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PLoS One. 2018 Apr 26;13(4):e0195595. doi: 10.1371/journal.pone.0195595. eCollection 2018.

Pathogen Box screening for hit identification against Mycobacterium abscessus.

Author information

1
Division of Applied Life Science (BK21plus Program), Gyeongsang National University, Jinju, South Korea.
2
Department of Clinical Laboratory Science, Semyung University, Jecheon, South Korea.
3
Division of Life Science, Research Institute of Life Science, Gyeongsang National University, Jinju, South Korea.

Abstract

Mycobacterium abscessus is a rapidly growing life-threatening mycobacterium with multiple drug-resistance mechanisms. However, there is no official regimen for M. abscessus therapy. In this study, we screened the Pathogen Box, which contains 400 drug-like molecules active against neglected diseases, to identify active molecules targeting Mycobacterium abscessus using resazurin live/dead assays. In this screening assay, the Z-factor was 0.7, as an indicator of the statistical confidence of the assay. A cut-off of 80% growth inhibition in the screening resulted in the identification of four different compounds at a single concentration (20 μM). Dose-response curves identified three different hit candidates, i.e., MMV688508, MMV688844, and MMV688845, which generated good inhibitory curves. All hit candidates were expected to have different molecular targets. Among them, MMV688844 showed the best minimum inhibitory concentration value for not only wild-type M. abscessus but also for nine different R and S morphotype clinical isolates. Thus, we found that MMV688844, identified from the Pathogen Box screen, may be a promising candidate in the M. abscessus drug discovery pipeline.

PMID:
29698397
PMCID:
PMC5919404
DOI:
10.1371/journal.pone.0195595
[Indexed for MEDLINE]
Free PMC Article

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