TY - JOUR
T1 - High-throughput prescreening of pharmaceuticals using a genome-wide bacterial bioreporter array
AU - Elad, Tal
AU - Seo, Ho Bin
AU - Belkin, Shimshon
AU - Gu, Man Bock
N1 - Publisher Copyright:
© 2015 The Authors.
PY - 2015/6/5
Y1 - 2015/6/5
N2 - 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.
AB - 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.
KW - Bacterial reporter
KW - Drug screening
KW - Fluorescent transcriptional reporter
KW - Luminescent bacteria
UR - http://www.scopus.com/inward/record.url?scp=84922309370&partnerID=8YFLogxK
U2 - 10.1016/j.bios.2015.01.067
DO - 10.1016/j.bios.2015.01.067
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C2 - 25668591
AN - SCOPUS:84922309370
SN - 0956-5663
VL - 68
SP - 699
EP - 704
JO - Biosensors and Bioelectronics
JF - Biosensors and Bioelectronics
ER -