Bookmark and Share
BioAssay: AID 488970

Screening for Inhibitors of Bacterial Caspule Biogenesis - Summary

This report summarizes the approaches used to discover small molecules inhibiting the formation of K1 polysialic acid capsule biogenesis with high specificity. Investigators have found that encapsulation is an important Uropathogenic Escherichia coli virulence factor. The K1 capsule type is closely associated with pathogenic isolates; not only is it the leading type in UTI, but it also accounts more ..
_
   
 Related BioAssays
 Related BioAssays
AID: 488970
Data Source: Southern Research Specialized Biocontainment Screening Center (EColi_Phage_Summary)
BioAssay Type: Summary, Candidate Probes/Leads with Supporting Evidence
Depositor Category: NIH Molecular Libraries Probe Production Network
BioAssay Version:
Deposit Date: 2010-10-29
Modify Date: 2013-02-12
Related Experiments
Show more
AIDNameTypeComment
488966Primary and Confirmatory Screening for Inhibitors of Bacterial Capsule BiogenesisConfirmatorydepositor-specified cross reference: primary and confirmatory screen
493020Cytotoxicity screening for potential Inhibitors of Bacterial Capsule BiogenesisConfirmatorydepositor-specified cross reference: Cytotoxicity counter screen
504349Screening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis InhibitionConfirmatorydepositor-specified cross reference: Screening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis Inhibition (Specificity Screen)
504358Screening for Inhibitors of Bacterial Capsule Biogenesis E.coli strain UT189 with C7 controlConfirmatorydepositor-specified cross reference: Screening for Inhibitors of Bacterial Capsule Biogenesis E.coli strain UT189 with C7 control
504538Screening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis Inhibition (2)Confirmatorydepositor-specified cross reference: Screening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis Inhibition (Specificity Screen)
504543Screening for Inhibitors of Bacterial Capsule Biogenesis E.coli strain UT189 with C7 control (2)Confirmatorydepositor-specified cross reference: Screening for Inhibitors of Bacterial Capsule Biogenesis E.coli strain UT189 with C7 control
504675Screening for Inhibitors of Bacterial Capsule Biogenesis E.coli strain UT189 with C7 control (3)Confirmatorydepositor-specified cross reference: Screening for Inhibitors of Bacterial Capsule Biogenesis E.coli strain UT189 with C7 control
504676Screening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis Inhibition (3)Confirmatorydepositor-specified cross reference: Screening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis Inhibition (Specificity Screen)
504733Orcinol Secondary Screening for Inhibitors of Bacterial Capsule BiogenesisOtherdepositor-specified cross reference: Orcinol Secondary Screening for Inhibitors of Bacterial Capsule Biogenesis
504767Screening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis Inhibition (4)Confirmatorydepositor-specified cross reference: Screening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis Inhibition (Specificity Screen)
504768Screening for Inhibitors of Bacterial Capsule Biogenesis E.coli strain UT189 with C7 control (4)Confirmatorydepositor-specified cross reference: Screening for Inhibitors of Bacterial Capsule Biogenesis E.coli strain UT189 with C7 control
504769Cytotoxicity screening for potential Inhibitors of Bacterial Capsule Biogenesis (2)Confirmatorydepositor-specified cross reference: Cytotoxicity counter screen
504831Cytotoxicity screening for potential Inhibitors of Bacterial Capsule Biogenesis (3)Confirmatorydepositor-specified cross reference: Cytotoxicity counter screen
588321Screening for Inhibitors of Bacterial Capsule Biogenesis E.coli strain UT189 (5).Confirmatorydepositor-specified cross reference: Screening for Inhibitors of Bacterial Capsule Biogenesis E.coli strain UT189
588322Screening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis Inhibition (5)Confirmatorydepositor-specified cross reference: Screening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis Inhibition (Specificity Screen)
588386Screening for Inhibitors of Bacterial Capsule Biogenesis E.coli strain UT189 (6)Confirmatorydepositor-specified cross reference: Screening for Inhibitors of Bacterial Capsule Biogenesis E.coli strain UT189
588395Screening for Inhibitors of Bacterial Capsule Biogenesis E.coli strain UT189 (7)Confirmatorydepositor-specified cross reference: Screening for Inhibitors of Bacterial Capsule Biogenesis E.coli strain UT189
588399Cytotoxicity screening for potential Inhibitors of Bacterial Capsule Biogenesis (4)Confirmatorydepositor-specified cross reference: Cytotoxicity counter screen
602408Confirmatory Screen for Inhibitors of Bacterial Capsule Biogenesis (2)Confirmatorydepositor-specified cross reference: confirmatory screen
602414Cytotoxicity screening for potential Inhibitors of Bacterial Capsule Biogenesis (5)Confirmatorydepositor-specified cross reference: Cytotoxicity counter screen
624055Screening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis Inhibition (6)Confirmatorydepositor-specified cross reference: Screening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis Inhibition (Specificity Screen)
624056Screening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis Inhibition (7)Confirmatorydepositor-specified cross reference: Screening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis Inhibition (Specificity Screen)
624060Orcinol Secondary Screening for Inhibitors of Bacterial Capsule Biogenesis (2)Otherdepositor-specified cross reference: Orincol
624061K5 Secondary Screening for Inhibitors of Bacterial Capsule BiogenesisOtherdepositor-specified cross reference: K5 Secondary
652019Screening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis Inhibition (Specificity Screen) (6)Confirmatorydepositor-specified cross reference
652021Cytotoxicity screening for potential Inhibitors of Bacterial Capsule Biogenesis (4)Confirmatorydepositor-specified cross reference
Description:
Southern Research's Specialized Biocontainment Screening Center (SRSBSC)
Southern Research Institute (Birmingham, Alabama)
NIH Molecular Libraries Probe Production Centers Network (MLPCN)
Assay Provider: Dr. Patrick Seed, Duke University, Durham, NC
Award: 1 R03 MH090791-01

This report summarizes the approaches used to discover small molecules inhibiting the formation of K1 polysialic acid capsule biogenesis with high specificity. Investigators have found that encapsulation is an important Uropathogenic Escherichia coli virulence factor. The K1 capsule type is closely associated with pathogenic isolates; not only is it the leading type in UTI, but it also accounts for much of the extra-urinary tract complications. Animals studies of E. coli K1 sepsis demonstrated that injection of K1 capsule degrading enzyme abrogates infection. However, the enzyme treatment is immunogenic; accordingly, chemical inhibition may prove to be a superior approach. Chemical modulators of capsule formation might represent a new avenue to combat the community-acquired urinary tract infections. To this end, we have adapted a 1536-well high-throughput bacterial cell-based screen suitable for the discovery of novel K1 capsule inhibitors.

Three lines of experiments were provided to get possible scaffolds for the SAR; 1) to screen a 300K of compounds library of MLSMR, 2) to select compounds specifically inhibit K1 capsule formation and screen out non-specific compounds that interfere with the assay in a dose response study and 3) to confirm the activities in a bacterial growth assay.
Categorized Comment - additional comments and annotations
From MLP Probe Report:
Probe count: 2
MLP Probe ML# for probe 1: ML317
PubChem Substance ID (SID) for probe 1: 103147605
PubChem Compound ID (CID) for probe 1: 23602075
Probe type for probe 1: Inhibitor
IC50/EC50 (nM) for probe 1: 4500 +/- 2400
Target for probe 1: K1 Capsule
Disease relevance for probe 1: UTI
Anti-target for probe 1: Mammalian cell toxicity
Fold selectivity for probe 1: >10.5
NCBI Book chapter link for probe 1: http://www.ncbi.nlm.nih.gov/books/NBK143534/ (ID: 3036446)
Grant number for probe 1: MH090791
MLP Probe ML# for probe 2: ML333
PubChem Substance ID (SID) for probe 2: 126587014
PubChem Compound ID (CID) for probe 2: 18109210
Probe type for probe 2: Inhibitor
IC50/EC50 (nM) for probe 2: 1.04
Target for probe 2: K1 Capsule
Disease relevance for probe 2: UTI
Anti-target for probe 2: Mammalian cell toxicity
Fold selectivity for probe 2: 230
NCBI Book chapter link for probe 2: http://www.ncbi.nlm.nih.gov/books/NBK148500/ (ID: 3040674)
Grant number for probe 2: MH090791-01
NCBI Book chapter title for probe 1: 3-(2,6-difluorobenzamido)-5-(4-ethoxyphenyl) thiophene-2-carboxylic acid inhibits E.coli UT189 bacterial capsule biogenesis
NCBI Book chapter title for probe 2: N-(pyridin-4-yl)benzo[d]thiazole-6-carboxamide inhibits E. coli UT189 bacterial capsule biogenesis
Additional Information
Grant Number: 1 R03 MH090791-01

PageFrom: