PMID- 27931684
OWN - NLM
STAT- MEDLINE
DCOM- 20180116
LR  - 20181113
IS  - 2212-554X (Electronic)
IS  - 2212-5531 (Print)
IS  - 2212-5531 (Linking)
VI  - 5
IP  - 4
DP  - 2016 Dec
TI  - Inhibition of apoptosis by Rv2456c through Nuclear factor-kappaB extends the survival 
      of Mycobacterium tuberculosis.
PG  - 426-436
LID - S2212-5531(16)30054-1 [pii]
LID - 10.1016/j.ijmyco.2016.06.018 [doi]
AB  - Mycobacterium tuberculosis, the causative agent of tuberculosis, is an 
      intracellular pathogen with several survival mechanisms aimed at subverting the 
      host immune system. Apoptosis has been shown to be mycobactericidal, to activate 
      CD8(+) T cells, and to be modulated by mycobacterial proteins. Since few 
      mycobacterial proteins have so far been directly implicated in the interactions 
      between M. tuberculosis and host cell apoptosis, we screened M. tuberculosis 
      H37Rv transposon mutants to identify mutants that fail to inhibit cell death 
      (FID). One of these FID mutants, FID19, had a transposon insertion in Rv2456c and 
      is important for survival in host cells. The lack of the protein resulted in 
      enhanced caspase-3 mediated apoptosis, which is probably due to an inability to 
      activate nuclear factor-kappaB. Additionally, FID19 infection enhanced polyfunctional 
      CD8(+) T cells and induced a higher frequency of interferon-gamma secreting immune 
      cells in a murine model. Taken together, our data suggest that Rv2456c is 
      important for the survival of H37Rv by subduing the innate and ultimately 
      adaptive immune responses of its host by preventing apoptosis of the infected 
      cell. Better understanding of the host-mycobacterial interactions may be 
      beneficial to develop novel drug targets and engineer more efficacious vaccine 
      strains against tuberculosis.
CI  - Copyright A(c) 2016 Asian-African Society for Mycobacteriology. Published by 
      Elsevier Ltd. All rights reserved.
FAU - Jurcic Smith, Kristen L
AU  - Jurcic Smith KL
AD  - Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA; 
      Department of Molecular Genetics and Microbiology, Duke University School of 
      Medicine, Durham, NC, USA.
FAU - Lee, Sunhee
AU  - Lee S
AD  - Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA; 
      Department of Molecular Genetics and Microbiology, Duke University School of 
      Medicine, Durham, NC, USA; Department of Pathology, Duke University School of 
      Medicine, Durham, NC, USA. Electronic address: Sunhee.lee@duke.edu.
LA  - eng
GR  - R21 AI090434/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20160721
PL  - India
TA  - Int J Mycobacteriol
JT  - International journal of mycobacteriology
JID - 101615660
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Bacterial Proteins)
RN  - 0 (DNA Transposable Elements)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Apoptosis Regulatory Proteins/*metabolism
MH  - Bacterial Proteins/*metabolism
MH  - Cell Line
MH  - DNA Transposable Elements
MH  - Disease Models, Animal
MH  - *Host-Pathogen Interactions
MH  - Humans
MH  - *Immunity, Innate
MH  - Mice, Inbred C57BL
MH  - *Microbial Viability
MH  - Mutagenesis, Insertional
MH  - Mycobacterium tuberculosis/immunology/*physiology
MH  - Tuberculosis/microbiology/pathology
PMC - PMC5975360
MID - NIHMS966558
OTO - NOTNLM
OT  - Apoptosis
OT  - Mycobacterium tuberculosis
OT  - Tuberculosis
OT  - Vaccine
COIS- Conflicts of interest The authors declare that the research was conducted in the 
      absence of any commercial or financial relationships that could be constructed as 
      a potential conflict of interest.
EDAT- 2016/12/10 06:00
MHDA- 2018/01/18 06:00
PMCR- 2018/05/30
CRDT- 2016/12/10 06:00
PHST- 2016/06/28 00:00 [received]
PHST- 2016/06/30 00:00 [accepted]
PHST- 2016/12/10 06:00 [entrez]
PHST- 2016/12/10 06:00 [pubmed]
PHST- 2018/01/18 06:00 [medline]
PHST- 2018/05/30 00:00 [pmc-release]
AID - S2212-5531(16)30054-1 [pii]
AID - 10.1016/j.ijmyco.2016.06.018 [doi]
PST - ppublish
SO  - Int J Mycobacteriol. 2016 Dec;5(4):426-436. doi: 10.1016/j.ijmyco.2016.06.018. 
      Epub 2016 Jul 21.