title: High-throughput prescreening of pharmaceuticals using a genome-wide bacterial bioreporter array.
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.
authors: The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, The Edmond J. Safra Campus, Jerusalem 91904, Israel.
authors: Tal
authors: T
authors: Elad
authors: College of Life Sciences and Biotechnology, Korea University, Anam-dong, Seongbuk-gu, 136-701 Seoul, Republic of Korea.
authors: Ho Bin
authors: HB
authors: Seo
authors: The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, The Edmond J. Safra Campus, Jerusalem 91904, Israel.
authors: Shimshon
authors: S
authors: Belkin
authors: College of Life Sciences and Biotechnology, Korea University, Anam-dong, Seongbuk-gu, 136-701 Seoul, Republic of Korea. Electronic address: mbgu@korea.ac.kr.
authors: Man Bock
authors: MB
authors: Gu
mesh_terms: D015374:Biosensing Techniques; D004249:DNA Damage / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D017930:Genes, Reporter / Q000187:drug effects; D016680:Genome, Bacterial / Q000187:drug effects; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D010600:Pharmacology
keywords: Bacterial reporter; Drug screening; Fluorescent transcriptional reporter; Luminescent bacteria