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      Quorum Sensing Inhibitors from the Sea Discovered Using Bacterial N-acyl-homoserine Lactone-Based Biosensors

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          Abstract

          Marine natural products with antibiotic activity have been a rich source of drug discovery; however, the emergence of antibiotic-resistant bacterial strains has turned attention towards the discovery of alternative innovative strategies to combat pathogens. In many pathogenic bacteria, the expression of virulence factors is under the regulation of quorum sensing (QS). QS inhibitors (QSIs) present a promising alternative or potential synergistic treatment since they disrupt the signaling pathway used for intra- and interspecies coordination of expression of virulence factors. This review covers the set of molecules showing QSI activity that were isolated from marine organisms, including plants (algae), animals (sponges, cnidarians, and bryozoans), and microorganisms (bacteria, fungi, and cyanobacteria). The compounds found and the methods used for their isolation are the emphasis of this review.

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          Most cited references113

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          The green fluorescent protein.

          R Tsien (1998)
          In just three years, the green fluorescent protein (GFP) from the jellyfish Aequorea victoria has vaulted from obscurity to become one of the most widely studied and exploited proteins in biochemistry and cell biology. Its amazing ability to generate a highly visible, efficiently emitting internal fluorophore is both intrinsically fascinating and tremendously valuable. High-resolution crystal structures of GFP offer unprecedented opportunities to understand and manipulate the relation between protein structure and spectroscopic function. GFP has become well established as a marker of gene expression and protein targeting in intact cells and organisms. Mutagenesis and engineering of GFP into chimeric proteins are opening new vistas in physiological indicators, biosensors, and photochemical memories.
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            Bacterial quorum sensing: its role in virulence and possibilities for its control.

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

              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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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Mar Drugs
                Mar Drugs
                marinedrugs
                Marine Drugs
                MDPI
                1660-3397
                23 February 2017
                March 2017
                : 15
                : 3
                : 53
                Affiliations
                [1 ]Department of Marine Biology, Leon H. Charney School of Marine Sciences, University of Haifa, Mt. Carmel, 31905 Haifa, Israel; lsteindler@ 123456univ.haifa.ac.il
                [2 ]The NeaNat Group, Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy; costanti@ 123456unina.it
                [3 ]Bacteriology Group, International Centre for Genetic Engineering & Biotechnology, Padriciano 99, 34149 Trieste, Italy; venturi@ 123456icgeb.org
                Author notes
                [* ]Correspondence: sauravverma17@ 123456gmail.com ; Tel.: +972-482-8898
                Article
                marinedrugs-15-00053
                10.3390/md15030053
                5367010
                28241461
                e72ab702-5822-46f9-9390-2e0d9f4991c9
                © 2017 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 27 January 2017
                : 16 February 2017
                Categories
                Review

                Pharmacology & Pharmaceutical medicine
                quorum-sensing inhibitors,quorum quenching,marine natural products,antimicrobial resistance,n-acyl homoserine lactones

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