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      Disruption of N‐acyl‐homoserine lactone‐specific signalling and virulence in clinical pathogens by marine sponge bacteria

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          Summary

          In recent years, the marine environment has been the subject of increasing attention from biotechnological and pharmaceutical industries. A combination of unique physicochemical properties and spatial niche‐specific substrates, in wide‐ranging and extreme habitats, underscores the potential of the marine environment to deliver on functionally novel bioactivities. One such area of ongoing research is the discovery of compounds that interfere with the cell–cell signalling process called quorum sensing ( QS). Described as the next generation of antimicrobials, these compounds can target virulence and persistence of clinically relevant pathogens, independent of any growth‐limiting effects. Marine sponges are a rich source of microbial diversity, with dynamic populations in a symbiotic relationship. In this study, we have harnessed the QS inhibition ( QSI) potential of marine sponge microbiota and through culture‐based discovery have uncovered small molecule signal mimics that neutralize virulence phenotypes in clinical pathogens. This study describes for the first time a marine sponge Psychrobacter sp. isolate B98C22 that blocks QS signalling, while also reporting dual QS/ QSI activity in the Pseudoalteromonas sp. J10 and Paracoccus JM45. Isolation of novel QSI activities has significant potential for future therapeutic development, of particular relevance in the light of the pending perfect storm of antibiotic resistance meeting antibiotic drug discovery decline.

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          Most cited references81

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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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            Bacterial quorum-sensing network architectures.

            Quorum sensing is a cell-cell communication process in which bacteria use the production and detection of extracellular chemicals called autoinducers to monitor cell population density. Quorum sensing allows bacteria to synchronize the gene expression of the group, and thus act in unison. Here, we review the mechanisms involved in quorum sensing with a focus on the Vibrio harveyi and Vibrio cholerae quorum-sensing systems. We discuss the differences between these two quorum-sensing systems and the differences between them and other paradigmatic bacterial signal transduction systems. We argue that the Vibrio quorum-sensing systems are optimally designed to precisely translate extracellular autoinducer information into internal changes in gene expression. We describe how studies of the V. harveyi and V. cholerae quorum-sensing systems have revealed some of the fundamental mechanisms underpinning the evolution of collective behaviors.
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              Adaptive and mutational resistance: role of porins and efflux pumps in drug resistance.

              The substantial use of antibiotics in the clinic, combined with a dearth of new antibiotic classes, has led to a gradual increase in the resistance of bacterial pathogens to these compounds. Among the various mechanisms by which bacteria endure the action of antibiotics, those affecting influx and efflux are of particular importance, as they limit the interaction of the drug with its intracellular targets and, consequently, its deleterious effects on the cell. This review evaluates the impact of porins and efflux pumps on two major types of resistance, namely, mutational and adaptive types of resistance, both of which are regarded as key phenomena in the global rise of antibiotic resistance among pathogenic microorganisms. In particular, we explain how adaptive and mutational events can dramatically influence the outcome of antibiotic therapy by altering the mechanisms of influx and efflux of antibiotics. The identification of porins and pumps as major resistance markers has opened new possibilities for the development of novel therapeutic strategies directed specifically against these mechanisms.
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                Author and article information

                Contributors
                f.ogara@ucc.ie
                Journal
                Microb Biotechnol
                Microb Biotechnol
                10.1111/(ISSN)1751-7915
                MBT2
                Microbial Biotechnology
                John Wiley and Sons Inc. (Hoboken )
                1751-7915
                03 November 2017
                September 2019
                : 12
                : 5 ( doiID: 10.1111/mbt2.v12.5 )
                : 1049-1063
                Affiliations
                [ 1 ] BIOMERIT Research Centre School of Microbiology University College Cork National University of Ireland Cork Ireland
                [ 2 ] School of Microbiology University College Cork National University of Ireland Cork Ireland
                [ 3 ] Human Microbiome Programme School of Biomedical Sciences Curtin Health Innovation Research Institute Curtin University Perth WA Australia
                [ 4 ] Curtin Health Innovation Research Institute (CHIRI) Curtin University Perth WA Australia
                [ 5 ] School of Biomedical Sciences Faculty of Health Sciences Curtin University Perth WA Australia
                [ 6 ]Present address: Instituto de Hortofruticultura Subtropical y Mediterránea La Mayora Departamento de Microbiología Facultad de Ciencias Universidad de Málaga 29071 Málaga Spain
                [ 7 ]Present address: Departamento de Ecología Facultad de Ciencias Universidad de Málaga 29071 Málaga Spain
                Author notes
                [*] [* ]For correspondence. E‐mail f.ogara@ 123456ucc.ie ; Tel. +353 (0)21 427 2097; Fax +353 (0)21 427 5934.
                Article
                MBT212867
                10.1111/1751-7915.12867
                6680641
                29105344
                9f3cc69e-68a3-48c3-b0bd-9c5a4b470eb7
                © 2017 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 June 2017
                : 31 August 2017
                Page count
                Figures: 3, Tables: 4, Pages: 15, Words: 10352
                Funding
                Funded by: European Commission
                Award ID: FP7‐PEOPLE‐2013‐ITN
                Award ID: 607786
                Award ID: FP7‐KBBE‐2012‐6
                Award ID: CP‐TP‐312184
                Award ID: FP7‐KBBE‐2012‐6
                Award ID: 311975
                Award ID: OCEAN 2011‐2
                Award ID: 287589
                Award ID: EU‐634486
                Funded by: Science Foundation Ireland
                Award ID: SSPC‐2
                Award ID: 12/RC/2275
                Award ID: 13/TIDA/B2625
                Award ID: 12/TIDA/B2411
                Award ID: 12/TIDA/B2405
                Award ID: 14/TIDA/2438
                Award ID: 15/TIDA/2977
                Funded by: Department of Agriculture and Food
                Award ID: FIRM 08/RDC/629
                Award ID: FIRM 1/F009/MabS
                Award ID: FIRM 13/F/516
                Funded by: Irish Research Council for Science, Engineering and Technology
                Award ID: PD/2011/2414
                Award ID: GOIPG/2014/647
                Funded by: Health Research Board/Irish Thoracic Society
                Award ID: MRCG‐2014‐6
                Funded by: Marine Institute
                Award ID: C2CRA 2007/082
                Funded by: Teagasc (Walsh Fellowship 2013)
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                mbt212867
                September 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.7 mode:remove_FC converted:05.08.2019

                Biotechnology
                Biotechnology

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