Ohmyungsamycins promote antimicrobial responses through autophagy activation via AMP-activated protein kinase pathway

Abstract The induction of host cell autophagy by various autophagy inducers contributes to the antimicrobial host defense against Mycobacterium tuberculosis (Mtb), a major pathogenic strain that causes human tuberculosis. In this study, we present a role for the newly identified cyclic peptides ohmy...

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Autores principales:	Tae Sung Kim, Yern-Hyerk Shin, Hye-Mi Lee, Jin Kyung Kim, Jin Ho Choe, Ji-Chan Jang, Soohyun Um, Hyo Sun Jin, Masaaki Komatsu, Guang-Ho Cha, Han-Jung Chae, Dong-Chan Oh, Eun-Kyeong Jo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/489e6c76f44f483d8f3a9b645195aedf
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spelling	oai:doaj.org-article:489e6c76f44f483d8f3a9b645195aedf2021-12-02T16:07:46ZOhmyungsamycins promote antimicrobial responses through autophagy activation via AMP-activated protein kinase pathway10.1038/s41598-017-03477-32045-2322https://doaj.org/article/489e6c76f44f483d8f3a9b645195aedf2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03477-3https://doaj.org/toc/2045-2322Abstract The induction of host cell autophagy by various autophagy inducers contributes to the antimicrobial host defense against Mycobacterium tuberculosis (Mtb), a major pathogenic strain that causes human tuberculosis. In this study, we present a role for the newly identified cyclic peptides ohmyungsamycins (OMS) A and B in the antimicrobial responses against Mtb infections by activating autophagy in murine bone marrow-derived macrophages (BMDMs). OMS robustly activated autophagy, which was essentially required for the colocalization of LC3 autophagosomes with bacterial phagosomes and antimicrobial responses against Mtb in BMDMs. Using a Drosophila melanogaster–Mycobacterium marinum infection model, we showed that OMS-A-induced autophagy contributed to the increased survival of infected flies and the limitation of bacterial load. We further showed that OMS triggered AMP-activated protein kinase (AMPK) activation, which was required for OMS-mediated phagosome maturation and antimicrobial responses against Mtb. Moreover, treating BMDMs with OMS led to dose-dependent inhibition of macrophage inflammatory responses, which was also dependent on AMPK activation. Collectively, these data show that OMS is a promising candidate for new anti-mycobacterial therapeutics by activating antibacterial autophagy via AMPK-dependent signaling and suppressing excessive inflammation during Mtb infections.Tae Sung KimYern-Hyerk ShinHye-Mi LeeJin Kyung KimJin Ho ChoeJi-Chan JangSoohyun UmHyo Sun JinMasaaki KomatsuGuang-Ho ChaHan-Jung ChaeDong-Chan OhEun-Kyeong JoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tae Sung Kim Yern-Hyerk Shin Hye-Mi Lee Jin Kyung Kim Jin Ho Choe Ji-Chan Jang Soohyun Um Hyo Sun Jin Masaaki Komatsu Guang-Ho Cha Han-Jung Chae Dong-Chan Oh Eun-Kyeong Jo Ohmyungsamycins promote antimicrobial responses through autophagy activation via AMP-activated protein kinase pathway
description	Abstract The induction of host cell autophagy by various autophagy inducers contributes to the antimicrobial host defense against Mycobacterium tuberculosis (Mtb), a major pathogenic strain that causes human tuberculosis. In this study, we present a role for the newly identified cyclic peptides ohmyungsamycins (OMS) A and B in the antimicrobial responses against Mtb infections by activating autophagy in murine bone marrow-derived macrophages (BMDMs). OMS robustly activated autophagy, which was essentially required for the colocalization of LC3 autophagosomes with bacterial phagosomes and antimicrobial responses against Mtb in BMDMs. Using a Drosophila melanogaster–Mycobacterium marinum infection model, we showed that OMS-A-induced autophagy contributed to the increased survival of infected flies and the limitation of bacterial load. We further showed that OMS triggered AMP-activated protein kinase (AMPK) activation, which was required for OMS-mediated phagosome maturation and antimicrobial responses against Mtb. Moreover, treating BMDMs with OMS led to dose-dependent inhibition of macrophage inflammatory responses, which was also dependent on AMPK activation. Collectively, these data show that OMS is a promising candidate for new anti-mycobacterial therapeutics by activating antibacterial autophagy via AMPK-dependent signaling and suppressing excessive inflammation during Mtb infections.
format	article
author	Tae Sung Kim Yern-Hyerk Shin Hye-Mi Lee Jin Kyung Kim Jin Ho Choe Ji-Chan Jang Soohyun Um Hyo Sun Jin Masaaki Komatsu Guang-Ho Cha Han-Jung Chae Dong-Chan Oh Eun-Kyeong Jo
author_facet	Tae Sung Kim Yern-Hyerk Shin Hye-Mi Lee Jin Kyung Kim Jin Ho Choe Ji-Chan Jang Soohyun Um Hyo Sun Jin Masaaki Komatsu Guang-Ho Cha Han-Jung Chae Dong-Chan Oh Eun-Kyeong Jo
author_sort	Tae Sung Kim
title	Ohmyungsamycins promote antimicrobial responses through autophagy activation via AMP-activated protein kinase pathway
title_short	Ohmyungsamycins promote antimicrobial responses through autophagy activation via AMP-activated protein kinase pathway
title_full	Ohmyungsamycins promote antimicrobial responses through autophagy activation via AMP-activated protein kinase pathway
title_fullStr	Ohmyungsamycins promote antimicrobial responses through autophagy activation via AMP-activated protein kinase pathway
title_full_unstemmed	Ohmyungsamycins promote antimicrobial responses through autophagy activation via AMP-activated protein kinase pathway
title_sort	ohmyungsamycins promote antimicrobial responses through autophagy activation via amp-activated protein kinase pathway
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/489e6c76f44f483d8f3a9b645195aedf
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Ohmyungsamycins promote antimicrobial responses through autophagy activation via AMP-activated protein kinase pathway

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