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Anti‐tuberculosis Drug Discovery from Phenotypic High‐throughput Screening of Actinomycete Cultures
Author(s) -
Grzelak Edyta Malgorzata,
Gao Wei,
Choules Mary P.,
Wan Baojie,
Wang Yuehong,
Cheng Jinhua,
Lee Hanki,
Suh JooWon,
Pauli Guido F.,
Franzblau Scott G.,
Jaki Birgit U.,
Cho SangHyun
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.lb633
Subject(s) - drug discovery , tuberculosis , mycobacterium tuberculosis , bioassay , isolation (microbiology) , biology , microbiology and biotechnology , drug , computational biology , medicine , pharmacology , bioinformatics , genetics , pathology
This report presents over a decade of efforts in anti‐tuberculosis (anti‐TB) drug discovery at the UIC Institute for Tuberculosis Research (ITR). During this period, a library of approximately 200,000 actinomycete‐derived extracts was screened directly against virulent Mycobacterium tuberculosis ( M. tb ) H37Rv using a luxABCDE reporter and the Microplate Alamar Blue Assay.1 The collection consisted of soil microorganisms from sites in Southeastern Asia with distinctive ecosystems and climate, e.g. , polar, tropical, volcanic, and deserted areas. The extracts of interest were subjected to extensive biological profiling under replicating and non‐replicating M. tb conditions, against mono‐drug resistant M. tb strains, and panels of microorganisms other than mycobacteria. The aim was to identify and validate the extracts with the most interesting activity profile by fractionation and bioassay‐guided isolation of the active principles. New approaches were implemented not only for the biological activity testing but also for the isolation and structure identification of the potential leads.2 The established anti‐TB drug discovery platform led to the discovery of the two anti‐mycobacterial cyclic peptides, ecumicin and rufomycin, which both target ClpC1 in M. tb . Support or Funding Information The Next‐Generation BioGreen 21 Program (No. PJ01328403), Rural Development Administration, Republic of Korea; and T32AT007533 from NCCIH/NIH. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .