A new cell-based AI-2-mediated quorum sensing interference assay in screening of LsrK-targeted inhibitors

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Gatta , V , Tomašič , T , Ilaš , J , Zidar , N , Peterlin Mašič , L , Barančoková , M , Frlan , R , Anderluh , M , Kikelj , D & Tammela , P 2020 , ' A new cell-based AI-2-mediated quorum sensing interference assay in screening of LsrK-targeted inhibitors ' , ChemBioChem : a European journal of chemical biology , vol. 21 , no. 13 , pp. 1918-1922 . https://doi.org/10.1002/cbic.201900773

Title: A new cell-based AI-2-mediated quorum sensing interference assay in screening of LsrK-targeted inhibitors
Author: Gatta, Viviana; Tomašič, Tihomir; Ilaš, Janez; Zidar, Nace; Peterlin Mašič, Lucija; Barančoková, Michaela; Frlan, Rok; Anderluh, Marko; Kikelj, Danijel; Tammela, Päivi
Contributor organization: Bioactivity Screening Group
Division of Pharmaceutical Biosciences
Drug Research Program
University Management
Date: 2020-07-01
Language: eng
Number of pages: 5
Belongs to series: ChemBioChem : a European journal of chemical biology
ISSN: 1439-4227
DOI: https://doi.org/10.1002/cbic.201900773
URI: http://hdl.handle.net/10138/326054
Abstract: 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.
Subject: AI-2
AUTOINDUCER-2
BIOFILM FORMATION
DOCKING
DRUGS
Gram-negative bacteria
IDENTIFICATION
LsrK
SYSTEMS
antivirulence
bioreporters
quorum sensing
116 Chemical sciences
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Rights: unspecified
Usage restriction: openAccess
Self-archived version: acceptedVersion
Funder: SUOMEN AKATEMIA
Grant number: 277001


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