Sirtuin 3 is essential for host defense against Mycobacterium abscessus infection through regulation of mitochondrial homeostasis

The global incidence of Mycobacterium 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 th...

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Autores principales:	Young Jae Kim, Sang-Hee Lee, Sang Min Jeon, Prashanta Silwal, Ju-Young Seo, Bui Thi Bich Hanh, June-Woo Park, Jake Whang, Min Joung Lee, Jun Young Heo, Soon Ha Kim, Jin-Man Kim, Gyu Yong Song, Jichan Jang, Eun-Kyeong Jo
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2020
Materias:	mycobacterium abscessus sirtuin 3 mitochondrial reactive oxygen species resveratrol host-directed therapy Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/b98d4c77587d4a2b9f8a6da145888eb7
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spelling	oai:doaj.org-article:b98d4c77587d4a2b9f8a6da145888eb72021-11-17T14:21:59ZSirtuin 3 is essential for host defense against Mycobacterium abscessus infection through regulation of mitochondrial homeostasis2150-55942150-560810.1080/21505594.2020.1809961https://doaj.org/article/b98d4c77587d4a2b9f8a6da145888eb72020-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21505594.2020.1809961https://doaj.org/toc/2150-5594https://doaj.org/toc/2150-5608The global incidence of Mycobacterium 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.Young Jae KimSang-Hee LeeSang Min JeonPrashanta SilwalJu-Young SeoBui Thi Bich HanhJune-Woo ParkJake WhangMin Joung LeeJun Young HeoSoon Ha KimJin-Man KimGyu Yong SongJichan JangEun-Kyeong JoTaylor & Francis Grouparticlemycobacterium abscessussirtuin 3mitochondrial reactive oxygen speciesresveratrolhost-directed therapyInfectious and parasitic diseasesRC109-216ENVirulence, Vol 11, Iss 1, Pp 1225-1239 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	mycobacterium abscessus sirtuin 3 mitochondrial reactive oxygen species resveratrol host-directed therapy Infectious and parasitic diseases RC109-216
spellingShingle	mycobacterium abscessus sirtuin 3 mitochondrial reactive oxygen species resveratrol host-directed therapy Infectious and parasitic diseases RC109-216 Young Jae Kim Sang-Hee Lee Sang Min Jeon Prashanta Silwal Ju-Young Seo Bui Thi Bich Hanh June-Woo Park Jake Whang Min Joung Lee Jun Young Heo Soon Ha Kim Jin-Man Kim Gyu Yong Song Jichan Jang Eun-Kyeong Jo Sirtuin 3 is essential for host defense against Mycobacterium abscessus infection through regulation of mitochondrial homeostasis
description	The global incidence of Mycobacterium 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.
format	article
author	Young Jae Kim Sang-Hee Lee Sang Min Jeon Prashanta Silwal Ju-Young Seo Bui Thi Bich Hanh June-Woo Park Jake Whang Min Joung Lee Jun Young Heo Soon Ha Kim Jin-Man Kim Gyu Yong Song Jichan Jang Eun-Kyeong Jo
author_facet	Young Jae Kim Sang-Hee Lee Sang Min Jeon Prashanta Silwal Ju-Young Seo Bui Thi Bich Hanh June-Woo Park Jake Whang Min Joung Lee Jun Young Heo Soon Ha Kim Jin-Man Kim Gyu Yong Song Jichan Jang Eun-Kyeong Jo
author_sort	Young Jae Kim
title	Sirtuin 3 is essential for host defense against Mycobacterium abscessus infection through regulation of mitochondrial homeostasis
title_short	Sirtuin 3 is essential for host defense against Mycobacterium abscessus infection through regulation of mitochondrial homeostasis
title_full	Sirtuin 3 is essential for host defense against Mycobacterium abscessus infection through regulation of mitochondrial homeostasis
title_fullStr	Sirtuin 3 is essential for host defense against Mycobacterium abscessus infection through regulation of mitochondrial homeostasis
title_full_unstemmed	Sirtuin 3 is essential for host defense against Mycobacterium abscessus infection through regulation of mitochondrial homeostasis
title_sort	sirtuin 3 is essential for host defense against mycobacterium abscessus infection through regulation of mitochondrial homeostasis
publisher	Taylor & Francis Group
publishDate	2020
url	https://doaj.org/article/b98d4c77587d4a2b9f8a6da145888eb7
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Sirtuin 3 is essential for host defense against Mycobacterium abscessus infection through regulation of mitochondrial homeostasis

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