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BioAssay: AID 588521

Broad Institute Quorum Sensing in Vibrio cholera: CqsS/LuxQ Agonist Probe Project

The long-term goal of this research is to explore the molecular mechanisms that bacteria use for cell-cell communication (i.e., quorum sensing). Until recently, the ability of bacteria to communicate was considered an anomaly that occurred only in a few marine Vibrio species. It is now clear that cell-cell communication is the norm in the bacterial world and that understanding this process is more ..
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AID: 588521
Data Source: Broad Institute (2132_Agonist_Project)
BioAssay Type: Summary, Candidate Probes/Leads with Supporting Evidence
Depositor Category: NIH Molecular Libraries Probe Production Network
BioAssay Version:
Deposit Date: 2011-10-14
Modify Date: 2013-11-14

Data Table ( Complete ):           Active    All
BioActive Compound: Chemical Probe: 1    Active: 1
Depositor Specified Assays
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AIDNameTypeComment
588436Cholera Quorum: HTS for inducers of light production in the absence ofautoinducers using BH1578 (luxS deficient, cqsA deficient) Measured in Microorganism System Using Plate Reader - 2132-01_Agonist_SinglePoint_HTS_Activityscreening350317 HTS compounds at SinglePoint in 2132-01 01 Cholera Quorum HTS measuring Activity
602243Cholera Quorum: HTS for inducers of light production in the absence of autoinducers using BH1578 (luxS deficient, cqsA deficient) Measured in Microorganism System Using Plate Reader - 2132-01_Agonist_Dose_CherryPick_Activityconfirmatory623 cherrypick compounds at dose in Cholera Quorum HTS measuring activity
624140Cytotoxicity at 24 hours in dose with HeLa cells Measured in Cell-Based System Using Plate Reader - 2132-02_Agonist_Dose_DryPowder_Activityconfirmatory26 drypowder compounds at dose in Cytotox measuring activity
624270Cholera Quorum: HTS for inducers of light production in the absence of#autoinducers using BH1578 (luxS deficient, cqsA deficient) Measured in Microorganism System Using Plate Reader - 2132-01_Agonist_Dose_DryPowder_Activityconfirmatory20 drypowder compounds at dose in 01 Cholera Quorum HTS measuring activity
624275Quorum CqsS/ LuxQ: Assay for inducers of light production in the absence of#autoinducers using WN1103 (delta luxQ) Measured in Microorganism System Using Plate Reader - 2132-05_Agonist_Dose_DryPowder_Activityconfirmatory20 drypowder compounds at dose in 05 Quorum CqsS/ LuxQ: WN1103 measuring activity
624281Quorum CqsS/ LuxQ: Assay for inducers of light production in the absence#of autoinducers using DH231 (delta cqsS) Measured in Microorganism System Using Plate Reader - 2132-04_Agonist_Dose_DryPowder_Activityconfirmatory20 drypowder compounds at dose in 04 Quorum CqsS/ LuxQ: DH231 measuring activity
651774Cytotoxicity at 24 hours in dose with HeLa cells Measured in Cell-Based System Using Plate Reader - 2132-02_Agonist_Dose_DryPowder_Activity_Set2confirmatory100 drypowder compounds at dose in Cytotox measuring activity set 2##
651808Quorum CqsS/ LuxQ: Assay for inducers of light production in the absence of autoinducers using DH231 (delta cqsS) Measured in Microorganism System Using Plate Reader - 2132-04_Agonist_Dose_DryPowder_Activity_Set2confirmatory28 drypowder compounds at dose in Quorum CqsS/ LuxQ: DH231 measuring activity set 2
651809Cholera Quorum: HTS for inducers of light production in the absence of autoinducers using BH1578 (luxS deficient, cqsA deficient) Measured in Microorganism System Using Plate Reader - 2132-01_Agonist_Dose_DryPowder_Activity_Set3confirmatory100 drypowder compounds at dose in Cholera Quorum HTS measuring activity set 3
651816Cholera Quorum: HTS for inducers of light production in the absence of autoinducers using BH1578 (luxS deficient, cqsA deficient) Measured in Microorganism System Using Plate Reader - 2132-01_Agonist_Dose_DryPowder_Activity_Set4confirmatory42 drypowder compounds at dose in Cholera Quorum HTS measuring activity set 4
651841Quorum CqsS/ LuxQ: Assay for inducers of light production in the absence of autoinducers using WN1103 (delta luxQ) Measured in Microorganism System Using Plate Reader - 2132-05_Agonist_Dose_DryPowder_Activity_Set2confirmatory42 drypowder compounds at dose in Quorum CqsS/ LuxQ: WN1103 measuring activity set 2
651854Cholera Quorum: HTS for inducers of light production in the absence of autoinducers using BH1578 (luxS deficient, cqsA deficient) Measured in Microorganism System Using Plate Reader - 2132-01_Agonist_Dose_DryPowder_Activity_Set2confirmatory51 drypowder compounds at dose in Cholera Quorum HTS measuring activity set 2
651864Cytotoxicity at 24 hours in dose with HeLa cells Measured in Cell-Based System Using Plate Reader - 2132-02_Agonist_Dose_DryPowder_Activity_Set3confirmatory45 drypowder compounds at dose in Cytotox measuring activity set 3##
651905CqsS In vitro Kinase Assay Measured in Biochemical System Using Imaging - 2132-10_Agonist_Dose_DryPowder_Activityother3 drypowder compounds at dose in 10 CqsS Kinase Assay measuring activity
686945Broad Institute Quorum Sensing in Vibrio cholera: LuxO Inhibitor Probe Projectsummary
686939Counterscreen for activators of the function of SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 2 (SMARCA2, BRM): Luminescence-based cell-based high throughput screening assay to identify non-selective compounds using the VP16 reporter assayscreening
686931Quorum CqsS/ LuxQ: Assay for inducers of light production in the absence of autoinducers using DH231 (delta cqsS) Measured in Microorganism System Using Plate Reader - 2132-04_Inhibitor_Dose_DryPowder_Activityconfirmatory
624254Quorum LuxO: Assay for inducers of light production in the absence of#autoinducers using BH1651 (luxOD47E) Measured in Microorganism System Using Plate Reader - 2132-03_Agonist_Dose_CherryPick_Activityconfirmatory
624269Quorum LuxO: Assay for inducers of light production in the absence of#autoinducers using BH1651 (luxOD47E) Measured in Microorganism System Using Plate Reader - 2132-03_Agonist_Dose_DryPowder_Activityconfirmatory
651847Quorum LuxO: Assay for inducers of light production in the absence of autoinducers using BH1651 (luxOD47E) Measured in Microorganism System Using Plate Reader - 2132-03_Agonist_Dose_DryPowder_Activity_Set3confirmatory
652219Quorum LuxO: Assay for change of GFP production in the absence of autoinducers using SL353 (luxOD47E, qrr4-gp) Measured in Microorganism System Using Plate Reader - 2132-06_Inhibitor_Dose_DryPowder_Activityconfirmatory
652239Cholera Quorum: HTS for inducers of light production in the absence of autoinducers using BH1578 (luxS deficient, cqsA deficient) Measured in Microorganism System Using Plate Reader - 2132-01_Inhibitor_Dose_DryPowder_Activityconfirmatory
686928Cytotoxicity at 24 hours in dose with HeLa cells Measured in Cell-Based System Using Plate Reader - 2132-02_Inhibitor_Dose_DryPowder_Activityconfirmatory
686929Cholera Quorum: HTS for inducers of light production in the absence of autoinducers using BH1578 (luxS deficient, cqsA deficient) Measured in Microorganism System Using Plate Reader - 2132-01_Inhibitor_Dose_DryPowder_Activity_Set2confirmatory
686930Quorum CqsS/ LuxQ: Assay for inducers of light production in the absence of autoinducers using WN1103 (delta luxQ) Measured in Microorganism System Using Plate Reader - 2132-05_Inhibitor_Dose_DryPowder_Activityconfirmatory
686936In vitro LuxO ATPase Assay Measured in Biochemical System Using Plate Reader - 2132-11_Inhibitor_Dose_DryPowder_Activityother
686942Quorum LuxO: Assay for change of GFP production in the absence of autoinducers using SL353 (luxOD47E, qrr4-gp) Measured in Microorganism System Using Plate Reader - 2132-06_Inhibitor_Dose_DryPowder_Activity_Set2confirmatory
Description:
Primary Collaborators:
Bonnie Bassler,Princeton University,bbassler@princeton.edu

Project Goal:
The long-term goal of this research is to explore the molecular mechanisms that bacteria use for cell-cell communication (i.e., quorum sensing). Until recently, the ability of bacteria to communicate was considered an anomaly that occurred only in a few marine Vibrio species. It is now clear that cell-cell communication is the norm in the bacterial world and that understanding this process is fundamental to all of microbiology, including industrial and clinical microbiology. Quorum sensing is mediated via two-component signaling receptors that are activated by ligands (e.g. CAI-1, AI-2). Very few ligands have been identified for bacterial two-component receptors, even though these receptors occur by the hundreds in diverse bacteria and are responsible for transducing a huge variety of sensory information into bacterial cells. Here we will carry out a high-throughput screen to identify small molecules that modulate quorum-sensing in the human pathogen Vibrio cholerae. Follow up studies to further characterize the lead compounds identified in the screens will combine synthetic organic chemistry, bacterial genetics, and biochemistry. Quorum-sensing
modulators identified through this work will provide lead compounds for the development of antibacterial drugs designed to interfere with quorum sensing which could have enormous ramifications for improving human health.



quorom sensing, Vibrio cholerae, Cqs, LuxQ
Biological Relevance:
Quorum sensing is a process of bacterial cell-cell communication that relies upon
the production, release, detection, and response to extracellular signaling molecules called autoinducers. Quorum sensing allows bacteria to synchronously alter behavior in response to changes in the population density and species composition of the vicinal bacterial community. Quorum sensing controls collective behaviors including bioluminescence, sporulation, virulence factor production, and biofilm formation. Vibrio cholerae is the etiological agent of the disease cholera and its life cycle consists of alternating between human hosts and the aquatic environment. In V. cholerae, quorum sensing represses biofilm formation and virulence factor production and it activates protease production.
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
ScoreThe BioAssay activity ranking scoreInteger
1ML_NUMString
2IC50FloatμM
Additional Information
Grant Number: R03 MH094166-01

Data Table (Concise)
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