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

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

doi:10.1039/b703021p

Cited by 219 publications

(273 citation statements)

References 76 publications

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“…Analogues have been found that exhibit a range of different activities, including no activity, pure agonism or pure antagonism, partial agonism, and synergistic agonism (167,(170)(171)(172). The different AHL analogues tested to date and their specific activities against the various receptor proteins are too numerous to report here in detail, so for a more comprehensive and specific discussion of these molecules we refer the reader to other recently published reviews (173,174). There are some general findings of these investigations, however, that we have chosen to discuss below, as well as several specific examples of AHL receptor antagonists that show promise for the future development of analogue-based QSI strategies.…”

Section: Inhibition Of Signal Detection Synthetic Signal Analogues Anmentioning

confidence: 99%

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

LaSarre

Federle

2013

Microbiol Mol Biol Rev

690

556

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

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Section: Inhibition Of Signal Detection Synthetic Signal Analogues Anmentioning

confidence: 99%

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

LaSarre

Federle

2013

Microbiol Mol Biol Rev

690

556

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“…Bacteria colonizing or infecting a host grow under hostile conditions, sense changing environmental stress via diverse quorum sensing, and other two-component systems, and respond by up-or downregulating the expression levels of appropriate proteins, which in turn can affect the susceptibility of the cell to antibiotics (2,11). Examples of environmental stress include, e.g., growth at extreme temperatures, pH, osmotic pressure, and depletion of nutrients, etc.…”

mentioning

confidence: 99%

Comparative In Vitro Activities of the Novel Antibacterial Finafloxacin against Selected Gram-Positive and Gram-Negative Bacteria Tested in Mueller-Hinton Broth and Synthetic Urine

Dalhoff

Stubbings

Schubert

2011

Antimicrob Agents Chemother

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Kill kinetics and MICs of finafloxacin and ciprofloxacin against 34 strains with defined resistance mechanisms grown in cation-adjusted Mueller-Hinton broth (CAMHB) at pH values of 7.2 and 5.8 and in synthetic urine at pH 5.8 were determined. In general, finafloxacin gained activity at low pH values in CAMHB and remained almost unchanged in artificial urine. Ciprofloxacin MICs increased and bactericidal activity decreased strain dependently in acidic CAMHB and particularly in artificial urine.Bacteria colonizing or infecting a host grow under hostile conditions, sense changing environmental stress via diverse quorum sensing, and other two-component systems, and respond by up-or downregulating the expression levels of appropriate proteins, which in turn can affect the susceptibility of the cell to antibiotics (2, 11). Examples of environmental stress include, e.g., growth at extreme temperatures, pH, osmotic pressure, and depletion of nutrients, etc.; Escherichia coli and Staphylococcus aureus causing uncomplicated cystitis or growing in urine or in biofilms on indwelling urethral catheters are such examples (3,8,24,28,31,34,35,38).Thus, it is physiologically relevant and clinically important to study the antibacterial activities of agents under test conditions which mimic the infectious focus most closely. Therefore, we used cation-adjusted Mueller-Hinton broth (CAMHB), pH 7.2 and pH 5.8 (Oxoid GmbH, Wesel, Germany), and synthetic urine, pH 5.8, containing 11 solutes each, in concentrations found in a 24-h period in the urine of healthy men (14) for the comparison of the bacteriostatic and -cidal activities of finafloxacin (batch CBC000288) and ciprofloxacin (batch CBC000290).(Part of the data presented in this paper were shown as a poster at the 48th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC, October 2008.)Thirty-four phenotyped and/or genotyped strains were used for the examination of MICs and kill kinetics, according to CLSI guidelines (6,7,19). S. aureus ATCC 29213, E. coli ATCC 25922, and Enterococcus faecalis ATCC 29212, as well as moxifloxacin as an external standard, served as controls. Tests were run in duplicate; the higher values were reported in case of deviation (1.2%). Kill kinetics were examined by using finafloxacin and ciprofloxacin at bioequivalent concentrations of 16ϫ, 4ϫ, and 1ϫ the individual MIC values, as measured in the corresponding media. Samples for determination of viable counts were taken at 0, 1, 2, 4, 6, 8, and 24 h. Drug carryover was minimized first by dilution and second by plating the aliquots on cation-enriched agar, thus inactivating the fluoroquinolones. In order to quantify the reduction of viable counts and the speed of kill, the times needed to reduce the inocula by 3-log 10 titers and kill rates were calculated as described recently (32). Furthermore, kill rates were normalized to a drug exposure of 1 mg/liter, as the drug concentration/isolate/media and pH associations vary considerably under the different growth conditions studie...

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“…The linkage between QS and the production of virulence factors in P. aeruginosa predicts that inhibition of AHL-mediated gene expression could render these bacteria nonpathogenic (5). Studies on the rational design of QS inhibitors have focused on modifying the basic structure of the AHL (4,9). High-throughput screening (HTS) of smallmolecule libraries is another approach for the identification of compounds that have novel chemical scaffolds for both the development of chemical probes and eventual therapeutic drug design.…”

mentioning

confidence: 99%

Identification of Synthetic Inducers and Inhibitors of the Quorum-Sensing Regulator LasR in Pseudomonas aeruginosa by High-Throughput Screening

Borlee¹,

Geske

Blackwell

et al. 2010

Appl Environ Microbiol

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We report the screening of 16,000 synthetic compounds for induction and inhibition of quorum sensing in a Pseudomonas putida N-acylated L-homoserine lactone (AHL) sensor strain engineered with the LasR transcriptional activator. LasR controls virulence gene expression in the opportunistic pathogen Pseudomonas aeruginosa and is of significant interest as a therapeutic target. Nine compounds that inhibit and 14 compounds that induce LasR activity were identified in our high-throughput screen.

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

Cited by 219 publications

References 76 publications

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

Comparative In Vitro Activities of the Novel Antibacterial Finafloxacin against Selected Gram-Positive and Gram-Negative Bacteria Tested in Mueller-Hinton Broth and Synthetic Urine

Identification of Synthetic Inducers and Inhibitors of the Quorum-Sensing Regulator LasR in Pseudomonas aeruginosa by High-Throughput Screening

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