PMID- 28802408
OWN - NLM
STAT- MEDLINE
DCOM- 20180717
LR  - 20231213
IS  - 1873-281X (Electronic)
IS  - 1472-9792 (Linking)
VI  - 106
DP  - 2017 Sep
TI  - Down-regulation of malate synthase in Mycobacterium tuberculosis H37Ra leads to 
      reduced stress tolerance, persistence and survival in macrophages.
PG  - 73-81
LID - S1472-9792(17)30128-2 [pii]
LID - 10.1016/j.tube.2017.07.006 [doi]
AB  - Malate synthase is a condensing enzyme responsible for conversion of glyoxylate 
      to malate in the presence of acetyl-CoA. This reaction helps in bypassing the TCA 
      cycle reactions involving carbon loss and leads to diverting some of the carbon 
      skeletons to gluconeogenic events while rest can continue to provide TCA cycle 
      intermediates. Malate synthase (GlcB) is encoded by MRA_1848 of Mycobacterium 
      tuberculosis H37Ra (Mtb-Ra). We developed a knockdown (KD) Mtb-Ra strain by 
      down-regulating GlcB. The survival studies suggested increased susceptibility to 
      oxidative and nitrosative stress as well as to rifampicin. The susceptibility 
      profile was reversed in the presence of free radical scavengers. Also, KD showed 
      reduced biofilm maturation, failed to enter persistent state, and showed reduced 
      growth inside macrophages. The study of post-endocytosis events showed 
      differences in late stage endosomal maturation behavior in macrophages infected 
      with KD compared to WT. Increased iNOS, LAMP1 and cathepsin D expression was 
      observed in macrophages infected with KD compared to WT.
CI  - Copyright (c) 2017 Elsevier Ltd. All rights reserved.
FAU - Singh, Kumar Sachin
AU  - Singh KS
AD  - Microbiology Division, CSIR-Central Drug Research Institute, B.S. 10/1, Sector 
      10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
FAU - Sharma, Rishabh
AU  - Sharma R
AD  - Microbiology Division, CSIR-Central Drug Research Institute, B.S. 10/1, Sector 
      10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
FAU - Keshari, Deepa
AU  - Keshari D
AD  - Microbiology Division, CSIR-Central Drug Research Institute, B.S. 10/1, Sector 
      10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
FAU - Singh, Nirbhay
AU  - Singh N
AD  - Microbiology Division, CSIR-Central Drug Research Institute, B.S. 10/1, Sector 
      10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
FAU - Singh, Sudheer Kumar
AU  - Singh SK
AD  - Microbiology Division, CSIR-Central Drug Research Institute, B.S. 10/1, Sector 
      10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India; Academy of 
      Scientific and Innovative Research (AcSIR), CSIR-Central Drug Research Institute, 
      B.S. 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India. 
      Electronic address: sudheer.vns@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170718
PL  - Scotland
TA  - Tuberculosis (Edinb)
JT  - Tuberculosis (Edinburgh, Scotland)
JID - 100971555
RN  - 0 (Antitubercular Agents)
RN  - 0 (Bacterial Proteins)
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Lamp1 protein, mouse)
RN  - 0 (Lysosomal Membrane Proteins)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
RN  - EC 2.3.3.9 (Malate Synthase)
RN  - EC 3.4.23.5 (Cathepsin D)
RN  - EC 3.4.23.5 (Ctsd protein, mouse)
SB  - IM
MH  - Animals
MH  - Antitubercular Agents/pharmacology
MH  - Bacterial Proteins/genetics/*metabolism
MH  - Biofilms/growth & development
MH  - Cathepsin D/metabolism
MH  - Cells, Cultured
MH  - Down-Regulation
MH  - Free Radical Scavengers/pharmacology
MH  - Gene Knockdown Techniques
MH  - Genotype
MH  - Host-Pathogen Interactions
MH  - Lysosomal Membrane Proteins/metabolism
MH  - Macrophages/drug effects/metabolism/*microbiology
MH  - Malate Synthase/genetics/*metabolism
MH  - Mice
MH  - Microbial Viability
MH  - Mycobacterium tuberculosis/drug effects/*enzymology/genetics/growth & development
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - *Nitrosative Stress/drug effects
MH  - *Oxidative Stress/drug effects
MH  - Phagosomes/metabolism/microbiology
MH  - Phenotype
MH  - Virulence
OTO - NOTNLM
OT  - Biofilm maturation
OT  - Knockdown
OT  - Malate synthase
OT  - Mycobacterium tuberculosis H37Ra
OT  - Persistence
OT  - Stress
EDAT- 2017/08/15 06:00
MHDA- 2018/07/18 06:00
CRDT- 2017/08/14 06:00
PHST- 2017/03/31 00:00 [received]
PHST- 2017/07/14 00:00 [revised]
PHST- 2017/07/16 00:00 [accepted]
PHST- 2017/08/14 06:00 [entrez]
PHST- 2017/08/15 06:00 [pubmed]
PHST- 2018/07/18 06:00 [medline]
AID - S1472-9792(17)30128-2 [pii]
AID - 10.1016/j.tube.2017.07.006 [doi]
PST - ppublish
SO  - Tuberculosis (Edinb). 2017 Sep;106:73-81. doi: 10.1016/j.tube.2017.07.006. Epub 
      2017 Jul 18.