High-throughput prescreening of pharmaceuticals using a genome-wide bacterial bioreporter array

Tal Elad, Ho Bin Seo, Shimshon Belkin, Man Bock Gu

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

We assessed the applicability of multi-strain bacterial bioreporter bioassays to drug screening. To this end, we investigated the reactions of a panel of 15 luminescent recombinant Escherichia coli bacterial bioreporters to a library of 420 pharmaceuticals. The panel included bacterial bioreporters associated with oxidative stress, DNA damage, heat shock, and efflux of excess metals. Eighty nine drugs elicited a response from at least one of the panel members and formed distinctive clusters, some of which contained closely related drugs. In addition, we tested a group of selected nine drugs against a collection of about 2000 different fluorescent transcriptional reporters that covers the great majority of gene promoters in E. coli. The sets of induced genes were in accord with the in vitro toxicity of the tested drugs, as reflected by the response patterns of the 15-member panel, and provided more insights into their toxicity mechanisms. Facilitated by microplates and robotic systems, all assays were conducted in high-throughput. Our results thus suggest that multi-strain assemblages of bacterial bioreporters have the potential for playing a significant role in drug development alongside current in vitro toxicity tests.

Original languageEnglish
Pages (from-to)699-704
Number of pages6
JournalBiosensors and Bioelectronics
Volume68
DOIs
Publication statusPublished - 2015 Jun 5

Fingerprint

Bacterial Genomes
Drug products
Toxicity
Genes
Throughput
Escherichia coli
Pharmaceutical Preparations
Oxidative stress
Bioassay
Assays
Screening
Robotics
DNA
Toxicity Tests
Preclinical Drug Evaluations
Drug-Related Side Effects and Adverse Reactions
Biological Assay
DNA Damage
Shock
Metals

Keywords

  • Bacterial reporter
  • Drug screening
  • Fluorescent transcriptional reporter
  • Luminescent bacteria

ASJC Scopus subject areas

  • Biophysics
  • Biomedical Engineering
  • Biotechnology
  • Electrochemistry

Cite this

High-throughput prescreening of pharmaceuticals using a genome-wide bacterial bioreporter array. / Elad, Tal; Seo, Ho Bin; Belkin, Shimshon; Gu, Man Bock.

In: Biosensors and Bioelectronics, Vol. 68, 05.06.2015, p. 699-704.

Research output: Contribution to journalArticle

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