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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 ..
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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
Depositor Specified Assays
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AIDNameTypeComment
488966Primary and Confirmatory Screening for Inhibitors of Bacterial Capsule Biogenesisconfirmatoryprimary and confirmatory screen
488966Primary and Confirmatory Screening for Inhibitors of Bacterial Capsule Biogenesisconfirmatoryconfirmatory screen
602408Confirmatory Screen for Inhibitors of Bacterial Capsule Biogenesis (2)confirmatoryconfirmatory screen
493020Cytotoxicity screening for potential Inhibitors of Bacterial Capsule BiogenesisconfirmatoryCytotoxicity counter screen
504769Cytotoxicity screening for potential Inhibitors of Bacterial Capsule Biogenesis (2)confirmatoryCytotoxicity counter screen
504831Cytotoxicity screening for potential Inhibitors of Bacterial Capsule Biogenesis (3)confirmatoryCytotoxicity counter screen
588399Cytotoxicity screening for potential Inhibitors of Bacterial Capsule Biogenesis (4)confirmatoryCytotoxicity counter screen
602414Cytotoxicity screening for potential Inhibitors of Bacterial Capsule Biogenesis (5)confirmatoryCytotoxicity counter screen
588321Screening for Inhibitors of Bacterial Capsule Biogenesis E.coli strain UT189 (5).confirmatoryScreening for Inhibitors of Bacterial Capsule Biogenesis E.coli strain UT189
588386Screening for Inhibitors of Bacterial Capsule Biogenesis E.coli strain UT189 (6)confirmatoryScreening for Inhibitors of Bacterial Capsule Biogenesis E.coli strain UT189
588395Screening for Inhibitors of Bacterial Capsule Biogenesis E.coli strain UT189 (7)confirmatoryScreening for Inhibitors of Bacterial Capsule Biogenesis E.coli strain UT189
504358Screening for Inhibitors of Bacterial Capsule Biogenesis E.coli strain UT189 with C7 controlconfirmatoryScreening for Inhibitors of Bacterial Capsule Biogenesis E.coli strain UT189 with C7 control
504543Screening for Inhibitors of Bacterial Capsule Biogenesis E.coli strain UT189 with C7 control (2)confirmatoryScreening 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)confirmatoryScreening for Inhibitors of Bacterial Capsule Biogenesis E.coli strain UT189 with C7 control
504768Screening for Inhibitors of Bacterial Capsule Biogenesis E.coli strain UT189 with C7 control (4)confirmatoryScreening for Inhibitors of Bacterial Capsule Biogenesis E.coli strain UT189 with C7 control
504349Screening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis InhibitionconfirmatoryScreening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis Inhibition (Specificity Screen)
504538Screening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis Inhibition (2)confirmatoryScreening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis Inhibition (Specificity Screen)
504676Screening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis Inhibition (3)confirmatoryScreening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis Inhibition (Specificity Screen)
504767Screening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis Inhibition (4)confirmatoryScreening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis Inhibition (Specificity Screen)
588322Screening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis Inhibition (5)confirmatoryScreening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis Inhibition (Specificity Screen)
624055Screening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis Inhibition (6)confirmatoryScreening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis Inhibition (Specificity Screen)
624056Screening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis Inhibition (7)confirmatoryScreening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis Inhibition (Specificity Screen)
624061K5 Secondary Screening for Inhibitors of Bacterial Capsule BiogenesisotherK5 Secondary
504733Orcinol Secondary Screening for Inhibitors of Bacterial Capsule BiogenesisotherOrcinol Secondary Screening for Inhibitors of Bacterial Capsule Biogenesis
624060Orcinol Secondary Screening for Inhibitors of Bacterial Capsule Biogenesis (2)otherOrincol
652019Screening for Inhibitors of Bacterial Capsule Biogenesis - T7 Lysis Inhibition (Specificity Screen) (6)confirmatory
652021Cytotoxicity screening for potential Inhibitors of Bacterial Capsule Biogenesis (4)confirmatory
488970Screening for Inhibitors of Bacterial Caspule Biogenesis - SummarysummarySummary AID
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.
Additional Information
Grant Number: 1 R03 MH090791-01

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