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

Chien-Yi Chang, Thiba Krishnan, Hao Wang, Ye Chen, Wai Fong Yin, Yee Meng Chong, Li Ying Tan, Teik Min Chong, Kok Gan Chan

    Research output: Contribution to journalArticle

    84 Citations (Scopus)

    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.

    Original languageEnglish
    Article number7245
    JournalScientific Reports
    Volume4
    DOIs
    Publication statusPublished - 28 Nov 2014

    ASJC Scopus subject areas

    • General

    Fingerprint Dive into the research topics of 'Non-antibiotic quorum sensing inhibitors acting against N-acyl homoserine lactone synthase as druggable target'. Together they form a unique fingerprint.

  • Cite this

    Chang, C-Y., Krishnan, T., Wang, H., Chen, Y., Yin, W. F., Chong, Y. M., Tan, L. Y., Chong, T. M., & Chan, K. G. (2014). Non-antibiotic quorum sensing inhibitors acting against N-acyl homoserine lactone synthase as druggable target. Scientific Reports, 4, [7245]. https://doi.org/10.1038/srep07245