Ohmyungsamycin promotes M1-like inflammatory responses to enhance host defence against Mycobacteroides abscessus infections

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...

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Published inVirulence Vol. 13; no. 1; pp. 1966 - 1984
Main Authors Jeon, Sang Min, Kim, Young Jae, Nguyen, Thanh Quang, Cui, Jinsheng, Thi Bich Hanh, Bui, Silwal, Prashanta, Kim, Jin Kyung, Kim, Jin-Man, Oh, Dong-Chan, Jang, Jichan, Jo, Eun-Kyeong
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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.
AbstractList 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.
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.
Ohmyungsamycin A (OMS) is a newly identified cyclic peptide that exerts antimicrobial effects against . However, its role in nontuberculous mycobacteria (NTMs) infections has not been clarified. (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 murine macrophages, and in zebrafish models . 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.
Author Cui, Jinsheng
Silwal, Prashanta
Kim, Jin Kyung
Jeon, Sang Min
Jo, Eun-Kyeong
Nguyen, Thanh Quang
Jang, Jichan
Kim, Young Jae
Kim, Jin-Man
Thi Bich Hanh, Bui
Oh, Dong-Chan
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  email: hayoungj@cnu.ac.kr
  organization: Chungnam National University School of Medicine
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Issue 1
Keywords nitric oxide
M1 macrophage responses
innate immunity
mitochondrial reactive oxygen species
Mycobacteroides abscessus
Ohmyungsamycins
Language English
License open-access: http://creativecommons.org/licenses/by/4.0/: http://creativecommons.org/licenses/by/4.0/: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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These authors contributed equally to this work
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Snippet Ohmyungsamycin A (OMS) is a newly identified cyclic peptide that exerts antimicrobial effects against Mycobacterium tuberculosis. However, its role in...
Ohmyungsamycin A (OMS) is a newly identified cyclic peptide that exerts antimicrobial effects against . However, its role in nontuberculous mycobacteria (NTMs)...
Ohmyungsamycin A (OMS) is a newly identified cyclic peptide that exerts antimicrobial effects against Mycobacterium tuberculosis . However, its role in...
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StartPage 1966
SubjectTerms Animals
Anti-Bacterial Agents - metabolism
Anti-Bacterial Agents - pharmacology
Anti-Bacterial Agents - therapeutic use
Humans
innate immunity
M1 macrophage responses
Macrophages - microbiology
Mice
mitochondrial reactive oxygen species
Mycobacterium abscessus
Mycobacterium Infections, Nontuberculous - metabolism
Mycobacteroides abscessus
nitric oxide
Ohmyungsamycins
Research Paper
Zebrafish
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Title Ohmyungsamycin promotes M1-like inflammatory responses to enhance host defence against Mycobacteroides abscessus infections
URI https://www.tandfonline.com/doi/abs/10.1080/21505594.2022.2138009
https://www.ncbi.nlm.nih.gov/pubmed/36271707
https://search.proquest.com/docview/2727644230
https://pubmed.ncbi.nlm.nih.gov/PMC9673965
https://doaj.org/article/83fd15d7698b4db2bdde503b572abb40
Volume 13
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