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

Viviana Gatta, Tihomir Tomašič, Janez Ilaš, Nace Zidar, Lucija Peterlin Mašič, Michaela Barančoková, Rok Frlan, Marko Anderluh, Danijel Kikelj, Päivi Tammela

Research output: Contribution to journalArticleScientificpeer-review

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.

Original languageEnglish
JournalChemBioChem : a European journal of chemical biology
Volume21
Issue number13
Pages (from-to)1918-1922
Number of pages5
ISSN1439-4227
DOIs
Publication statusPublished - 1 Jul 2020
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 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

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