Sirtuin 3 is essential for host defense againstMycobacterium abscessusinfection through regulation of mitochondrial homeostasisopen access
- Kim, Young Jae; Lee, Sang-Hee; Jeon, Sang Min; Silwal, Prashanta; Seo, Ju-Young; Hanh, Bui Thi Bich; Park, June-Woo; Whang, Jake; Lee, Min Joung; Heo, Jun Young; Kim, Soon Ha; Kim, Jin-Man; Song, Gyu Yong; Jang, Jichan; Jo, Eun-Kyeong
- Issue Date
- TAYLOR & FRANCIS INC
- Mycobacterium abscessus; sirtuin 3; mitochondrial reactive oxygen species; resveratrol; host-directed therapy
- VIRULENCE, v.11, no.1, pp.1225 - 1239
- Journal Title
- Start Page
- End Page
- The global incidence ofMycobacterium abscessus(Mabc), a rapidly growing nontuberculous mycobacterial strain that causes treatment-refractory pulmonary diseases, is increasing. Despite this, the host factors that allow for protection against infection are largely unknown. In this study, we found that sirtuin 3 (SIRT3), a mitochondrial protein deacetylase, plays a critical role in host defense against Mabc infection. Mabc decreased SIRT3 and upregulated mitochondrial oxidative stress in macrophages. SIRT3 deficiency led to increased bacterial loads, histopathological, and mitochondrial damage, and pathological inflammation during Mabc infection. Administration of scavengers of mitochondrial reactive oxygen species significantly decreased the in vivo Mabc burden and excessive inflammation, and induced SIRT3 expression in infected lungs. Notably, SIRT3 agonist (resveratrol) significantly decreased Mabc growth and attenuated inflammation in mice and zebrafishes, indicating the key role for SIRT3 in metazoan host defense. Collectively, these data strongly suggest that SIRT3 is a host-directed therapeutic target against Mabc infection by controlling mitochondrial homeostasis.
- Files in This Item
- There are no files associated with this item.
- Appears in
- 자연과학대학 > Division of Life Sciences > Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.