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Open AccessFeature PaperArticle

Thiostrepton: A Novel Therapeutic Drug Candidate for Mycobacterium abscessus Infection

1
Molecular Mechanisms of Antibiotics, Division of Life Science, Research Institute of Life Science, Gyeongsang National University, Jinju 52828, Korea
2
Division of Applied Life Science (BK21plus Program), Gyeongsang National University, Jinju 52828, Korea
3
Clinical Research Centre, Masan National Tuberculosis Hospital, Changwon 51755, Korea
4
Future Environmental Research Center, Korea Institute of Toxicology, Jinju 52834, Korea
5
Human and Environmental Toxicology Program, Korea University of Science and Technology (UST), Daejeon 34113, Korea
6
Department of Microbiology, College of Medicine, Chungnam National University, Daejeon 35015, Korea
7
Infection Control Convergence Research Center, Chungnam National University, Daejeon 35015, Korea
8
Department of Bionano Technology, Hanyang University, Seoul 04763, Korea
9
Department of Radiopharmaceutical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Korea
*
Author to whom correspondence should be addressed.
The authors contributed equally to this work.
Academic Editor: Seung Seo Lee
Molecules 2019, 24(24), 4511; https://doi.org/10.3390/molecules24244511
Received: 9 September 2019 / Revised: 6 December 2019 / Accepted: 6 December 2019 / Published: 10 December 2019
(This article belongs to the Special Issue Chemical Biology of Antimicrobial Resistance)
Mycobacterium abscessus is a rapid-growing, multidrug-resistant, non-tuberculous mycobacterial species responsible for a variety of human infections, such as cutaneous and pulmonary infections. M. abscessus infections are very difficult to eradicate due to the natural and acquired multidrug resistance profiles of M. abscessus. Thus, there is an urgent need for the development of effective drugs or regimens against M. abscessus infections. Here, we report the activity of a US Food and Drug Administration approved drug, thiostrepton, against M. abscessus. We found that thiostrepton significantly inhibited the growth of M. abscessus wild-type strains, subspecies, clinical isolates, and drug-resistant mutants in vitro and in macrophages. In addition, treatment of macrophages with thiostrepton significantly decreased proinflammatory cytokine production in a dose-dependent manner, suggesting an inhibitory effect of thiostrepton on inflammation induced during M. abscessus infection. We further showed that thiostrepton exhibits antimicrobial effects in vivo using a zebrafish model of M. abscessus infection. View Full-Text
Keywords: thiostrepton; Mycobacterium abscessus; zebrafish bacterial infection; drug resistance; non-tuberculous mycobacteria thiostrepton; Mycobacterium abscessus; zebrafish bacterial infection; drug resistance; non-tuberculous mycobacteria
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Kim, T.H.; Hanh, B.T.B.; Kim, G.; Lee, D.-G.; Park, J.-W.; Lee, S.E.; Kim, J.-S.; Kim, B.S.; Ryoo, S.; Jo, E.-K.; Jang, J. Thiostrepton: A Novel Therapeutic Drug Candidate for Mycobacterium abscessus Infection. Molecules 2019, 24, 4511.

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