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

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

doi:10.3390/ijms20123112

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

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

Tutkimustuotos: Artikkelijulkaisu › Artikkeli › Tieteellinen › vertaisarvioitu

Abstrakti

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

Alkuperäiskieli	englanti
Artikkeli	3112
Lehti	International Journal of Molecular Sciences
Vuosikerta	20
Numero	12
Sivumäärä	17
ISSN	1422-0067
DOI - pysyväislinkit	https://doi.org/10.3390/ijms20123112
Tila	Julkaistu - 2 kesäk. 2019
OKM-julkaisutyyppi	A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Tieteenalat

116 Kemia
1182 Biokemia, solu- ja molekyylibiologia
317 Farmasia

Pääsy asiakirjaan

10.3390/ijms20123112Lisenssi: CC BY

Gatta et al 2019Lopullinen julkaistu versio, 1,26 MBLisenssi: CC BY

2 Päättynyt

INTEGRATE: Interdisciplinary Training Network for Validation of Gram-negative Antibacterial Targets (H2020-MCSA-ITN-2014)
Tammela, P., Peltonen, K. & Gatta, V.
European Commission / Horizon 2020
01/01/2015 → 31/12/2018
Projekti: Tutkimusprojekti
Phenotypic biosensor-based HTS and mode of action analysis by metabolomics and transcriptomics for enhancing antimicrobial drug discovery against Gram-negative bacteria
Tammela, P.
01/09/2014 → 31/08/2019
Projekti: Tutkimusprojekti

Siteeraa tätä

@article{9e1f911133e8477c836df8af83a2ca67,

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 = jun,

day = "2",

doi = "10.3390/ijms20123112",

language = "English",

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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

VL - 20

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 12

M1 - 3112

ER -

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

Abstrakti

Tieteenalat

Pääsy asiakirjaan

Projektit

INTEGRATE: Interdisciplinary Training Network for Validation of Gram-negative Antibacterial Targets (H2020-MCSA-ITN-2014)

Phenotypic biosensor-based HTS and mode of action analysis by metabolomics and transcriptomics for enhancing antimicrobial drug discovery against Gram-negative bacteria

Siteeraa tätä