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Non-antibiotic quorum sensing inhibitors acting against N-acyl homoserine lactone synthase as druggable target

N-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 synthas...

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Autores principales: Chang, Chien-Yi, Krishnan, Thiba, Wang, Hao, Chen, Ye, Yin, Wai-Fong, Chong, Yee-Meng, Tan, Li Ying, Chong, Teik Min, Chan, Kok-Gan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4246208/
https://www.ncbi.nlm.nih.gov/pubmed/25430794
http://dx.doi.org/10.1038/srep07245
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author Chang, Chien-Yi
Krishnan, Thiba
Wang, Hao
Chen, Ye
Yin, Wai-Fong
Chong, Yee-Meng
Tan, Li Ying
Chong, Teik Min
Chan, Kok-Gan
author_facet Chang, Chien-Yi
Krishnan, Thiba
Wang, Hao
Chen, Ye
Yin, Wai-Fong
Chong, Yee-Meng
Tan, Li Ying
Chong, Teik Min
Chan, Kok-Gan
author_sort Chang, Chien-Yi
collection PubMed
description N-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.
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spelling pubmed-42462082014-12-05 Non-antibiotic quorum sensing inhibitors acting against N-acyl homoserine lactone synthase as druggable target Chang, Chien-Yi Krishnan, Thiba Wang, Hao Chen, Ye Yin, Wai-Fong Chong, Yee-Meng Tan, Li Ying Chong, Teik Min Chan, Kok-Gan Sci Rep Article N-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. Nature Publishing Group 2014-11-28 /pmc/articles/PMC4246208/ /pubmed/25430794 http://dx.doi.org/10.1038/srep07245 Text en Copyright © 2014, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/4.0/ 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/
spellingShingle Article
Chang, Chien-Yi
Krishnan, Thiba
Wang, Hao
Chen, Ye
Yin, Wai-Fong
Chong, Yee-Meng
Tan, Li Ying
Chong, Teik Min
Chan, Kok-Gan
Non-antibiotic quorum sensing inhibitors acting against N-acyl homoserine lactone synthase as druggable target
title Non-antibiotic quorum sensing inhibitors acting against N-acyl homoserine lactone synthase as druggable target
title_full Non-antibiotic quorum sensing inhibitors acting against N-acyl homoserine lactone synthase as druggable target
title_fullStr Non-antibiotic quorum sensing inhibitors acting against N-acyl homoserine lactone synthase as druggable target
title_full_unstemmed Non-antibiotic quorum sensing inhibitors acting against N-acyl homoserine lactone synthase as druggable target
title_short Non-antibiotic quorum sensing inhibitors acting against N-acyl homoserine lactone synthase as druggable target
title_sort non-antibiotic quorum sensing inhibitors acting against n-acyl homoserine lactone synthase as druggable target
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4246208/
https://www.ncbi.nlm.nih.gov/pubmed/25430794
http://dx.doi.org/10.1038/srep07245
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