PUBLICATION
Thiostrepton: A Novel Therapeutic Drug Candidate for Mycobacterium abscessus Infection
- Authors
- 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.
- ID
- ZDB-PUB-191215-1
- Date
- 2019
- Source
- Molecules 24(24): (Journal)
- Registered Authors
- Keywords
- Mycobacterium abscessus, drug resistance, non-tuberculous mycobacteria, thiostrepton, zebrafish bacterial infection
- MeSH Terms
-
- Animals
- Anti-Bacterial Agents/chemistry
- Anti-Bacterial Agents/pharmacology*
- Anti-Bacterial Agents/therapeutic use
- Cell Line
- Cytokines/biosynthesis
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Humans
- Inflammation Mediators/metabolism
- Macrophages/drug effects
- Macrophages/immunology
- Macrophages/metabolism
- Microbial Sensitivity Tests
- Molecular Structure
- Mycobacterium Infections, Nontuberculous/drug therapy
- Mycobacterium Infections, Nontuberculous/metabolism
- Mycobacterium Infections, Nontuberculous/microbiology*
- Mycobacterium abscessus/classification
- Mycobacterium abscessus/drug effects*
- Mycobacterium abscessus/genetics
- Thiostrepton/pharmacology*
- Thiostrepton/therapeutic use
- Zebrafish
- PubMed
- 31835481 Full text @ Molecules
Citation
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. (2019) Thiostrepton: A Novel Therapeutic Drug Candidate for Mycobacterium abscessus Infection. Molecules. 24(24):.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping