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dc.contributor.authorChang, Chien-Yi*
dc.contributor.authorKrishnan, T.*
dc.contributor.authorWang, H.*
dc.contributor.authorChen, Y.*
dc.contributor.authorYin, W.*
dc.contributor.authorChong, Y.*
dc.contributor.authorTan, L.Y.*
dc.contributor.authorChong, T.M.*
dc.contributor.authorChan, K.*
dc.date.accessioned2018-02-23T15:23:15Z
dc.date.available2018-02-23T15:23:15Z
dc.date.issued2014-11
dc.identifier.citationChang C, Krishnan T, Wang H et al (2014) Non-antibiotic quorum sensing inhibitors acting against N-acyl homoserine lactone synthase as druggable target. Scientific Reports. 4:7245.en_US
dc.identifier.urihttp://hdl.handle.net/10454/15066
dc.descriptionYesen_US
dc.description.abstractN-acylhomoserine lactone (AHL)-based quorum sensing (QS) is important for the regulation of proteobacterial virulence determinants. Thus, the inhibition of AHL synthases offers non-antibiotics-based therapeutic potentials against QS-mediated bacterial infections. In this work, functional AHL synthases of Pseudomonas aeruginosa LasI and RhlI were heterologously expressed in an AHL-negative Escherichia coli followed by assessments on their AHLs production using AHL biosensors and high resolution liquid chromatography–mass spectrometry (LCMS). These AHL-producing E. coli served as tools for screening AHL synthase inhibitors. Based on a campaign of screening synthetic molecules and natural products using our approach, three strongest inhibitors namely are salicylic acid, tannic acid and trans-cinnamaldehyde have been identified. LCMS analysis further confirmed tannic acid and trans-cinnemaldehyde efficiently inhibited AHL production by RhlI. We further demonstrated the application of trans-cinnemaldehyde inhibiting Rhl QS system regulated pyocyanin production in P. aeruginosa up to 42.06%. Molecular docking analysis suggested that trans-cinnemaldehyde binds to the LasI and EsaI with known structures mainly interacting with their substrate binding sites. Our data suggested a new class of QS-inhibiting agents from natural products targeting AHL synthase and provided a potential approach for facilitating the discovery of anti-QS signal synthesis as basis of novel anti-infective approach.en_US
dc.description.sponsorshipUniversity of Malaya High Impact Research (HIR) Grant (UM-MOHE HIR Grant UM.C/625/1/HIR/MOHE/CHAN/14/1, no. H-50001-A000027) given to K.G.C. and National Natural Science Foundation of China (no. 81260481) given to H.W.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttp://dx.doi.org/10.1038/srep07245en_US
dc.rights© 2014 The Authors. Reproduced in accordance with the publisher's selfarchiving policy. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.subjectN-acylhomoserine lactone (AHL); Non-antibiotic quorum sensing; Escherichia coli; QS-inhibiting agentsen_US
dc.titleNon-antibiotic quorum sensing inhibitors acting against N-acyl homoserine lactone synthase as druggable targeten_US
dc.status.refereedYesen_US
dc.date.Accepted2014-11-11
dc.date.application2014-11-28
dc.typeArticleen_US
dc.type.versionPublished versionen_US
refterms.dateFOA2018-07-29T03:09:44Z


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