Document Detail


A Novel High-Throughput Cell Based Assay Aimed at Identifying Inhibitors of DNA Metabolism in Bacteria.
MedLine Citation:
PMID:  25246396     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Bacterial biosensor strains can be useful tools for discovery and characterization of antibacterial compounds. A plasmid-based reporter vector, containing a transcriptional fusion between the recA promoter and green fluorescence protein gene, was introduced into an Escherichia coli ΔtolC strain to create a biosensor strain that selectively senses inhibitors of DNA metabolism via the SOS response. The strain was used to develop a high-throughput assay to identify new inhibitors of DNA metabolism. Screening the AstraZeneca compound library with this strain identified known inhibitors of DNA metabolism, as well as novel chemotypes. The cellular target of one novel series was elucidated as DNA gyrase through genetic characterization of laboratory-generated resistant mutants followed by IC50 measurements in a DNA gyrase activity assay. These studies validated the use of this antibiotic biosensor strain to identify novel selective inhibitors of DNA metabolism by high-throughput screening.
Authors:
Jun Fan; Boudewijn L M de Jonge; Kathy MacCormack; Shubha Sriram; Robert E McLaughlin; Helen Plant; Marian Preston; Paul R Fleming; Robert Albert; Melinda Foulk; Scott D Mills
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-9-22
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  -     ISSN:  1098-6596     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-9-23     Completed Date:  -     Revised Date:  2014-9-24    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014, American Society for Microbiology. All Rights Reserved.
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