ArticleAntimicrobial agents and chemotherapy2014
A novel high-throughput cell-based assay aimed at identifying inhibitors of DNA metabolism in bacteria.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Chemical genetic approaches for the discovery of bacterial cell wall inhibitors.RSC medicinal chemistry · 2023Review
- Transcriptional Responses of Pseudomonas aeruginosa to Inhibition of Lipoprotein Transport by a Small Molecule Inhibitor.Journal of bacteriology · 2020Article
- A Putative Microcin Amplifies Shiga Toxin 2a Production of Escherichia coli O157:H7.Journal of bacteriology · 2019Article
- A Whole-Cell Screen for Adjunctive and Direct Antimicrobials Active against Carbapenem-Resistant Enterobacteriaceae.SLAS discovery : advancing life sciences R & D · 2019Article
- Sorting Out Antibiotics' Mechanisms of Action: a Double Fluorescent Protein Reporter for High-Throughput Screening of Ribosome and DNA Biosynthesis Inhibitors.Antimicrobial agents and chemotherapy · 2016Article
- Bioluminescent Reporters for Rapid Mechanism of Action Assessment in Tuberculosis Drug Discovery.Antimicrobial agents and chemotherapy · 2016Article
- Inhibition of Neisseria gonorrhoeae Type II Topoisomerases by the Novel Spiropyrimidinetrione AZD0914.The Journal of biological chemistry · 2015Article
- Novel antibacterial targets and compounds revealed by a high-throughput cell wall reporter assay.Journal of bacteriology · 2015Article
- Article
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bacterial biosensor strains can be useful tools for the 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 of 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 50% inhibitory concentration 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.
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