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High-throughput prescreening of pharmaceuticals using a genome-wide bacterial bioreporter array
Tal Elad1, Ho Bin Seo2, Shimshon Belkin1
1The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, The Edmond J. Safra Campus, Jerusalem 91904, Israel.
Biosensors & Bioelectronics
|February 11, 2015
Summary
Multi-strain bacterial bioreporter bioassays show promise for drug screening. These assays effectively identified drug responses and provided insights into toxicity mechanisms, aiding drug development.
Area of Science:
- Microbiology
- Toxicology
- Biotechnology
Background:
- Bacterial bioreporters offer a sensitive method for detecting cellular responses.
- High-throughput screening is crucial for efficient drug discovery.
Purpose of the Study:
- To evaluate the utility of multi-strain bacterial bioreporter bioassays in pharmaceutical drug screening.
- To investigate the responses of bacterial bioreporters to a diverse drug library and understand toxicity mechanisms.
Main Methods:
- A panel of 15 luminescent recombinant Escherichia coli bacterial bioreporters was exposed to 420 pharmaceuticals.
- Selected drugs were further tested against approximately 2000 fluorescent transcriptional reporters in E. coli.
- Assays were conducted using microplates and robotic systems for high-throughput analysis.
Main Results:
- Eighty-nine drugs triggered responses from the bioreporter panel, forming distinct clusters.
- Drug-induced gene expression patterns correlated with in vitro toxicity and provided mechanistic insights.
- The bacterial bioreporter panel effectively identified drug-specific responses.
Conclusions:
- Multi-strain bacterial bioreporter assemblages are valuable tools for drug development.
- These bioassays can complement existing in vitro toxicity tests.
- Bacterial bioreporters offer a scalable and informative approach for drug screening and toxicity assessment.
