Ohmyungsamycins promote antimicrobial responses through autophagy activation via AMP-activated protein kinase pathway
| Autor: | Soohyun Um, Eun-Kyeong Jo, Masaaki Komatsu, Yern-Hyerk Shin, Jin Kyung Kim, Tae Sung Kim, Dong-Chan Oh, Hye-Mi Lee, Jichan Jang, Guang-Ho Cha, Han-Jung Chae, Hyo Sun Jin, Jin Ho Choe |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Science Peptides Cyclic Article Microbiology 03 medical and health sciences Mice 0302 clinical medicine AMP-activated protein kinase AMP-Activated Protein Kinase Kinases Phagosome maturation Autophagy Macrophage Animals Humans Protein kinase A Cells Cultured Phagosome Mycobacterium Infections Multidisciplinary biology Macrophages AMPK Mycobacterium tuberculosis Antimicrobial Streptomyces Anti-Bacterial Agents Mice Inbred C57BL 030104 developmental biology biology.protein Medicine Protein Kinases 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports Scientific Reports, Vol 7, Iss 1, Pp 1-14 (2017) SCIENTIFIC REPORTS(7) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|