PMID- 27317487
OWN - NLM
STAT- MEDLINE
DCOM- 20170619
LR  - 20211204
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 477
IP  - 2
DP  - 2016 Aug 19
TI  - ESAT6 inhibits autophagy flux and promotes BCG proliferation through MTOR.
PG  - 195-201
LID - S0006-291X(16)30960-3 [pii]
LID - 10.1016/j.bbrc.2016.06.042 [doi]
AB  - In recent years, increasing studies have found that pathogenic Mycobacterium 
      tuberculosis (Mtb) inhibits autophagy, which mediates the anti-mycobacterial 
      response, but the mechanism is not clear. We previously reported that secretory 
      acid phosphatase (SapM) of Mtb can negatively regulate autophagy flux. Recently, 
      another virulence factor of Mtb, early secretory antigenic target 6 (ESAT6), has 
      been found to be involved in inhibiting autophagy, but the mechanism remains 
      unclear. In this study, we show that ESAT6 hampers autophagy flux to boost 
      bacillus Calmette-Guerin (BCG) proliferation and reveals a mechanism by which 
      ESAT6 blocks autophagosome-lysosome fusion in a mammalian target of rapamycin 
      (MTOR)-dependent manner. In both Raw264.7 cells and primary macrophages derived 
      from the murine abdominal cavity (ACM), ESAT6 repressed autophagy flux by 
      interfering with the autophagosome-lysosome fusion, which resulted in an 
      increased load of BCG. Impaired degradation of LC3Ⅱ and SQSTM1 by ESAT6 was 
      related to the upregulated activity of MTOR. Contrarily, inhibiting MTOR with 
      Torin1 removed the ESAT6-induced autophagy block and lysosome dysfunction. 
      Furthermore, in both Raw264.7 and ACM cells, MTOR inhibition significantly 
      suppressed the survival of BCG. In conclusion, our study highlights how ESAT6 
      blocks autophagy and promotes BCG survival in a way that activates MTOR.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Dong, Hu
AU  - Dong H
AD  - Department of Medical Immunology, Medical School, Anhui University of Science and 
      Technology, China; Medical Inspection Center, Anhui University of Science and 
      Technology, Huainan, China. Electronic address: austhudong@126.com.
FAU - Jing, Wu
AU  - Jing W
AD  - Department of Medical Immunology, Medical School, Anhui University of Science and 
      Technology, China; Medical Inspection Center, Anhui University of Science and 
      Technology, Huainan, China. Electronic address: wujing8008@126.com.
FAU - Runpeng, Zhao
AU  - Runpeng Z
AD  - Department of Medical Immunology, Medical School, Anhui University of Science and 
      Technology, China.
FAU - Xuewei, Xu
AU  - Xuewei X
AD  - Department of Medical Immunology, Medical School, Anhui University of Science and 
      Technology, China.
FAU - Min, Mu
AU  - Min M
AD  - Department of Medical Immunology, Medical School, Anhui University of Science and 
      Technology, China.
FAU - Ru, Cai
AU  - Ru C
AD  - Department of Medical Immunology, Medical School, Anhui University of Science and 
      Technology, China.
FAU - Yingru, Xing
AU  - Yingru X
AD  - Affiliated Cancer Hospital, Anhui University of Science and Technology, China.
FAU - Shengfa, Ni
AU  - Shengfa N
AD  - Affiliated Cancer Hospital, Anhui University of Science and Technology, China.
FAU - Rongbo, Zhang
AU  - Rongbo Z
AD  - Department of Medical Immunology, Medical School, Anhui University of Science and 
      Technology, China; Medical Inspection Center, Anhui University of Science and 
      Technology, Huainan, China.
LA  - eng
PT  - Journal Article
DEP - 20160615
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Bacterial Proteins)
RN  - 0 (ESAT-6 protein, Mycobacterium tuberculosis)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Antigens, Bacterial/*metabolism
MH  - Autophagy
MH  - Bacterial Load/physiology
MH  - Bacterial Proteins/*metabolism
MH  - Cell Proliferation/physiology
MH  - Cell Survival/*physiology
MH  - Cells, Cultured
MH  - Macrophages/cytology/*microbiology/*physiology
MH  - Mice
MH  - Mycobacterium bovis/*physiology
MH  - RAW 264.7 Cells
MH  - TOR Serine-Threonine Kinases/*metabolism
OTO - NOTNLM
OT  - Autophagy
OT  - Early secretory antigenic target 6
OT  - Lysosome
OT  - Macrophage
OT  - Mammalian target of rapamycin
OT  - Mycobacterium tuberculosis
EDAT- 2016/06/19 06:00
MHDA- 2017/06/20 06:00
CRDT- 2016/06/19 06:00
PHST- 2016/06/03 00:00 [received]
PHST- 2016/06/09 00:00 [accepted]
PHST- 2016/06/19 06:00 [entrez]
PHST- 2016/06/19 06:00 [pubmed]
PHST- 2017/06/20 06:00 [medline]
AID - S0006-291X(16)30960-3 [pii]
AID - 10.1016/j.bbrc.2016.06.042 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2016 Aug 19;477(2):195-201. doi: 
      10.1016/j.bbrc.2016.06.042. Epub 2016 Jun 15.