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

Autor: Sang Min Jeon, Young Jae Kim, Thanh Quang Nguyen, Jinsheng Cui, Bui Thi Bich Hanh, Prashanta Silwal, Jin Kyung Kim, Jin-Man Kim, Dong-Chan Oh, Jichan Jang, Eun-Kyeong Jo
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Virulence, Vol 13, Iss 1, Pp 1966-1984 (2022)
Druh dokumentu: article
ISSN: 21505594
2150-5608
2150-5594
DOI: 10.1080/21505594.2022.2138009
Popis: 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.
Databáze: Directory of Open Access Journals
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