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

Authors
Elad, TalSeo, Ho BinBelkin, ShimshonGu, Man Bock
Issue Date
15-6월-2015
Publisher
ELSEVIER ADVANCED TECHNOLOGY
Keywords
Luminescent bacteria; Bacterial reporter; Fluorescent transcriptional reporter; Drug screening
Citation
BIOSENSORS & BIOELECTRONICS, v.68, pp.699 - 704
Indexed
SCIE
SCOPUS
Journal Title
BIOSENSORS & BIOELECTRONICS
Volume
68
Start Page
699
End Page
704
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/93258
DOI
10.1016/j.bios.2015.01.067
ISSN
0956-5663
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. (C) 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license.
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