Targeting Quorum Sensing: High-Throughput Screening to Identify Novel LsrK Inhibitors

Viviana Gatta, Polina Ilina, Alison Porter, Stuart McElroy, Päivi Tammela

Research output: Contribution to journalArticlepeer-review

Abstract

Since quorum sensing (QS) is linked to the establishment of bacterial infection, its inactivation represents one of the newest strategies to fight bacterial pathogens. LsrK is a kinase playing a key role in the processing of autoinducer-2 (AI-2), a quorum-sensing mediator in gut enteric bacteria. Inhibition of LsrK might thus impair the quorum-sensing cascade and consequently reduce bacterial pathogenicity. Aiming for the development of a target-based assay for the discovery of LsrK inhibitors, we evaluated different assay set-ups based on ATP detection and optimized an automation-compatible method for the high-throughput screening of chemical libraries. The assay was then used to perform the screening of a 2000-compound library, which provided 12 active compounds with an IC50

Original languageEnglish
Article number3112
JournalInternational Journal of Molecular Sciences
Volume20
Issue number12
Number of pages17
ISSN1422-0067
DOIs
Publication statusPublished - 2 Jun 2019
MoE publication typeA1 Journal article-refereed

Fields of Science

  • ACID
  • AI-2
  • ANTIOXIDANT
  • CELASTROL
  • DRUGS
  • IDENTIFICATION
  • IN-VIVO
  • SYSTEMS
  • VIRULENCE
  • antivirulence agent
  • bacterial communication
  • harpagoside
  • rosolic acid
  • virulence
  • 116 Chemical sciences
  • 1182 Biochemistry, cell and molecular biology
  • 317 Pharmacy

Cite this