PMID- 22275355
OWN - NLM
STAT- MEDLINE
DCOM- 20120619
LR  - 20211203
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 287
IP  - 16
DP  - 2012 Apr 13
TI  - Mycobacterial induction of autophagy varies by species and occurs independently 
      of mammalian target of rapamycin inhibition.
PG  - 12668-78
LID - 10.1074/jbc.M111.320135 [doi]
AB  - The interaction of host cells with mycobacteria is complex and can lead to 
      multiple outcomes ranging from bacterial clearance to latent infection. Although 
      many factors are involved, the mammalian autophagy pathway is recognized as a 
      determinant that can influence the course of infection. Intervention aimed at 
      utilizing autophagy to clear infection requires an examination of the autophagy 
      and signal transduction induced by mycobacteria under native conditions. With 
      both pathogenic and non-pathogenic mycobacteria, we show that infection 
      correlates with an increase in the mammalian target of rapamycin (mTOR) activity 
      indicating that autophagy induction by mycobacteria occurs in an mTOR-independent 
      manner. Analysis of Mycobacterium smegmatis and Mycobacterium bovis bacille 
      Calmette-Guerin (BCG), which respectively induce high and low autophagy 
      responses, indicates that lipid material is capable of inducing both autophagy 
      and mTOR signaling. Although mycobacterial infection potently induces mTOR 
      activity, we confirm that bacterial viability can be reduced by rapamycin 
      treatment. In addition, our work demonstrates that BCG can reduce autophagy 
      responses to M. smegmatis suggesting that specific mechanisms are used by BCG to 
      minimize host cell autophagy. We conclude that autophagy induction and mTOR 
      signaling take place concurrently during mycobacterial infection and that host 
      autophagy responses to any given mycobacterium stem from multiple factors, 
      including the presence of activating macromolecules and inhibitory mechanisms.
FAU - Zullo, Alfred J
AU  - Zullo AJ
AD  - Human Vaccine Institute and Department of Medicine, Duke University, Medical 
      Center, Durham, North Carolina 27710, USA.
FAU - Lee, Sunhee
AU  - Lee S
LA  - eng
GR  - R21 AI095723/AI/NIAID NIH HHS/United States
GR  - UC6 AI058607/AI/NIAID NIH HHS/United States
GR  - R21 AI095723-02/AI/NIAID NIH HHS/United States
GR  - R21 AI095723-01/AI/NIAID NIH HHS/United States
GR  - U54 AI057157/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120124
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Autophagy/*physiology
MH  - Cell Line
MH  - Female
MH  - Lipid Metabolism/physiology
MH  - Macrophages/immunology/*microbiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mycobacterium/growth & development/*metabolism
MH  - Mycobacterium Infections/immunology/metabolism/*microbiology
MH  - Mycobacterium bovis/growth & development/metabolism
MH  - Mycobacterium fortuitum/growth & development/metabolism
MH  - Mycobacterium smegmatis/growth & development/metabolism
MH  - Mycobacterium tuberculosis/growth & development/metabolism
MH  - Phagocytosis/immunology
MH  - Species Specificity
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC3339952
EDAT- 2012/01/26 06:00
MHDA- 2012/06/20 06:00
PMCR- 2013/04/13
CRDT- 2012/01/26 06:00
PHST- 2012/01/26 06:00 [entrez]
PHST- 2012/01/26 06:00 [pubmed]
PHST- 2012/06/20 06:00 [medline]
PHST- 2013/04/13 00:00 [pmc-release]
AID - S0021-9258(20)53008-1 [pii]
AID - M111.320135 [pii]
AID - 10.1074/jbc.M111.320135 [doi]
PST - ppublish
SO  - J Biol Chem. 2012 Apr 13;287(16):12668-78. doi: 10.1074/jbc.M111.320135. Epub 
      2012 Jan 24.