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      Quorum Quenching Enzymes and Their Application in Degrading Signal Molecules to Block Quorum Sensing-Dependent Infection

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          Abstract

          With the emergence of antibiotic-resistant strains of bacteria, the available options for treating bacterial infections have become very limited, and the search for a novel general antibacterial therapy has received much greater attention. Quorum quenching can be used to control disease in a quorum sensing system by triggering the pathogenic phenotype. The interference with the quorum sensing system by the quorum quenching enzyme is a potential strategy for replacing traditional antibiotics because the quorum quenching strategy does not aim to kill the pathogen or limit cell growth but to shut down the expression of the pathogenic gene. Quorum quenching enzymes have been identified in quorum sensing and non-quorum sensing microbes, including lactonase, acylase, oxidoreductase and paraoxonase. Lactonase is widely conserved in a range of bacterial species and has variable substrate spectra. The existence of quorum quenching enzymes in the quorum sensing microbes can attenuate their quorum sensing, leading to blocking unnecessary gene expression and pathogenic phenotypes. In this review, we discuss the physiological function of quorum quenching enzymes in bacterial infection and elucidate the enzymatic protection in quorum sensing systems for host diseases and their application in resistance against microbial diseases.

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          Establishment of Pseudomonas aeruginosa infection: lessons from a versatile opportunist.

          Pseudomonas aeruginosa is an ubiquitous pathogen capable of infecting virtually all tissues. A large variety of virulence factors contribute to its importance in burn wounds, lung infection and eye infection. Prominent factors include pili, flagella, lipopolysaccharide, proteases, quorum sensing, exotoxin A and exoenzymes secreted by the type III secretion system.
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            Quorum-sensing inhibitors as anti-pathogenic drugs.

            Quorum-sensing (QS) signalling systems of pathogens are central regulators for the expression of virulence factors and represent highly attractive targets for the development of novel therapeutics. In Pseudomonas aeruginosa, QS systems are also involved in elevated antibiotic tolerance of biofilms as well as elevated tolerance to the activity of the innate immune system. Gram-negative bacteria commonly use N-acyl homoserine lactones (AHL) as QS signal molecules. The use of signal molecule based drugs to attenuate bacterial pathogenecity rather than bacterial growth is attractive for several reasons, particularly considering the emergence of increasingly antibiotic-resistant bacteria. Compounds capable of this type of interference have been termed anti-pathogenic drugs. A large variety of synthetic AHL analogues and natural products libraries have been screened and a number of QS inhibitors (QSI) have been identified. Promising QSI compounds have been shown to make biofilms more susceptible to antimicrobial treatments, and are capable of reducing mortality and virulence as well as promoting clearance of bacteria in experimental animal models of infection.
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              AHL-driven quorum-sensing circuits: their frequency and function among the Proteobacteria.

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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                Molecular Diversity Preservation International (MDPI)
                1422-0067
                September 2013
                26 August 2013
                : 14
                : 9
                : 17477-17500
                Affiliations
                School of Biological Engineering, Dalian Polytechnic University, Dalian 116034, China; E-Mails: sanmiancxh@ 123456163.com (F.C.); yuxindl2006@ 123456163.com (Y.G.); cxyrain@ 123456hotmail.com (X.C.); yuzhimin2005@ 123456163.com (Z.Y.)
                Author notes
                [†]

                These authors contributed equally to this work.

                [* ]Author to whom correspondence should be addressed; E-Mail: xianzhen@ 123456mail.com ; Tel.: +86-411-8632-3717; Fax: +86-411-8632-3646.
                Article
                ijms-14-17477
                10.3390/ijms140917477
                3794736
                24065091
                cb403b4a-b8a7-4f84-873a-9c296001e469
                © 2013 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 license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 31 May 2013
                : 23 July 2013
                : 16 August 2013
                Categories
                Review

                Molecular biology
                quorum sensing,quorum quenching,lactonase,acylase,acyl homoserine lactone,specificity

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