazilian Coast including 26 sponges, seven soft corals, five algae and one zooanthid. The results showed that crude extracts from the soft coral Eunicea laciniata, and the sponges Svenzea tubulosa, Ircinia felix and Neopetrosia carbonaria were the most promising source of quorum sensing inhibitors compounds without affecting bacterial growth, unlike the raw extracts of Agelas citrina, Agelas tubulata, Iotrochota arenosa, Topsentia ophiraphidites, Niphates caycedoi, Cliona tenuis, Ptilocaulis walpersi, Petrosia pellasarca, and the algae Laurencia catarinensis and Laurencia obtusa, which displayed potent antibacterial activity against the biosensors employed. The crude extract from the sponge I. felix was fractionated, obtaining furanosesterterpenes which were identified and evaluated as quorum sensing inhibitors, showing a moderate activity without affecting the biosensor's growth.

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

Science.gov (United States)

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

2011-12-01

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

Modification and Assembly of a Versatile Lactonase for Bacterial Quorum Quenching

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Melissa K. Rhoads

2018-02-01

Full Text Available This work sets out to provide a self-assembled biopolymer capsule activated with a multi-functional enzyme for localized delivery. This enzyme, SsoPox, which is a lactonase and phosphotriesterase, provides a means of interrupting bacterial communication pathways that have been shown to mediate pathogenicity. Here we demonstrate the capability to express, purify and attach SsoPox to the natural biopolymer chitosan, preserving its activity to “neutralize” long-chain autoinducer-1 (AI-1 communication molecules. Attachment is shown via non-specific binding and by engineering tyrosine and glutamine affinity ‘tags’ at the C-terminus for covalent linkage. Subsequent degradation of AI-1, in this case N-(3-oxododecanoyl-l-homoserine lactone (OdDHL, serves to “quench” bacterial quorum sensing (QS, silencing intraspecies communication. By attaching enzymes to pH-responsive chitosan that, in turn, can be assembled into various forms, we demonstrate device-based flexibility for enzyme delivery. Specifically, we have assembled quorum-quenching capsules consisting of an alginate inner core and an enzyme “decorated” chitosan shell that are shown to preclude bacterial QS crosstalk, minimizing QS mediated behaviors.

Quorum-sensing regulators control virulence gene expression in Vibrio cholerae

OpenAIRE

Zhu, Jun; Miller, Melissa B.; Vance, Russell E.; Dziejman, Michelle; Bassler, Bonnie L.; Mekalanos, John J.

2002-01-01

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

Prevalence of Active and Latent Yaws in the Solomon Islands 18 Months after Azithromycin Mass Drug Administration for Trachoma.

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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

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.

Stability study of azithromycin in ophthalmic preparations

Directory of Open Access Journals (Sweden)

Andréia de Haro Moreno

2009-06-01

Full Text Available A stability study of azithromycin in ophthalmic preparations was developed by submission to different types of light, temperature and pH, using the biodiffusion assay (cylinder 3 x 3 for the quantifications. Bacillus subtilis, ATCC 9372, was used as test organism. The used concentration range was of 50 to 200 µg/mL. The study demonstrated that the drug suffered degradation when submitted to the ultraviolet light, germicide light, solar luminosity, acid solution, basic solution and hydrogen peroxide solution. The results were analyzed by the analysis of variance (ANOVA.O estudo de estabilidade de azitromicina em preparações oftálmicas foi realizado após exposição a diferentes tipos de luz, temperatura e pH, utilizando o método de difusão em ágar (cilindros 3 x 3 para as quantificações. A faixa de concentração foi de 50 a 200 µg/mL. O estudo demonstrou que o fármaco sofreu degradação quando submetido às luzes ultravioleta, germicida e solar, e a soluções ácida, alcalina e de peróxido de hidrogênio. Os resultados foram analisados através da análise da variância (ANOVA.

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

Science.gov (United States)

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

2002-08-01

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

Effects of clarithromycin treatment in scrub typhus in children: comparison with chloramphenicol and azithromycin.

Science.gov (United States)

Lee, Min; Kim, June; Jo, Dae Sun

2017-04-01

Chloramphenicol and tetracycline are not recommended for treating scrub typhus in pediatric patients because of potential side effects, such as aplastic anemia or tooth discoloration. While clarithromycin has recently been used in adults, few reports have been published on its effects in pediatric patients. We report the clinical profiles of pediatric scrub typhus and the effects of clarithromycin on scrub typhus in children. We retrospectively analyzed medical records of 56 children with scrub typhus who were admitted between 2004 and 2013 to Chonbuk National University Hospital, Jeonju, Korea. Cases were divided into 3 groups based on thetreatment drug (chloramphenicol, azithromycin, and clarithromycin). We compared their clinical manifestations and laboratory findings. All patients exhibited fever and rash. Other common clinical manifestations were eschars (66%), lymphadenopathy (48%), upper respiratory symptoms (42%), abdominal pain (32%), and hepatosplenomegaly (14%). Elevated levels of C-reactive protein, erythrocyte sedimentation rates, aspartate transaminase, and alanine transaminase were detected in 95%, 96%, 84%, and 77% of patients, respectively. Additionally, decreased platelet and white blood cell levels were observed in 43% and 36% of patients, respectively. There were no statistical differences between the treatment groups in mean age ( P =0.114) or sex ( P =0.507). However, time to defervescence after the treatments differed significantly, being the shortest in the clarithromycin group ( P =0.019). All patients recovered without complications related to the disease or drugs. Clarithromycin was as effective as chloramphenicol and azithromycin in pediatric scrub typhus patients and may be used as a first-line treatment drug.

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

International Nuclear Information System (INIS)

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

2013-01-01

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

Beneficial effects of bacteria-plant communication based on quorum sensing molecules of the N-acyl homoserine lactone group.

Science.gov (United States)

Schikora, Adam; Schenk, Sebastian T; Hartmann, Anton

2016-04-01

Bacterial quorum sensing (QS) mechanisms play a crucial role in the proper performance and ecological fitness of bacterial populations. Many key physiological processes are regulated in a QS-dependent manner by auto-inducers, like the N-acyl homoserine lactones (AHLs) in numerous Gram-negative bacteria. In addition, also the interaction between bacteria and eukaryotic hosts can be regulated by AHLs. Those mechanisms gained much attention, because of the positive effects of different AHL molecules on plants. This positive impact ranges from growth promotion to induced resistance and is quite contrasting to the rather negative effects observed in the interactions between bacterial AHL molecules and animals. Only very recently, we began to understand the molecular mechanisms underpinning plant responses to AHL molecules. In this review, we gathered the latest information in this research field. The first part gives an overview of the bacterial aspects of quorum sensing. Later we focus on the impact of AHLs on plant growth and AHL-priming, as one of the most understood phenomena in respect to the inter-kingdom interactions based on AHL-quorum sensing molecules. Finally, we discuss the potential benefits of the understanding of bacteria-plant interaction for the future agricultural applications.

Failure of oral antibiotic therapy, including azithromycin, in the treatment of a recurrent breast abscess caused by Salmonella enterica serotype Paratyphi A.

Science.gov (United States)

Fernando, Shelanah; Molland, Janice Gail; Gottlieb, Thomas

2012-10-01

We report a case of recurrent, multifocal Salmonella enterica serotype Paratyphi A breast abscesses, resistant to ciprofloxacin, which relapsed despite surgery, aspiration and multiple courses of antibiotics, including co-trimoxazole and azithromycin. The patient was cured after a prolonged course of intravenous ceftriaxone.

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

NARCIS (Netherlands)

Tjalsma, H.; Koetje, E.J.; Kiewiet, R.; Kuipers, O.P.; Kolkman, M.J.M.; Laan, J.H. van der; Daskin, R.; Ferrari, E.; Bron, S.

2004-01-01

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

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

NARCIS (Netherlands)

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

2004-01-01

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

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

DEFF Research Database (Denmark)

Skindersø, Mette Elena; Zeuthen, Louise; Pedersen, Susanne Brix

2009-01-01

Pseudomonas aeruginosa releases a wide array of toxins and tissue-degrading enzymes. Production of these malicious virulence factors is controlled by interbacterial communication in a process known as quorum sensing. An increasing body of evidence reveals that the bacterial signal molecule N-(3-o...

Inhibition of Steptococcus mutans biofilm formation by extracts of Tenacibaculum sp. 20J, a bacterium with wide-spectrum quorum quenching activity

OpenAIRE

Muras, Andrea; Mayer, Celia; Romero, Manuel; Camino, Tamara; Ferrer, Maria D.; Mira, Alex; Otero, Ana

2018-01-01

ABSTRACT Background: Previous studies have suggested the quorum sensing signal AI-2 as a potential target to prevent the biofilm formation by Streptococcus mutans, a pathogen involved in tooth decay. Objective: To obtain inhibition of biofilm formation by S. mutans by extracts obtained from the marine bacterium Tenacibaculum sp. 20J interfering with the AI-2 quorum sensing system. Design: The AI-2 inhibitory activity was tested with the biosensors Vibrio harveyi BB170 and JMH597. S. mutans AT...

Antimicrobial susceptibilities and molecular typing of neisseria gonorrhoeae isolates at a medical centre in Taiwan, 2001-2013 with an emphasis on high rate of azithromycin resistance among the isolates.

Science.gov (United States)

Liu, Yen-Hung; Huang, Yu-Tsung; Liao, Chun-Hsing; Hsueh, Po-Ren

2018-05-01

A high prevalence of gonococcal resistance to various antimicrobials and Neisseria gonorrhoeae isolates exhibiting resistance to extended-spectrum cephalosporins have been reported in the past few decades. A total of 226 N. gonorrhoeae isolates obtained from the National Taiwan University Hospital from 2001 to 2013 were evaluated. The minimum inhibitory concentrations (MICs) of the isolates to antimicrobials were determined by the agar dilution method and interpreted using the 2017 clinical breakpoints or epidemiological cut-off values recommended by the Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST). The genetic relatedness of these isolates was determined by multilocus sequence typing. None of the isolates was resistant to ceftriaxone and cefotaxime, and the resistance rates to cefixime, spectinomycin, cefpodoxime, ciprofloxacin, and penicillin were 0.4%, 0.4%, 13.3%, 91.6%, and 87.6%, respectively. The rate of isolates resistant to azithromycin was 14.6% (EUCAST criteria), which is higher than in previous surveillance studies. A total of 57 sequence types (ST) were identified, and ST1901, ST7365, and ST1927 prevailed. Isolates of ST8143 emerged after 2011. ST1901 isolates had relatively higher MIC values for ceftriaxone and azithromycin than those of the other STs. In conclusion, ceftriaxone remains an effective drug of choice for gonorrhoeal management in Taiwan. High rates of azithromycin resistance among N. gonorrhoeae isolates were found. The circulating ST1901 strains with high MIC values for ceftriaxone and azithromycin and the emerging ST8143 strains were alarming. Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

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

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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.

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

DEFF Research Database (Denmark)

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

2002-01-01

Novel molecular tools have been constructed which allow for in situ detection of N-acyl homoserine lactone (AHL)-mediated quorum sensing in Pseudomonas aeruginosa biofilms. The reporter responds to AHL activation of LasR lay expression of an unstable version of the green-fluorescent protein (Gfp...

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...

EFFECTS OF PSYCHOTROPIC DRUGS AS BACTERIAL EFFLUX PUMP INHIBITORS ON QUORUM SENSING REGULATED BEHAVIORS

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Aynur Aybey

2014-10-01

Full Text Available Psychotropic drugs are known to have antimicrobial activity against several groups of microorganisms. The antidepressant agents such as duloxetine, paroxetine, hydroxyzine and venlafaxine are shown to act as efflux pump inhibitors in bacterial cells. In order to the investigation of the effects of psychotropic drugs were determined for clinically significant pathogens by using standart broth microdillusion method. The anti-quorum sensing (anti-QS activity of psychotropic drugs was tested against four test pathogens using the agar well diffusion method. All drugs showed strong inhibitory effect on the growth of S. typhimurium. Additionally, quorum sensing-regulated behaviors of Pseudomonas aeruginosa, including swarming, swimming and twitching motility and alkaline protease production were investigated. Most effective drugs on swarming, swimming and twitching motility and alkaline protease production, respectively, were paroxetine and duloxetine; duloxetine; hydroxyzine and venlafaxine; paroxetine and venlafaxine; venlafaxine. Accordingly, psychotropic drugs were shown strongly anti-QS activity by acting as bacterial efflux pump inhibitors and effection on motility and alkaline protease production of P. aeruginosa.

Quorum quenching by an N-acyl-homoserine lactone acylase from Pseudomonas aeruginosa PAO1

NARCIS (Netherlands)

Sio, CF; Otten, LG; Cool, RH; Diggle, SP; Braun, PG; Daykin, M; Camara, M; Williams, P; Quax, WJ; Bos, R

The virulence of the opportunistic human pathogen Pseudomonas aeruginosa PAO1 is controlled by an N-acyl-homoserine lactone (AHL)-dependent quorum-sensing system. During functional analysis of putative acylase genes in the P. aeruginosa PAO1 genome, the PA2385 gene was found to encode an acylase

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

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

2011-03-01

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

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

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Cheng-Siang Wong

2013-09-01

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

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

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

2014-04-01

Urinary tract infection is caused primarily by the quorum sensing (QS)-dependent biofilm forming ability of uropathogens. In the present investigation, an anti-quorum sensing (anti-QS) agent curcumin from Curcuma longa (turmeric) was shown to inhibit the biofilm formation of uropathogens, such as Escherichia coli, Pseudomonas aeruginosa PAO1, Proteus mirabilis and Serratia marcescens, possibly by interfering with their QS systems. The antibiofilm potential of curcumin on uropathogens as well as its efficacy in disturbing the mature biofilms was examined under light microscope and confocal laser scanning microscope. The treatment with curcumin was also found to attenuate the QS-dependent factors, such as exopolysaccharide production, alginate production, swimming and swarming motility of uropathogens. Furthermore, it was documented that curcumin enhanced the susceptibility of a marker strain and uropathogens to conventional antibiotics. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

DEFF Research Database (Denmark)

Rasmussen, Bastian Barker; Nielsen, Kristian Fog; Machado, Henrique

2014-01-01

Bacterial quorum sensing (QS) and the corresponding signals, acyl homoserine lactones (AHLs), were first described for a luminescent Vibrio species. Since then, detailed knowledge has been gained on the functional level of QS; however, the abundance of AHLs in the family of Vibrionaceae in the en......Bacterial quorum sensing (QS) and the corresponding signals, acyl homoserine lactones (AHLs), were first described for a luminescent Vibrio species. Since then, detailed knowledge has been gained on the functional level of QS; however, the abundance of AHLs in the family of Vibrionaceae...... violaceum reporter strains. Ethyl acetate extracts of the cultures were analysed by ultra-high performance liquid chromatography-high resolution mass spectrometry (MS) with automated tandem MS confirmation for AHLs. N-(3-hydroxy-hexanoyl) (OH-C6) and N-(3-hydroxy-decanoyl) (OH-C10) homoserine lactones were...

The effects of Lactobacillus reuteri probiotics combined with azithromycin on peri-implantitis: A randomized placebo-controlled study.

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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.

Reduced persistence of the macrolide antibiotics erythromycin, clarithromycin and azithromycin in agricultural soil following several years of exposure in the field

Energy Technology Data Exchange (ETDEWEB)

Topp, Edward, E-mail: ed.topp@agr.gc.ca; Renaud, Justin; Sumarah, Mark; Sabourin, Lyne

2016-08-15

The macrolide antibiotics erythromycin, clarithromycin and azithromycin are very important in human and animal medicine, and can be entrained onto agricultural ground through application of sewage sludge or manures. In the present study, a series of replicated field plots were left untreated or received up to five annual spring applications of a mixture of three drugs to achieve a nominal concentration for each of 10 or 0.1 mg kg{sup −1} soil; the latter an environmentally relevant concentration. Soil samples were incubated in the laboratory, and supplemented with antibiotics to establish the dissipation kinetics of erythromycin and clarithromycin using radioisotope methods, and azithromycin using HPLC-MS/MS. All three drugs were dissipated significantly more rapidly in soils with a history of field exposure to 10 mg kg{sup −1} macrolides, and erythromycin and clarithromycin were also degraded more rapidly in field soil exposed to 0.1 mg kg{sup −1} macrolides. Rapid mineralization of {sup 14}C-labelled erythromycin and clarithromycin are consistent with biodegradation. Analysis of field soils revealed no carryover of parent compound from year to year. Azithromycin transformation products were detected consistent with removal of the desosamine and cladinose moieties. Overall, these results have revealed that following several years of exposure to macrolide antibiotics these are amenable to accelerated degradation. The potential accelerated degradation of these drugs in soils amended with manure and sewage sludge should be investigated as this phenomenon would attenuate environmental exposure and selection pressure for clinically relevant resistance. - Highlights: • The impact of field exposure on persistence of macrolide antibiotics was evaluated. • Soil samples were incubated in the laboratory with macrolides. • Field exposure resulted in more rapid dissipation of all macrolides. • Radiolabelled erythromycin and clarithromycin were rapidly mineralized

Reduced persistence of the macrolide antibiotics erythromycin, clarithromycin and azithromycin in agricultural soil following several years of exposure in the field

International Nuclear Information System (INIS)

Topp, Edward; Renaud, Justin; Sumarah, Mark; Sabourin, Lyne

2016-01-01

The macrolide antibiotics erythromycin, clarithromycin and azithromycin are very important in human and animal medicine, and can be entrained onto agricultural ground through application of sewage sludge or manures. In the present study, a series of replicated field plots were left untreated or received up to five annual spring applications of a mixture of three drugs to achieve a nominal concentration for each of 10 or 0.1 mg kg"−"1 soil; the latter an environmentally relevant concentration. Soil samples were incubated in the laboratory, and supplemented with antibiotics to establish the dissipation kinetics of erythromycin and clarithromycin using radioisotope methods, and azithromycin using HPLC-MS/MS. All three drugs were dissipated significantly more rapidly in soils with a history of field exposure to 10 mg kg"−"1 macrolides, and erythromycin and clarithromycin were also degraded more rapidly in field soil exposed to 0.1 mg kg"−"1 macrolides. Rapid mineralization of "1"4C-labelled erythromycin and clarithromycin are consistent with biodegradation. Analysis of field soils revealed no carryover of parent compound from year to year. Azithromycin transformation products were detected consistent with removal of the desosamine and cladinose moieties. Overall, these results have revealed that following several years of exposure to macrolide antibiotics these are amenable to accelerated degradation. The potential accelerated degradation of these drugs in soils amended with manure and sewage sludge should be investigated as this phenomenon would attenuate environmental exposure and selection pressure for clinically relevant resistance. - Highlights: • The impact of field exposure on persistence of macrolide antibiotics was evaluated. • Soil samples were incubated in the laboratory with macrolides. • Field exposure resulted in more rapid dissipation of all macrolides. • Radiolabelled erythromycin and clarithromycin were rapidly mineralized. • Macrolides

Effects of ambroxol on biofilm adhesion and viability of Pseudomonas aeruginosa quorum sensing defective strain

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Qi LU

2013-07-01

Full Text Available Objective　To investigate the effects of ambroxol on the biofilm viability and pristine adhesion of Pseudomonas aeruginosa wild (PAO1 and quorum sensing defective strain (QS, gene deletion of ∆lasI and ∆rhlI. Methods　The biofilm was treated by different concentrations (0, 1.875, 3.75mg/ml of ambroxol. The number of colony was measured with agar plate, multifunction fluorometer was used to measure the fluorescence intensity of PAO1 and QS strains at the bottom of 96-well plate. The adhesion ratio (% was calculated to determine the effects of ambroxol on bacterial biofilm adhesion. Results　Ambroxol treatment reduced the survival rate of the mutant strains compared to that of wild strain, even though the QS strain had increased the adhesion in the presence of ambroxol compared to that of wild strain (P<0.05. Conclusion　Ambroxol has a property of significantly antagonizing quorum-sensing system, suggesting that it might be of importance in treatment against chronic Pseudomonasaeruginosainfections.

Cross-species comparison of the Burkholderia pseudomallei, Burkholderia thailandensis, and Burkholderia mallei quorum-sensing regulons.

Science.gov (United States)

Majerczyk, Charlotte D; Brittnacher, Mitchell J; Jacobs, Michael A; Armour, Christopher D; Radey, Matthew C; Bunt, Richard; Hayden, Hillary S; Bydalek, Ryland; Greenberg, E Peter

2014-11-01

Burkholderia pseudomallei, Burkholderia thailandensis, and Burkholderia mallei (the Bptm group) are close relatives with very different lifestyles: B. pseudomallei is an opportunistic pathogen, B. thailandensis is a nonpathogenic saprophyte, and B. mallei is a host-restricted pathogen. The acyl-homoserine lactone quorum-sensing (QS) systems of these three species show a high level of conservation. We used transcriptome sequencing (RNA-seq) to define the quorum-sensing regulon in each species, and we performed a cross-species analysis of the QS-controlled orthologs. Our analysis revealed a core set of QS-regulated genes in all three species, as well as QS-controlled factors shared by only two species or unique to a given species. This global survey of the QS regulons of B. pseudomallei, B. thailandensis, and B. mallei serves as a platform for predicting which QS-controlled processes might be important in different bacterial niches and contribute to the pathogenesis of B. pseudomallei and B. mallei. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Cross-Species Comparison of the Burkholderia pseudomallei, Burkholderia thailandensis, and Burkholderia mallei Quorum-Sensing Regulons

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Majerczyk, Charlotte D.; Brittnacher, Mitchell J.; Jacobs, Michael A.; Armour, Christopher D.; Radey, Matthew C.; Bunt, Richard; Hayden, Hillary S.; Bydalek, Ryland

2014-01-01

Burkholderia pseudomallei, Burkholderia thailandensis, and Burkholderia mallei (the Bptm group) are close relatives with very different lifestyles: B. pseudomallei is an opportunistic pathogen, B. thailandensis is a nonpathogenic saprophyte, and B. mallei is a host-restricted pathogen. The acyl-homoserine lactone quorum-sensing (QS) systems of these three species show a high level of conservation. We used transcriptome sequencing (RNA-seq) to define the quorum-sensing regulon in each species, and we performed a cross-species analysis of the QS-controlled orthologs. Our analysis revealed a core set of QS-regulated genes in all three species, as well as QS-controlled factors shared by only two species or unique to a given species. This global survey of the QS regulons of B. pseudomallei, B. thailandensis, and B. mallei serves as a platform for predicting which QS-controlled processes might be important in different bacterial niches and contribute to the pathogenesis of B. pseudomallei and B. mallei. PMID:25182491

Effects of quorum-sensing on immunoglobulin G responses in a rat model of chronic lung infection with Pseudomonas aeruginosa

DEFF Research Database (Denmark)

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

2004-01-01

Levels of serum antibodies against Pseudomonas aeruginosa were observed for 106 days in a rat model of chronic lung infection. Significantly weaker responses of serum IgG and IgG1 and a lower ratio of IgGI/IgG2a were found in the rats infected with the quorum-signal-deficient mutant, PAO1 (rhl......I, lasI), compared with the wild-type PAO1. Four out of 15 rats infected with wild-type PAO1 contained bacteria in the lungs on day 106, whereas no bacteria were found in the mutant PAO1 group. The results indicate that quorum signals contribute to the persistence of the infection and influence...

Sustained release of a novel anti-quorum-sensing agent against oral fungal biofilms.

Science.gov (United States)

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

2015-04-01

Thiazolidinedione-8 (S-8) has recently been identified as a potential anti-quorum-sensing/antibiofilm agent against bacteria and fungi. Based on these results, we investigated the possibility of incorporating S-8 in a sustained-release membrane (SRM) to increase its pharmaceutical potential against Candida albicans biofilm. We demonstrated that SRM containing S-8 inhibits fungal biofilm formation in a time-dependent manner for 72 h, due to prolonged release of S-8. Moreover, the SRM effectively delivered the agent in its active form to locations outside the membrane reservoir. In addition, eradication of mature biofilm by the SRM containing S-8 was also significant. Of note, S-8-containing SRM affected the characteristics of mature C. albicans biofilm, such as thickness, exopolysaccharide (EPS) production, and morphogenesis of fungal cells. The concept of using an antibiofilm agent with no antifungal activity incorporated into a sustained-release delivery system is new in medicine and dentistry. This concept of an SRM containing a quorum-sensing quencher with an antibiofilm effect could pave the way for combating oral fungal infectious diseases. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

The hydrocarbon-degrading marine bacterium Cobetia sp. strain MM1IDA2H-1 produces a biosurfactant that interferes with quorum sensing of fish pathogens by signal hijacking

Science.gov (United States)

Ibacache-Quiroga, C; Ojeda, J; Espinoza-Vergara, G; Olivero, P; Cuellar, M; Dinamarca, M A

2013-01-01

Summary Biosurfactants are produced by hydrocarbon-degrading marine bacteria in response to the presence of water-insoluble hydrocarbons. This is believed to facilitate the uptake of hydrocarbons by bacteria. However, these diffusible amphiphilic surface-active molecules are involved in several other biological functions such as microbial competition and intra-or inter-species communication. We report the isolation and characterization of a marine bacterial strain identified as Cobetia sp. MM1IDA2H-1, which can grow using the sulfur-containing heterocyclic aromatic hydrocarbon dibenzothiophene (DBT). As with DBT, when the isolated strain is grown in the presence of a microbial competitor, it produces a biosurfactant. Because the obtained biosurfactant was formed by hydroxy fatty acids and extracellular lipidic structures were observed during bacterial growth, we investigated whether the biosurfactant at its critical micelle concentration can interfere with bacterial communication systems such as quorum sensing. We focused on Aeromonas salmonicida subsp. salmonicida, a fish pathogen whose virulence relies on quorum sensing signals. Using biosensors for quorum sensing based on Chromobacterium violaceum and Vibrio anguillarum, we showed that when the purified biosurfactant was mixed with N-acyl homoserine lactones produced by A. salmonicida, quorum sensing was inhibited, although bacterial growth was not affected. In addition, the transcriptional activities of A. salmonicida virulence genes that are controlled by quorum sensing were repressed by both the purified biosurfactant and the growth in the presence of Cobetia sp. MM1IDA2H-1. We propose that the biosurfactant, or the lipid structures interact with the N-acyl homoserine lactones, inhibiting their function. This could be used as a strategy to interfere with the quorum sensing systems of bacterial fish pathogens, which represents an attractive alternative to classical antimicrobial therapies in fish

PimT, an amino acid exporter controls polyene production via secretion of the quorum sensing pimaricin-inducer PI-factor in Streptomyces natalensis

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Guerra Susana M

2009-06-01

Full Text Available Abstract Background Polyenes represent a major class of antifungal agents characterised by the presence of a series of conjugated double bonds in their planar hydroxylated macrolide ring structure. Despite their general interest, very little is known about the factors that modulate their biosynthesis. Among these factors, we have recently discovered a new inducing compound (PI-factor in the pimaricin producer Streptomyces natalensis, which elicits polyene production in a manner characteristic of quorum sensing. Here, we describe the involvement of an amino-acid exporter from S. natalensis in modulating the expression of pimaricin biosynthetic genes via secretion of the quorum-sensing pimaricin-inducer PI-factor. Results Adjacent to the pimaricin gene cluster lies a member of the RhtB family of amino-acid exporters. Gene deletion and complementation experiments provided evidence for a role for PimT in the export of L-homoserine, L-serine, and L-homoserine lactone. Expression of the gene was shown to be induced by homoserine and by the quorum-sensing pimaricin-inducer PI-factor. Interestingly, the mutant displayed 65% loss of pimaricin production, and also 50% decrease in the production of PI, indicating that PimT is used as PI-factor exporter, and suggesting that the effect in antifungal production might be due to limited secretion of the inducer. Conclusion This report describes the involvement of an amino acid exporter (encoded by pimT in the vicinity of the pimaricin cluster in modulating the expression of antibiotic biosynthetic genes via secretion of the quorum-sensing pimaricin-inducer PI-factor. The discovery of the participation of amino acid exporters in a signal transduction cascade for the production of polyene macrolides is unexpected, and represents an important step forward towards understanding the regulatory network for polyene regulation. Additionally, this finding constitutes the first detailed characterization of an amino

Quorum sensing signal profile of Acinetobacter strains from nosocomial and environmental sources Perfil de sensores de quórum en cepas nosocomiales y ambientales de Acinetobacter

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R. H. González

2009-06-01

Full Text Available A set of 43 strains corresponding to 20 classified and unclassified genomic Acinetobacter species was analyzed for the production of typical N-acyl homoserine lactone quorum sensing molecules in culture broths. A large percentage of the strains (74% displayed quorum sensing signals that could be separated into three statistically significantly different chromatographic groups (p Rf2 > Rf1. None of the three signals could be specifically assigned to a particular species in the genus; furthermore, no distinction could be made between the quorum sensing signals secreted by typical opportunistic strains of the A. calcoaceticus-A. baumannii complex, isolated from patients, with respect to the other species of the genus, except for the Rf1 signal which was present in all the QS positive strains belonging to this complex and DNA group 13 TU. In conclusion, quorum sensors in Acinetobacter are not homogenously distributed among species and one of them is present in most of the A. calcoaceticus-baumannii complex.Se analizó la producción de moléculas típicas de N-acil homoserina lactona con actividad de quorum sensing en cultivos líquidos de un grupo de 43 cepas correspondientes a 20 especies genómicas clasificadas y no clasificadas de Acinetobacter. Un porcentaje alto de las cepas (74% mostraron señales de quorum sensing que pudieron ser separadas en tres grupos cromatográficos significativamente diferentes entre sí (p Rf2 > Rf1. Ninguna de las tres señales pudo ser asignada a una especie en particular dentro del género; es más, no se encontró diferencia entre las señales producidas por las cepas típicamente oportunistas (complejo A. calcoaceticus-A. baumannii aisladas de pacientes respecto de las producidas por otras cepas del mismo género, excepto para el caso de Rf1, que se encontró presente en todos los aislamientos quorum sensing positivos del mencionado complejo y en las cepas del grupo de DNA 13TU. En conclusión, los sensores de

On the Performance of Quorum Replication on the Internet

Science.gov (United States)

2008-10-31

ISP in Cambridge, MA MA2 ISP in Cambridge, MA MA3 ISP in Martha’s Vineyard, MA MA4 ISP in Massachusetts, MA MD ISP in Laurel, MD MEX National...1523 171 96% 58% MA2 28% 742 1517 230 94% 59% NC 32% 465 616 255 90% 63% ISR2 3% 424 70 400 100% 97% UT1 27% 979 1847 189 96% 55% MA1 29% 645 712 238... MA2 UT2 UT1 CA1 AUS NC NZ TW KR CA2 CA3 Fig. 4. Our crumbling wall quorum system. of the first row are in North America. TW, which has lossy

VanT, a central regulator of quorum sensing signalling in Vibrio anguillarum

OpenAIRE

Croxatto, Antony

2006-01-01

Many bacteria produce signal molecules that serve in a cell-to-cell communication system termed quorum sensing. This signalling system allows a bacterial population to co-ordinately regulate functions according to their cell number in a defined environment. As bacterial growth progresses towards the stationary phase, signalling molecules accumulate in the growth medium and, above a certain threshold level, regulate the expression of genes involved in diverse functions. Most of the functions m...

Bulk input queues with quorum and multiple vacations

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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.

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....... 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...... 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...

Treatment Outcomes for Rectal Lymphogranuloma Venereum in Men Who Have Sex with Men Using Doxycycline, Azithromycin, or Both: A Review of Clinical Cases.

Science.gov (United States)

Leeyaphan, Charussri; Ong, Jason J; Chow, Eric P F; Dimovski, Karolina; Kong, Fabian Y S; Hocking, Jane S; Howden, Ben; Bissessor, Melanie; Fairley, Christopher K; Bradshaw, Catriona; Read, Timothy; Chen, Marcus

2017-04-01

Treatment for rectal lymphogranuloma venereum where doxycycline 100 mg twice daily for 21 days was used-either alone or together with azithromycin 1 g single dose-resulted in microbiological cure of 97%. These data support doxycycline 100 mg twice daily for 21 days as the preferred treatment for rectal lymphogranuloma venereum.

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

Science.gov (United States)

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

2014-12-23

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

Xylella fastidiosa outer membrane vesicles modulate plant colonization by blocking attachment to surfaces.

Science.gov (United States)

Ionescu, Michael; Zaini, Paulo A; Baccari, Clelia; Tran, Sophia; da Silva, Aline M; Lindow, Steven E

2014-09-16

Outer membrane vesicles (OMVs) of Gram-negative bacteria have been studied intensively in recent years, primarily in their role in delivering virulence factors and antigens during pathogenesis. However, the near ubiquity of their production suggests that they may play other roles, such as responding to envelope stress or trafficking various cargoes to prevent dilution or degradation by other bacterial species. Here we show that OMVs produced by Xylella fastidiosa, a xylem-colonizing plant pathogenic bacterium, block its interaction with various surfaces such as the walls of xylem vessels in host plants. The release of OMVs was suppressed by the diffusible signal factor-dependent quorum-sensing system, and a X. fastidiosa ΔrpfF mutant in which quorum signaling was disrupted was both much more virulent to plants and less adhesive to glass and plant surfaces than the WT strain. The higher virulence of the ΔrpfF mutant was associated with fivefold higher numbers of OMVs recovered from xylem sap of infected plants. The frequency of attachment of X. fastidiosa to xylem vessels was 20-fold lower in the presence of OMVs than in their absence. OMV production thus is a strategy used by X. fastidiosa cells to adjust attachment to surfaces in its transition from adhesive cells capable of insect transmission to an "exploratory" lifestyle for systemic spread within the plant host which would be hindered by attachment. OMV production may contribute to the movement of other bacteria in porous environments by similarly reducing their contact with environmental constituents.

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

Science.gov (United States)

Rein, Markus; Heinß, Nike; Schmid, Friederike; Speck, Thomas

2016-02-05

We study a generic model for quorum-sensing bacteria in circular confinement. Every bacterium produces signaling molecules, the local concentration of which triggers a response when a certain threshold is reached. If this response lowers the motility, then an aggregation of bacteria occurs which differs fundamentally from standard motility-induced phase separation due to the long-ranged nature of the concentration of signal molecules. We analyze this phenomenon analytically and by numerical simulations employing two different protocols leading to stationary cluster and ring morphologies, respectively.

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...

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....... The rat model of P. aeruginosa lung infection was used in the present study. The rats were killed on days 3, 7, 14 and 28 after infection with the P. aeruginosa strains. The results showed that during the early stages of infection, the PAO1 double mutant induced a stronger serum antibody response, higher...... number of lung bacteria, and minor serum IgG and IgG1 responses but increased lung interferon gamma production were detected in the group infected with the PAO1 double mutant when compared with the PAO1-infected group. Delayed immune responses were observed in the PAO1-infected group and they might...

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

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Stephanie Forschner-Dancause

2016-07-01

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

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

DEFF Research Database (Denmark)

Smyth, Alan R; Cifelli, Paramita M; Ortori, Catharine A

2010-01-01

Pseudomonas aeruginosa forms biofilms in the cystic fibrosis lung. Quorum sensing (QS) controls biofilm maturation, immune evasion, antibiotic tolerance and virulence factor production. Garlic shows QS inhibitory activity in vitro and in animal models. We report the first clinical trial in man of...

Combined impact of quorum quenching and backwashing on biofouling control in a semi-pilot scale mbr treating real wastewater

International Nuclear Information System (INIS)

Hasnain, G.; Khan, S.J.; Arshad, M.Z.; Abdullah, H.Y.

2017-01-01

This study demonstrates the combined effect of quorum quenching (QQ) and backwashing on biofouling control in MBR treating real wastewater. The quorum quenching mechanism is an emerging biological technique using Rhodococcus sp. entrapped in polymer coated sodium alginate beads whereas, backwashing is a distinguished physical technique for biofouling control. Two parallel semi-pilot scale MBRs i.e., QQ-MBR (quorum quenching MBR) with cell-entrapping beads (CEBs) and C-MBR (conventional MBR) with vacant CEBs at 0.5% effective volume of the bioreactor, were monitored for comparative performance evaluation. In the first phase, both the MBRs were operated without backwashing having operational cycle of eight min filtration and two min relaxation and in the second phase; MBRs were operated with backwashing having operation cycle of eight min filtration, one min relaxation and one min backwashing. QQ-MBR-with backwashing exhibited greater biofouling control capability and elongated filtration duration with respect to QQ-MBR without backwashing. Comparatively less soluble EPS concentrations were detected in QQ-MBR as compare to C-MBR in both modes of operation while backwashing contributed to retard the rapid increase in trans-membrane pressure (TMP) also known as TMP jump. Study reveals the novelty of successful application of combined influence of permeate backflushing technique and QQ (anti-biofouling) strategy in MBR and potential use for full scale applications. (author)

Dynamic Channel Slot Allocation Scheme and Performance Analysis of Cyclic Quorum Multichannel MAC Protocol

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Xing Hu

2017-01-01

Full Text Available In high diversity node situation, multichannel MAC protocol can improve the frequency efficiency, owing to fewer collisions compared with single-channel MAC protocol. And the performance of cyclic quorum-based multichannel (CQM MAC protocol is outstanding. Based on cyclic quorum system and channel slot allocation, it can avoid the bottleneck that others suffered from and can be easily realized with only one transceiver. To obtain the accurate performance of CQM MAC protocol, a Markov chain model, which combines the channel-hopping strategy of CQM protocol and IEEE 802.11 distributed coordination function (DCF, is proposed. The results of numerical analysis show that the optimal performance of CQM protocol can be obtained in saturation bound situation. And then we obtain the saturation bound of CQM system by bird swarm algorithm. In addition, to improve the performance of CQM protocol in unsaturation situation, a dynamic channel slot allocation of CQM (DCQM protocol is proposed, based on wavelet neural network. Finally, the performance of CQM protocol and DCQM protocol is simulated by Qualnet platform. And the simulation results show that the analytic and simulation results match very well; the DCQM performs better in unsaturation situation.

Indirect pathogenicity of Haemophilus influenzae and Moraxella catarrhalis in polymicrobial otitis media occurs via interspecies quorum signaling.

Science.gov (United States)

Armbruster, Chelsie E; Hong, Wenzhou; Pang, Bing; Weimer, Kristin E D; Juneau, Richard A; Turner, James; Swords, W Edward

2010-07-06

Otitis media (OM) is among the leading diseases of childhood and is caused by opportunists that reside within the nasopharynx, such as Haemophilus influenzae and Moraxella catarrhalis. As with most airway infections, it is now clear that OM infections involve multiple organisms. This study addresses the hypothesis that polymicrobial infection alters the course, severity, and/or treatability of OM disease. The results clearly show that coinfection with H. influenzae and M. catarrhalis promotes the increased resistance of biofilms to antibiotics and host clearance. Using H. influenzae mutants with known biofilm defects, these phenotypes were shown to relate to biofilm maturation and autoinducer-2 (AI-2) quorum signaling. In support of the latter mechanism, chemically synthesized AI-2 (dihydroxypentanedione [DPD]) promoted increased M. catarrhalis biofilm formation and resistance to antibiotics. In the chinchilla infection model of OM, polymicrobial infection promoted M. catarrhalis persistence beyond the levels seen in animals infected with M. catarrhalis alone. Notably, no such enhancement of M. catarrhalis persistence was observed in animals infected with M. catarrhalis and a quorum signaling-deficient H. influenzae luxS mutant strain. We thus conclude that H. influenzae promotes M. catarrhalis persistence within polymicrobial biofilms via interspecies quorum signaling. AI-2 may therefore represent an ideal target for disruption of chronic polymicrobial infections. Moreover, these results strongly imply that successful vaccination against the unencapsulated H. influenzae strains that cause airway infections may also significantly impact chronic M. catarrhalis disease by removing a reservoir of the AI-2 signal that promotes M. catarrhalis persistence within biofilm.

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

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Jesus Olivero-Verbel

2014-09-01

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

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

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Chhabra Siri

2011-03-01

Full Text Available Abstract Background Cell-to-cell communication (quorum sensing (QS co-ordinates bacterial behaviour at a population level. Consequently the behaviour of a natural multi-species community is likely to depend at least in part on co-existing QS and quorum quenching (QQ activities. Here we sought to discover novel N-acylhomoserine lactone (AHL-dependent QS and QQ strains by investigating a bacterial community associated with the rhizosphere of ginger (Zingiber officinale growing in the Malaysian rainforest. Results By using a basal growth medium containing N-(3-oxohexanoylhomoserine lactone (3-oxo-C6-HSL as the sole source of carbon and nitrogen, the ginger rhizosphere associated bacteria were enriched for strains with AHL-degrading capabilities. Three isolates belonging to the genera Acinetobacter (GG2, Burkholderia (GG4 and Klebsiella (Se14 were identified and selected for further study. Strains GG2 and Se14 exhibited the broadest spectrum of AHL-degrading activities via lactonolysis while GG4 reduced 3-oxo-AHLs to the corresponding 3-hydroxy compounds. In GG2 and GG4, QQ was found to co-exist with AHL-dependent QS and GG2 was shown to inactivate both self-generated and exogenously supplied AHLs. GG2, GG4 and Se14 were each able to attenuate virulence factor production in both human and plant pathogens. Conclusions Collectively our data show that ginger rhizosphere bacteria which make and degrade a wide range of AHLs are likely to play a collective role in determining the QS-dependent phenotype of a polymicrobial community.

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

Many pathogens control production of virulence factors by self-produced signals in a process called quorum sensing (QS). We demonstrate that acyl homoserine lactone (AHL) signals, which enable bacteria to express certain phenotypes in relation to cell density, are produced by a wide spectrum...... of Aeromonas salmonicida strains. All 31 typical strains were AHL producers as were 21 of 26 atypical strains, but on a strain population basis, production of virulence factors such as protease, lipase, A-layer or pigment did not correlate with the production and accumulation of AHLs in the growth medium...... of Aeromonas salmonicida. The most efficient compound N-(heptylsulfanylacetyl)-L-homoserine lactone (HepS-AHL), reduced protease production by a factor of 10. Five extracellular proteases were detected on gelatin-containing sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) gels and 3...

The Effects of Chinese Herbal Medicines on the Quorum Sensing-Regulated Virulence in Pseudomonas aeruginosa PAO1

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Yee Meng Chong

2018-04-01

Full Text Available The quorum sensing (QS system has been used by many opportunistic pathogenic bacteria to coordinate their virulence determinants in relation to cell-population density. As antibiotic-resistant bacteria are on the rise, interference with QS has been regarded as a novel way to control bacterial infections. As such, many plant-based natural products have been widely explored for their therapeutic roles. These natural products may contain anti-QS compounds that could block QS signals generation or transmission to combat QS pathogens. In this study, we report the anti-QS activities of four different Chinese herbal plant extracts: Poria cum Radix pini, Angelica dahurica, Rhizoma cibotii and Schizonepeta tenuifolia, on Pseudomonas aeruginosa PAO1. All the plants extracted using hexane, chloroform and methanol were tested and found to impair swarming motility and pyocyanin production in P. aeruginosa PAO1, particularly by Poria cum Radix pini. In addition, all the plant extracts also inhibited violacein production in C. violaceum CV026 up to 50% while bioluminescence activities were reduced in lux-based E. coli biosensors, pSB401 and pSB1075, up to about 57%. These anti-QS properties of the four medicinal plants are the first documentation that demonstrates a potential approach to attenuate pathogens’ virulence determinants.

The quorum sensing luxS gene is induced in Lactobacillus acidophilus NCFM in response to Listeria monocytogenes

DEFF Research Database (Denmark)

Moslehi Jenabian, Saloomeh; Vogensen, Finn Kvist; Jespersen, Lene

2011-01-01

The luxS gene involved in quorum sensing has been shown to control different behaviour of probiotic lactobacilli. In this study we investigated if luxS in Lactobacillus acidophilus NCFM was up-regulated in response to Listeria monocytogenes EGD-e. The two bacterial strains were grown in mono......-killed cells of L. monocytogenes have no effect on luxS transcription. The luxS gene involved in quorum sensing has been shown to control different behaviour of probiotic lactobacilli. In this study we investigated if luxS in Lactobacillus acidophilus NCFM was up-regulated in response to Listeria monocytogenes...

Inhibition of Steptococcus mutans biofilm formation by extracts of Tenacibaculum sp. 20J, a bacterium with wide-spectrum quorum quenching activity

Science.gov (United States)

Muras, Andrea; Mayer, Celia; Romero, Manuel; Camino, Tamara; Ferrer, Maria D.; Mira, Alex; Otero, Ana

2018-01-01

ABSTRACT Background: Previous studies have suggested the quorum sensing signal AI-2 as a potential target to prevent the biofilm formation by Streptococcus mutans, a pathogen involved in tooth decay. Objective: To obtain inhibition of biofilm formation by S. mutans by extracts obtained from the marine bacterium Tenacibaculum sp. 20J interfering with the AI-2 quorum sensing system. Design: The AI-2 inhibitory activity was tested with the biosensors Vibrio harveyi BB170 and JMH597. S. mutans ATCC25175 biofilm formation was monitored using impedance real-time measurements with the xCELLigence system®, confocal laser microscopy, and the crystal violet quantification method. Results: The addition of the cell extract from Tenacibaculum sp. 20J reduced biofilm formation in S. mutans ATCC25175 by 40–50% compared to the control without significantly affecting growth. A decrease of almost 40% was also observed in S. oralis DSM20627 and S. dentisani 7747 biofilms. Conclusions: The ability of Tenacibaculum sp. 20J to interfere with AI-2 and inhibit biofilm formation in S. mutans was demonstrated. The results indicate that the inhibition of quorum sensing processes may constitute a suitable strategy for inhibiting dental plaque formation, although additional experiments using mixed biofilm models would be required. PMID:29410771

Post-secretional activation of Protease IV by quorum sensing in Pseudomonas aeruginosa

OpenAIRE

Oh, Jungmin; Li, Xi-Hui; Kim, Soo-Kyong; Lee, Joon-Hee

2017-01-01

Protease IV (PIV), a key virulence factor of Pseudomonas aeruginosa is a secreted lysyl-endopeptidase whose expression is induced by quorum sensing (QS). We found that PIV expressed in QS mutant has severe reduction of activity in culture supernatant (CS), even though it is overexpressed to high level. PIV purified from the QS mutant (M-PIV) had much lower activity than the PIV purified from wild type (P-PIV). We found that the propeptide cleaved from prepro-PIV was co-purified with M-PIV, bu...

A cross-sectional study of 'yaws' in districts of Ghana which have previously undertaken azithromycin mass drug administration for trachoma control.

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Rosanna Ghinai

2015-01-01

Full Text Available Yaws, caused by Treponema pallidum ssp. pertenue, is reportedly endemic in Ghana. Mass distribution of azithromycin is now the cornerstone of the WHO yaws eradication campaign. Mass distribution of azithromycin at a lower target dose was previously undertaken in two regions of Ghana for the control of trachoma. Ongoing reporting of yaws raises the possibility that resistance may have emerged in T. pallidum pertenue, or that alternative infections may be responsible for some of the reported cases. We conducted a cross-sectional survey in thirty communities in two districts of Ghana where MDA for trachoma had previously been conducted. Children aged 5-17 years with ulcerative lesions compatible with yaws were enrolled. Samples for treponemal serology and lesion PCR were collected from all children. 90 children with 98 lesions were enrolled. Syphilis serology was negative in all of them. PCR for T. pallidum ssp pertenue was negative in all children, but Haemophilus ducreyi DNA was detected in 9 lesions. In these communities, previously treated for trachoma, we found no evidence of ongoing transmission of yaws. H. ducreyi was associated with a proportion of skin lesions, but the majority of lesions remain unexplained. Integration of diagnostic testing into both pre and post-MDA surveillance systems is required to better inform yaws control programmes.

The APPLe study: a randomized, community-based, placebo-controlled trial of azithromycin for the prevention of preterm birth, with meta-analysis.

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Nynke R van den Broek

2009-12-01

Full Text Available Premature birth is the major cause of perinatal mortality and morbidity in both high- and low-income countries. The causes of preterm labour are multiple but infection is important. We have previously described an unusually high incidence of preterm birth (20% in an ultrasound-dated, rural, pregnant population in Southern Malawi with high burdens of infective morbidity. We have now studied the impact of routine prophylaxis with azithromycin as directly observed, single-dose therapy at two gestational windows to try to decrease the incidence of preterm birth.We randomized 2,297 pregnant women attending three rural and one peri-urban health centres in Southern Malawi to a placebo-controlled trial of oral azithromycin (1 g given at 16-24 and 28-32 wk gestation. Gestational age was determined by ultrasound before 24 wk. Women and their infants were followed up until 6 wk post delivery. The primary outcome was incidence of preterm delivery, defined as 6,200 pregnancies shows no effect on preterm birth (relative risk 1.02, 95% confidence interval 0.86-1.22.This study provides no support for the use of antibiotics as routine prophylaxis to prevent preterm birth in high risk populations; prevention of preterm birth requires alternative strategies.Current Controlled Trials ISRCTN84023116

THE QUORUM SENSİNG INHIBITION ACTIVITY OF THE ETHYL ACETATE EXTRACT OF STREPTOMYCES GRİSEOFLAVUS OC. 124-2

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Gultekin Akdamar

2016-05-01

Full Text Available Streptomyces griseoflavus OC. 124-2 used in this study was isolated from the field soil of Dalaman Directorate of Agricultural Enterprises Muğla. As a result of phenotypic and molecular characterization, the isolate was identified as Streptomyces griseoflavus and named as OC. 124-2. The fermentation liquid of Streptomyces griseoflavus OC. 124-2 was obtained in optimum fermentation conditions, and then it was filtered and extracted with ethyl acetate 1:1. The extract containing the active compounds was obtained by evaporating the solvent. Biomonitor strains, Chromobacterium violaceum CV026 for the determination of anti-quorum sensing activity (anti-QS, Chromobacterium violaceum CV12472 for the determination of inhibition of violacein pigment production and Pseudomonas aeruginosa PA01 for the determination of anti-swarming activity were used at MIC and sub-MIC concentrations. The anti-quorum sensing and anti-swarming activities could not be detected for the extract. Violacein production was inhibited by 100%, 74.86%, 65.74% and 31.99% at MIC, MIC/2, MIC/4 and MIC/8 concentrations of the extract treatment, respectively. While the detected inhibition of violacein pigment production did not inhibit the bacterial growth, it was revealed that it inhibited the quorum-sensing-regulated signaling systems. Accordingly, it was shown that the active compounds obtained from ethyl acetate extract of OC. 124-2 constituted a non-selective pressure for the growth of drug resistant pathogen bacteria and they may be used as an alternative at treatment of these bacteria.

Quorum Sensing Signaling and Quenching in the Multidrug-Resistant Pathogen Stenotrophomonas maltophilia

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Pol Huedo

2018-04-01

Full Text Available Stenotrophomonas maltophilia is an opportunistic Gram-negative pathogen with increasing incidence in clinical settings. The most critical aspect of S. maltophilia is its frequent resistance to a majority of the antibiotics of clinical use. Quorum Sensing (QS systems coordinate bacterial populations and act as major regulatory mechanisms of pathogenesis in both pure cultures and poly-microbial communities. Disruption of QS systems, a phenomenon known as Quorum Quenching (QQ, represents a new promising paradigm for the design of novel antimicrobial strategies. In this context, we review the main advances in the field of QS in S. maltophilia by paying special attention to Diffusible Signal Factor (DSF signaling, Acyl Homoserine Lactone (AHL responses and the controversial Ax21 system. Advances in the DSF system include regulatory aspects of DSF synthesis and perception by both rpf-1 and rpf-2 variant systems, as well as their reciprocal communication. Interaction via DSF of S. maltophilia with unrelated organisms including bacteria, yeast and plants is also considered. Finally, an overview of the different QQ mechanisms involving S. maltophilia as quencher and as object of quenching is presented, revealing the potential of this species for use in QQ applications. This review provides a comprehensive snapshot of the interconnected QS network that S. maltophilia uses to sense and respond to its surrounding biotic or abiotic environment. Understanding such cooperative and competitive communication mechanisms is essential for the design of effective anti QS strategies.

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

DEFF Research Database (Denmark)

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

2002-01-01

Recent reports have shown that several strains of Pseudomonas putida produce N-acylhomoserine lactones (AHLs). These signal molecules enable bacteria to coordinately express certain phenotypic traits in a density-dependent manner in a process referred to as quorum sensing. In this study we have...

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

Energy Technology Data Exchange (ETDEWEB)

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

2009-01-01

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

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

Science.gov (United States)

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

2015-03-11

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

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

International Nuclear Information System (INIS)

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

2014-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-03-01

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

Use of Whole-Cell Bioassays for Screening Quorum Signaling, Quorum Interference, and Biofilm Dispersion.

Science.gov (United States)

Thornhill, Starla G; McLean, Robert J C

2018-01-01

In most bacteria, a global level of regulation, termed quorum sensing (QS), exists involving intercellular communication via the production and response to cell density-dependent signal molecules. QS has been associated with a number of important features in bacteria including virulence regulation and biofilm formation. Consequently, there is considerable interest in understanding, detecting, and inhibiting QS. N-acylated homoserine lactones (AHLs) are used as extracellular QS signals by a variety of Gram-negative bacteria. Chromobacterium violaceum, commonly found in soil and water, produces the characteristic purple pigment violacein, regulated by AHL-mediated QS. Based on this readily observed pigmentation phenotype, C. violaceum strains can be used to detect various aspects of AHL-mediated QS activity. In another commonly used bioassay organism, Agrobacterium tumefaciens, QS can be detected by the use of a reporter gene such as lacZ. Here, we describe several commonly used approaches incorporating C. violaceum and A. tumefaciens that can be used to detect AHL and QS inhibitors. Due to the inherent low susceptibility of biofilm bacteria to antimicrobial agents, biofilm dispersion, whereby bacteria reenter the planktonic community, is another increasingly important area of research. At least one signal, distinct from traditional QS, has been identified and there are a variety of other environmental factors that also trigger dispersion. We describe a microtiter-based experimental strategy whereby potential biofilm dispersion compounds can be screened.

How Quorum Sensing Connects Sporulation to Necrotrophism in Bacillus thuringiensis.

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

2016-08-01

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

Antimicrobial and anti-Quorum Sensing activities of selected medicinal plants of Ethiopia: Implication for development of potent antimicrobial agents.

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Bacha, Ketema; Tariku, Yinebeb; Gebreyesus, Fisseha; Zerihun, Shibru; Mohammed, Ali; Weiland-Bräuer, Nancy; Schmitz, Ruth A; Mulat, Mulugeta

2016-07-11

Traditional medicinal plants have been used as an alternative medicine in many parts of the world, including Ethiopia. There are many documented scientific reports on antimicrobial activities of the same. To our knowledge, however, there is no report on the anti-Quorum Sensing (Quorum Quenching, QQ) potential of traditional Ethiopian medicinal plants. As many of the opportunistic pathogenic bacteria depend on Quorum Sensing (QS) systems to coordinate their virulence expression, interference with QS could be a novel approach to control bacterial infections. Thus, the aim of this study was to evaluate selected medicinal plants from Ethiopia for their antimicrobial activities against bacterial and fungal pathogens; and to assess the interference of these plant extracts with QS of bacteria. Antimicrobial activities of plant extracts (oil, resins and crude extracts) were evaluated following standard agar diffusion technique. The minimum inhibitory concentrations (MIC) of potent extracts were determined using 96 well micro-titer plates and optical densities were measured using an ELISA Microplate reader. Interference with Quorum Sensing activities of extracts was determined using the recently established E. coli based reporter strain AI1-QQ.1 and signaling molecule N-(ß-ketocaproyl)-L-homoserine lactone (3-oxo-C6-HSL). Petroleum ether extract of seed of Nigella sativa exhibited the highest activity against both the laboratory isolated Bacillus cereus [inhibition zone (IZ), 44 ± 0.31 mm] and B. cereus ATCC 10987 (IZ, 40 ± 2.33 mm). Similarly, oil extract from mature ripe fruit husk of Aframomum corrorima and mature unripe fruit of A. corrorima revealed promising activities against Candida albicans ATCC 90028 (IZ, 35 ± 1.52 mm) and Staphylococcus aureus DSM 346 (IZ, 25 ± 1.32 mm), respectively. Antimicrobial activities of oil extract from husk of A. corrorima and petroleum ether extract of seed of N. sativa were significantly higher than that of

Effect of Quorum Sensing by Staphylococcus epidermidis on the Attraction Response of Female Adult Yellow Fever Mosquitoes, Aedes aegypti aegypti (Linnaeus) (Diptera: Culicidae), to a Blood-Feeding Source.

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Zhang, Xinyang; Crippen, Tawni L; Coates, Craig J; Wood, Thomas K; Tomberlin, Jeffery K

2015-01-01

Aedes aegypti, the principal vector of yellow fever and dengue fever, is responsible for more than 30,000 deaths annually. Compounds such as carbon dioxide, amino acids, fatty acids and other volatile organic compounds (VOCs) have been widely studied for their role in attracting Ae. aegypti to hosts. Many VOCs from humans are produced by associated skin microbiota. Staphyloccocus epidermidis, although not the most abundant bacteria according to surveys of relative 16S ribosomal RNA abundance, commonly occurs on human skin. Bacteria demonstrate population level decision-making through quorum sensing. Many quorum sensing molecules, such as indole, volatilize and become part of the host odor plum. To date, no one has directly demonstrated the link between quorum sensing (i.e., decision-making) by bacteria associated with a host as a factor regulating arthropod vector attraction. This study examined this specific question with regards to S. epidermidis and Ae. aegypti. Pairwise tests were conducted to examine the response of female Ae. aegypti to combinations of tryptic soy broth (TSB) and S. epidermidis wildtype and agr- strains. The agr gene expresses an accessory gene regulator for quorum sensing; therefore, removing this gene inhibits quorum sensing of the bacteria. Differential attractiveness of mosquitoes to the wildtype and agr- strains was observed. Both wildtype and the agr- strain of S. epidermidis with TSB were marginally more attractive to Ae. aegypti than the TSB alone. Most interestingly, the blood-feeder treated with wildtype S. epidermidis/TSB attracted 74% of Ae. aegypti compared to the agr- strain of S. epidermidis/TSB (P ≤ 0.0001). This study is the first to suggest a role for interkingdom communication between host symbiotic bacteria and mosquitoes. This may have implications for mosquito decision-making with regards to host detection, location and acceptance. We speculate that mosquitoes "eavesdrop" on the chemical discussions occurring between

Effect of Quorum Sensing by Staphylococcus epidermidis on the Attraction Response of Female Adult Yellow Fever Mosquitoes, Aedes aegypti aegypti (Linnaeus (Diptera: Culicidae, to a Blood-Feeding Source.

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Xinyang Zhang

Full Text Available Aedes aegypti, the principal vector of yellow fever and dengue fever, is responsible for more than 30,000 deaths annually. Compounds such as carbon dioxide, amino acids, fatty acids and other volatile organic compounds (VOCs have been widely studied for their role in attracting Ae. aegypti to hosts. Many VOCs from humans are produced by associated skin microbiota. Staphyloccocus epidermidis, although not the most abundant bacteria according to surveys of relative 16S ribosomal RNA abundance, commonly occurs on human skin. Bacteria demonstrate population level decision-making through quorum sensing. Many quorum sensing molecules, such as indole, volatilize and become part of the host odor plum. To date, no one has directly demonstrated the link between quorum sensing (i.e., decision-making by bacteria associated with a host as a factor regulating arthropod vector attraction. This study examined this specific question with regards to S. epidermidis and Ae. aegypti. Pairwise tests were conducted to examine the response of female Ae. aegypti to combinations of tryptic soy broth (TSB and S. epidermidis wildtype and agr- strains. The agr gene expresses an accessory gene regulator for quorum sensing; therefore, removing this gene inhibits quorum sensing of the bacteria. Differential attractiveness of mosquitoes to the wildtype and agr- strains was observed. Both wildtype and the agr- strain of S. epidermidis with TSB were marginally more attractive to Ae. aegypti than the TSB alone. Most interestingly, the blood-feeder treated with wildtype S. epidermidis/TSB attracted 74% of Ae. aegypti compared to the agr- strain of S. epidermidis/TSB (P ≤ 0.0001. This study is the first to suggest a role for interkingdom communication between host symbiotic bacteria and mosquitoes. This may have implications for mosquito decision-making with regards to host detection, location and acceptance. We speculate that mosquitoes "eavesdrop" on the chemical discussions

One man's poison is another man's meat: using azithromycin-induced phospholipidosis to promote ocular surface health.

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Liu, Yang; Kam, Wendy R; Ding, Juan; Sullivan, David A

2014-06-05

Drug-induced phospholipidosis (PLD) is a common adverse effect which has led to the termination of clinical trials for many candidate pharmaceuticals. However, this lipid-inducing effect may be beneficial in the treatment of meibomian gland dysfunction (MGD). MGD is the major cause of dry eye disease (DED), which affects 40 million people in the USA and has no cure. Azithromycin (AZM) is a PLD-inducing antibiotic that is used off-label to treat MGD, and is presumably effective because it suppresses the MGD-associated conjunctival inflammation (i.e. posterior blepharitis) and growth of lid bacteria. We hypothesize that AZM can act directly to promote the function of human meibomian gland epithelial cells by inducing PLD in these cells, characterized by the accumulation of lipids and lysosomes. Immortalized human meibomian gland epithelial cells (HMGEC) were cultured with or without azithromycin for 5 days. Cells were evaluated for cholesterol (Filipin) and neutral lipid (LipidTox) staining, as well as the appearance of lysosomes (LysoTracker) and lamellar bodies (transmission electron microscopy, TEM). The lipid composition of cellular lysates was analyzed by high performance thin-layer chromatography. Our findings demonstrate that AZM stimulates the accumulation of free cholesterol, neutral lipids and lysosomes in HMGEC. This AZM-induced increase of neutral lipid content occurred predominantly within lysosomes. Many of these vesicles appeared to be lamellar bodies by TEM, which is the characteristic of PLD. Our findings also show that AZM promotes an accumulation of free and esterified cholesterol, as well as phospholipids in HMGECimmortalized. Our results support our hypothesis and confirm the beneficial effect of PLD induced by AZM on HMGEC. Our discovery reveals a new potential use of PLD-inducing drugs, and makes this adverse effect a beneficial effect. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The role of quorum sensing in the pathogenicity of the cunning aggressor Pseudomonas aeruginosa

DEFF Research Database (Denmark)

Bjarnsholt, Thomas; Givskov, Michael Christian

2007-01-01

that bacteria preferentially live in communities in the form of primitive organisms in which the behavior of individual cells is coordinated by cell-cell communication, known as quorum sensing (QS). Bacteria use QS for regulation of the processes involved in their interaction with each other, their environment...... in the protective mechanisms of P. aeruginosa and show how disruption of the QS can be used as an approach to control this cunning aggressor....

Comparative Plasma Exposure and Lung Distribution of Two Human Use Commercial Azithromycin Formulations Assessed in Murine Model: A Preclinical Study

OpenAIRE

Rivulgo, Virginia Margarita; Sparo, Mónica; Ceci, Mónica; Fumuso, Elida; Confalonieri, Alejandra; Delpech, Gastón; Sanchez Bruni, Sergio Fabian

2016-01-01

Azithromycin(AZM)therapeutic failure and relapses of patients treated with generic -35 formulations have been observed in clinical practice.The main goal of this research was 36 to compare in a pre-clinical study the serum exposure and lung tissue concentrationof 37 two commercial formulations AZM-based in murine model. The current study involved 38 264 healthy Balb-C.Mice were divided in two groups (n=44): Animals of Group A 39 (Reference Formulation ?R-) were orally treated with AZM suspens...

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....... The rat model of P. aeruginosa lung infection was used in the present study. The rats were killed on days 3, 7, 14 and 28 after infection with the P. aeruginosa strains. The results showed that during the early stages of infection, the PAO1 double mutant induced a stronger serum antibody response, higher...... number of lung bacteria, and minor serum IgG and IgG1 responses but increased lung interferon gamma production were detected in the group infected with the PAO1 double mutant when compared with the PAO1-infected group. Delayed immune responses were observed in the PAO1-infected group and they might...

A randomized, double-masked, parallel-group, comparative study to evaluate the clinical efficacy and safety of 1% azithromycin–0.1% dexamethasone combination compared to 1% azithromycin alone, dexamethasone 0.1% alone, and vehicle in the treatment of subjects with blepharitis

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Hosseini K

2016-08-01

Full Text Available Kamran Hosseini,1 Richard L Lindstrom,2,3 Gary Foulks,4 Kelly K Nichols5 1InSite Vision, Alameda, CA, 2Minnesota Eye Consultants, 3Department of Ophthalmology and Visual Neurosciences, University of Minnesota Medical School, Minneapolis, MN, 4Department of Ophthalmology and Vision Science, School of Medicine, University of Louisville, Louisville, KY, 5School of Optometry, University of Alabama at Birmingham, Birmingham, AL, USA Purpose: To evaluate the clinical efficacy and safety of a 1% azithromycin–0.1% dexamethasone combination in DuraSite (“combination” compared to 0.1% dexamethasone in DuraSite, 1% azithromycin in DuraSite, and vehicle in the treatment of subjects with blepharitis.Materials and methods: This was a Phase III, double-masked, vehicle-controlled, four-arm study in which 907 subjects with blepharitis were randomized to combination (n=305, 0.1% dexamethasone (n=298, 1% azithromycin (n=155, or vehicle (n=149. Ten study visits were scheduled: screening visit, days 1 and 4 (dosing phase and 15, and months 1–6 (follow-up phase. On day 1, subjects applied one drop of the study drug to the eyelid of the inflamed eye(s twice daily, and continued with twice-daily dosing for 14 days. After completing 14 days of dosing, subjects were followed for 6 months for efficacy and safety.Results: A total of 57 subjects (6.3% had complete clinical resolution at day 15: 25 (8.2%, 17 (5.7%, 8 (5.2%, and 7 (4.7% subjects in the combination-, 0.1% dexamethasone-, 1% azithromycin-, and vehicle-treatment groups, respectively. The combination was superior to 1% azithromycin and vehicle alone, but not to 0.1% dexamethasone alone. Mean composite (total clinical sign and symptom scores improved in all four treatment groups during the posttreatment evaluation phase for the intent-to-treat population, but outcomes were superior when a drop containing 0.1% dexamethasone was utilized. Clinical response was noted as early as day 4, and persisted as long

AI-2 does not function as a quorum sensing molecule in Campylobacter jejuni during exponential growth in vitro

NARCIS (Netherlands)

Holmes, K.; Tavender, T.J.; Winzer, K.; Wells, J.; Hardie, K.

2009-01-01

Background - Campylobacter jejuni contains a homologue of the luxS gene shown to be responsible for the production of the signalling molecule autoinducer-2 (AI-2) in Vibrio harveyi and Vibrio cholerae. The aim of this study was to determine whether AI-2 acted as a diffusible quorum sensing signal

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

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Abd-Alla, Mohamed H; Bashandy, Shymaa R

2012-01-01

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

Quorum quenching bacteria can be used to inhibit the biofouling of reverse osmosis membranes.

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Oh, Hyun-Suk; Tan, Chuan Hao; Low, Jiun Hui; Rzechowicz, Miles; Siddiqui, Muhammad Faisal; Winters, Harvey; Kjelleberg, Staffan; Fane, Anthony G; Rice, Scott A

2017-04-01

Over the last few decades, significant efforts have concentrated on mitigating biofouling in reverse osmosis (RO) systems, with a focus on non-toxic and sustainable strategies. Here, we explored the potential of applying quorum quenching (QQ) bacteria to control biofouling in a laboratory-scale RO system. For these experiments, Pantoea stewartii was used as a model biofilm forming organism because it was previously shown to be a relevant wastewater isolate that also forms biofilms in a quorum sensing (QS) dependent fashion. A recombinant Escherichia coli strain, which can produce a QQ enzyme, was first tested in batch biofilm assays and significantly reduced biofilm formation by P. stewartii. Subsequently, RO membranes were fouled with P. stewartii and the QQ bacterium was introduced into the RO system using two different strategies, direct injection and immobilization within a cartridge microfilter. When the QQ bacterial cells were directly injected into the system, N-acylhomoserine lactone signals were degraded, resulting in the reduction of biofouling. Similarly, the QQ bacteria controlled biofouling when immobilized within a microfilter placed downstream of the RO module to remove QS signals circulating in the system. These results demonstrate the proof-of-principle that QQ can be applied to control biofouling of RO membranes and may be applicable for use in full-scale plants. Copyright © 2017 Elsevier Ltd. All rights reserved.

The quorum-quenching N-acyl homoserine lactone acylase PvdQ is an Ntn-hydrolase with an unusual substrate-binding pocket

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Bokhove, Marcel; Jimenez, Pol Nadal; Quax, Wim J.; Dijkstra, Bauke W.

2010-01-01

In many Gram-negative pathogens, their virulent behavior is regulated by quorum sensing, in which diffusible signals such as N-acyl homoserine lactones (AHLs) act as chemical messaging compounds. Enzymatic degradation of these diffusible signals by, e. g., lactonases or amidohydrolases abolishes AHL

Phase transition approach to bursting in neuronal cultures: quorum percolation models

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Monceau, P.; Renault, R.; Métens, S.; Bottani, S.; Fardet, T.

2017-10-01

The Quorum Percolation model has been designed in the context of neurobiology to describe bursts of activity occurring in neuronal cultures from the point of view of statistical physics rather than from a dynamical synchronization approach. It is based upon information propagation on a directed graph with a threshold activation rule; this leads to a phase diagram which exhibits a giant percolation cluster below some critical value mC of the excitability. We describe the main characteristics of the original model and derive extensions according to additional relevant biological features. Firstly, we investigate the effects of an excitability variability on the phase diagram and show that the percolation transition can be destroyed by a sufficient amount of such a disorder; we stress the weakly averaging character of the order parameter and show that connectivity and excitability can be seen as two overlapping aspects of the same reality. Secondly, we elaborate a discrete time stochastic model taking into account the decay originating from ionic leakage through the membrane of neurons and synaptic depression; we give evidence that the decay softens and shifts the transition, and conjecture than decay destroys the transition in the thermodynamical limit. We were able to develop mean-field theories associated with each of the two effects; we discuss the framework of their agreement with Monte Carlo simulations. It turns out that the the critical point mC from which information on the connectivity of the network can be inferred is affected by each of these additional effects. Lastly, we show how dynamical simulations of bursts with an adaptive exponential integrateand- fire model can be interpreted in terms of Quorum Percolation. Moreover, the usefulness of the percolation model including the set of sophistication we investigated can be extended to many scientific fields involving information propagation, such as the spread of rumors in sociology, ethology, ecology.

Flagellin and F4 fimbriae have opposite effects on biofilm formation and quorum sensing in F4ac+ enterotoxigenic Escherichia coli.

Science.gov (United States)

Zhou, Mingxu; Guo, Zhiyan; Yang, Yang; Duan, Qiangde; Zhang, Qi; Yao, Fenghua; Zhu, Jun; Zhang, Xinjun; Hardwidge, Philip R; Zhu, Guoqiang

2014-01-10

Bacteria that form biofilms are often highly resistant to antibiotics and are capable of evading the host immune system. To evaluate the role of flagellin and F4 fimbriae on biofilm formation by enterotoxigenic Escherichia coli (ETEC), we deleted the fliC (encoding the major flagellin protein) and/or the faeG (encoding the major subunit of F4 fimbriae) genes from ETEC C83902. Biofilm formation was reduced in the fliC mutant but increased in the faeG mutant, as compared with the wild-type strain. The expression of AI-2 quorum sensing associated genes was regulated in the fliC and faeG mutants, consistent with the biofilm formation of these strains. But, deleting fliC and/or faeG also inhibited AI-2 quorum sensing activity. Copyright © 2013 Elsevier B.V. All rights reserved.

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

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Kirnasovsky Oleg U

2010-04-01

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

Toxicity and disruption of quorum sensing in Aliivibrio fisheri by environmental chemicals: Impacts of selected contaminants and microplastics

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François Gagné

2017-11-01

Full Text Available The purpose of this study was to examine the effects of dissolved and particulate compounds on quorum sensing in the marine luminescent bacterium Aliivibrio fisheri. Bacteria were exposed to increasing concentrations of CuSO4 (Cu2+, gadolinium chloride (Gd3+, 20-nm silver nanoparticles (nanoAg and 1-3 μm microplastic polyethylene beads for 250 min. During this period, luminescence measurements were taken at 5-min intervals. Toxicity was first examined by measuring luminescence output at 5-min and 30-min incubation time. Based on the effective concentration that decreases luminescence by 20% (EC20, the compounds were toxic at the following concentrations in decreasing toxicity: Cu2+ (3.2 mg/L < nanoAg (3.4 mg/L, reported < Gd3+ (34 mg/L < microplastics (2.6 g/L. The data revealed that luminescence changed non-linearly over time. In control bacteria, luminescence changed at eight specific major frequencies between 0.04 and 0.27 cycle/min after Fourier transformation of time-dependent luminescence data. The addition of dissolved Cu2+ and Gd3+ eliminated the amplitude changes at these frequencies in a concentration-dependent manner, indicating loss of quorum sensing between bacteria at concentrations below EC20. In the presence of nanoAg and microplastic beads, the decreases in amplitudes were modest but compressed the luminescence profiles, with shorter frequencies appearing at concentrations well below EC20. Thus, loss of communication between bacteria occurs at non-toxic concentrations. In addition, with exposure to a mixture of the above compounds at concentrations that do not produce effects for Gd3+, nanoAg and microplastics, Cu2+ toxicity was significantly enhanced, suggesting synergy. This study revealed for the first time that small microplastic particles and nanoparticles can disrupt quorum sensing in marine bacteria.

Why Quorum Sensing Controls Private Goods

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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.

Failure of both azithromycin and antimony to treat cutaneous leishmaniasis in Manaus, AM, Brazil Falha da azitromicina e do antimonial no tratamento da leishmaniose cutânea em Manaus, AM, Brasil

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Alan César Teixeira

2008-06-01

Full Text Available A non-randomized controlled clinical trial was carried outin order to evaluate both azithromycin and antimony efficacy in cutaneous leishmaniasis in Manaus, AM, Brazil. Forty nine patients from both genders, aged 14 to 70, with cutaneous ulcers for less than three months and a positive imprint for Leishmania spp. amastigotes were recruited into two groups. Group I (26 patients received a daily-single oral dose of 500 mg of azithromycin for 20 days and Group II (23 patients received a daily-single intramuscular dose of 20 mg/kg of meglumine antimony, also for 20 days. Azithromycin cured three of 24 (12.5% patients on days 60, 90 and 120 respectively whereas therapeutic failure was considered in 21 of 24 (87.5% cases. In group II, antimony cured eight of 19 (42.1% cases as follows: three on day 30, one each on day 60 and day 90, and three on day 120. Therapeutic failure occurred in 11 of 19 (57.9% individuals. The efficacy of antimony for leishmaniasis was better than azithromycin but analysis for the intention-to-treat response rate did not show statistical difference between them. Although azithromycin was better tolerated, it showed a very low efficacy to treat cutaneous leishmaniasis in Manaus.Com o objetivo de avaliar a eficácia da azitromicina no tratamento da leishmaniose cutânea, foi realizado ensaio comparativo, em Manaus. Foram recrutados 49 pacientes de ambos os sexos, com idades entre 14 e 70 anos que apresentassem úlceras cutâneas com menos de três meses de evolução e que tivessem exame direto positivo para amastigotas de leishmânia. Estes pacientes foram alocados em dois grupos assim: Grupo I (26 recebeu uma dose diária de 500 mg de azitromicina pela via oral durante 20 dias e o Grupo II, recebeu uma dose diária de 20 mg/kg de antimoniato de meglumina por via intramuscular, durante 20 dias. Do grupo da azitromicina, três (12,5% de 24 pacientes curaram 60, 90 e 120 dias, respectivamente, enquanto, em 21 (87,5% de 24 houve

Facile synthesis of the necklace-like graphene oxide-multi-walled carbon nanotube nanohybrid and its application in electrochemical sensing of Azithromycin

Energy Technology Data Exchange (ETDEWEB)

Zhang, Kaixin [Jiangxi Key Laboratory of Organic Chemistry, Jiangxi Science and Technology Normal University, Nanchang 330013 (China); Lu, Limin; Wen, Yangping [Jiangxi Key Laboratory of Organic Chemistry, Jiangxi Science and Technology Normal University, Nanchang 330013 (China); College of Science, Jiangxi Agricultural University, Nanchang 330045 (China); Xu, Jingkun, E-mail: xujingkun@tsinghua.org.cn [Jiangxi Key Laboratory of Organic Chemistry, Jiangxi Science and Technology Normal University, Nanchang 330013 (China); Duan, Xuemin; Zhang, Long; Hu, Dufen [Jiangxi Key Laboratory of Organic Chemistry, Jiangxi Science and Technology Normal University, Nanchang 330013 (China); Nie, Tao [Jiangxi Key Laboratory of Organic Chemistry, Jiangxi Science and Technology Normal University, Nanchang 330013 (China); College of Science, Jiangxi Agricultural University, Nanchang 330045 (China)

2013-07-17

Graphical abstract: -- Highlights: •The necklace-like GO-MWCNTs nanohybrid was facilely synthesized by ultrasonication. •The nanocomposites can be effectively used for the detection of Azithromycin. •Low detection limit with wide linear range could be obtained. •The method was applied to determine Azi in real samples. -- Abstract: A novel electrochemical platform was designed for the determination of Azithromycin (Azi), a widely used macrolide antibiotic, by combining the hydrophilic properties of graphene oxide (GO) and the excellent electronic and antifouling properties of multi-walled carbon nanotubes (MWCNTs). Stable MWCNTs aqueous dispersion has been prepared using GO nano-sheets as surfactant and the obtained GO-MWCNTs nanohybrid was characterized by UV–vis spectroscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, transmission electron microscopy and electrochemical impedance spectroscopy, which confirmed that GO nano-sheets were attached onto the wall of MWCNTs to form a necklace-like structure. Electrochemical results obviously reveal that the oxidation peak currents of Azi obtained at the GC electrode modified with GO-MWCNTs hybrid are much higher than those at the MWCNTs/GC, GO/GC and bare GC electrodes. Under optimized conditions, the anodic peak current was linear to the concentration of Azi in the range from 0.1 to 10 μM with the detection limit of 0.07 μM. To further validate its possible application, the proposed method was successfully used for the determination of Azi in pharmaceutical formulations with satisfactory results.

Facile synthesis of the necklace-like graphene oxide-multi-walled carbon nanotube nanohybrid and its application in electrochemical sensing of Azithromycin

International Nuclear Information System (INIS)

Zhang, Kaixin; Lu, Limin; Wen, Yangping; Xu, Jingkun; Duan, Xuemin; Zhang, Long; Hu, Dufen; Nie, Tao

2013-01-01

Graphical abstract: -- Highlights: •The necklace-like GO-MWCNTs nanohybrid was facilely synthesized by ultrasonication. •The nanocomposites can be effectively used for the detection of Azithromycin. •Low detection limit with wide linear range could be obtained. •The method was applied to determine Azi in real samples. -- Abstract: A novel electrochemical platform was designed for the determination of Azithromycin (Azi), a widely used macrolide antibiotic, by combining the hydrophilic properties of graphene oxide (GO) and the excellent electronic and antifouling properties of multi-walled carbon nanotubes (MWCNTs). Stable MWCNTs aqueous dispersion has been prepared using GO nano-sheets as surfactant and the obtained GO-MWCNTs nanohybrid was characterized by UV–vis spectroscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, transmission electron microscopy and electrochemical impedance spectroscopy, which confirmed that GO nano-sheets were attached onto the wall of MWCNTs to form a necklace-like structure. Electrochemical results obviously reveal that the oxidation peak currents of Azi obtained at the GC electrode modified with GO-MWCNTs hybrid are much higher than those at the MWCNTs/GC, GO/GC and bare GC electrodes. Under optimized conditions, the anodic peak current was linear to the concentration of Azi in the range from 0.1 to 10 μM with the detection limit of 0.07 μM. To further validate its possible application, the proposed method was successfully used for the determination of Azi in pharmaceutical formulations with satisfactory results

The Belgian trial with azithromycin for acute COPD exacerbations requiring hospitalization: an investigator-initiated study protocol for a multicenter, randomized, double-blind, placebo-controlled trial

Directory of Open Access Journals (Sweden)

Vermeersch K

2016-03-01

Full Text Available Kristina Vermeersch,1 Maria Gabrovska,2 Griet Deslypere,3 Ingel K Demedts,4 Hans Slabbynck,5 Joseph Aumann,3 Vincent Ninane,2 Geert M Verleden,1 Thierry Troosters,1,6 Kris Bogaerts,7,8 Guy G Brusselle,9 Wim Janssens1 On behalf of the BACE Trial Investigators 1KU Leuven, Laboratory of Respiratory Diseases, Department of Clinical and Experimental Medicine, Faculty of Medicine, Leuven, Belgium; 2Department of Pneumology, Centre Hospitalier Universitaire Saint-Pierre, Brussels, Belgium; 3Department of Pneumology, Jessa Ziekenhuis, Hasselt, Belgium; 4Department of Respiratory Medicine, AZ Delta Roeselare-Menen, Roeselare, Belgium; 5Department of Respiratory Medicine, ZNA Middelheim, Antwerpen, Belgium; 6KU Leuven, Department of Rehabilitation Sciences, Faculty of Kinesiology and Rehabilitation Sciences, Leuven, Belgium; 7KU Leuven, Department of Public Health and Primary Care, I-BioStat, Leuven, Belgium; 8Hasselt University, Hasselt, Belgium; 9Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium Background: Long-term use of macrolide antibiotics is effective to prevent exacerbations in chronic obstructive pulmonary disease (COPD. As risks and side effects of long-term intervention outweigh the benefits in the general COPD population, the optimal dose, duration of treatment, and target population are yet to be defined. Hospitalization for an acute exacerbation (AE of COPD may offer a targeted risk group and an obvious risk period for studying macrolide interventions.Methods/design: Patients with COPD, hospitalized for an AE, who have a smoking history of ≥10 pack-years and had ≥1 exacerbation in the previous year will be enrolled in a multicenter, randomized, double-blind, placebo-controlled trial (NCT02135354. On top of a standardized treatment of systemic corticosteroids and antibiotics, subjects will be randomized to receive either azithromycin or placebo during 3 months, at an uploading dose of 500 mg once a day for

Inhibition of quorum sensing-mediated virulence in Serratia marcescens by Bacillus subtilis R-18.

Science.gov (United States)

Devi, Kannan Rama; Srinivasan, Subramaniyan; Ravi, Arumugam Veera

2018-04-13

Serratia marcescens is an opportunistic human pathogen causing various nosocomial infections, most importantly urinary tract infections (UTIs). It exhibits increased resistance towards the conventional antibiotics. This study was aimed to evaluate the anti-virulence effect of a rhizosphere soil bacterium Bacillus subtilis strain R-18 against the uropathogen S. marcescens. First, the bacterial cell-free culture supernatant (CFCS) of B. subtilis strain R-18 was evaluated for its quorum sensing inhibitory (QSI) potential against biomarker strain Chromobacterium violaceum and the test pathogen S. marcescens. The B. subtilis R-18 CFCS effectively inhibited the quorum sensing (QS)-mediated violacein pigment production in C. violaceum and prodigiosin pigment production in S. marcescens. Furthermore, B. subtilis R-18 CFCS was successively extracted with different solvent systems. Of these solvents, B. subtilis R-18 petroleum ether (PE) extract showed inhibition in biofilm formation, protease, lipase, and hemolysin productions in S. marcescens. Fourier transform infrared spectroscopic (FT-IR) analysis revealed the alterations in the cellular components of bacterial cell pellets obtained from B. subtilis R-18 PE extract treated and untreated S. marcescens. The differential gene expression study further validated the downregulation of virulence-associated genes. Characterization of the active principle in B. subtilis R-18 PE extract by gas chromatography-mass spectrometry (GC-MS) analysis showed the presence of multiple compounds with therapeutic values, which could possibly reduce the QS-dependent phenotypes in S. marcescens. Copyright © 2018. Published by Elsevier Ltd.

Effect of organic acids on biofilm formation and quorum signaling of pathogens from fresh fruits and vegetables.

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Amrutha, Balagopal; Sundar, Kothandapani; Shetty, Prathapkumar Halady

2017-10-01

Organic acids are known to be used as food preservatives due to their antimicrobial potential. This study evaluated the ability of three organic acids, namely, acetic acid, citric acid and lactic acid to manage E. coli and Salmonella sp. from fresh fruits and vegetables. Effect of these organic acids on biofilm forming ability and anti-quorum potential was also investigated. The effect of organic acids on inactivation of E. coli and Salmonella sp. on the surface of a selected vegetable (cucumber) was determined. The minimum inhibitory concentration of the organic acids were found to be 1.5, 2 and 0.2% in E. coli while it was observed to be 1, 1.5 and 1% in Salmonella sp. for acetic, citric and lactic acids respectively. Maximum inhibition of biofilm formation was recorded at 39.13% with lactic acid in E. coli and a minimum of 22.53% with citric acid in Salmonella sp. EPS production was affected in E. coli with lactic acid showing reduction by 13.42% while citric acid and acetic acid exhibited only 6.25% and 10.89% respectively. Swimming and swarming patterns in E. coli was notably affected by both acetic and lactic acids. Lactic and acetic acids showed higher anti-quorum sensing (QS) potential when compared to citric acid. 2% lactic acid showed a maximum inhibition of violacein production by 37.7%. Organic acids can therefore be used as potential quorum quenching agents in food industry. 2% lactic acid treatment on cucumber demonstrated that it was effective in inactivating E. coli and Salmonella sp. There was 1 log reduction in microbial count over a period of 6 days after the lactic acid treatment. Thus, organic acids can act as effective potential sanitizers in reducing the microbial load associated with fresh fruits and vegetables. Copyright © 2017 Elsevier Ltd. All rights reserved.

Where antibiotic resistance mutations meet quorum-sensing

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Rok Krašovec

2014-06-01

Full Text Available We do not need to rehearse the grim story of the global rise of antibiotic resistant microbes. But what if it were possible to control the rate with which antibiotic resistance evolves by de novo mutation? It seems that some bacteria may already do exactly that: they modify the rate at which they mutate to antibiotic resistance dependent on their biological environment. In our recent study [Krašovec, et al. Nat. Commun. (2014, 5, 3742] we find that this modification depends on the density of the bacterial population and cell-cell interactions (rather than, for instance, the level of stress. Specifically, the wild-type strains of Escherichia coli we used will, in minimal glucose media, modify their rate of mutation to rifampicin resistance according to the density of wild-type cells. Intriguingly, the higher the density, the lower the mutation rate (Figure 1. Why this novel density-dependent ‘mutation rate plasticity’ (DD-MRP occurs is a question at several levels. Answers are currently fragmentary, but involve the quorum-sensing gene luxS and its role in the activated methyl cycle.

Quorum-sensing and cheating in bacterial biofilms

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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

Saturation mutagenesis of a CepR binding site as a means to identify new quorum-regulated promoters in Burkholderia cenocepacia

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Burkholderia cenocepacia, an opportunistic pathogen of humans, encodes the CepI and CepR proteins, which resemble the LuxI and LuxR quorum sensing proteins of Vibrio fischeri. CepI directs the synthesis of octanoylhomoserine lactone (OHL), while CepR is an OHL dependent transcription factor. In pr...

Quorum-sensing-regulated virulence factors in Pseudomonas aeruginosa are toxic to Lucilia sericata maggots

DEFF Research Database (Denmark)

Andersen, A S; Joergensen, B; Bjarnsholt, T

2010-01-01

Maggot debridement therapy (MDT) is widely used for debridement of chronic infected wounds; however, for wounds harbouring specific bacteria limited effect or failure of the treatment has been described. Here we studied the survival of Lucilia sericata maggots encountering Pseudomonas aeruginosa...... PAO1 in a simple assay with emphasis on the quorum-sensing (QS)-regulated virulence. The maggots were challenged with GFP-tagged P. aeruginosa wild-type (WT) PAO1 and a GFP-tagged P. aeruginosa DeltalasR rhlR (DeltaRR) QS-deficient mutant in different concentrations. Maggots were killed...

Influence of Nutrient Availability and Quorum Sensing on the Formation of Metabolically Inactive Microcolonies Within Structurally Heterogeneous Bacterial Biofilms: An Individual-Based 3D Cellular Automata Model.

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Machineni, Lakshmi; Rajapantul, Anil; Nandamuri, Vandana; Pawar, Parag D

2017-03-01

The resistance of bacterial biofilms to antibiotic treatment has been attributed to the emergence of structurally heterogeneous microenvironments containing metabolically inactive cell populations. In this study, we use a three-dimensional individual-based cellular automata model to investigate the influence of nutrient availability and quorum sensing on microbial heterogeneity in growing biofilms. Mature biofilms exhibited at least three structurally distinct strata: a high-volume, homogeneous region sandwiched between two compact sections of high heterogeneity. Cell death occurred preferentially in layers in close proximity to the substratum, resulting in increased heterogeneity in this section of the biofilm; the thickness and heterogeneity of this lowermost layer increased with time, ultimately leading to sloughing. The model predicted the formation of metabolically dormant cellular microniches embedded within faster-growing cell clusters. Biofilms utilizing quorum sensing were more heterogeneous compared to their non-quorum sensing counterparts, and resisted sloughing, featuring a cell-devoid layer of EPS atop the substratum upon which the remainder of the biofilm developed. Overall, our study provides a computational framework to analyze metabolic diversity and heterogeneity of biofilm-associated microorganisms and may pave the way toward gaining further insights into the biophysical mechanisms of antibiotic resistance.

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

OpenAIRE

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

2013-01-01

Various parts of Piper nigrum, Piper betle and Gnetum gnemon are used as food sources by Malaysians. The purpose of this study is to examine the anti-quorum sensing (anti-QS) properties of P. nigrum, P. betle and G. gnemon extracts. The hexane, chloroform and methanol extracts of these plants were assessed in bioassays involving Pseudomonas aeruginosa PA01, Escherichia coli [pSB401], E. coli [pSB1075] and Chromobacterium violaceum CV026. It was found that the extracts of these three plants ha...

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

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Zheng eWang

2013-12-01

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

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

Science.gov (United States)

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

2013-01-01

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

A Pyranose-2-Phosphate Motif Is Responsible for Both Antibiotic Import and Quorum-Sensing Regulation in Agrobacterium tumefaciens.

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Abbas El Sahili

2015-08-01

Full Text Available Periplasmic binding proteins (PBPs in association with ABC transporters select and import a wide variety of ligands into bacterial cytoplasm. They can also take up toxic molecules, as observed in the case of the phytopathogen Agrobacterium tumefaciens strain C58. This organism contains a PBP called AccA that mediates the import of the antibiotic agrocin 84, as well as the opine agrocinopine A that acts as both a nutrient and a signalling molecule for the dissemination of virulence genes through quorum-sensing. Here, we characterized the binding mode of AccA using purified agrocin 84 and synthetic agrocinopine A by X-ray crystallography at very high resolution and performed affinity measurements. Structural and affinity analyses revealed that AccA recognizes an uncommon and specific motif, a pyranose-2-phosphate moiety which is present in both imported molecules via the L-arabinopyranose moiety in agrocinopine A and the D-glucopyranose moiety in agrocin 84. We hypothesized that AccA is a gateway allowing the import of any compound possessing a pyranose-2-phosphate motif at one end. This was structurally and functionally confirmed by experiments using four synthetic compounds: agrocinopine 3'-O-benzoate, L-arabinose-2-isopropylphosphate, L-arabinose-2-phosphate and D-glucose-2-phosphate. By combining affinity measurements and in vivo assays, we demonstrated that both L-arabinose-2-phosphate and D-glucose-2-phosphate, which are the AccF mediated degradation products of agrocinopine A and agrocin 84 respectively, interact with the master transcriptional regulator AccR and activate the quorum-sensing signal synthesis and Ti plasmid transfer in A. tumefaciens C58. Our findings shed light on the role of agrocinopine and antibiotic agrocin 84 on quorum-sensing regulation in A. tumefaciens and reveal how the PBP AccA acts as vehicle for the importation of both molecules by means of a key-recognition motif. It also opens future possibilities for the

A Pyranose-2-Phosphate Motif Is Responsible for Both Antibiotic Import and Quorum-Sensing Regulation in Agrobacterium tumefaciens.

Science.gov (United States)

El Sahili, Abbas; Li, Si-Zhe; Lang, Julien; Virus, Cornelia; Planamente, Sara; Ahmar, Mohammed; Guimaraes, Beatriz G; Aumont-Nicaise, Magali; Vigouroux, Armelle; Soulère, Laurent; Reader, John; Queneau, Yves; Faure, Denis; Moréra, Solange

2015-08-01

Periplasmic binding proteins (PBPs) in association with ABC transporters select and import a wide variety of ligands into bacterial cytoplasm. They can also take up toxic molecules, as observed in the case of the phytopathogen Agrobacterium tumefaciens strain C58. This organism contains a PBP called AccA that mediates the import of the antibiotic agrocin 84, as well as the opine agrocinopine A that acts as both a nutrient and a signalling molecule for the dissemination of virulence genes through quorum-sensing. Here, we characterized the binding mode of AccA using purified agrocin 84 and synthetic agrocinopine A by X-ray crystallography at very high resolution and performed affinity measurements. Structural and affinity analyses revealed that AccA recognizes an uncommon and specific motif, a pyranose-2-phosphate moiety which is present in both imported molecules via the L-arabinopyranose moiety in agrocinopine A and the D-glucopyranose moiety in agrocin 84. We hypothesized that AccA is a gateway allowing the import of any compound possessing a pyranose-2-phosphate motif at one end. This was structurally and functionally confirmed by experiments using four synthetic compounds: agrocinopine 3'-O-benzoate, L-arabinose-2-isopropylphosphate, L-arabinose-2-phosphate and D-glucose-2-phosphate. By combining affinity measurements and in vivo assays, we demonstrated that both L-arabinose-2-phosphate and D-glucose-2-phosphate, which are the AccF mediated degradation products of agrocinopine A and agrocin 84 respectively, interact with the master transcriptional regulator AccR and activate the quorum-sensing signal synthesis and Ti plasmid transfer in A. tumefaciens C58. Our findings shed light on the role of agrocinopine and antibiotic agrocin 84 on quorum-sensing regulation in A. tumefaciens and reveal how the PBP AccA acts as vehicle for the importation of both molecules by means of a key-recognition motif. It also opens future possibilities for the rational design of

Mechanistic explanation of time-dependent cross-phenomenon based on quorum sensing: A case study of the mixture of sulfonamide and quorum sensing inhibitor to bioluminescence of Aliivibrio fischeri.

Science.gov (United States)

Sun, Haoyu; Pan, Yongzheng; Gu, Yue; Lin, Zhifen

2018-07-15

Cross-phenomenon in which the concentration-response curve (CRC) for a mixture crosses the CRC for the reference model has been identified in many studies, expressed as a heterogeneous pattern of joint toxic action. However, a mechanistic explanation of the cross-phenomenon has thus far been extremely insufficient. In this study, a time-dependent cross-phenomenon was observed, in which the cross-concentration range between the CRC for the mixture of sulfamethoxypyridazine (SMP) and (Z-)-4-Bromo-5-(bromomethylene)-2(5H)-furanone (C30) to the bioluminescence of Aliivibrio fischeri (A. fischeri) and the CRC for independent action model with 95% confidence bands varied from low-concentration to higher-concentration regions in a timely manner expressed the joint toxic action of the mixture changing with an increase of both concentration and time. Through investigating the time-dependent hormetic effects of SMP and C30 (by measuring the expression of protein mRNA, simulating the bioluminescent reaction and analyzing the toxic action), the underlying mechanism was as follows: SMP and C30 acted on the quorum sensing (QS) system of A. fischeri, which induced low-concentration stimulatory effects and high-concentration inhibitory effects; in the low-concentration region, the stimulatory effects of SMP and C30 made the mixture produce a synergistic stimulation on the bioluminescence; thus, the joint toxic action exhibited antagonism. In the high-concentration region, the inhibitory effects of SMP and C30 in the mixture caused a double block in the loop circuit of the QS system; thus, the joint toxic action exhibited synergism. With the increase of time, these stimulatory and inhibitory effects of SMP and C30 were changed by the variation of the QS system at different growth phases, resulting in the time-dependent cross-phenomenon. This study proposes an induced mechanism for time-dependent cross-phenomenon based on QS, which may provide new insight into the mechanistic

Signal Integration in Quorum Sensing Enables Cross-Species Induction of Virulence in Pectobacterium wasabiae

Directory of Open Access Journals (Sweden)

Rita S. Valente

2017-05-01

Full Text Available Bacterial communities can sense their neighbors, regulating group behaviors in response to cell density and environmental changes. The diversity of signaling networks in a single species has been postulated to allow custom responses to different stimuli; however, little is known about how multiple signals are integrated and the implications of this integration in different ecological contexts. In the plant pathogen Pectobacterium wasabiae (formerly Erwinia carotovora, two signaling networks—the N-acyl homoserine lactone (AHL quorum-sensing system and the Gac/Rsm signal transduction pathway—control the expression of secreted plant cell wall-degrading enzymes, its major virulence determinants. We show that the AHL system controls the Gac/Rsm system by affecting the expression of the regulatory RNA RsmB. This regulation is mediated by ExpR2, the quorum-sensing receptor that responds to the P. wasabiae cognate AHL but also to AHLs produced by other bacterial species. As a consequence, this level of regulation allows P. wasabiae to bypass the Gac-dependent regulation of RsmB in the presence of exogenous AHLs or AHL-producing bacteria. We provide in vivo evidence that this pivotal role of RsmB in signal transduction is important for the ability of P. wasabiae to induce virulence in response to other AHL-producing bacteria in multispecies plant lesions. Our results suggest that the signaling architecture in P. wasabiae was coopted to prime the bacteria to eavesdrop on other bacteria and quickly join the efforts of other species, which are already exploiting host resources.

Detection of possible AI-2-mediated quorum sensing system in commensal intestinal bacteria.

Science.gov (United States)

Lukás, F; Gorenc, G; Kopecný, J

2008-01-01

The Vibrio harveyi strain BB170-autoinducer bioassay was used to detect possible quorum sensing autoinducer-2 molecule (AI-2) in culture fluids of commensal intestinal bacteria. Culture fluids of Bacteroides vulgatus, Clostridium proteoclasticum, Escherichia coli, Eubacterium rectale, Lachnospira multipara, Pseudobutyrivibrio ruminis, Roseburia intestinalis, Ruminococcus albus and Ruminococcus flavefaciens contained AI-2-like molecules. The PCR bands from some of the tested strains could be also amplified using primers designed for the luxS gene. These findings suggest that AI-2 is present in the gastrointestinal tract; however, it has not yet been proved whether it is used for bacterial cell-to-cell communication.

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

Science.gov (United States)

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

2015-08-01

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

An efficient, block-by-block algorithm for inverting a block tridiagonal, nearly block Toeplitz matrix

International Nuclear Information System (INIS)

Reuter, Matthew G; Hill, Judith C

2012-01-01

We present an algorithm for computing any block of the inverse of a block tridiagonal, nearly block Toeplitz matrix (defined as a block tridiagonal matrix with a small number of deviations from the purely block Toeplitz structure). By exploiting both the block tridiagonal and the nearly block Toeplitz structures, this method scales independently of the total number of blocks in the matrix and linearly with the number of deviations. Numerical studies demonstrate this scaling and the advantages of our method over alternatives.

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.

Attenuation of Vibrio fischeri quorum sensing using rationally designed polymers.

Science.gov (United States)

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

2010-04-12

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

Qualitative and quantitative determination of quorum sensing inhibition in vitro

DEFF Research Database (Denmark)

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

2011-01-01

of reporter strains consisting of a lasB-gfp or rhlA-gfp fusion in P. aeruginosa for qualitative and quantitative evaluation of the inhibition of the two major QS pathways, monitored as reduced expression of green fluorescence. By the use of an in vitro flow cell system it is possible to study the QSI...... 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...... activity by monitoring its ability to interfere with the protective functions of bacterial biofilm. For evaluation of the global effects of QSI compounds, we present a protocol for the DNA microarray-based transcriptomics. Using these in vitro methods it is possible to evaluate the potential of various QSI...

Panax ginseng has anti-infective activity against opportunistic pathogen Pseudomonas aeruginosa by inhibiting quorum sensing, a bacterial communication process critical for establishing infection

DEFF Research Database (Denmark)

Song, Z; Kong, K F; Wu, H

2010-01-01

Virulent factors produced by pathogens play an important role in the infectious process, which is regulated by a cell-to-cell communication mechanism called quorum sensing (QS). Pseudomonas aeruginosa is an important opportunistic human pathogen, which causes infections in patients with compromis...

Two homologous Agr-like quorum-sensing systems cooperatively control adherence, cell morphology, and cell viability properties in Lactobacillus plantarum WCFS1

NARCIS (Netherlands)

Fujii, T.; Ingham, C.J.; Nakayama, J.; Beerthuyzen, M.M.; Kunuki, R.; Molenaar, D.; Sturme, M.H.J.; Vaughan, E.E.; Kleerebezem, M.; Vos, de W.M.

2008-01-01

A two-component regulatory system of Lactobacillus plantarum, encoded by genes designated lamK and lamR (hpk10 and rrp10), was studied. The lamK and lamR genes encode proteins which are highly homologous to the quorum-sensing histidine kinase LamC and the response regulator LamA, respectively.

A novel screen-printed mast cell-based electrochemical sensor for detecting spoilage bacterial quorum signaling molecules (N-acyl-homoserine-lactones) in freshwater fish.

Science.gov (United States)

Jiang, Donglei; Liu, Yan; Jiang, Hui; Rao, Shengqi; Fang, Wu; Wu, Mangang; Yuan, Limin; Fang, Weiming

2018-04-15

A novel screen-printed cell-based electrochemical sensor was developed to assess bacterial quorum signaling molecules, N-acylhomoserine lactones (AHLs). Screen-printed carbon electrode (SPCE), which possesses excellent properties such as low-cost, disposable and energy-efficient, was modified with multi-walled carbon nanotubes (MWNTs) to improve electrochemical signals and enhance the sensitivity. Rat basophilic leukemia (RBL-2H3) mast cells encapsulated in alginate/graphene oxide (NaAgl/GO) hydrogel were immobilized on the MWNTs/SPCE to serve as recognition element. Electrochemical impedance spectroscopy (EIS) was employed to record the cell impedance signal as-influenced by Pseudomonas aeruginosa quorum-sensing molecule, N-3-oxododecanoyl homoserine lactone (3OC 12 -HSL). Experimental results show that 3OC 12 -HSL caused a significant decrease in cell viability in a dose dependent manner. The EIS value decreased with concentrations of 3OC 12 -HSL in the range of 0.1-1μM, and the detection limit for 3OC 12 -HSL was calculated to be 0.094μM. These results were confirmed via cell viability, SEM, TEM analysis. Next, the sensor was successfully applied to monitoring the production of AHLs by spoilage bacteria in three different freshwater fish juice samples which efficiently proved the practicability of this cell based method. Therefore, the proposed cell sensor may serve as an innovative and effective approach to the measurement of quorum signaling molecule and thus provides a new avenue for real-time monitoring the spoilage bacteria in freshwater fish production. Copyright © 2017 Elsevier B.V. All rights reserved.

Anti-Quorum Sensing Potential of Potato Rhizospheric Bacteria

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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.

Autoinducer-2 Quorum Sensing Contributes to Regulation of Microcin PDI in Escherichia coli

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Shao-Yeh Lu

2017-12-01

Full Text Available The Escherichia coli quorum sensing (QS signal molecule, autoinducer-2 (AI-2, reaches its maximum concentration during mid-to-late growth phase after which it quickly degrades during stationary phase. This pattern of AI-2 concentration coincides with the up- then down-regulation of a recently described microcin PDI (mccPDI effector protein (McpM. To determine if there is a functional relationship between these systems, a prototypical mccPDI-expressing strain of E. coli 25 was used to generate ΔluxS, ΔlsrACDBFG (Δlsr, and ΔlsrR mutant strains that are deficient in AI-2 production, transportation, and AI-2 transport regulation, respectively. Trans-complementation, RT-qPCR, and western blot assays were used to detect changes of microcin expression and synthesis under co-culture and monoculture conditions. Compared to the wild-type strain, the AI-2-deficient strain (ΔluxS and -uptake negative strain (Δlsr were >1,000-fold less inhibitory to susceptible bacteria (P < 0.05. With in trans complementation of luxS, the AI-2 deficient mutant reduced the susceptible E. coli population by 4-log, which was within 1-log of the wild-type phenotype. RT-qPCR and western blot results for the AI-2 deficient E. coli 25 showed a 5-fold reduction in mcpM transcription with an average 2-h delay in McpM synthesis. Furthermore, overexpression of sRNA micC and micF (both involved in porin protein regulation was correlated with mcpM regulation, consistent with a possible link between QS and mcpM regulation. This is the direct first evidence that microcin regulation can be linked to quorum sensing in a Gram-negative bacterium.

Auto Poisoning of the Respiratory Chain by a Quorum Sensing Regulated Molecule Favors Biofilm Formation and Antibiotic Tolerance

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Hazan, Ronen; Que, Yok Ai; Maura, Damien; Strobel, Benjamin; Majcherczyk, Paul Anthony; Hopper, Laura Rose; Wilbur, David J.; Hreha, Teri N.; Barquera, Blanca; Rahme, Laurence G.

2015-01-01

Summary Bacterial programmed cell death and quorum sensing are direct examples of prokaryote group behaviors, wherein cells coordinate their actions to function cooperatively like one organism for the benefit of the whole culture. We demonstrate here that 2-n-heptyl-4-hydroxyquinoline-N-oxide (HQNO), a Pseudomonas aeruginosa quorum sensing -regulated low-molecular-weight excreted molecule, and triggers autolysis by self-perturbing the electron transfer reactions of the cytochrome bc1 complex. HQNO induces specific self-poisoning by disrupting the flow of electrons through the respiratory chain at the cytochrome bc1 complex, causing a leak of reducing equivalents to O2 whereby electrons that would normally be passed to cytochrome c are donated directly to O2. The subsequent mass production of reactive oxygen species (ROS) reduces membrane potential and disrupts membrane integrity, causing bacterial cell autolysis and DNA release. DNA subsequently promotes biofilm formation and increases antibiotic tolerance to beta-lactams, suggesting that HQNO-dependent cell autolysis is advantageous to the bacterial populations. These data both identify a new programmed cell death system, and a novel role for HQNO as a critical-inducer of biofilm formation and antibiotic tolerance. This newly identified pathway suggests intriguing mechanistic similarities with the initial mitochondrial-mediated steps of eukaryotic apoptosis. PMID:26776731

Does “quorum sensing” imply a new type of biological information?

DEFF Research Database (Denmark)

Bruni, Luis Emilio

2002-01-01

When dealing with biological communication and information, unifying concepts are necessary in order to couple the different “codes” that are being inductively “cracked” and defined at different emergent and “de-emergent” levels of the biological hierarchy. In this paper I compare the type...... of biological information implied by genetic information with that implied in the concept of “quorum sensing” (which refers to a prokaryotic cell-to-cell communication system) in order to explore if such integration is being achieved. I use the Lux operon paradigm and the Vibrio fischeri – Euprymna scolopes...... symbiotic partnership to exemplify the emergence of informational contexts along the biological hierarchy (from molecules to ecologies). I suggest that the biosemiotic epistemological framework can play an integra¬tive role to overcome the limits of dyadic mechanistic descriptions when relating...

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

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Leyla Slamti

2014-07-01

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

Effects of inhibitory neurons on the quorum percolation model and dynamical extension with the Brette-Gerstner model

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Fardet, Tanguy; Bottani, Samuel; Métens, Stéphane; Monceau, Pascal

2018-06-01

The Quorum Percolation model (QP) has been designed in the context of neurobiology to describe the initiation of activity bursts occurring in neuronal cultures from the point of view of statistical physics rather than from a dynamical synchronization approach. This paper aims at investigating an extension of the original QP model by taking into account the presence of inhibitory neurons in the cultures (IQP model). The first part of this paper is focused on an equivalence between the presence of inhibitory neurons and a reduction of the network connectivity. By relying on a simple topological argument, we show that the mean activation behavior of networks containing a fraction η of inhibitory neurons can be mapped onto purely excitatory networks with an appropriately modified wiring, provided that η remains in the range usually observed in neuronal cultures, namely η ⪅ 20%. As a striking result, we show that such a mapping enables to predict the evolution of the critical point of the IQP model with the fraction of inhibitory neurons. In a second part, we bridge the gap between the description of bursts in the framework of percolation and the temporal description of neural networks activity by showing how dynamical simulations of bursts with an adaptive exponential integrate-and-fire model lead to a mean description of bursts activation which is captured by Quorum Percolation.

Synergistic antibacterial efficacy of early combination treatment with tobramycin and quorum-sensing inhibitors against Pseudomonas aeruginosa in an intraperitoneal foreign-body infection mouse model

DEFF Research Database (Denmark)

Christensen, Louise; van Gennip, Maria; Jakobsen, Tim H

2012-01-01

Quorum sensing (QS)-deficient Pseudomonas aeruginosa biofilms formed in vitro are more susceptible to tobramycin than QS-proficient P. aeruginosa biofilms, and combination treatment with a QS inhibitor (QSI) and tobramycin shows synergistic effects on the killing of in vitro biofilms. We extended...

One man's poison is another man's meat: Using azithromycin-induced phospholipidosis to promote ocular surface health

International Nuclear Information System (INIS)

Liu, Yang; Kam, Wendy R.; Ding, Juan; Sullivan, David A.

2014-01-01

Drug-induced phospholipidosis (PLD) is a common adverse effect which has led to the termination of clinical trials for many candidate pharmaceuticals. However, this lipid-inducing effect may be beneficial in the treatment of meibomian gland dysfunction (MGD). MGD is the major cause of dry eye disease (DED), which affects 40 million people in the USA and has no cure. Azithromycin (AZM) is a PLD-inducing antibiotic that is used off-label to treat MGD, and is presumably effective because it suppresses the MGD-associated conjunctival inflammation (i.e. posterior blepharitis) and growth of lid bacteria. We hypothesize that AZM can act directly to promote the function of human meibomian gland epithelial cells by inducing PLD in these cells, characterized by the accumulation of lipids and lysosomes. Immortalized human meibomian gland epithelial cells (HMGEC) were cultured with or without azithromycin for 5 days. Cells were evaluated for cholesterol (Filipin) and neutral lipid (LipidTox) staining, as well as the appearance of lysosomes (LysoTracker) and lamellar bodies (transmission electron microscopy, TEM). The lipid composition of cellular lysates was analyzed by high performance thin-layer chromatography. Our findings demonstrate that AZM stimulates the accumulation of free cholesterol, neutral lipids and lysosomes in HMGEC. This AZM-induced increase of neutral lipid content occurred predominantly within lysosomes. Many of these vesicles appeared to be lamellar bodies by TEM, which is the characteristic of PLD. Our findings also show that AZM promotes an accumulation of free and esterified cholesterol, as well as phospholipids in HMGECimmortalized. Our results support our hypothesis and confirm the beneficial effect of PLD induced by AZM on HMGEC. Our discovery reveals a new potential use of PLD-inducing drugs, and makes this adverse effect a beneficial effect

Switch of SpnR function from activating to inhibiting quorum sensing by its exogenous addition

International Nuclear Information System (INIS)

Takayama, Yuriko; Kato, Norihiro

2016-01-01

The opportunistic human pathogen Serratia marcescens AS-1 produces the N-hexanoylhomoserine lactone (C6HSL) receptor SpnR, a homologue of LuxR from Vibrio fischeri, which activates pig clusters to produce the antibacterial prodigiosin. In this study, we attempted to artificially regulate quorum sensing (QS) by changing the role of SpnR in N-acylhomoserine lactone (AHL)-mediated QS. SpnR was obtained as a fusion protein tagged with maltose-binding protein (MBP) from overexpression in Escherichia coli, and its specific affinity to C6HSL was demonstrated by quartz crystal microbalance analysis and AHL-bioassay with Chromobacterium violaceum CV026. Prodigiosin production was effectively inhibited by externally added MBP-SpnR in both wild-type AS-1 and the AHL synthase-defective mutant AS-1(ΔspnI). For the mutant, the induced amount of prodigiosin was drastically reduced to approximately 4% with the addition of 18 μM MBP-SpnR to the liquid medium, indicating 81% trapping of C6HSL. A system for inhibiting QS can be constructed by adding exogenous AHL receptor to the culture broth to keep the concentration of free AHL low, whereas intracellular SpnR naturally functions as the activator in response to QS. - Highlights: • Quorum sensing (QS) regulates the expression of some bacterial genes. • We added an AHL receptor to culture media to inhibit QS in Serratia marcescens AS-1. • The exogenous receptor effectively bound C6HSL and inhibited QS. • This approach can be used to artificially regulate AHL-mediated QS.

Switch of SpnR function from activating to inhibiting quorum sensing by its exogenous addition

Energy Technology Data Exchange (ETDEWEB)

Takayama, Yuriko [Department of Innovation Systems Engineering, Graduate School of Engineering, Utsunomiya University, 7-1-2 Yoto, Utsunomiya, Tochigi 321-8585 (Japan); CREST, Japan Science and Technology Agency, 7-1-2 Yoto, Utsunomiya, Tochigi 321-8585 (Japan); Kato, Norihiro, E-mail: katon@cc.utsunomiya-u.ac.jp [CREST, Japan Science and Technology Agency, 7-1-2 Yoto, Utsunomiya, Tochigi 321-8585 (Japan); Department of Material and Environmental Chemistry, Graduate School of Engineering, Utsunomiya University, 7-1-2 Yoto, Utsunomiya, Tochigi 321-8585 (Japan)

2016-09-02

The opportunistic human pathogen Serratia marcescens AS-1 produces the N-hexanoylhomoserine lactone (C6HSL) receptor SpnR, a homologue of LuxR from Vibrio fischeri, which activates pig clusters to produce the antibacterial prodigiosin. In this study, we attempted to artificially regulate quorum sensing (QS) by changing the role of SpnR in N-acylhomoserine lactone (AHL)-mediated QS. SpnR was obtained as a fusion protein tagged with maltose-binding protein (MBP) from overexpression in Escherichia coli, and its specific affinity to C6HSL was demonstrated by quartz crystal microbalance analysis and AHL-bioassay with Chromobacterium violaceum CV026. Prodigiosin production was effectively inhibited by externally added MBP-SpnR in both wild-type AS-1 and the AHL synthase-defective mutant AS-1(ΔspnI). For the mutant, the induced amount of prodigiosin was drastically reduced to approximately 4% with the addition of 18 μM MBP-SpnR to the liquid medium, indicating 81% trapping of C6HSL. A system for inhibiting QS can be constructed by adding exogenous AHL receptor to the culture broth to keep the concentration of free AHL low, whereas intracellular SpnR naturally functions as the activator in response to QS. - Highlights: • Quorum sensing (QS) regulates the expression of some bacterial genes. • We added an AHL receptor to culture media to inhibit QS in Serratia marcescens AS-1. • The exogenous receptor effectively bound C6HSL and inhibited QS. • This approach can be used to artificially regulate AHL-mediated QS.

Revealing strategies of quorum sensing in Azospirillum brasilense strains Ab-V5 and Ab-V6.

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Fukami, Josiane; Abrantes, Julia Laura Fernandes; Del Cerro, Pablo; Nogueira, Marco Antonio; Ollero, Francisco Javier; Megías, Manuel; Hungria, Mariangela

2018-01-01

Azospirillum brasilense is an important plant-growth promoting bacterium (PGPB) that requires several critical steps for root colonization, including biofilm and exopolysaccharide (EPS) synthesis and cell motility. In several bacteria these mechanisms are mediated by quorum sensing (QS) systems that regulate the expression of specific genes mediated by the autoinducers N-acyl-homoserine lactones (AHLs). We investigated QS mechanisms in strains Ab-V5 and Ab-V6 of A. brasilense, which are broadly used in commercial inoculants in Brazil. Neither of these strains carries a luxI gene, but there are several luxR solos that might perceive AHL molecules. By adding external AHLs we verified that biofilm and EPS production and cell motility (swimming and swarming) were regulated via QS in Ab-V5, but not in Ab-V6. Differences were observed not only between strains, but also in the specificity of LuxR-type receptors to AHL molecules. However, Ab-V6 was outstanding in indole acetic acid (IAA) synthesis and this molecule might mimic AHL signals. We also applied the quorum quenching (QQ) strategy, obtaining transconjugants of Ab-V5 and Ab-V6 carrying a plasmid with acyl-homoserine lactonase. When maize (Zea mays L.) was inoculated with the wild-type and transconjugant strains, plant growth was decreased with the transconjugant of Ab-V5-confirming the importance of an AHL-mediated QS system-but did not affect plant growth promotion by Ab-V6.

Prospective open randomized study comparing efficacies and safeties of a 3-day course of azithromycin and a 10-day course of erythromycin in children with community-acquired acute lower respiratory tract infections

NARCIS (Netherlands)

Roord, JJ; Goossens, MMHT; Kimpen, JLL; Wolf, B.H.

1996-01-01

The efficacies and safeties of a 3-day, 3-dose course of azithromycin (10 mg/kg of body weight per day) and a 10-day, 30-dose course of erythromycin (40 mg/kg/day) for the treatment of acute lower respiratory tract infections in children were compared in an open randomized multicenter study.

Analysis of iodinated quorum sensing peptides by LC–UV/ESI ion trap mass spectrometry

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Yorick Janssens

2018-02-01

Full Text Available Five different quorum sensing peptides (QSP were iodinated using different iodination techniques. These iodinated peptides were analyzed using a C18 reversed phase HPLC system, applying a linear gradient of water and acetonitrile containing 0.1% (m/v formic acid as mobile phase. Electrospray ionization (ESI ion trap mass spectrometry was used for the identification of the modified peptides, while semi-quantification was performed using total ion current (TIC spectra. Non-iodinated peptides and mono- and di-iodinated peptides (NIP, MIP and DIP respectively were well separated and eluted in that order. Depending on the used iodination method, iodination yields varied from low (2% to high (57%.

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

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Quadri Luis EN

2006-10-01

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

Mitigation of membrane biofouling by a quorum quenching bacterium for membrane bioreactors.

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Ham, So-Young; Kim, Han-Shin; Cha, Eunji; Park, Jeong-Hoon; Park, Hee-Deung

2018-06-01

In this study, a quorum-quenching (QQ) bacterium named HEMM-1 was isolated at a membrane bioreactor (MBR) plant. HEMM-1 has diplococcal morphology and 99% sequence identity to Enterococcus species. The HEMM-1 cell-free supernatant (CFS) showed higher QQ activities than the CFS of other QQ bacteria, mostly by degrading N-acyl homoserine lactones (AHLs) with short acyl chains. Instrumental analyses revealed that HEMM-1 CFS degraded AHLs via lactonase activity. Under static, flow, and shear conditions, the HEMM-1 CFS was effective in reducing bacterial and activated-sludge biofilms formed on membrane surfaces. In conclusion, the HEMM-1 isolate is a QQ bacterium applicable to the control of biofouling in MBRs via inhibition of biofilm formation on membrane surfaces. Copyright © 2018 Elsevier Ltd. All rights reserved.

Quorum-sensing regulation of the biofilm matrix genes (pel) of Pseudomonas aeruginosa.

Science.gov (United States)

Sakuragi, Yumiko; Kolter, Roberto

2007-07-01

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

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.

QStatin, a Selective Inhibitor of Quorum Sensing in Vibrio Species.

Science.gov (United States)

Kim, Byoung Sik; Jang, Song Yee; Bang, Ye-Ji; Hwang, Jungwon; Koo, Youngwon; Jang, Kyung Ku; Lim, Dongyeol; Kim, Myung Hee; Choi, Sang Ho

2018-01-30

Pathogenic Vibrio species cause diseases in diverse marine animals reared in aquaculture. Since their pathogenesis, persistence, and survival in marine environments are regulated by quorum sensing (QS), QS interference has attracted attention as a means to control these bacteria in aquatic settings. A few QS inhibitors of Vibrio species have been reported, but detailed molecular mechanisms are lacking. Here, we identified a novel, potent, and selective Vibrio QS inhibitor, named QStatin [1-(5-bromothiophene-2-sulfonyl)-1H-pyrazole], which affects Vibrio harveyi LuxR homologues, the well-conserved master transcriptional regulators for QS in Vibrio species. Crystallographic and biochemical analyses showed that QStatin binds tightly to a putative ligand-binding pocket in SmcR, the LuxR homologue in V. vulnificus , and changes the flexibility of the protein, thereby altering its transcription regulatory activity. Transcriptome analysis revealed that QStatin results in SmcR dysfunction, affecting the expression of SmcR regulon required for virulence, motility/chemotaxis, and biofilm dynamics. Notably, QStatin attenuated representative QS-regulated phenotypes in various Vibrio species, including virulence against the brine shrimp ( Artemia franciscana ). Together, these results provide molecular insights into the mechanism of action of an effective, sustainable QS inhibitor that is less susceptible to resistance than other antimicrobial agents and useful in controlling the virulence of Vibrio species in aquacultures. IMPORTANCE Yields of aquaculture, such as penaeid shrimp hatcheries, are greatly affected by vibriosis, a disease caused by pathogenic Vibrio infections. Since bacterial cell-to-cell communication, known as quorum sensing (QS), regulates pathogenesis of Vibrio species in marine environments, QS inhibitors have attracted attention as alternatives to conventional antibiotics in aquatic settings. Here, we used target-based high-throughput screening to identify

Screening of Natural Product Derivatives Identifies Two Structurally Related Flavonoids as Potent Quorum Sensing Inhibitors against Gram-Negative Bacteria

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Suvi Manner

2018-05-01

Full Text Available Owing to the failure of conventional antibiotics in biofilm control, alternative approaches are urgently needed. Inhibition of quorum sensing (QS represents an attractive target since it is involved in several processes essential for biofilm formation. In this study, a compound library of natural product derivatives (n = 3040 was screened for anti-quorum sensing activity using Chromobacterium violaceum as reporter bacteria. Screening assays, based on QS-mediated violacein production and viability, were performed in parallel to identify non-bactericidal QS inhibitors (QSIs. Nine highly active QSIs were identified, while 328 compounds were classified as moderately actives and 2062 compounds as inactives. Re-testing of the highly actives at a lower concentration against C. violaceum, complemented by a literature search, led to the identification of two flavonoid derivatives as the most potent QSIs, and their impact on biofilm maturation in Escherichia coli and Pseudomonas aeruginosa was further investigated. Finally, effects of these leads on swimming and swarming motility of P. aeruginosa were quantified. The identified flavonoids affected all the studied QS-related functions at micromolar concentrations. These compounds can serve as starting points for further optimization and development of more potent QSIs as adjunctive agents used with antibiotics in the treatment of biofilms.

Septic arthritis of the hip in a Cambodian child caused by multidrug-resistant Salmonella enterica serovar Typhi with intermediate susceptibility to ciprofloxacin treated with ceftriaxone and azithromycin.

Science.gov (United States)

Pocock, J M; Khun, P A; Moore, C E; Vuthy, S; Stoesser, N; Parry, C M

2014-08-01

Septic arthritis is a rare complication of typhoid fever. A 12-year-old boy without pre-existing disease attended a paediatric hospital in Cambodia with fever and left hip pain. A hip synovial fluid aspirate grew multidrug-resistant Salmonella enterica ser. Typhi with intermediate susceptibility to ciprofloxacin. Arthrotomy, 2 weeks of intravenous ceftriaxone and 4 weeks of oral azithromycin led to resolution of symptoms. The optimum management of septic arthritis in drug-resistant typhoid is undefined.

Role and regulation of the orphan AphA protein of quorum sensing in pathogenic Vibrios.

Science.gov (United States)

Lu, Renfei; Osei-Adjei, George; Huang, Xinxiang; Zhang, Yiquan

2018-03-01

Quorum sensing (QS), a cell-to-cell communication process, is widely distributed in the bacterial kingdom. Bacteria use QS to control gene expression in response to cell density by detecting the signal molecules called autoinducers. AphA protein is the master QS regulator of vibrios operating at low cell density. It regulates the expression of a variety of genes, especially those encoding virulence factors, flagella/motility and biofilm formation. The role and regulation of AphA in vibrios, especially in human pathogenic vibrios, are summarized in this review. Clarification of the roles of AphA will help us to understand the pathogenesis of vibrios.

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

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Kok-Gan Chan

2014-01-01

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

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

Science.gov (United States)

Iida, Aya; Ohnishi, Yasuo; Horinouchi, Sueharu

2008-07-01

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

Functions and regulation of quorum-sensing in Agrobacterium tumefaciens

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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.

Short-term azithromycin treatment promotes cornea allograft survival in the rat.

Science.gov (United States)

Wacker, Katrin; Denker, Sophy; Hildebrand, Antonia; Eberwein, Philipp; Reinhard, Thomas; Schwartzkopff, Johannes

2013-01-01

Any inflammatory response following corneal transplantation may induce rejection and irreversible graft failure. The purpose of this study is to analyze the anti-inflammatory effect of azithromycin (AZM) following experimental keratoplasty in rats. Corneal transplants were performed between Fisher-donor and Lewis-recipient rats. Recipients were postoperatively treated three times daily with AZM, miglyol, ofloxacin or dexamethasone eye drops. As an additional control, AZM was applied following syngeneic keratoplasty. Furthermore, short-term treatments with AZM for seven days perioperatively or with AZM only three days prior to the transplantation were compared to appropriate controls. All transplants were monitored clinically for opacity, edema, and vascularization. Infiltrating CD45(+), CD4(+), CD8(+), CD25(+), CD161(+) and CD163(+) cells were quantified via immunohistochemistry. AZM significantly promoted corneal graft survival compared with miglyol or ofloxacin treatment. This effect was comparable to topical dexamethasone. No adverse AZM effect was observed. Histology confirmed a significant reduction of infiltrating leukocytes. The short-term application of AZM for three days prior to transplantation or for seven days perioperatively reduced corneal graft rejection significantly compared with the controls. Along with antibiotic properties, topical AZM has a strong anti-inflammatory effect. Following keratoplasty, this effect is comparable to topical dexamethasone without the risk of steroid-induced adverse effects. Short-term treatment with AZM three days prior to the transplantation was sufficient to promote graft survival in the rat keratoplasty model. We therefore suggest further assessing the anti-inflammatory function of topical AZM following keratoplasty in humans.

Short-term azithromycin treatment promotes cornea allograft survival in the rat.

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Katrin Wacker

Full Text Available Any inflammatory response following corneal transplantation may induce rejection and irreversible graft failure. The purpose of this study is to analyze the anti-inflammatory effect of azithromycin (AZM following experimental keratoplasty in rats.Corneal transplants were performed between Fisher-donor and Lewis-recipient rats. Recipients were postoperatively treated three times daily with AZM, miglyol, ofloxacin or dexamethasone eye drops. As an additional control, AZM was applied following syngeneic keratoplasty. Furthermore, short-term treatments with AZM for seven days perioperatively or with AZM only three days prior to the transplantation were compared to appropriate controls. All transplants were monitored clinically for opacity, edema, and vascularization. Infiltrating CD45(+, CD4(+, CD8(+, CD25(+, CD161(+ and CD163(+ cells were quantified via immunohistochemistry.AZM significantly promoted corneal graft survival compared with miglyol or ofloxacin treatment. This effect was comparable to topical dexamethasone. No adverse AZM effect was observed. Histology confirmed a significant reduction of infiltrating leukocytes. The short-term application of AZM for three days prior to transplantation or for seven days perioperatively reduced corneal graft rejection significantly compared with the controls.Along with antibiotic properties, topical AZM has a strong anti-inflammatory effect. Following keratoplasty, this effect is comparable to topical dexamethasone without the risk of steroid-induced adverse effects. Short-term treatment with AZM three days prior to the transplantation was sufficient to promote graft survival in the rat keratoplasty model. We therefore suggest further assessing the anti-inflammatory function of topical AZM following keratoplasty in humans.

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...... salmonicida and Vibrio splendidus were also positive. Aeromonas species produced N-butanoyl homoserine lactone (BHL) and N-hexanoyl homoserine lactone (HHL) and 1 additional product, whereas N-3-oxo-hexanoyl homoserine lactone (OHHL) and HHL were detected in Vibrio salmonicida. N-3-oxo-octanoyl homoserine...... lactone (OOHL) and N-3-octanoyl homoserine lactone (OHL) were detected in Y. ruckeii. AHLs were not detected from strains of Photobacterium damselae, Flavobacterium psychrophilum or Moritella viscosa. AHLs were extracted from fish infected with Y. ruckeri but not from fish infected with A. salmonicida...

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

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Louise Kjaerulff

2013-12-01

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

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

Science.gov (United States)

Iida, Aya; Ohnishi, Yasuo; Horinouchi, Sueharu

2008-01-01

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

Streptococcus gordonii LuxS/autoinducer-2 quorum-sensing system modulates the dual-species biofilm formation with Streptococcus mutans.

Science.gov (United States)

Wang, Xiao; Li, Xiaolan; Ling, Junqi

2017-07-01

Dental plaques are mixed-species biofilms that are related to the development of dental caries. Streptococcus mutans (S. mutans) is an important cariogenic bacterium that forms mixed-species biofilms with Streptococcus gordonii (S. gordonii), an early colonizer of the tooth surface. The LuxS/autoinducer-2(AI-2) quorum sensing system is involved in the regulation of mixed-species biofilms, and AI-2 is proposed as a universal signal for the interaction between bacterial species. In this work, a S. gordonii luxS deficient strain was constructed to investigate the effect of the S. gordonii luxS gene on dual-species biofilm formed by S. mutans and S. gordonii. In addition, AI-2 was synthesized in vitro by incubating recombinant LuxS and Pfs enzymes of S. gordonii together. The effect of AI-2 on S. mutans single-species biofilm formation and cariogenic virulence gene expression were also assessed. The results showed that luxS disruption in S. gordonii altered dual-species biofilm formation, architecture, and composition, as well as the susceptibility to chlorhexidine. And the in vitro synthesized AI-2 had a concentration-dependent effect on S. mutans biofilm formation and virulence gene expression. These findings indicate that LuxS/AI-2 quorum-sensing system of S. gordonii plays a role in regulating the dual-species biofilm formation with S. mutans. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Erythromycin and azithromycin transport into Haemophilus influenzae ATCC 19418 under conditions of depressed proton motive force (delta mu H)

Energy Technology Data Exchange (ETDEWEB)

Capobianco, J.O.; Goldman, R.C. (Abbott Laboratories, IL (USA))

1990-09-01

The effect of collapsing the electrochemical proton gradient (delta mu H) on ({sup 3}H)erythromycin and ({sup 14}C)azithromycin transport in Haemophilus influenzae ATCC 19418 was studied. The proton gradient and membrane potential were determined from the distribution of (2-{sup 14}C)dimethadione and rubidium-86, respectively. delta mu H was reduced from 124 to 3 mV in EDTA-valinomycin-treated cells at 22{degrees}C with 150 mM KCl and 0.1 mM carbonyl cyanide m-chlorophenylhydrazone. During the collapse of delta mu H, macrolide uptake increased. Erythromycin efflux studies strongly suggested that this increase was not due to an energy-dependent efflux pump but was likely due to increased outer membrane permeability. These data indicated that macrolide entry was not a delta mu H-driven active transport process but rather a passive diffusion process.

Azithromycin effectiveness against intracellular infections of Francisella

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Mann Barbara J

2010-04-01

Full Text Available Abstract Background Macrolide antibiotics are commonly administered for bacterial respiratory illnesses. Azithromycin (Az is especially noted for extremely high intracellular concentrations achieved within macrophages which is far greater than the serum concentration. Clinical strains of Type B Francisella (F. tularensis have been reported to be resistant to Az, however our laboratory Francisella strains were found to be sensitive. We hypothesized that different strains/species of Francisella (including Type A may have different susceptibilities to Az, a widely used and well-tolerated antibiotic. Results In vitro susceptibility testing of Az confirmed that F. tularensis subsp. holarctica Live Vaccine Strain (LVS (Type B was not sensitive while F. philomiragia, F. novicida, and Type A F. tularensis (NIH B38 and Schu S4 strain were susceptible. In J774A.1 mouse macrophage cells infected with F. philomiragia, F. novicida, and F. tularensis LVS, 5 μg/ml Az applied extracellularly eliminated intracellular Francisella infections. A concentration of 25 μg/ml Az was required for Francisella-infected A549 human lung epithelial cells, suggesting that macrophages are more effective at concentrating Az than epithelial cells. Mutants of RND efflux components (tolC and ftlC in F. novicida demonstrated less sensitivity to Az by MIC than the parental strain, but the tolC disc-inhibition assay demonstrated increased sensitivity, indicating a complex role for the outer-membrane transporter. Mutants of acrA and acrB mutants were less sensitive to Az than the parental strain, suggesting that AcrAB is not critical for the efflux of Az in F. novicida. In contrast, F. tularensis Schu S4 mutants ΔacrB and ΔacrA were more sensitive than the parental strain, indicating that the AcrAB may be important for Az efflux in F. tularensis Schu S4. F. novicida LPS O-antigen mutants (wbtN, wbtE, wbtQ and wbtA were found to be less sensitive in vitro to Az compared to the wild

Heterogeneity in quorum sensing-regulated bioluminescence of Vibrio harveyi.

Science.gov (United States)

Anetzberger, Claudia; Pirch, Torsten; Jung, Kirsten

2009-07-01

Quorum sensing (QS) refers to the ability of bacterial populations to read out the local environment for cell density and to collectively activate gene expression. Vibrio harveyi, one of the best characterized model organisms in QS, was used to address the question how single cells behave within a QS-activated community in a homogeneous environment. Analysis of the QS-regulated bioluminescence of a wild type strain revealed that even at high cell densities only 69% of the cells of the population produced bioluminescence, 25% remained dark and 6% were dead. Moreover, light intensities greatly varied from cell to cell at high population density. Addition of autoinducer to a bright liquid culture of V. harveyi increased the percentage of luminescent cells up to 98%, suggesting that V. harveyi produces and/or keeps the autoinducers at non-saturating concentrations. In contrast, all living cells of a constitutive QS-active mutant (DeltaluxO) produced light. We also found that QS affects biofilm formation in V. harveyi. Our data provide first evidence that a heterogeneous population produces more biofilm than a homogeneous one. It is suggested that even a QS-committed population of V. harveyi takes advantage of heterogeneity, which extends the current view of QS-regulated uniformity.

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.

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.

Additive Effects of Quorum Sensing Anti-Activators on Pseudomonas aeruginosa Virulence Traits and Transcriptome

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Kyle L. Asfahl

2018-01-01

Full Text Available In the opportunistic pathogen Pseudomonas aeruginosa, quorum sensing (QS via acyl-homoserine lactone (AHL signals coordinates virulence gene expression. AHL signals must reach a critical threshold before enough is bound by cognate regulators LasR and RhlR to drive transcription of target genes. In addition, three anti-activator proteins, QteE, QscR, and QslA, sequester QS regulators to increase the threshold for induction and delay expression of QS target genes. It remains unclear how multiple anti-activators work together to achieve the quorum threshold. Here, we employed a combination of mutational, kinetic, phenotypic, and transcriptomic analysis to examine regulatory effects and interactions of the three distinct anti-activators. We observed combinatorial, additive effects on QS gene expression. As measured by reporter gene fusion, individual deletion of each anti-activator gene increased lasB expression and QS-controlled virulence factor production. Deletion of qslA in combination with the deletion of any other anti-activator gene resulted in the greatest increase and earliest activation of lasB gene expression. Western analysis revealed that relative increases in soluble LasR in anti-activator mutants correlate with increased lasB expression and QS-controlled virulence factor production. RNA-seq of the previously uncharacterized QslA and QteE regulons revealed overlapping, yet distinct groups of differentially expressed genes. Simultaneous inactivation of qteE and qslA had the largest effect on gene expression with 999 genes induced and 798 genes repressed in the double mutant vs. wild-type. We found that LasR and RhlR-activated QS genes formed a subset of the genes induced in the qteE, qslA, and double mutant. The activation of almost all of these QS genes was advanced from stationary phase to log phase in the qteE qslA double mutant. Taken together, our results identify additive effects of anti-activation on QS gene expression, likely

Analysis of Block OMP using Block RIP

OpenAIRE

Wang, Jun; Li, Gang; Zhang, Hao; Wang, Xiqin

2011-01-01

Orthogonal matching pursuit (OMP) is a canonical greedy algorithm for sparse signal reconstruction. When the signal of interest is block sparse, i.e., it has nonzero coefficients occurring in clusters, the block version of OMP algorithm (i.e., Block OMP) outperforms the conventional OMP. In this paper, we demonstrate that a new notion of block restricted isometry property (Block RIP), which is less stringent than standard restricted isometry property (RIP), can be used for a very straightforw...

Effect of the synthetic cannabinoid HU-210 on quorum sensing and on the production of quorum sensing-mediated virulence factors by Vibrio harveyi.

Science.gov (United States)

Soni, Divya; Smoum, Reem; Breuer, Aviva; Mechoulam, Raphael; Steinberg, Doron

2015-08-12

Bacterial populations communicate through the cell density-dependent mechanism of quorum sensing (QS). Vibrio harveyi, one of the best studied model organisms for QS, was used to explore effects of the synthetic cannabinoid HU-210 on QS and different QS-regulated physiological processes in bacteria. Analysis of QS-regulated bioluminescence in wild-type and mutant strains of V. harveyi revealed that HU-210 affects the autoinducer-2 (AI-2) pathway, one of three known QS cascades of V. harveyi. Furthermore, QS-mediated biofilm formation and swimming motility in the mutant strain BB152 (AI-1(-), AI-2(+)) were significantly reduced in the presence of HU-210. HU-210 inhibited QS-mediated virulence factor production without any inhibitory effect on bacterial growth. It also alters the expression of several genes, which are regulated by QS, specifically downregulating the genes of the AI-2 QS cascade. First evidence is being provided for interference of bacterial signal-transduction systems by a synthetic cannabinoid. The effect of HU-210 was specific to the AI-2 cascade in V. harveyi. AI-2 is known as a "universal autoinducer" and interference with its activity opens a broad spectrum of applications for synthetic cannabinoids in future research as a potential anti-QS agent.

The effect of quorum sensing system for growth competitiveness on Shigella flexneri.

Science.gov (United States)

Xu, Ping; Yang, Jing; Lu, Li-lan; Feng, Er-ling; Wang, Heng-liang; Lu, Ying; Zhu, Li

2015-05-01

Quorum sensing (QS) regulates the onset of bacterial social responses related to cell density. Comparison between the gene sequences of all components of QS system of Escherichia coli and Shigella strains, shows that the QS system is generally lost or mutated in Shigella. Since AI-2 is produced and processed by the lsr operon, we analyzed the potential function of the lsr operon. We first detected AI-2 in Shigella flexneri 2a strain 301 through the reporter bacteria Vibrio harveyi BB170, indicating that S. flexneri can produce AI-2. Then, the lsr operon of E. coli MG1655 was cloned into S. flexneri using the Golden Gate method. Colony counting experiments showed that the QS system recovery strain had growth advantage over the wild-type strain when they were mixed and cultured. The preliminary comparative proteomics analysis showed that the lsr operon could be expressed and the abundance of stress response proteins also changed when the QS system was introduced into S. flexneri.

Inhibition of quorum sensing and biofilm formation in Vibrio harveyi by 4-fluoro-DPD; a novel potent inhibitor of signalling.

Science.gov (United States)

Kadirvel, Manikandan; Fanimarvasti, Fariba; Forbes, Sarah; McBain, Andrew; Gardiner, John M; Brown, Gavin D; Freeman, Sally

2014-05-21

(S)-4,5-Dihydroxypentane-2,3-dione [(S)-DPD, (1)] is a precursor for , a quorum sensing signalling molecule for inter- and intra-species bacterial communication. The synthesis of its fluoro-analogue, 4-fluoro-5-hydroxypentane-2,3-dione () is reported. An intermediate in this route also enables a new, shorter synthesis of the native (S)-DPD. 4-Fluoro-DPD (2) completely inhibited bioluminescence and bacterial growth of Vibrio harveyi BB170 strain at 12.5 μM and 100 μM, respectively.

31 CFR 595.301 - Blocked account; blocked property.

Science.gov (United States)

2010-07-01

... (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY TERRORISM SANCTIONS REGULATIONS General Definitions § 595.301 Blocked account; blocked property. The terms blocked account and blocked...

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.

Periodontitis, Porphyromonas gingivalis y su relación con la expresión de quorum sensing Periodontitis, Porphyromonas gingivalis and its relation to quorum sensing expression

Directory of Open Access Journals (Sweden)

Antonio Díaz Caballero

2010-12-01

Full Text Available Los mecanismos de señalización bacteriana desempeñan un papel fundamental en el establecimiento y progresión de la enfermedad periodontal. Dadas estas circunstancias es crucial profundizar en el entendimiento de estos mecanismos para intentar proveer estrategias terapéuticas novedosas. El presente artículo de revisión, de carácter narrativo, tiene como objetivo conducir un análisis crítico de la evidencia disponible sobre la influencia de Porphyromonas gingivalis (Pg y expresión de quorum sensing (Qs en enfermedad periodontal. Se realizó una búsqueda a través de bases de datos como Ovid (MEDLINE, ScienceDirect, Hinari. El conocimiento actual de estos mecanismos ofrece la posibilidad de desarrollar nuevos y profundos estudios (teóricos y experimentales sobre la expresión del QS en pacientes con enfermedad periodontal y permitirá un novedoso campo de investigación con el que no se cuenta en la actualidad. Desde su descubrimiento, el QS se vislumbra como un espacio de investigación valioso en el cual se debe insistir de manera permanente. La anterior evidencia permite concluir que a través de la regulación de la expresión de determinados genes en bacterias como la PG, se puede efectuar la inhibición de la formación de las biopelículas que tiene efectos directos e indirectos sobre el desarrollo de la enfermedad periodontal.The bacterial signaling mechanisms play a key role in the establishment and progression of periodontal disease. Due to these circumstances it is crucial to deepen in the understanding of these mechanisms to try to provide novel therapeutic strategies. The objective of present narrative literature review was to make a critical analyze of the available evidence on the influence of Porphyromonas gingivalis (PG and the quorum sensing expression in periodontal disease. Using the Ovid (MEDLINE ScienceDirect, Hinari database we made a search. The current knowledge of these mechanisms offers the possibility of

Engineering nanoparticles to silence bacterial communication

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Kristen Publicover Miller

2015-03-01

Full Text Available The alarming spread of bacterial resistance to traditional antibiotics has warranted the study of alternative antimicrobial agents. Quorum sensing is a chemical cell-to-cell communication mechanism utilized by bacteria to coordinate group behaviors and establish infections. Quorum sensing is integral to bacterial survival, and therefore provides a unique target for antimicrobial therapy. In this study, silicon dioxide nanoparticles (Si-NP were engineered to target the signaling molecules (i.e. acylhomoserine lactones (HSL used for quorum sensing in order to halt bacterial communication. Specifically, when Si-NP were surface functionalized with beta-cyclodextrin (beta-CD, then added to cultures of bacteria (Vibrio fischeri, whose luminous output depends upon HSL-mediated quorum sensing, the cell-to-cell communication was dramatically reduced. Reductions in luminescence were further verified by quantitative polymerase chain reaction (qPCR analyses of luminescence genes. Binding of AHLs to Si-NPs was examined using nuclear magnetic resonance (NMR spectroscopy. The results indicated that by delivering high concentrations of engineered NPs with associated quenching compounds, the chemical signals were removed from the immediate bacterial environment. In actively-metabolizing cultures, this treatment blocked the ability of bacteria to communicate and regulate quorum sensing, effectively silencing and isolating the cells. Si-NPs provide a scaffold and critical stepping-stone for more pointed developments in antimicrobial therapy, especially with regard to quorum sensing – a target that will reduce resistance pressures imposed by traditional antibiotics.

Metabolic dependent and independent pH-drop shuts down VirSR quorum sensing in Clostridium perfringens.

Science.gov (United States)

Adachi, Keika; Ohtani, Kaori; Kawano, Michio; Singh, Ravindra Pal; Yousuf, Basit; Sonomoto, Kenji; Shimizu, Tohru; Nakayama, Jiro

2018-05-01

Clostridium perfringens produces various exotoxins and enzymes that cause food poisoning and gas gangrene. The genes involved in virulence are regulated by the agr-like quorum sensing (QS) system, which consists of a QS signal synthesis system and a VirSR two-component regulatory system (VirSR TCS) which is a global regulatory system composed of signal sensor kinase (VirS) and response regulator (VirR). We found that the perfringolysin O gene (pfoA) was transiently expressed during mid-log phase of bacterial growth; its expression was rapidly shut down thereafter, suggesting the existence of a self-quorum quenching (sQQ) system. The sQQ system was induced by the addition of stationary phase culture supernatant (SPCS). Activity of the sQQ system was heat stable, and was present following filtration through the ultrafiltration membrane, suggesting that small molecules acted as sQQ agents. In addition, sQQ was also induced by pure acetic and butyric acids at concentrations equivalent to those in the stationary phase culture, suggesting that organic acids produced by C. perfringens were involved in sQQ. In pH-controlled batch culture, sQQ was greatly diminished; expression level of pfoA extended to late-log growth phase, and was eventually increased by one order of magnitude. Furthermore, hydrochloric acid induced sQQ at the same pH as was used in organic acids. SPCS also suppressed the expression of genes regulated by VirSR TCS. Overall, the expression of virulence factors of C. perfringens was downregulated by the sQQ system, which was mediated by primary acidic metabolites and acidic environments. This suggested the possibility of pH-controlled anti-virulence strategies. Copyright © 2018 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Nerve Blocks

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... News Physician Resources Professions Site Index A-Z Nerve Blocks A nerve block is an injection to ... the limitations of Nerve Block? What is a Nerve Block? A nerve block is an anesthetic and/ ...

Inhibition of biofilm formation, quorum sensing and infection in Pseudomonas aeruginosa by natural products-inspired organosulfur compounds.

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Nathaniel C Cady

Full Text Available Using a microplate-based screening assay, the effects on Pseudomonas aeruginosa PAO1 biofilm formation of several S-substituted cysteine sulfoxides and their corresponding disulfide derivatives were evaluated. From our library of compounds, S-phenyl-L-cysteine sulfoxide and its breakdown product, diphenyl disulfide, significantly reduced the amount of biofilm formation by P. aeruginosa at levels equivalent to the active concentration of 4-nitropyridine-N-oxide (NPO (1 mM. Unlike NPO, which is an established inhibitor of bacterial biofilms, our active compounds did not reduce planktonic cell growth and only affected biofilm formation. When used in a Drosophila-based infection model, both S-phenyl-L-cysteine sulfoxide and diphenyl disulfide significantly reduced the P. aeruginosa recovered 18 h post infection (relative to the control, and were non-lethal to the fly hosts. The possibility that the observed biofilm inhibitory effects were related to quorum sensing inhibition (QSI was investigated using Escherichia coli-based reporters expressing P. aeruginosa lasR or rhIR response proteins, as well as an endogenous P. aeruginosa reporter from the lasI/lasR QS system. Inhibition of quorum sensing by S-phenyl-L-cysteine sulfoxide was observed in all of the reporter systems tested, whereas diphenyl disulfide did not exhibit QSI in either of the E. coli reporters, and showed very limited inhibition in the P. aeruginosa reporter. Since both compounds inhibit biofilm formation but do not show similar QSI activity, it is concluded that they may be functioning by different pathways. The hypothesis that biofilm inhibition by the two active compounds discovered in this work occurs through QSI is discussed.

Testing block subdivision algorithms on block designs

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Wiseman, Natalie; Patterson, Zachary

2016-01-01

Integrated land use-transportation models predict future transportation demand taking into account how households and firms arrange themselves partly as a function of the transportation system. Recent integrated models require parcels as inputs and produce household and employment predictions at the parcel scale. Block subdivision algorithms automatically generate parcel patterns within blocks. Evaluating block subdivision algorithms is done by way of generating parcels and comparing them to those in a parcel database. Three block subdivision algorithms are evaluated on how closely they reproduce parcels of different block types found in a parcel database from Montreal, Canada. While the authors who developed each of the algorithms have evaluated them, they have used their own metrics and block types to evaluate their own algorithms. This makes it difficult to compare their strengths and weaknesses. The contribution of this paper is in resolving this difficulty with the aim of finding a better algorithm suited to subdividing each block type. The proposed hypothesis is that given the different approaches that block subdivision algorithms take, it's likely that different algorithms are better adapted to subdividing different block types. To test this, a standardized block type classification is used that consists of mutually exclusive and comprehensive categories. A statistical method is used for finding a better algorithm and the probability it will perform well for a given block type. Results suggest the oriented bounding box algorithm performs better for warped non-uniform sites, as well as gridiron and fragmented uniform sites. It also produces more similar parcel areas and widths. The Generalized Parcel Divider 1 algorithm performs better for gridiron non-uniform sites. The Straight Skeleton algorithm performs better for loop and lollipop networks as well as fragmented non-uniform and warped uniform sites. It also produces more similar parcel shapes and patterns.

Differential inhibition of activity, activation and gene expression of MMP-9 in THP-1 cells by azithromycin and minocycline versus bortezomib: A comparative study.

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Jennifer Vandooren

Full Text Available Gelatinase B or matrix metalloproteinase-9 (MMP-9 (EC 3.4.24.35 is increased in inflammatory processes and cancer, and is associated with disease progression. In part, this is due to MMP-9-mediated degradation of extracellular matrix, facilitating influx of leukocytes into inflamed tissues and invasion or metastasis of cancer cells. MMP-9 is produced as proMMP-9 and its propeptide is subsequently removed by other proteases to generate proteolytically active MMP-9. The significance of MMP-9 in pathologies triggered the development of specific inhibitors of this protease. However, clinical trials with synthetic inhibitors of MMPs in the fight against cancer were disappointing. Reports on active compounds which inhibit MMP-9 should be carefully examined in this regard. In a considerable set of recent publications, two antibiotics (minocycline and azythromycin and the proteasome inhibitor bortezomib, used in cancers, were reported to inhibit MMP-9 at different stages of its expression, activation or activity. The current study was undertaken to compare and to verify the impact of these compounds on MMP-9. With exception of minocycline at high concentrations (>100 μM, the compounds did not affect processing of proMMP-9 into MMP-9, nor did they affect direct MMP-9 gelatinolytic activity. In contrast, azithromycin specifically reduced MMP-9 mRNA and protein levels without affecting NF-κB in endotoxin-challenged monocytic THP-1 cells. Bortezomib, although being highly toxic, had no MMP-9-specific effects but significantly upregulated cyclooxygenase-2 (COX-2 activity and PGE2 levels. Overall, our study clarified that azithromycin decreased the levels of MMP-9 by reduction of gene and protein expression while minocycline inhibits proteolytic activity at high concentrations.

New α-Pyridones with Quorum-Sensing Inhibitory Activity from Diversity-Enhanced Extracts of a Streptomyces sp. Derived from Marine Algae.

Science.gov (United States)

Du, Yuqi; Sun, Jian; Gong, Qianhong; Wang, Yi; Fu, Peng; Zhu, Weiming

2018-02-28

Four new α-pyrones (1-4) and eight known analogues (5-12) were identified from the secondary metabolites of Streptomyces sp. OUCMDZ-3436 derived from the marine green algae Enteromorpha prolifera. Seven new α-pyridones (14-20) were constructed by diversity-oriented synthesis, which has been an effective approach to expanding the chemical space of natural-product-like compounds. Compounds 16, 17, 19, and 20 were found to have inhibitory effect on the gene expression controlled by quorum sensing in Pseudomonas aeruginosa QSIS-lasI.

Cutaneous Sensory Block Area, Muscle-Relaxing Effect, and Block Duration of the Transversus Abdominis Plane Block

DEFF Research Database (Denmark)

Støving, Kion; Rothe, Christian; Rosenstock, Charlotte V

2015-01-01

BACKGROUND AND OBJECTIVES: The transversus abdominis plane (TAP) block is a widely used nerve block. However, basic block characteristics are poorly described. The purpose of this study was to assess the cutaneous sensory block area, muscle-relaxing effect, and block duration. METHODS: Sixteen...... healthy volunteers were randomized to receive an ultrasound-guided unilateral TAP block with 20 mL 7.5 mg/mL ropivacaine and placebo on the contralateral side. Measurements were performed at baseline and 90 minutes after performing the block. Cutaneous sensory block area was mapped and separated...... into a medial and lateral part by a vertical line through the anterior superior iliac spine. We measured muscle thickness of the 3 lateral abdominal muscle layers with ultrasound in the relaxed state and during maximal voluntary muscle contraction. The volunteers reported the duration of the sensory block...

Activities of two novel macrolides, GW 773546 and GW 708408, compared with those of telithromycin, erythromycin, azithromycin, and clarithromycin against Haemophilus influenzae.

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Kosowska, Klaudia; Credito, Kim; Pankuch, Glenn A; Hoellman, Dianne; Lin, Gengrong; Clark, Catherine; Dewasse, Bonifacio; McGhee, Pamela; Jacobs, Michael R; Appelbaum, Peter C

2004-11-01

The MIC at which 50% of strains are inhibited (MIC(50)) and the MIC(90) of GW 773546, a novel macrolide, were 1.0 and 2.0 microg/ml, respectively, for 223 beta-lactamase-positive, beta-lactamase-negative, and beta-lactamase-negative ampicillin-resistant Haemophilus influenzae strains. The MIC(50)s and MIC(90)s of GW 708408, a second novel macrolide, and telithromycin, an established ketolide, were 2.0 and 4.0 microg/ml, respectively, while the MIC(50) and MIC(90) of azithromycin were 1.0 and 2.0 microg/ml, respectively. The MIC(50) and MIC(90) of erythromycin were 4.0 and 8.0 microg/ml, respectively; and those of clarithromycin were 4.0 and 16.0 microg/ml, respectively. All compounds except telithromycin were bactericidal (99.9% killing) against nine strains at two times the MIC after 24 h. Telithromycin was bactericidal against eight of the nine strains. In addition, both novel macrolides and telithromycin at two times the MIC showed 99% killing of all nine strains after 12 h and 90% killing of all strains after 6 h. After 24 h, all drugs were bactericidal against four to seven strains when they were tested at the MIC. Ten of 11 strains tested by multistep selection analysis yielded resistant clones after 14 to 43 passages with erythromycin. Azithromycin gave resistant clones of all strains after 20 to 50 passages, and clarithromycin gave resistant clones of 9 of 11 strains after 14 to 41 passages. By comparison, GW 708408 gave resistant clones of 9 of 11 strains after 14 to 44 passages, and GW 773546 gave resistant clones of 10 of 11 strains after 14 to 45 passages. Telithromycin gave resistant clones of 7 of 11 strains after 18 to 45 passages. Mutations mostly in the L22 and L4 ribosomal proteins and 23S rRNA were detected in resistant strains selected with all compounds, with alterations in the L22 protein predominating. Single-step resistance selection studies at the MIC yielded spontaneous resistant mutants at frequencies of 1.5 x 10(-9) to 2.2 x 10(-6) with

A quorum-sensing molecule acts as a morphogen controlling gas vesicle organelle biogenesis and adaptive flotation in an enterobacterium

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Ramsay, Joshua P.; Williamson, Neil R.; Spring, David R.; Salmond, George P. C.

2011-01-01

Gas vesicles are hollow intracellular proteinaceous organelles produced by aquatic Eubacteria and Archaea, including cyanobacteria and halobacteria. Gas vesicles increase buoyancy and allow taxis toward air–liquid interfaces, enabling subsequent niche colonization. Here we report a unique example of gas vesicle-mediated flotation in an enterobacterium; Serratia sp. strain ATCC39006. This strain is a member of the Enterobacteriaceae previously studied for its production of prodigiosin and carbapenem antibiotics. Genes required for gas vesicle synthesis mapped to a 16.6-kb gene cluster encoding three distinct homologs of the main structural protein, GvpA. Heterologous expression of this locus in Escherichia coli induced copious vesicle production and efficient cell buoyancy. Gas vesicle morphogenesis in Serratia enabled formation of a pellicle-like layer of highly vacuolated cells, which was dependent on oxygen limitation and the expression of ntrB/C and cheY-like regulatory genes within the gas-vesicle gene cluster. Gas vesicle biogenesis was strictly controlled by intercellular chemical signaling, through an N-acyl homoserine lactone, indicating that in this system the quorum-sensing molecule acts as a morphogen initiating organelle development. Flagella-based motility and gas vesicle morphogenesis were also oppositely regulated by the small RNA-binding protein, RsmA, suggesting environmental adaptation through physiological control of the choice between motility and flotation as alternative taxis modes. We propose that gas vesicle biogenesis in this strain represents a distinct mechanism of mobility, regulated by oxygen availability, nutritional status, the RsmA global regulatory system, and the quorum-sensing morphogen. PMID:21873216

Contribution of the RgfD Quorum Sensing Peptide to rgf Regulation and Host Cell Association in Group B Streptococcus

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Robert E. Parker

2017-01-01

Full Text Available Streptococcus agalactiae (group B Streptococcus; GBS is a common inhabitant of the genitourinary and/or gastrointestinal tract in up to 40% of healthy adults; however, this opportunistic pathogen is able to breach restrictive host barriers to cause disease and persist in harsh and changing conditions. This study sought to identify a role for quorum sensing, a form of cell to cell communication, in the regulation of the fibrinogen-binding (rgfBDAC two-component system and the ability to associate with decidualized endometrial cells in vitro. To do this, we created a deletion in rgfD, which encodes the putative autoinducing peptide, in a GBS strain belonging to multilocus sequence type (ST-17 and made comparisons to the wild type. Sequence variation in the rgf operon was detected in 40 clinical strains and a non-synonymous single nucleotide polymorphism was detected in rgfD in all of the ST-17 genomes that resulted in a truncation. Using qPCR, expression of rgf operon genes was significantly decreased in the ST-17 ΔrgfD mutant during exponential growth with the biggest difference (3.3-fold occurring at higher cell densities. Association with decidualized endometrial cells was decreased 1.3-fold in the mutant relative to the wild type and rgfC expression was reduced 22-fold in ΔrgfD following exposure to the endometrial cells. Collectively, these data suggest that this putative quorum sensing molecule is important for attachment to human tissues and demonstrate a role for RgfD in GBS pathogenesis through regulation of rgfC.

A quorum-sensing molecule acts as a morphogen controlling gas vesicle organelle biogenesis and adaptive flotation in an enterobacterium.

Science.gov (United States)

Ramsay, Joshua P; Williamson, Neil R; Spring, David R; Salmond, George P C

2011-09-06

Gas vesicles are hollow intracellular proteinaceous organelles produced by aquatic Eubacteria and Archaea, including cyanobacteria and halobacteria. Gas vesicles increase buoyancy and allow taxis toward air-liquid interfaces, enabling subsequent niche colonization. Here we report a unique example of gas vesicle-mediated flotation in an enterobacterium; Serratia sp. strain ATCC39006. This strain is a member of the Enterobacteriaceae previously studied for its production of prodigiosin and carbapenem antibiotics. Genes required for gas vesicle synthesis mapped to a 16.6-kb gene cluster encoding three distinct homologs of the main structural protein, GvpA. Heterologous expression of this locus in Escherichia coli induced copious vesicle production and efficient cell buoyancy. Gas vesicle morphogenesis in Serratia enabled formation of a pellicle-like layer of highly vacuolated cells, which was dependent on oxygen limitation and the expression of ntrB/C and cheY-like regulatory genes within the gas-vesicle gene cluster. Gas vesicle biogenesis was strictly controlled by intercellular chemical signaling, through an N-acyl homoserine lactone, indicating that in this system the quorum-sensing molecule acts as a morphogen initiating organelle development. Flagella-based motility and gas vesicle morphogenesis were also oppositely regulated by the small RNA-binding protein, RsmA, suggesting environmental adaptation through physiological control of the choice between motility and flotation as alternative taxis modes. We propose that gas vesicle biogenesis in this strain represents a distinct mechanism of mobility, regulated by oxygen availability, nutritional status, the RsmA global regulatory system, and the quorum-sensing morphogen.

31 CFR 594.301 - Blocked account; blocked property.

Science.gov (United States)

2010-07-01

... (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY GLOBAL TERRORISM SANCTIONS REGULATIONS General Definitions § 594.301 Blocked account; blocked property. The terms blocked account and...

Boolean network model of the Pseudomonas aeruginosa quorum sensing circuits.

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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.

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

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Simon Fellous

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

Antisense locked nucleic acids targeting agrA inhibit quorum sensing and pathogenesis of community-associated methicillin-resistant Staphylococcus aureus.

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Da, F; Yao, L; Su, Z; Hou, Z; Li, Z; Xue, X; Meng, J; Luo, X

2017-01-01

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is commonly associated with nonnosocomial skin and soft tissue infections due to its virulence, which is mainly controlled by the accessory gene regulator (agr) quorum sensing (QS) system. In this study (KFF) 3 K peptide-conjugated locked nucleic acids (PLNAs) targeting agrA mRNA were developed to inhibit agr activity and arrest the pathogenicity of CA-MRSA. Two PLNAs were designed, and synthesized, after predicting the secondary structure of agrA mRNA. The influence on bacterial growth was tested using a growth curve assay. RT-qPCR, haemolysis assay, lactate dehydrogenase release assay and chemotaxis assay were used to evaluate the effects of the PLNAs on inhibiting agr QS. A mouse skin infection model was employed to test the protective effect of the PLNAs in vivo. None of the PLNAs were found to be bacteriostatic or bactericidal in vitro. However, one PLNA, PLNA34, showed strong ability to suppress expression of agrA and the effector molecule RNAIII in USA300 LAC strain. Furthermore, PLNA34 inhibited the expression of virulence genes that are upregulated by agr, including hla, psmα, psmβ and pvl. The haemolytic activity of the supernatants from PLNA34-treated bacteria was also dramatically reduced, as well as the capacity to lyse and recruit neutrophils. Moreover, PLNA34 showed high levels of protection in the CA-MRSA mouse skin infection model. The anti-agrA PLNA34 can effectively inhibit the agr QS and suppress CA-MRSA pathogenicity. agrA is a promising target for the development of antisense oligonucleotides to block agr QS. Journal of Applied Microbiology © 2016 The Society for Applied Microbiology.

["Habitual" left branch block alternating with 2 "disguised" bracnch block].

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Lévy, S; Jullien, G; Mathieu, P; Mostefa, S; Gérard, R

1976-10-01

Two cases of alternating left bundle branch block and "masquerading block" (with left bundle branch morphology in the stnadard leads and right bundle branch block morphology in the precordial leads) were studied by serial tracings and his bundle electrocardiography. In case 1 "the masquerading" block was associated with a first degree AV block related to a prolongation of HV interval. This case is to our knowledge the first cas of alternating bundle branch block in which his bundle activity was recorded in man. In case 2, the patient had atrial fibrilation and His bundle recordings were performed while differents degrees of left bundle branch block were present: The mechanism of the alternation and the concept of "masquerading" block are discussed. It is suggested that this type of block represents a right bundle branch block associated with severe lesions of the "left system".

Geospatial Distribution and Clustering of Chlamydia trachomatis in Communities Undergoing Mass Azithromycin Treatment

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Yohannan, Jithin; He, Bing; Wang, Jiangxia; Greene, Gregory; Schein, Yvette; Mkocha, Harran; Munoz, Beatriz; Quinn, Thomas C.; Gaydos, Charlotte; West, Sheila K.

2014-01-01

Purpose. We detected spatial clustering of households with Chlamydia trachomatis infection (CI) and active trachoma (AT) in villages undergoing mass treatment with azithromycin (MDA) over time. Methods. We obtained global positioning system (GPS) coordinates for all households in four villages in Kongwa District, Tanzania. Every 6 months for a period of 42 months, our team examined all children under 10 for AT, and tested for CI with ocular swabbing and Amplicor. Villages underwent four rounds of annual MDA. We classified households as having ≥1 child with CI (or AT) or having 0 children with CI (or AT). We calculated the difference in the K function between households with and without CI or AT to detect clustering at each time point. Results. Between 918 and 991 households were included over the 42 months of this analysis. At baseline, 306 households (32.59%) had ≥1 child with CI, which declined to 73 households (7.50%) at 42 months. We observed borderline clustering of households with CI at 12 months after one round of MDA and statistically significant clustering with growing cluster sizes between 18 and 24 months after two rounds of MDA. Clusters diminished in size at 30 months after 3 rounds of MDA. Active trachoma did not cluster at any time point. Conclusions. This study demonstrates that CI clusters after multiple rounds of MDA. Clusters of infection may increase in size if the annual antibiotic pressure is removed. The absence of growth after the three rounds suggests the start of control of transmission. PMID:24906862

Study protocol, rationale and recruitment in a European multi-centre randomized controlled trial to determine the efficacy and safety of azithromycin maintenance therapy for 6 months in primary ciliary dyskinesia

DEFF Research Database (Denmark)

Kobbernagel, Helene Elgaard; Buchvald, Frederik F; Haarman, Eric G

2016-01-01

maintenance therapy in PCD. METHODS: The BESTCILIA trial is a European multi-centre, double-blind, randomized, placebo-controlled, parallel group study. The intervention is tablets of azithromycin 250/500 mg according to body weight or placebo administered three times a week for 6 months. Subjects...... prescribed in other chronic respiratory disorders. Furthermore, the trial will utilize the Lung clearance index and new, PCD-specific quality of life instruments as outcome measures for PCD. Recruitment is hampered by frequent occurrence of Pseudomonas aeruginosa infection, exacerbations at enrolment...

E-Block: A Tangible Programming Tool with Graphical Blocks

Directory of Open Access Journals (Sweden)

Danli Wang

2013-01-01

Full Text Available This paper designs a tangible programming tool, E-Block, for children aged 5 to 9 to experience the preliminary understanding of programming by building blocks. With embedded artificial intelligence, the tool defines the programming blocks with the sensors as the input and enables children to write programs to complete the tasks in the computer. The symbol on the programming block's surface is used to help children understanding the function of each block. The sequence information is transferred to computer by microcomputers and then translated into semantic information. The system applies wireless and infrared technologies and provides user with feedbacks on both screen and programming blocks. Preliminary user studies using observation and user interview methods are shown for E-Block's prototype. The test results prove that E-Block is attractive to children and easy to learn and use. The project also highlights potential advantages of using single chip microcomputer (SCM technology to develop tangible programming tools for children.

E-Block: A Tangible Programming Tool with Graphical Blocks

OpenAIRE

Danli Wang; Yang Zhang; Shengyong Chen

2013-01-01

This paper designs a tangible programming tool, E-Block, for children aged 5 to 9 to experience the preliminary understanding of programming by building blocks. With embedded artificial intelligence, the tool defines the programming blocks with the sensors as the input and enables children to write programs to complete the tasks in the computer. The symbol on the programming block's surface is used to help children understanding the function of each block. The sequence information is transfer...

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

Science.gov (United States)

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

2009-12-01

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

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

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Francisco Pérez-Montaño

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

Piper nigrum, Piper betle and Gnetum gnemon- Natural Food Sourcewith Anti-Quorum Sensing Properties

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Li Ying Tan

2013-03-01

Full Text Available Various parts of Piper nigrum, Piper betle and Gnetum gnemon are used as food sources by Malaysians. The purpose of this study is to examine the anti-quorum sensing (anti-QS properties of P. nigrum, P. betle and G. gnemon extracts. The hexane, chloroform and methanol extracts of these plants were assessed in bioassays involving Pseudomonas aeruginosa PA01, Escherichia coli [pSB401], E. coli [pSB1075] and Chromobacterium violaceum CV026. It was found that the extracts of these three plants have anti-QS ability. Interestingly, the hexane, chloroform and methanol extracts from P. betle showed the most potent anti-QS activity as judged by the bioassays. Since there is a variety of plants that serve as food sources in Malaysia that have yet to be tested for anti-QS activity, future work should focus on identification of these plants and isolation of the anti-QS compounds.

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

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Nina Yusrina Muhamad Yunos

2014-06-01

Full Text Available Quorum sensing (QS is a bacterial cell-to-cell communication system controlling QS-mediated genes which is synchronized with the population density. The regulation of specific gene activity is dependent on the signaling molecules produced, namely N-acyl homoserine lactones (AHLs. We report here the identification and characterization of AHLs produced by bacterial strain ND07 isolated from a Malaysian fresh water sample. Molecular identification showed that strain ND07 is clustered closely to Pseudomonas cremoricolorata. Spent culture supernatant extract of P. cremoricolorata strain ND07 activated the AHL biosensor Chromobacterium violaceum CV026. Using high resolution triple quadrupole liquid chromatography-mass spectrometry, it was confirmed that P. cremoricolorata strain ND07 produced N-octanoyl-l-homoserine lactone (C8-HSL and N-decanoyl-l-homoserine lactone (C10-HSL. To the best of our knowledge, this is the first documentation on the production of C10-HSL in P. cremoricolorata strain ND07.

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.

QStatin, a Selective Inhibitor of Quorum Sensing in Vibrio Species

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Byoung Sik Kim

2018-01-01

Full Text Available Pathogenic Vibrio species cause diseases in diverse marine animals reared in aquaculture. Since their pathogenesis, persistence, and survival in marine environments are regulated by quorum sensing (QS, QS interference has attracted attention as a means to control these bacteria in aquatic settings. A few QS inhibitors of Vibrio species have been reported, but detailed molecular mechanisms are lacking. Here, we identified a novel, potent, and selective Vibrio QS inhibitor, named QStatin [1-(5-bromothiophene-2-sulfonyl-1H-pyrazole], which affects Vibrio harveyi LuxR homologues, the well-conserved master transcriptional regulators for QS in Vibrio species. Crystallographic and biochemical analyses showed that QStatin binds tightly to a putative ligand-binding pocket in SmcR, the LuxR homologue in V. vulnificus, and changes the flexibility of the protein, thereby altering its transcription regulatory activity. Transcriptome analysis revealed that QStatin results in SmcR dysfunction, affecting the expression of SmcR regulon required for virulence, motility/chemotaxis, and biofilm dynamics. Notably, QStatin attenuated representative QS-regulated phenotypes in various Vibrio species, including virulence against the brine shrimp (Artemia franciscana. Together, these results provide molecular insights into the mechanism of action of an effective, sustainable QS inhibitor that is less susceptible to resistance than other antimicrobial agents and useful in controlling the virulence of Vibrio species in aquacultures.

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

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Sándor Pongor

2013-07-01

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

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

Science.gov (United States)

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

2013-01-01

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

Microbial growth and quorum sensing antagonist activities of herbal plants extracts.

Science.gov (United States)

Al-Hussaini, Reema; Mahasneh, Adel M

2009-09-03

Antimicrobial and antiquorum sensing (AQS) activities of fourteen ethanolic extracts of different parts of eight plants were screened against four Gram-positive, five Gram-negative bacteria and four fungi. Depending on the plant part extract used and the test microorganism, variable activities were recorded at 3 mg per disc. Among the Grampositive bacteria tested, for example, activities of Laurus nobilis bark extract ranged between a 9.5 mm inhibition zone against Bacillus subtilis up to a 25 mm one against methicillin resistant Staphylococcus aureus. Staphylococcus aureus and Aspergillus fumigatus were the most susceptible among bacteria and fungi tested towards other plant parts. Of interest is the tangible antifungal activity of a Tecoma capensis flower extract, which is reported for the first time. However, minimum inhibitory concentrations (MIC's) for both bacteria and fungi were relatively high (0.5-3.0 mg). As for antiquorum sensing activity against Chromobacterium violaceum, superior activity (>17 mm QS inhibition) was associated with Sonchus oleraceus and Laurus nobilis extracts and weak to good activity (8-17 mm) was recorded for other plants. In conclusion, results indicate the potential of these plant extracts in treating microbial infections through cell growth inhibition or quorum sensing antagonism, which is reported for the first time, thus validating their medicinal use.

Microbial Growth and Quorum Sensing Antagonist Activities of Herbal Plants Extracts

Directory of Open Access Journals (Sweden)

Reema Al-Hussaini

2009-09-01

Full Text Available Antimicrobial and antiquorum sensing (AQS activities of fourteen ethanolic extracts of different parts of eight plants were screened against four Gram-positive, five Gram-negative bacteria and four fungi. Depending on the plant part extract used and the test microorganism, variable activities were recorded at 3 mg per disc. Among the Grampositive bacteria tested, for example, activities of Laurus nobilis bark extract ranged between a 9.5 mm inhibition zone against Bacillus subtilis up to a 25 mm one against methicillin resistant Staphylococcus aureus. Staphylococcus aureus and Aspergillus fumigatus were the most susceptible among bacteria and fungi tested towards other plant parts. Of interest is the tangible antifungal activity of a Tecoma capensis flower extract, which is reported for the first time. However, minimum inhibitory concentrations (MIC's for both bacteria and fungi were relatively high (0.5-3.0 mg. As for antiquorum sensing activity against Chromobacterium violaceum, superior activity (>17 mm QS inhibition was associated with Sonchus oleraceus and Laurus nobilis extracts and weak to good activity (8-17 mm was recorded for other plants. In conclusion, results indicate the potential of these plant extracts in treating microbial infections through cell growth inhibition or quorum sensing antagonism, which is reported for the first time, thus validating their medicinal use.

Poly(ferrocenylsilane)-block-Polylactide Block Copolymers

NARCIS (Netherlands)

Roerdink, M.; van Zanten, Thomas S.; Hempenius, Mark A.; Zhong, Zhiyuan; Feijen, Jan; Vancso, Gyula J.

2007-01-01

A PFS/PLA block copolymer was studied to probe the effect of strong surface interactions on pattern formation in PFS block copolymer thin films. Successful synthesis of PFS-b-PLA was demonstrated. Thin films of these polymers show phase separation to form PFS microdomains in a PLA matrix, and

Piper nigrum, Piper betle and Gnetum gnemon--natural food sources with anti-quorum sensing properties.

Science.gov (United States)

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

2013-03-20

Various parts of Piper nigrum, Piper betle and Gnetum gnemon are used as food sources by Malaysians. The purpose of this study is to examine the anti-quorum sensing (anti-QS) properties of P. nigrum, P. betle and G. gnemon extracts. The hexane, chloroform and methanol extracts of these plants were assessed in bioassays involving Pseudomonas aeruginosa PA01, Escherichia coli [pSB401], E. coli [pSB1075] and Chromobacterium violaceum CV026. It was found that the extracts of these three plants have anti-QS ability. Interestingly, the hexane, chloroform and methanol extracts from P. betle showed the most potent anti-QS activity as judged by the bioassays. Since there is a variety of plants that serve as food sources in Malaysia that have yet to be tested for anti-QS activity, future work should focus on identification of these plants and isolation of the anti-QS compounds.

Quorum sensing communication between bacteria and human cells: signals, targets and functions

Directory of Open Access Journals (Sweden)

Angelika eHolm

2014-06-01

Full Text Available Both direct and long-range interactions between pathogenic Pseudomonas aeruginosa bacteria and their eukaryotic hosts are important in the outcome of infections. For cell-to-cell communication, these bacteria employ the quorum sensing (QS system to pass on information of the density of the bacterial population and collectively switch on virulence factor production, biofilm formation and resistance development. Thus, QS allows bacteria to behave as a community to perform tasks which would be impossible for individual cells, e.g. to overcome defense and immune systems and establish infections in higher organisms. This review highlights these aspects of QS and our own recent research on how P.aeruginosa communicates with human cells using the small QS signal molecules N-acyl homoserine lactones (AHL. We focus on how this conversation changes the behavior and function of neutrophils, macrophages and epithelial cells and on how the signaling machinery in human cells responsible for the recognition of AHL. Understanding the bacteria-host relationships at both cellular and molecular levels is essential for the identification of new targets and for the development of novel strategies to fight bacterial infections in the future.

Flavonoids from Piper delineatum modulate quorum-sensing-regulated phenotypes in Vibrio harveyi.

Science.gov (United States)

Martín-Rodríguez, Alberto J; Ticona, Juan C; Jiménez, Ignacio A; Flores, Ninoska; Fernández, José J; Bazzocchi, Isabel L

2015-09-01

Quorum sensing (QS), or bacterial cell-to-cell communication, is a key process for bacterial colonization of substrata through biofilm formation, infections, and production of virulence factors. In an ongoing investigation of bioactive secondary metabolites from Piper species, four new flavonoids (1-4), along with five known ones (5-9) were isolated from the leaves of Piper delineatum. Their stereostructures were established by spectroscopic and spectrometric methods, including 1D and 2D NMR experiments, and comparison with data reported in the literature. The compounds were screened for their ability to interfere with QS signaling in the bacterial model Vibrio harveyi. Four compounds from this series (2, 3, 6, and 7) exhibited remarkable activity in the micromolar range, being compounds 3 and 7 particularly attractive since they did not affect bacterial growth. The results suggest that these flavonoids disrupt QS-mediated bioluminescence by interaction with elements downstream LuxO in the QS circuit of V. harveyi, and also, they exhibited a strong dose-dependent inhibition of biofilm formation. The present findings shed light on the QS inhibition mechanisms of flavonoids, underlining their potential applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

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James E. Trosko

2016-06-01

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

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

Science.gov (United States)

Trosko, James E

2016-06-15

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

Block and sub-block boundary strengthening in lath martensite

NARCIS (Netherlands)

Du, C.; Hoefnagels, J.P.M.; Vaes, R.; Geers, M.G.D.

2016-01-01

Well-defined uniaxial micro-tensile tests were performed on lath martensite single block specimens and multi-block specimens with different number of block boundaries parallel to the loading direction. Detailed slip trace analyses consistently revealed that in the {110}<111> slip system with the

On the Eigenvalues and Eigenvectors of Block Triangular Preconditioned Block Matrices

KAUST Repository

Pestana, Jennifer

2014-01-01

Block lower triangular matrices and block upper triangular matrices are popular preconditioners for 2×2 block matrices. In this note we show that a block lower triangular preconditioner gives the same spectrum as a block upper triangular preconditioner and that the eigenvectors of the two preconditioned matrices are related. © 2014 Society for Industrial and Applied Mathematics.

Powder wastes confinement block and manufacturing process of this block

International Nuclear Information System (INIS)

Dagot, L.; Brunel, G.

1996-01-01

This invention concerns a powder wastes containment block and a manufacturing process of this block. In this block, the waste powder is encapsulated in a thermo hardening polymer as for example an epoxy resin, the encapsulated resin being spread into cement. This block can contain between 45 and 55% in mass of wastes, between 18 and 36% in mass of polymer and between 14 and 32% in mass of cement. Such a containment block can be used for the radioactive wastes storage. (O.M.). 4 refs

Quorum sensing controls the synthesis of virulence factors by modulating rsmA gene expression in Erwinia carotovora subsp. carotovora.

Science.gov (United States)

Kõiv, V; Mäe, A

2001-04-01

The plant-pathogenic bacterium Erwinia carotovora subsp. carotovora (Ecc) causes disease mainly by means of a number of extracellular plant cell wall-degrading enzymes (PCWDEs), also referred to as virulence factors. The production of PCWDEs is coordinately activated by the diffusible signal molecule N-acyl-homoserine lactone (HSL) in a population density-dependent manner ("quorum sensing"). ExpI is the enzyme responsible for the synthesis of HSL. The Rsm system negatively regulates the production of PCWDEs. It includes three components: RsmA is an RNA-binding protein which promotes mRNA decay; rsmB is a unique regulator RNA, and RsmC regulates expression of rsmA positively and of rsmB negatively. We report here that in an expI knockout mutant of Ecc strain SCC3193, the levels of rsmA and rsmB RNA are remarkably enhanced in comparison to the wild-type strain, while the level of the rsmC transcript is not affected. The increase in transcription of rsmA in the expI strain represses production of PCWDEs, which in turn leads to the avirulent phenotype of this mutant. In the expI- mutant, addition of exogenous HSL caused repression of rsmA and rsmB transcription to the wild-type level, whereas the expression of rsmC was not affected. Taken together, these data suggest that HSL affects the expression of rsmA, and that this effect is not mediated by RsmC. This specific effect and the previous demonstration that HSL is required for PCWDE production in Ecc support the hypothesis that regulation by quorum sensing in Ecc, in contrast to most other systems already described, requires HSL to repress rsmA transcription, which in turn leads to the activation of PCWDE production. A model is presented that explains how HSL controls the production of PCWDEs by modulating the expression of rsmA.

Blocked Randomization with Randomly Selected Block Sizes

Directory of Open Access Journals (Sweden)

Jimmy Efird

2010-12-01

Full Text Available When planning a randomized clinical trial, careful consideration must be given to how participants are selected for various arms of a study. Selection and accidental bias may occur when participants are not assigned to study groups with equal probability. A simple random allocation scheme is a process by which each participant has equal likelihood of being assigned to treatment versus referent groups. However, by chance an unequal number of individuals may be assigned to each arm of the study and thus decrease the power to detect statistically significant differences between groups. Block randomization is a commonly used technique in clinical trial design to reduce bias and achieve balance in the allocation of participants to treatment arms, especially when the sample size is small. This method increases the probability that each arm will contain an equal number of individuals by sequencing participant assignments by block. Yet still, the allocation process may be predictable, for example, when the investigator is not blind and the block size is fixed. This paper provides an overview of blocked randomization and illustrates how to avoid selection bias by using random block sizes.

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…

Metabolites with Gram-negative bacteria quorum sensing inhibitory activity from the marine animal endogenic fungus Penicillium sp. SCS-KFD08.

Science.gov (United States)

Kong, Fan Dong; Zhou, Li Man; Ma, Qing Yun; Huang, Sheng Zhuo; Wang, Pei; Dai, Hao Fu; Zhao, You Xing

2017-01-01

Three new compounds named penicitor A, aculene E and penicitor B, as well as four known compounds, were isolated from the fermentation broth of Penicillium sp. SCS-KFD08 associated with a marine animal Sipunculus nudus from the Haikou bay of China. Their planar structures and absolute configurations were unambiguously elucidated by spectroscopic data, Mosher's method, CD spectrum analysis along with quantum ECD calculation. Among them, compounds 2-7 showed quorum sensing inhibitory activity against Chromobacterium violaceum CV026, and could significantly reduce violacein production in N-hexanoyl-l-homoserine lactone (C6-HSL) induced C. violaceum CV026 cultures at sub-inhibitory concentrations.

Chitosan nanoparticles enhances the anti-quorum sensing activity of kaempferol.

Science.gov (United States)

Ilk, Sedef; Sağlam, Necdet; Özgen, Mustafa; Korkusuz, Feza

2017-01-01

Quorum sensing (QS) is a cell density dependent expression of species in bacteria mediated by compounds called autoinducers (AI). Several processes responsible for successful establishment of bacterial infection are mediated by QS. Inhibition of QS is therefore being considered as a new target for antimicrobial chemotherapy. Flavonoid compounds are strong antioxidant and antimicrobial agents but their applications are limited due to their poor dissolution and bioavailability. Our objective was to investigate the effect of kaempferol loaded chitosan nanoparticles on modulating QS mediated by AI in model bioassay test systems. For this purpose, kaempferol loaded nanoparticles were synthesized and characterized in terms of hydrodynamic diameter, hydrogen bonding, amorphous transformation and antioxidant activity. QS inhibition in time dependent manner of nanoparticles was measured in violacein pigment producing using the biosensor strain Chromobacterium violaceum CV026 mediated by AI known as acylated homoserine lactone (AHL). Our results indicated that the average kaempferol loaded chitosan/TPP nanoparticle size and zeta potential were 192.27±13.6nm and +35mV, respectively. The loading and encapsulation efficiency of kaempferol into chitosan/TPP nanoparticles presented higher values between 78 and 93%. Kaempferol loaded chitosan/TPP nanoparticle during the 30 storage days significantly inhibited the production of violacein pigment in Chromobacterium violaceum CV026. The observation that kaempferol encapsulated chitosan nanoparticles can inhibit QS related processes opens up an exciting new strategy for antimicrobial chemotherapy as stable QS-based anti-biofilm agents. Copyright © 2016 Elsevier B.V. All rights reserved.

Inhibiting effect of bioactive metabolites produced by mushroom cultivation on bacterial quorum sensing-regulated behaviors.

Science.gov (United States)

Zhu, Hu; Wang, Shou-Xian; Zhang, Shuai-Shuai; Cao, Chun-Xu

2011-01-01

This study aimed to search for novel quorum sensing (QS) inhibitors from mushroom and to analyze their inhibitory activity, with a view to their possible use in controlling detrimental infections. The bioactive metabolites produced by mushroom cultivation were tested for their abilities to inhibit QS-regulated behavior. All mushroom strains were cultivated in potato-dextrose medium by large-scale submerged fermentation. The culture supernatant was condensed into 0.2 vol by freeze-drying. The condensed supernatant was sterilized by filtration through a 0.22-μm membrane filter and added to Chromobacterium violaceum CV026 cultures, which were used to monitor QS inhibition. Inhibitory activity was measured by quantifying violacein production using a microplate reader. The results have revealed that, of 102 mushroom strains, the bioactive metabolites produced by 14 basidiomycetes were found to inhibit violacein production, a QS-regulated behavior in C. violaceum. Higher fungi can produce QS-inhibitory compounds. Copyright © 2011 S. Karger AG, Basel.

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

Science.gov (United States)

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

2013-01-01

Various parts of Piper nigrum, Piper betle and Gnetum gnemon are used as food sources by Malaysians. The purpose of this study is to examine the anti-quorum sensing (anti-QS) properties of P. nigrum, P. betle and G. gnemon extracts. The hexane, chloroform and methanol extracts of these plants were assessed in bioassays involving Pseudomonas aeruginosa PA01, Escherichia coli [pSB401], E. coli [pSB1075] and Chromobacterium violaceum CV026. It was found that the extracts of these three plants have anti-QS ability. Interestingly, the hexane, chloroform and methanol extracts from P. betle showed the most potent anti-QS activity as judged by the bioassays. Since there is a variety of plants that serve as food sources in Malaysia that have yet to be tested for anti-QS activity, future work should focus on identification of these plants and isolation of the anti-QS compounds. PMID:23519352

Minimum description length block finder, a method to identify haplotype blocks and to compare the strength of block boundaries.

Science.gov (United States)

Mannila, H; Koivisto, M; Perola, M; Varilo, T; Hennah, W; Ekelund, J; Lukk, M; Peltonen, L; Ukkonen, E

2003-07-01

We describe a new probabilistic method for finding haplotype blocks that is based on the use of the minimum description length (MDL) principle. We give a rigorous definition of the quality of a segmentation of a genomic region into blocks and describe a dynamic programming algorithm for finding the optimal segmentation with respect to this measure. We also describe a method for finding the probability of a block boundary for each pair of adjacent markers: this gives a tool for evaluating the significance of each block boundary. We have applied the method to the published data of Daly and colleagues. The results expose some problems that exist in the current methods for the evaluation of the significance of predicted block boundaries. Our method, MDL block finder, can be used to compare block borders in different sample sets, and we demonstrate this by applying the MDL-based method to define the block structure in chromosomes from population isolates.

A chemical biology approach to interrogate quorum-sensing regulated behaviors at the molecular and cellular level.

Science.gov (United States)

Lowery, Colin A; Matamouros, Susana; Niessen, Sherry; Zhu, Jie; Scolnick, Jonathan; Lively, Jenny M; Cravatt, Benjamin F; Miller, Samuel I; Kaufmann, Gunnar F; Janda, Kim D

2013-07-25

Small molecule probes have been used extensively to explore biologic systems and elucidate cellular signaling pathways. In this study, we use an inhibitor of bacterial communication to monitor changes in the proteome of Salmonella enterica serovar Typhimurium with the aim of discovering unrecognized processes regulated by AI-2-based quorum-sensing (QS), a mechanism of bacterial intercellular communication that allows for the coordination of gene expression in a cell density-dependent manner. In S. typhimurium, this system regulates the uptake and catabolism of intercellular signals and has been implicated in pathogenesis, including the invasion of host epithelial cells. We demonstrate that our QS antagonist is capable of selectively inhibiting the expression of known QS-regulated proteins in S. typhimurium, thus attesting that QS inhibitors may be used to confirm proposed and elucidate previously unidentified QS pathways without relying on genetic manipulation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Reduced intracellular c-di-GMP content increases expression of quorum sensing-regulated genes in Pseudomonas aeruginosa

DEFF Research Database (Denmark)

Chua, Song Lin; Liu, Yang; Li, Yingying

2017-01-01

Cyclic-di-GMP (c-di-GMP) is an intracellular secondary messenger which controls the biofilm life cycle in many bacterial species. High intracellular c-di-GMP content enhances biofilm formation via the reduction of motility and production of biofilm matrix, while low c-di-GMP content in biofilm...... cells leads to increased motility and biofilm dispersal. While the effect of high c-di-GMP levels on bacterial lifestyles is well studied, the physiology of cells at low c-di-GMP levels remains unclear. Here, we showed that Pseudomonas aeruginosa cells with high and low intracellular c-di-GMP contents...... possessed distinct transcriptome profiles. There were 535 genes being upregulated and 432 genes downregulated in cells with low c-di-GMP, as compared to cells with high c-di-GMP. Interestingly, both rhl and pqs quorum-sensing (QS) operons were expressed at higher levels in cells with low intracellular c-di-GMP...

Quorum sensing molecules production by nosocomial and soil isolates Acinetobacter baumannii.

Science.gov (United States)

Erdönmez, Demet; Rad, Abbas Yousefi; Aksöz, Nilüfer

2017-12-01

Acinetobacter species remain alive in hospitals on various surfaces, both dry and moist, forming an important source of hospital infections. These bacteria are naturally resistant to many antibiotic classes. Although the role of the quorum sensing system in regulating the virulence factors of Acinetobacter species has not been fully elucidated, it has been reported that they play a role in bacterial biofilm formation. The biofilm formation helps them to survive under unfavorable growth conditions and antimicrobial treatments. It is based on the accumulation of bacterial communication signal molecules in the area. In this study, we compared the bacterial signal molecules of 50 nosocomial Acinetobacter baumannii strain and 20 A. baumannii strain isolated from soil. The signal molecules were detected by the biosensor bacteria (Chromobacterium violaceum 026, Agrobacterium tumefaciens A136, and Agrobacterium tumefaciens NTL1) and their separation was determined by thin-layer chromatography. As a result, it has been found that soil-borne isolates can produce 3-oxo-C8-AHL and C8-AHL, whereas nosocomial-derived isolates can produce long-chain signals such as C10-AHL, C12-AHL, C14-AHL and C16-AHL. According to these results, it is possible to understand that these signal molecules are found in the infection caused by A. baumannii. The inhibition of this signaling molecules in a communication could use to prevent multiple antibiotic resistance of these bacteria.

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

Science.gov (United States)

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

2014-12-05

Avian pathogenic Escherichia coli (APEC) induce septicemia in chickens by invading type II pneumocytes to breach the blood-air barrier. The virulence of APEC can be regulated by quorum sensing (QS). Andrographolide is a QS inhibitor of Pseudomonas aeruginosa (P. aeruginosa). Therefore, we investigate whether andrographolide inhibits the injury of chicken type II pneumocytes by avian pathogenic E. coli O78 (APEC-O78) by disrupting the bacterial QS system. The results showed that sub-MIC of andrographolide significantly reduced the release of lactate dehydrogenase (LDH), F-actin cytoskeleton polymerization, and the degree of the adherence to chicken type II pneumocytes induced by APEC-O78. Further, we found that andrographolide significantly decreased the autoinducer-2 (AI-2) activity and the expression of virulence factors of APEC-O78. These results suggest that andrographolide reduce the pathogenicity of APEC-O78 in chicken type II pneumocytes by interfering QS and decreasing virulence. These results provide new evidence for colibacillosis prevention methods in chickens. Copyright © 2014 Elsevier B.V. All rights reserved.

Characterization of type 2 quorum sensing in Klebsiella pneumoniae and relationship with biofilm formation

DEFF Research Database (Denmark)

Balestrino, D.; Haagensen, Janus Anders Juul; Rich, C.

2005-01-01

Quorum sensing is a process by which bacteria communicate by using secreted chemical signaling molecules called autoinducers. Many bacterial species modulate the expression of a wide variety of physiological functions in response to changes in population density by this mechanism. In this study, ...... steps of biofilm formation. These data suggest that a LuxS-dependent signal plays a role in the early stages of biofilm formation by K. pneumoniae....... observed in minimal medium supplemented with glycerol. To determine the potential role of luxS in colonization processes, a K. pneumoniae luxS isogenic mutant was constructed and tested for its capacity to form biofilms in vitro on an abiotic surface and to colonize the intestinal tract in a murine model....... No difference was observed in the level of intestinal colonization between the wild-type strain and the luxS mutant. Microscopic analysis of biofilm structures revealed that the luxS mutant was able to form a mature biofilm but with reduced capacities in the development of microcolonies, mostly in the early...

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.

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

DEFF Research Database (Denmark)

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

2003-01-01

direction, designated estA, which encodes an esterase that belongs to family II of lipolytic enzymes. EstA was heterologously expressed in Escherichia coli, and the substrate specificity of the enzyme was determined in crude extracts. With the aid of zymograms visualizing EstA on polyacrylamide gels...... and by the analysis of a transcriptional fusion of the estA promoter to the promoterless lux4B genes, we showed that expression of the esterase is not regulated by the swr quorum-sensing system. An estA mutant was generated and was found to exhibit growth defects on minimal medium containing Tween 20 or Tween 80...

Azithromycin attenuates myofibroblast differentiation and lung fibrosis development through proteasomal degradation of NOX4.

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Tsubouchi, Kazuya; Araya, Jun; Minagawa, Shunsuke; Hara, Hiromichi; Ichikawa, Akihiro; Saito, Nayuta; Kadota, Tsukasa; Sato, Nahoko; Yoshida, Masahiro; Kurita, Yusuke; Kobayashi, Kenji; Ito, Saburo; Fujita, Yu; Utsumi, Hirofumi; Yanagisawa, Haruhiko; Hashimoto, Mitsuo; Wakui, Hiroshi; Yoshii, Yutaka; Ishikawa, Takeo; Numata, Takanori; Kaneko, Yumi; Asano, Hisatoshi; Yamashita, Makoto; Odaka, Makoto; Morikawa, Toshiaki; Nakayama, Katsutoshi; Nakanishi, Yoichi; Kuwano, Kazuyoshi

2017-08-03

Accumulation of profibrotic myofibroblasts is involved in the process of fibrosis development during idiopathic pulmonary fibrosis (IPF) pathogenesis. TGFB (transforming growth factor β) is one of the major profibrotic cytokines for myofibroblast differentiation and NOX4 (NADPH oxidase 4) has an essential role in TGFB-mediated cell signaling. Azithromycin (AZM), a second-generation antibacterial macrolide, has a pleiotropic effect on cellular processes including proteostasis. Hence, we hypothesized that AZM may regulate NOX4 levels by modulating proteostasis machineries, resulting in inhibition of TGFB-associated lung fibrosis development. Human lung fibroblasts (LF) were used to evaluate TGFB-induced myofibroblast differentiation. With respect to NOX4 regulation via proteostasis, assays for macroautophagy/autophagy, the unfolded protein response (UPR), and proteasome activity were performed. The potential anti-fibrotic property of AZM was examined by using bleomycin (BLM)-induced lung fibrosis mouse models. TGFB-induced NOX4 and myofibroblast differentiation were clearly inhibited by AZM treatment in LF. AZM-mediated NOX4 reduction was restored by treatment with MG132, a proteasome inhibitor. AZM inhibited autophagy and enhanced the UPR. Autophagy inhibition by AZM was linked to ubiquitination of NOX4 via increased protein levels of STUB1 (STIP1 homology and U-box containing protein 1), an E3 ubiquitin ligase. An increased UPR by AZM was associated with enhanced proteasome activity. AZM suppressed lung fibrosis development induced by BLM with concomitantly reduced NOX4 protein levels and enhanced proteasome activation. These results suggest that AZM suppresses NOX4 by promoting proteasomal degradation, resulting in inhibition of TGFB-induced myofibroblast differentiation and lung fibrosis development. AZM may be a candidate for the treatment of the fibrotic lung disease IPF.

Quorum Sensing Regulation of Competence and Bacteriocins in Streptococcus pneumoniae and mutans

Science.gov (United States)

Shanker, Erin; Federle, Michael J.

2017-01-01

The human pathogens Streptococcus pneumoniae and Streptococcus mutans have both evolved complex quorum sensing (QS) systems that regulate the production of bacteriocins and the entry into the competent state, a requirement for natural transformation. Natural transformation provides bacteria with a mechanism to repair damaged genes or as a source of new advantageous traits. In S. pneumoniae, the competence pathway is controlled by the two-component signal transduction pathway ComCDE, which directly regulates SigX, the alternative sigma factor required for the initiation into competence. Over the past two decades, effectors of cellular killing (i.e., fratricides) have been recognized as important targets of the pneumococcal competence QS pathway. Recently, direct interactions between the ComCDE and the paralogous BlpRH pathway, regulating bacteriocin production, were identified, further strengthening the interconnections between these two QS systems. Interestingly, a similar theme is being revealed in S. mutans, the primary etiological agent of dental caries. This review compares the relationship between the bacteriocin and the competence QS pathways in both S. pneumoniae and S. mutans, and hopes to provide clues to regulatory pathways across the genus Streptococcus as a potential tool to efficiently investigate putative competence pathways in nontransformable streptococci. PMID:28067778

Broad spectrum pro-quorum-sensing molecules as inhibitors of virulence in vibrios.

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Wai-Leung Ng

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

A Lux-like Quorum Sensing System in the Extreme Acidophile Acidithiobacillus ferrooxidans

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MARIELLA RIVAS

2005-01-01

Full Text Available The genome of the acidophilic, proteobacterium Acidithiobacillus ferrooxidans, contains linked but divergently oriented genes, termed afeI and afeR, whose predicted protein products are significantly similar to the LuxI and LuxR families of proteins. A possible promoter and Lux box are predicted upstream of afeI. A cloned copy of afeI, expressed in E. coli, encodes an enzyme that catalyzes the production of a diffusible compound identified by gas chromatography and mass spectrometry as an unsubstituted N-acyl homoserine lactone (AHL of chain length C14. This AHL can be detected by a reporter strain of Sinorhizobium meliloti Rm41 suggesting that it is biologically active. The reporter strain also responds to extracts of the supernatant of A. ferrooxidans grown to early stationary phase in sulfur medium indicating that a diffusible AHL is produced by this microorganism. Semi-quantitative RT-PCR experiments indicate that afeI and afeR are expressed maximally in early stationary phase and are more expressed when A. ferrooxidans is grown in sulfur- rather than iron-containing medium. Given the predicted amino acid sequence and functional properties of AfeI and AfeR it is proposed that A. ferrooxidans has a quorum sensing system similar to the LuxI-LuxR paradigm.

Modulating the Global Response Regulator, LuxO of V. cholerae Quorum Sensing System Using a Pyrazine Dicarboxylic Acid Derivative (PDCApy: An Antivirulence Approach

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M. Hema

2017-10-01

Full Text Available Vibrio cholerae is a Gram-negative pathogen which causes acute diarrhoeal disease, cholera by the expression of virulence genes through quorum sensing (QS mechanism. The QS circuit of V. cholerae is controlled by the global quorum regulator, LuxO, which at low cell density (LCD state produces major virulence factors such as, toxin co-regulated pilus (TCP and cholera toxin (CT to mediate infection. On the contrary, at the high cell density (HCD state the virulent genes are downregulated and the vibrios are detached from the host intestinal epithelial cells, promoted by HapA protease. Hence, targeting the global regulator LuxO would be a promising approach to modulate the QS to curtail V. cholerae pathogenesis. In our earlier studies, LuxO targeted ligand, 2,3 pyrazine dicarboxylic acid (PDCA and its derivatives having desired pharmacophore properties were chemically synthesized and were shown to have biofilm inhibition as well as synergistic activity with the conventionally used antibiotics. In the present study, the QS modulatory effect of the PDCA derivative with pyrrolidine moiety designated as PDCApy against the V. cholerae virulence gene expression was analyzed at various growth phases. The data significantly showed a several fold reduction in the expression of the genes, tcp and ct whereas the expression of hapR was upregulated at the LCD state. In addition, PDCApy reduced the adhesion and invasion of the vibrios onto the INT407 intestinal cell lines. Collectively, our data suggest that PDCApy could be a potential QS modulator (QSM for the antivirulence therapeutic approach.

Generalized Block Failure

DEFF Research Database (Denmark)

Jönsson, Jeppe

2015-01-01

Block tearing is considered in several codes as a pure block tension or a pure block shear failure mechanism. However in many situations the load acts eccentrically and involves the transfer of a substantial moment in combination with the shear force and perhaps a normal force. A literature study...... shows that no readily available tests with a well-defined substantial eccentricity have been performed. This paper presents theoretical and experimental work leading towards generalized block failure capacity methods. Simple combination of normal force, shear force and moment stress distributions along...... yield lines around the block leads to simple interaction formulas similar to other interaction formulas in the codes....

Relationship between maternal c-reactive protein level and neonatal outcome in patients with preterm premature rupture of membranes treated with Ampicillin and Azithromycin.

Science.gov (United States)

Serdar Kutuk, Mehmet; Bastug, Osman; Ozdemir, Ahmet; Adnan Ozturk, Mehmet; Tuncay Ozgun, Mahmut; Basbug, Mustafa; Gunes, Tamer; Kurtoglu, Selim

2016-08-01

This historical cohort study aimed to assess the relationship between antenatal maternal C-reactive protein (CRP) level and neonatal outcome preterm premature rupture of membranes (PPROM). We reviewed the records of 70 singleton pregnancies with PPROM between 24 and 34 weeks. Maternal CRP levels of neonates with respiratory distress syndrome, neonatal sepsis, grade 3-4 intraventricular haemorrhage and stage 2-3 necrotizing enterocolitis, perinatal mortality were compared with those without these complications. Administration of corticosteroid, tocolysis for two days and prophylactic antibiotics (intravenous ampicillin/sulbactam, and oral azithromycin) were the standard management protocol. The mean age at PPROM was 29 weeks 2 days (±3 weeks), the mean age at birth was 30 weeks 5 days (±20 days). CRP levels were not different between groups. Uni/multivariate analysis showed that maternal CRP levels were not related with neonatal outcomes. Neonatal complications in PPROM are related with the degree of prematurity and maternal WBC counts.

Epidural block

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... page: //medlineplus.gov/ency/patientinstructions/000484.htm Epidural block - pregnancy To use the sharing features on this page, please enable JavaScript. An epidural block is a numbing medicine given by injection (shot) ...

The fsr Quorum-Sensing System and Cognate Gelatinase Orchestrate the Expression and Processing of Proprotein EF_1097 into the Mature Antimicrobial Peptide Enterocin O16.

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Dundar, Halil; Brede, Dag A; La Rosa, Sabina Leanti; El-Gendy, Ahmed Osama; Diep, Dzung B; Nes, Ingolf F

2015-07-01

A novel antimicrobial peptide designated enterocin O16 was purified from Enterococcus faecalis. Mass spectrometry showed a monoisotopic mass of 7,231 Da, and N-terminal Edman degradation identified a 29-amino-acid sequence corresponding to residues 90 to 119 of the EF_1097 protein. Bioinformatic analysis showed that enterocin O16 is composed of the 68 most C-terminal residues of the EF_1097 protein. Introduction of an in-frame isogenic deletion in the ef1097 gene abolished the production of enterocin O16. Enterocin O16 has a narrow inhibitory spectrum, as it inhibits mostly lactobacilli. Apparently, E. faecalis is intrinsically resistant to the antimicrobial peptide, as no immunity connected to the production of enterocin O16 could be identified. ef1097 has previously been identified as one of three loci regulated by the fsr quorum-sensing system. The introduction of a nonsense mutation into fsrB consistently impaired enterocin O16 production, but externally added gelatinase biosynthesis-activating pheromone restored the antimicrobial activity. Functional genetic analysis showed that the EF_1097 proprotein is processed extracellularly into enterocin O16 by the metalloprotease GelE. Thus, it is evident that the fsr quorum-sensing system constitutes the regulatory unit that controls the expression of the EF_1097 precursor protein and the protease GelE and that the latter is required for the formation of enterocin O16. On the basis of these results, this study identified antibacterial antagonism as a novel aspect related to the function of fsr and provides a rationale for why ef1097 is part of the fsr regulon. The fsr quorum-sensing system modulates important physiological functions in E. faecalis via the activity of GelE. The present study presents a new facet of fsr signaling. The system controls the expression of three primary target operons (fsrABCD, gelE-sprE, and ef1097-ef1097b). We demonstrate that the concerted expression of these operons constitutes the

Predictability of blocking

International Nuclear Information System (INIS)

Tosi, E.; Ruti, P.; Tibaldi, S.; D'Andrea, F.

1994-01-01

Tibaldi and Molteni (1990, hereafter referred to as TM) had previously investigated operational blocking predictability by the ECMWF model and the possible relationships between model systematic error and blocking in the winter season of the Northern Hemisphere, using seven years of ECMWF operational archives of analyses and day 1 to 10 forecasts. They showed that fewer blocking episodes than in the real atmosphere were generally simulated by the model, and that this deficiency increased with increasing forecast time. As a consequence of this, a major contribution to the systematic error in the winter season was shown to derive from the inability of the model to properly forecast blocking. In this study, the analysis performed in TM for the first seven winter seasons of the ECMWF operational model is extended to the subsequent five winters, during which model development, reflecting both resolution increases and parametrisation modifications, continued unabated. In addition the objective blocking index developed by TM has been applied to the observed data to study the natural low frequency variability of blocking. The ability to simulate blocking of some climate models has also been tested

Detection of anorectal and cervicovaginal Chlamydia trachomatis infections following azithromycin treatment: prospective cohort study with multiple time-sequential measures of rRNA, DNA, quantitative load and symptoms.

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Nicole H T M Dukers-Muijrers

Full Text Available Determination of Chlamydia trachomatis (Ct treatment success is hampered by current assessment methods, which involve a single post-treatment measurement only. Therefore, we evaluated Ct detection by applying multiple laboratory measures on time-sequential post-treatment samples.A prospective cohort study was established with azithromycin-treated (1000 mg Ct patients (44 cervicovaginal and 15 anorectal cases. Each patient provided 18 self-taken samples pre-treatment and for 8 weeks post-treatment (response: 96%; 1,016 samples. Samples were tested for 16S rRNA (TMA, bacterial load (quantitative PCR; Chlamydia plasmid DNA and type (serovar and multilocus sequence typing. Covariates (including behavior, pre-treatment load, anatomic site, symptoms, age, and menstruation were tested for their potential association with positivity and load at 3-8 weeks using regression analyses controlling for repeated measures.By day 9, Ct positivity decreased to 20% and the median load to 0.3 inclusion-forming units (IFU per ml (pre-treatment: 170 IFU/ml. Of the 35 cases who reported no sex, sex with a treated partner or safe sex with a new partner, 40% had detection, i.e. one or more positive samples from 3-8 weeks (same Ct type over time, indicating possible antimicrobial treatment failure. Cases showed intermittent positive detection and the number of positive samples was higher in anorectal cases than in cervicovaginal cases. The highest observed bacterial load between 3-8 weeks post-treatment was 313 IFU/ml, yet the majority (65% of positive samples showed a load of ≤ 2 IFU/ml. Pre-treatment load was found to be associated with later load in anorectal cases.A single test at 3-8 weeks post-treatment frequently misses Ct. Detection reveals intermittent low loads, with an unknown risk of later complications or transmission. These findings warrant critical re-evaluation of the clinical management of single dose azithromycin-treated Ct patients and fuel the debate

Relationship between time to clinical response and outcomes among Pneumonia Outcomes Research Team (PORT) risk class III and IV hospitalized patients with community-acquired pneumonia who received ceftriaxone and azithromycin.

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Zasowski, Evan; Butterfield, Jill M; McNutt, Louise-Ann; Cohen, Jason; Cosler, Leon; Pai, Manjunath P; Gottwald, Joseph; Chen, Wen Zhen; Lodise, Thomas P

2014-07-01

Recent Food and Drug Administration (FDA) guidance endorses the use of an early clinical response endpoint as the primary outcome for community-acquired bacterial pneumonia (CABP) trials. While antibiotics will now be approved for CABP, in practice they will primarily be used to treat patients with community-acquired pneumonia (CAP). More importantly, it is unclear how achievement of the new FDA CABP early response endpoint translates into clinically applicable real-world outcomes for patients with CAP. To address this, a retrospective cohort study was conducted among adult patients who received ceftriaxone and azithromycin for CAP of Pneumonia Outcomes Research Team (PORT) risk class III and IV at an academic medical center. The clinical response was defined as clinical stability for 24 h with improvement in at least one pneumonia symptom and with no symptom worsening. A classification and regression tree (CART) was used to determine the delay in response time, measured in days, associated with the greatest risk of a prolonged hospital length of stay (LOS) and adverse outcomes (in-hospital mortality or 30-day CAP-related readmission). A total of 250 patients were included. On average, patients were discharged 2 days following the achievement of a clinical response. In the CART analysis, adverse clinical outcomes were higher among day 5 nonresponders than those who responded by day 5 (22.4% versus 6.9%, P = 0.001). The findings from this study indicate that time to clinical response, as defined by the recent FDA guidance, is a reasonable prognostic indicator of real-world effectiveness outcomes among hospitalized PORT risk class III and IV patients with CAP who received ceftriaxone and azithromycin. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Maternal Azithromycin Therapy for Ureaplasma Intra-Amniotic Infection Delays Preterm Delivery and Reduces Fetal Lung Injury in a Primate Model

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Grigsby, Peta L.; Novy, Miles J.; Sadowsky, Drew W.; Morgan, Terry K.; Long, Mary; Acosta, Ed; Duffy, Lynn B; Waites, Ken B.

2012-01-01

Objective We assessed the efficacy of a maternal multi–dose azithromycin (AZI) regimen, with and without anti–inflammatory agents to delay preterm birth and to mitigate fetal lung injury associated with Ureaplasma parvum intra–amniotic infection (IAI). Study Design Long–term catheterized rhesus monkeys (n=16) received intra–amniotic inoculation of U. parvum (107 CFU/ml, serovar 1). After contraction onset, rhesus monkeys received either no treatment (n=6); AZI (12.5mg/kg, q12h, IV for 10 days; n=5); or AZI plus dexamethasone (DEX) and indomethacin (INDO; n=5). Outcomes included amniotic fluid pro–inflammatory mediators, U. parvum cultures & PCR, AZI pharmacokinetics and the extent of fetal lung inflammation. Results Maternal AZI therapy eradicated U. parvum IAI from the amniotic fluid within 4 days. Placenta and fetal tissues were 90% culture negative at delivery. AZI therapy significantly delayed preterm delivery and prevented advanced fetal lung injury, although residual acute chorioamnionitis persisted. Conclusions Specific maternal antibiotic therapy can eradicate U. parvum from the amniotic fluid and key fetal organs, with subsequent prolongation of pregnancy which provides a therapeutic window of opportunity to effectively reduce the severity of fetal lung injury. PMID:23111115

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.

Bacterial Quorum Sensing Stabilizes Cooperation by Optimizing Growth Strategies.

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Bruger, Eric L; Waters, Christopher M

2016-11-15

Communication has been suggested as a mechanism to stabilize cooperation. In bacteria, chemical communication, termed quorum sensing (QS), has been hypothesized to fill this role, and extracellular public goods are often induced by QS at high cell densities. Here we show, with the bacterium Vibrio harveyi, that QS provides strong resistance against invasion of a QS defector strain by maximizing the cellular growth rate at low cell densities while achieving maximum productivity through protease upregulation at high cell densities. In contrast, QS mutants that act as defectors or unconditional cooperators maximize either the growth rate or the growth yield, respectively, and thus are less fit than the wild-type QS strain. Our findings provide experimental evidence that regulation mediated by microbial communication can optimize growth strategies and stabilize cooperative phenotypes by preventing defector invasion, even under well-mixed conditions. This effect is due to a combination of responsiveness to environmental conditions provided by QS, lowering of competitive costs when QS is not induced, and pleiotropic constraints imposed on defectors that do not perform QS. Cooperation is a fundamental problem for evolutionary biology to explain. Conditional participation through phenotypic plasticity driven by communication is a potential solution to this dilemma. Thus, among bacteria, QS has been proposed to be a proximate stabilizing mechanism for cooperative behaviors. Here, we empirically demonstrate that QS in V. harveyi prevents cheating and subsequent invasion by nonproducing defectors by maximizing the growth rate at low cell densities and the growth yield at high cell densities, whereas an unconditional cooperator is rapidly driven to extinction by defectors. Our findings provide experimental evidence that QS regulation prevents the invasion of cooperative populations by QS defectors even under unstructured conditions, and they strongly support the role of

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

Quorum sensing activity of Citrobacter amalonaticus L8A, a bacterium isolated from dental plaque.

Science.gov (United States)

Goh, Share-Yuan; Khan, Saad Ahmed; Tee, Kok Keng; Abu Kasim, Noor Hayaty; Yin, Wai-Fong; Chan, Kok-Gan

2016-02-10

Cell-cell communication is also known as quorum sensing (QS) that happens in the bacterial cells with the aim to regulate their genes expression in response to increased cell density. In this study, a bacterium (L8A) isolated from dental plaque biofilm was identified as Citrobacter amalonaticus by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). Its N-acylhomoserine-lactone (AHL) production was screened by using two types of AHL biosensors namely Chromobacterium violaceum CV026 and Escherichia coli [pSB401]. Citrobacter amalonaticus strain L8A was identified and confirmed producing numerous types of AHL namely N-butyryl-L-homoserine lactone (C4-HSL), N-hexanoyl-L-homoserine lactone (C6-HSL), N-octanoyl-L-homoserine lactone (C8-HSL) and N-hexadecanoyl-L-homoserine lactone (C16-HSL). We performed the whole genome sequence analysis of this oral isolate where its genome sequence reveals the presence of QS signal synthase gene and our work will pave the ways to study the function of the related QS genes in this bacterium.

Detection block

International Nuclear Information System (INIS)

Bezak, A.

1987-01-01

A diagram is given of a detection block used for monitoring burnup of nuclear reactor fuel. A shielding block is an important part of the detection block. It stabilizes the fuel assembly in the fixing hole in front of a collimator where a suitable gamma beam is defined for gamma spectrometry determination of fuel burnup. The detector case and a neutron source case are placed on opposite sides of the fixing hole. For neutron measurement for which the water in the tank is used as a moderator, the neutron detector-fuel assembly configuration is selected such that neutrons from spontaneous fission and neutrons induced with the neutron source can both be measured. The patented design of the detection block permits longitudinal travel and rotation of the fuel assembly to any position, and thus more reliable determination of nuclear fuel burnup. (E.S.). 1 fig

Selection of Functional Quorum Sensing Systems by Lysogenic Bacteriophages in Pseudomonas aeruginosa

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Miguel A. Saucedo-Mora

2017-08-01

Full Text Available Quorum sensing (QS in Pseudomonas aeruginosa coordinates the expression of virulence factors, some of which are used as public goods. Since their production is a cooperative behavior, it is susceptible to social cheating in which non-cooperative QS deficient mutants use the resources without investing in their production. Nevertheless, functional QS systems are abundant; hence, mechanisms regulating the amount of cheating should exist. Evidence that demonstrates a tight relationship between QS and the susceptibility of bacteria against the attack of lytic phages is increasing; nevertheless, the relationship between temperate phages and QS has been much less explored. Therefore, in this work, we studied the effects of having a functional QS system on the susceptibility to temperate bacteriophages and how this affects the bacterial and phage dynamics. We find that both experimentally and using mathematical models, that the lysogenic bacteriophages D3112 and JBD30 select QS-proficient P. aeruginosa phenotypes as compared to the QS-deficient mutants during competition experiments with mixed strain populations in vitro and in vivo in Galleria mellonella, in spite of the fact that both phages replicate better in the wild-type background. We show that this phenomenon restricts social cheating, and we propose that temperate phages may constitute an important selective pressure toward the conservation of bacterial QS.

Post-secretional activation of Protease IV by quorum sensing in Pseudomonas aeruginosa.

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Oh, Jungmin; Li, Xi-Hui; Kim, Soo-Kyong; Lee, Joon-Hee

2017-06-30

Protease IV (PIV), a key virulence factor of Pseudomonas aeruginosa is a secreted lysyl-endopeptidase whose expression is induced by quorum sensing (QS). We found that PIV expressed in QS mutant has severe reduction of activity in culture supernatant (CS), even though it is overexpressed to high level. PIV purified from the QS mutant (M-PIV) had much lower activity than the PIV purified from wild type (P-PIV). We found that the propeptide cleaved from prepro-PIV was co-purified with M-PIV, but never with P-PIV. Since the activity of M-PIV was restored by adding the CS of QS-positive and PIV-deficient strain, we hypothesized that the propeptide binds to and inhibits PIV, and is degraded to activate PIV by a QS-dependent factor. In fact, the CS of the QS-positive and PIV-deficient strain was able to degrade the propeptide. Since the responsible factor should be a QS-dependently expressed extracellular protease, we tested QS-dependent proteases of P. aeruginosa and found that LasB (elastase) can degrade the propeptide and activate M-PIV. We purified the propeptide of PIV and confirmed that the propeptide can bind to and inhibit PIV. We suggest that PIV is post-secretionally activated through the extracellular degradation of the propeptide by LasB, a QS-dependent protease.

Cross-kingdom signalling: exploitation of bacterial quorum sensing molecules by the green seaweed Ulva.

Science.gov (United States)

Joint, Ian; Tait, Karen; Wheeler, Glen

2007-07-29

The green seaweed Ulva has been shown to detect signal molecules produced by bacteria. Biofilms that release N-acylhomoserine lactones (AHLs) attract zoospores--the motile reproductive stages of Ulva. The evidence for AHL involvement is based on several independent lines of evidence, including the observation that zoospores are attracted to wild-type bacteria that produce AHLs but are not attracted to mutants that do not produce signal molecules. Synthetic AHL also attracts zoospores and the attraction is lost in the presence of autoinducer inactivation (AiiA) protein. The mechanism of attraction is not chemotactic but involves chemokinesis. When zoospores detect AHLs, the swimming rate is reduced and this results in accumulation of cells at the source of the AHL. It has been demonstrated that the detection of AHLs results in calcium influx into the zoospore. This is the first example of a calcium signalling event in a eukaryote in response to bacterial quorum sensing molecules. The role of AHLs in the ecology of Ulva is discussed. It is probable that AHLs act as cues for the settlement of zoospores, rather than being directly involved as a signalling mechanism.

Synthesis of amylose-block-polystyrene rod-coil block copolymers

NARCIS (Netherlands)

Loos, Katja; Stadler, Reimund

1997-01-01

In the present communication we demonstrate the synthesis of a hybrid block copolymer based on the combination of a biopolymer (amylose) with a synthetic block (polystyrene). To obtain such materials, amino-functionalized polymers were modified with maltoheptaose moieties that serve as initiators