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

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 ≤

SUBMITTER: Gatta V 

PROVIDER: S-EPMC6627609 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature