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 journalArticleScientificpeer-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

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title = "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",
keywords = "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",
author = "Viviana Gatta and Polina Ilina and Alison Porter and Stuart McElroy and P{\"a}ivi Tammela",
year = "2019",
month = "6",
day = "2",
doi = "10.3390/ijms20123112",
language = "English",
volume = "20",
journal = "International Journal of Molecular Sciences",
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Targeting Quorum Sensing : High-Throughput Screening to Identify Novel LsrK Inhibitors. / Gatta, Viviana; Ilina, Polina; Porter, Alison; McElroy, Stuart; Tammela, Päivi.

In: International Journal of Molecular Sciences, Vol. 20, No. 12, 3112, 02.06.2019.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Targeting Quorum Sensing

T2 - High-Throughput Screening to Identify Novel LsrK Inhibitors

AU - Gatta, Viviana

AU - Ilina, Polina

AU - Porter, Alison

AU - McElroy, Stuart

AU - Tammela, Päivi

PY - 2019/6/2

Y1 - 2019/6/2

N2 - 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

AB - 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

KW - ACID

KW - AI-2

KW - ANTIOXIDANT

KW - CELASTROL

KW - DRUGS

KW - IDENTIFICATION

KW - IN-VIVO

KW - SYSTEMS

KW - VIRULENCE

KW - antivirulence agent

KW - bacterial communication

KW - harpagoside

KW - rosolic acid

KW - virulence

KW - 116 Chemical sciences

KW - 1182 Biochemistry, cell and molecular biology

KW - 317 Pharmacy

U2 - 10.3390/ijms20123112

DO - 10.3390/ijms20123112

M3 - Article

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JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

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M1 - 3112

ER -