PUBLICATION
A Screening of the MMV Pandemic Response Box Reveals Epetraborole as a New Potent Inhibitor against Mycobacterium abscessus
- Authors
- Kim, T., Hanh, B.T., Heo, B., Quang, N., Park, Y., Shin, J., Jeon, S., Park, J.W., Samby, K., Jang, J.
- ID
- ZDB-PUB-210603-37
- Date
- 2021
- Source
- International Journal of Molecular Sciences 22(11): (Journal)
- Registered Authors
- Keywords
- Mycobacterium abscessus, antibiotics, benzoxaboroles, drug discovery, epetraborole
- MeSH Terms
-
- Animals
- Anti-Bacterial Agents/pharmacology*
- Boron Compounds/pharmacology*
- Drug Evaluation, Preclinical
- Drug Repositioning
- Mycobacterium Infections, Nontuberculous/drug therapy*
- Mycobacterium abscessus/drug effects*
- Zebrafish
- PubMed
- 34073006 Full text @ Int. J. Mol. Sci.
Citation
Kim, T., Hanh, B.T., Heo, B., Quang, N., Park, Y., Shin, J., Jeon, S., Park, J.W., Samby, K., Jang, J. (2021) A Screening of the MMV Pandemic Response Box Reveals Epetraborole as a New Potent Inhibitor against Mycobacterium abscessus. International Journal of Molecular Sciences. 22(11):.
Abstract
Mycobacterium abscessus is the one of the most feared bacterial respiratory pathogens in the world. Unfortunately, there are many problems with the current M. abscessus therapies available. These problems include misdiagnoses, high drug resistance, poor long-term treatment outcomes, and high costs. Until now, there have only been a few new compounds or drug formulations which are active against M. abscessus, and these are present in preclinical and clinical development only. With that in mind, new and more powerful anti-M. abscessus medicines need to be discovered and developed. In this study, we conducted an in vitro-dual screen against M. abscessus rough (R) and smooth (S) variants using a Pandemic Response Box and identified epetraborole as a new effective candidate for M. abscessus therapy. For further validation, epetraborole showed significant activity against the growth of the M. abscessus wild-type strain, three subspecies, drug-resistant strains and clinical isolates in vitro, while also inhibiting the growth of M. abscessus that reside in macrophages without cytotoxicity. Furthermore, the in vivo efficacy of epetraborole in the zebrafish infection model was greater than that of tigecycline. Thus, we concluded that epetraborole is a potential anti-M. abscessus candidate in the M. abscessus drug search.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping