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Non-antibiotic quorum sensing inhibitors acting against N-acyl homoserine lactone synthase as druggable target
Chang, Chien-Yi Krishnan, T. Wang, H. Chen, Y. Yin, W. Chong, Y. Tan, L.Y. Chong, T.M. Chan, K.
Chang, Chien-Yi
Krishnan, T.
Wang, H.
Chen, Y.
Yin, W.
Chong, Y.
Tan, L.Y.
Chong, T.M.
Chan, K.
Publication Date
2014-11
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openAccess
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2014-11-11
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Abstract
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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Citation
Chang 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.
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Article