ePrints

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

Lookup NU author(s): Dr Chien-Yi ChangORCiD

Downloads

• Published version [.pdf]

Licence

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).

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.

Publication metadata

Author(s): Chang CY, Krishnan T, Wang H, Chen Y, Yin WF, Chong YM, Tan LY, Chong TM, Chan KG

Publication type: Article

Publication status: Published

Journal: Scientific Reports

Year: 2014

Volume: 4

Online publication date: 28/11/2014

Acceptance date: 11/11/2014

Date deposited: 12/11/2015

ISSN (electronic): 2045-2322

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/srep07245

DOI: 10.1038/srep07245

Altmetrics

Funding

Share