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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 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.

SUBMITTER: Kim TS 

PROVIDER: S-EPMC5469788 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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

Kim Tae Sung TS   Shin Yern-Hyerk YH   Lee Hye-Mi HM   Kim Jin Kyung JK   Choe Jin Ho JH   Jang Ji-Chan JC   Um Soohyun S   Jin Hyo Sun HS   Komatsu Masaaki M   Cha Guang-Ho GH   Chae Han-Jung HJ   Oh Dong-Chan DC   Jo Eun-Kyeong EK  

Scientific reports 20170613 1


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 essentiall  ...[more]

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