PUBLICATION
Ohmyungsamycin Promotes M1-like Inflammatory Responses to Enhance Host Defense against Mycobacteroides abscessus Infections
- Authors
- Jeon, S.M., Kim, Y.J., Nguyen, T.Q., Cui, J., Thi Bich Hanh, B., Silwal, P., Kim, J.K., Kim, J.M., Oh, D.C., Jang, J., Jo, E.K.
- ID
- ZDB-PUB-221023-4
- Date
- 2022
- Source
- Virulence 13(1): 1966-1984 (Journal)
- Registered Authors
- Keywords
- Innate immunity, M1 macrophage responses, Mitochondrial reactive oxygen species, Mycobacteroides abscessus, Nitric oxide, Ohmyungsamycins
- MeSH Terms
-
- Animals
- Anti-Bacterial Agents/metabolism
- Anti-Bacterial Agents/pharmacology
- Anti-Bacterial Agents/therapeutic use
- Humans
- Macrophages/microbiology
- Mice
- Mycobacterium Infections, Nontuberculous*/metabolism
- Mycobacterium abscessus*
- Zebrafish
- PubMed
- 36271707 Full text @ Virulence
Citation
Jeon, S.M., Kim, Y.J., Nguyen, T.Q., Cui, J., Thi Bich Hanh, B., Silwal, P., Kim, J.K., Kim, J.M., Oh, D.C., Jang, J., Jo, E.K. (2022) Ohmyungsamycin Promotes M1-like Inflammatory Responses to Enhance Host Defense against Mycobacteroides abscessus Infections. Virulence. 13(1):1966-1984.
Abstract
Ohmyungsamycin A (OMS) is a newly identified cyclic peptide that exerts antimicrobial effects against Mycobacterium tuberculosis. However, its role in nontuberculous mycobacteria (NTMs) infections has not been clarified. Mycobacteroides abscessus (Mabc) is a rapidly growing NTM that has emerged as a human pathogen in both immunocompetent and immunosuppressed individuals. In this study, we demonstrated that OMS had significant antimicrobial effects against Mabc infection in both immunocompetent and immunodeficient mice, and in macrophages. OMS treatment amplified Mabc-induced expression of M1-related proinflammatory cytokines and inducible nitric oxide synthase, and significantly downregulated arginase-1 expression in murine macrophages. In addition, OMS augmented Mabc-mediated production of mitochondrial reactive oxygen species (mtROS), which promoted M1-like proinflammatory responses in Mabc-infected macrophages. OMS-induced production of mtROS and nitric oxide was critical for OMS-mediated antimicrobial responses during Mabc infections. Notably, the combination of OMS and rifabutin had a synergistic effect on the antimicrobial responses against Mabc infections in vitro, in murine macrophages, and in zebrafish models in vivo. Collectively, these data strongly suggest that OMS may be an effective M1-like adjunctive therapeutic against Mabc infections, either alone or in combination with antibiotics.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
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