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A New Cell‐Based AI‐2‐Mediated Quorum Sensing Interference Assay in Screening of LsrK‐Targeted Inhibitors
Author(s) -
Gatta Viviana,
Tomašič Tihomir,
Ilaš Janez,
Zidar Nace,
Peterlin Mašič Lucija,
Barančoková Michaela,
Frlan Rok,
Anderluh Marko,
Kikelj Danijel,
Tammela Päivi
Publication year - 2020
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201900773
Subject(s) - quorum sensing , bioreporter , virulence , escherichia coli , high throughput screening , biology , autoinducer , computational biology , bacteria , microbiology and biotechnology , chemistry , biochemistry , reporter gene , genetics , gene , gene expression
Quorum sensing (QS), a bacterial communication strategy, has been recognized as one of the control mechanisms of virulence in bacteria. Thus, targeting QS offers an interesting opportunity to impair bacterial pathogenicity and develop antivirulence agents. Aiming to enhance the discovery of QS inhibitors, we developed a bioreporter Escherichia coli JW5505 pET‐Plsrlux and set up a cell‐based assay for identifying inhibitors of autoinducer‐2 (AI‐2)‐mediated QS. A comparative study on the performance of target‐ versus cell‐based assays was performed, and 91 compounds selected with the potential to target the ATP binding pocket of LsrK, a key enzyme in AI‐2 processing, were tested in an LsrK inhibition assay, providing 36 hits. The same set of compounds was tested by the AI‐2‐mediated QS interference assay, resulting in 24 active compounds. Among those, six were also found to be active against LsrK, whereas 18 might target other components of the pathway. Thus, this AI‐2‐mediated QS interference cell‐based assay is an effective tool for complementing target‐based assays, yet also stands as an independent assay for primary screening.

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