High-Content Screening of Raw Actinomycete Extracts for the Identification of Antituberculosis Activities.
The feasibility and relevance of screening a library of raw actinomycete extracts (ECUM library) for the identification of antituberculosis activities was assessed on 11,088 extracts using a multiple-screening approach. Each extract was first tested at two concentrations against noninfected macrophages as a control, then against Mycobacterium tuberculosis growing in broth medium as well as infecting murine macrophages. The screening results indicated a library of good quality with an apparent low proportion of cytotoxic extracts. A correlation was found between both bacterial assays, but the intracellular assay showed limitations due to low rates of cell survival. Several extracts of interest were highlighted by this multiple screening. A focus on the strain producing the two most effective revealed similarities with known producers of active molecules, suggesting the possibility of selecting relevant extracts using this strategy.
1 Institut Pasteur Korea, Assay Development & Screening, Seongnam, Gyeonggi, Republic of Korea.
Jinyeong
J
Heo
1 Institut Pasteur Korea, Assay Development & Screening, Seongnam, Gyeonggi, Republic of Korea.
Jiyoun
J
Nam
2 Molecular Mechanism of Antibiotics, Division of Life Science, Research Institute of Life Science, Gyeongsang National University, Jinju, Gyeongnam, Republic of Korea.
Jichan
J
Jang
1 Institut Pasteur Korea, Assay Development & Screening, Seongnam, Gyeonggi, Republic of Korea.
David
D
Shum
3 Institut Pasteur Korea, Automation & Logistics Management, Seongnam, Gyeonggi, Republic of Korea.
Constantin
C
Radu
4 Division of Bioscience and Bioinformatics, College of Natural Science, Myongji University, Yongin, Gyeonggi, Republic of Korea.|5 Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin, Gyeonggi, Republic of Korea.
Jinhua
J
Cheng
5 Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin, Gyeonggi, Republic of Korea.|6 Interdisciplinary Program of Biomodulation, Myongji University, Yongin, Gyeonggi, Republic of Korea.
Hanki
H
Lee
4 Division of Bioscience and Bioinformatics, College of Natural Science, Myongji University, Yongin, Gyeonggi, Republic of Korea.|5 Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin, Gyeonggi, Republic of Korea.
Joo-Won
JW
Suh
7 Institut Pasteur Korea, Tuberculosis Research Laboratory, Seongnam, Gyeonggi, Republic of Korea.
Vincent
V
Delorme
D039903:Actinobacteria / Q000737:chemistry*; D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology; D051379:Mice; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology
D000995:Antitubercular Agents
actinomycetes; high-content screening; natural extracts; tuberculosis