PMID- 28611371
OWN - NLM
STAT- MEDLINE
DCOM- 20190107
LR  - 20211204
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Jun 13
TI  - Ohmyungsamycins promote antimicrobial responses through autophagy activation via 
      AMP-activated protein kinase pathway.
PG  - 3431
LID - 10.1038/s41598-017-03477-3 [doi]
LID - 3431
AB  - 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.
FAU - Kim, Tae Sung
AU  - Kim TS
AD  - Department of Microbiology, Chungnam National University School of Medicine, 
      Daejeon, 35015, South Korea.
AD  - Department of Medical Science, Chungnam National University School of Medicine, 
      Daejeon, 35015, South Korea.
FAU - Shin, Yern-Hyerk
AU  - Shin YH
AD  - Natural Products Research Institute, College of Pharmacy, Seoul National 
      University, Seoul, 08826, South Korea.
FAU - Lee, Hye-Mi
AU  - Lee HM
AD  - Department of Microbiology, Chungnam National University School of Medicine, 
      Daejeon, 35015, South Korea.
FAU - Kim, Jin Kyung
AU  - Kim JK
AD  - Department of Microbiology, Chungnam National University School of Medicine, 
      Daejeon, 35015, South Korea.
AD  - Department of Medical Science, Chungnam National University School of Medicine, 
      Daejeon, 35015, South Korea.
FAU - Choe, Jin Ho
AU  - Choe JH
AD  - Department of Microbiology, Chungnam National University School of Medicine, 
      Daejeon, 35015, South Korea.
AD  - Department of Medical Science, Chungnam National University School of Medicine, 
      Daejeon, 35015, South Korea.
FAU - Jang, Ji-Chan
AU  - Jang JC
AD  - Molecular Mechanism of Antibiotics, Division of Life Science, Research Institute 
      of Life Science, Gyeongsang National University, Jinju, 52828, South Korea.
FAU - Um, Soohyun
AU  - Um S
AD  - Natural Products Research Institute, College of Pharmacy, Seoul National 
      University, Seoul, 08826, South Korea.
FAU - Jin, Hyo Sun
AU  - Jin HS
AD  - Department of Microbiology, Chungnam National University School of Medicine, 
      Daejeon, 35015, South Korea.
FAU - Komatsu, Masaaki
AU  - Komatsu M
AD  - Department of Biochemistry, Niigata University Graduate School of Medical and 
      Dental Sciences, Niigata, 9518510, Japan.
FAU - Cha, Guang-Ho
AU  - Cha GH
AD  - Department of Infection Biology, Chungnam National University School of Medicine, 
      Daejeon, 35015, South Korea.
FAU - Chae, Han-Jung
AU  - Chae HJ
AD  - Department of Pharmacology, Chonbuk National University Medical School, Jeonju, 
      54907, South Korea.
FAU - Oh, Dong-Chan
AU  - Oh DC
AD  - Natural Products Research Institute, College of Pharmacy, Seoul National 
      University, Seoul, 08826, South Korea. dongchanoh@snu.ac.kr.
FAU - Jo, Eun-Kyeong
AU  - Jo EK
AD  - Department of Microbiology, Chungnam National University School of Medicine, 
      Daejeon, 35015, South Korea. hayoungj@cnu.ac.kr.
AD  - Department of Medical Science, Chungnam National University School of Medicine, 
      Daejeon, 35015, South Korea. hayoungj@cnu.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170613
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Peptides, Cyclic)
RN  - 0 (ohmyungsamycin A)
RN  - 0 (ohmyungsamycin B)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.3 (AMP-Activated Protein Kinase Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinase Kinases
MH  - Animals
MH  - Anti-Bacterial Agents/*pharmacology/therapeutic use
MH  - *Autophagy
MH  - Cells, Cultured
MH  - Humans
MH  - Macrophages/drug effects/metabolism/microbiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mycobacterium Infections/*drug therapy
MH  - Mycobacterium tuberculosis/drug effects/pathogenicity
MH  - Peptides, Cyclic/*pharmacology/therapeutic use
MH  - Protein Kinases/*metabolism
MH  - Streptomyces/drug effects/pathogenicity
PMC - PMC5469788
COIS- The authors declare that they have no competing interests.
EDAT- 2017/06/15 06:00
MHDA- 2019/01/08 06:00
PMCR- 2017/06/13
CRDT- 2017/06/15 06:00
PHST- 2016/11/10 00:00 [received]
PHST- 2017/04/28 00:00 [accepted]
PHST- 2017/06/15 06:00 [entrez]
PHST- 2017/06/15 06:00 [pubmed]
PHST- 2019/01/08 06:00 [medline]
PHST- 2017/06/13 00:00 [pmc-release]
AID - 10.1038/s41598-017-03477-3 [pii]
AID - 3477 [pii]
AID - 10.1038/s41598-017-03477-3 [doi]
PST - epublish
SO  - Sci Rep. 2017 Jun 13;7(1):3431. doi: 10.1038/s41598-017-03477-3.