Projects per year
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 language | English |
---|---|
Journal | ChemBioChem : a European journal of chemical biology |
Volume | 21 |
Issue number | 13 |
Pages (from-to) | 1918-1922 |
Number of pages | 5 |
ISSN | 1439-4227 |
DOIs | |
Publication status | Published - 1 Jul 2020 |
MoE publication type | A1 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
Projects
- 1 Finished
-
Phenotypic biosensor-based HTS and mode of action analysis by metabolomics and transcriptomics for enhancing antimicrobial drug discovery against Gram-negative bacteria
01/09/2014 → 31/08/2019
Project: Research project