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      Challenges and Limitations of Anti-quorum Sensing Therapies

      brief-report
      *
      Frontiers in Microbiology
      Frontiers Media S.A.
      quorum sensing, quorum quenching, microbiota, pathogenicity, virulence, resistance

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          Abstract

          Quorum sensing (QS) is a mechanism allowing microorganisms to sense population density and synchronously control genes expression. It has been shown that QS supervises the activity of many processes important for microbial pathogenicity, e.g., sporulation, biofilm formation, and secretion of enzymes or membrane vesicles. This contributed to the concept of anti-QS therapy [also called quorum quenching (QQ)] and the opportunity of its application in fighting against various types of pathogens. In recent years, many published articles reported promising results indicating the possibility of reducing pathogenicity of tested microorganisms and their easier eradication when co-treated with antibiotics. The aim of the present article is to point to the opposite, negative side of the QQ therapy, with particular emphasis on three fundamental properties attributed to anti-QS substances: the selectivity, virulence reduction, and lack of resistance against QQ. This point of view may highlight new directions of research, which should be taken into account in the future before the widespread introduction of QQ therapies in the treatment of people.

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          Most cited references149

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          The hierarchy quorum sensing network in Pseudomonas aeruginosa

          Pseudomonas aeruginosa causes severe and persistent infections in immune compromised individuals and cystic fibrosis sufferers. The infection is hard to eradicate as P. aeruginosa has developed strong resistance to most conventional antibiotics. The problem is further compounded by the ability of the pathogen to form biofilm matrix, which provides bacterial cells a protected environment withstanding various stresses including antibiotics. Quorum sensing (QS), a cell density-based intercellular communication system, which plays a key role in regulation of the bacterial virulence and biofilm formation, could be a promising target for developing new strategies against P. aeruginosa infection. The QS network of P. aeruginosa is organized in a multi-layered hierarchy consisting of at least four interconnected signaling mechanisms. Evidence is accumulating that the QS regulatory network not only responds to bacterial population changes but also could react to environmental stress cues. This plasticity should be taken into consideration during exploration and development of anti-QS therapeutics.
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            Structural identification of a bacterial quorum-sensing signal containing boron.

            Cell-cell communication in bacteria is accomplished through the exchange of extracellular signalling molecules called autoinducers. This process, termed quorum sensing, allows bacterial populations to coordinate gene expression. Community cooperation probably enhances the effectiveness of processes such as bioluminescence, virulence factor expression, antibiotic production and biofilm development. Unlike other autoinducers, which are specific to a particular species of bacteria, a recently discovered autoinducer (AI-2) is produced by a large number of bacterial species. AI-2 has been proposed to serve as a 'universal' signal for inter-species communication. The chemical identity of AI-2 has, however, proved elusive. Here we present the crystal structure of an AI-2 sensor protein, LuxP, in a complex with autoinducer. The bound ligand is a furanosyl borate diester that bears no resemblance to previously characterized autoinducers. Our findings suggest that addition of naturally occurring borate to an AI-2 precursor generates active AI-2. Furthermore, they indicate a potential biological role for boron, an element required by a number of organisms but for unknown reasons.
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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
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                31 October 2019
                2019
                : 10
                : 2473
                Affiliations
                Department of Microbiology, Wroclaw Medical University , Wrocław, Poland
                Author notes

                Edited by: Sebastian Guenther, University of Greifswald, Germany

                Reviewed by: Brett Mellbye, Oregon State University, United States; Rodolfo García-Contreras, National Autonomous University of Mexico, Mexico

                *Correspondence: Paweł Krzyżek, krojcerpawel@ 123456gmail.com

                This article was submitted to Antimicrobials, Resistance and Chemotherapy, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2019.02473
                6834643
                31736912
                c75bc377-2f40-4a96-9baf-f43dc08dae08
                Copyright © 2019 Krzyżek.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 09 July 2019
                : 15 October 2019
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 167, Pages: 10, Words: 9401
                Funding
                Funded by: Wroclaw Medical University 10.13039/501100009687
                Award ID: SUB.A130.19.021
                Categories
                Microbiology
                Perspective

                Microbiology & Virology
                quorum sensing,quorum quenching,microbiota,pathogenicity,virulence,resistance
                Microbiology & Virology
                quorum sensing, quorum quenching, microbiota, pathogenicity, virulence, resistance

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