Fatty Acids as an alternative Energy Source in the form of triglycerides in
Mycobacterium tuberculosis during dormancy
Laxman S. Meena
CSIR-Institute of Genomics and Integrative Biology, Council of Scientific and Industrial Research, Mall Road, Delhi-110007
Corresponding author: Laxman S. Meena, CSIR-Institute of Genomics and Integrative Biology, Council of Scientific and
Industrial Research, E-mail: Laxmansm72@yahoo.com, Tel:+ 011-27666156
Citation: Laxman S. Meena (2016) Fatty Acids as an alternative Energy Source in the form of triglycerides in Mycobacterium
tuberculosis during dormancy. Int J Biotech & Bioeng. 2:2, 78-79
Copyright: © 2016 Laxman S. Meena. This is an open-access article distributed under the terms of the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are
Recieved Date: September 16, 2016; Accepted Date:
October 07, 2016; Published Date:
October 30, 2016
M. tuberculosis; Triglycerides; Fatty acids; Granulomas; Dormancy
Brief Summary on Triglycerides in MTB :
One of the major problems in tuberculosis control is strong
viability of Mycobacterium tuberculosis (M. tuberculosis) in host
under various harsh circumstances, along with the resistance to
few antituberculosis drugs available. Among many unresolved
questions, one of the important aspects is to discover by which
mechanism M. tuberculosis survives during the dormancy period
and what are the energy sources on which it survives. A likely
possibility is that the fatty acids stored in the host tissue is used by
the pathogen as energy reserve in the form of triglycerides (TG),
just as hibernating animals and migratory birds are known to do.
In fact recently TG inclusion bodies were found in the pathogen
obtained from the infected host  that could reflect the conditions
of dormant bacilli.
However, the source of fatty acids remain unclear, it might be
possible that fatty acids which are undergoing degradation in host
tissue can serve as an energy source to M. tuberculosis. It has been
observed that in mycobacterial cell culture, such lipid storing bodies
are formed in cells when exogenous fatty acids were provided [1-3].
These TGs serve as an ideal energy source for long-term survival
of the dormant pathogen. Developing alternative mechanism for
generating energy by M. tuberculosis during dormancy period
is an important phenomenon for its persistence in macrophages;
however, least is known about the source and nature of fatty acids
required for TB inside the macrophages. Although, tubercle bacilli
(TB) were long considered to rely solely on anaerobic metabolism.
It is known, Isocitrate lyase (ICL) and malate synthase (MS)
together form the glyoxylate shunt, which bypass the CO2-
generating steps of the tricarboxylic acid (TCA) cycle. The net
result of the glyoxylate shunt is the consumption of two molecules
of acetyl-CoA to generate one molecule of succinate. Lipids are a
source of acetyl-CoA; succinate is a precursor for the synthesis of
glucose. Therefore, the glyoxylate shunt allows M. tuberculosis to
synthesize carbohydrates from fatty acids. When the TCA cycle
and the glyoxylate shunt run simultaneously, fatty acids can supply
cells with energy from both, through TCA cycle and precursors
for carbohydrate synthesis via glyoxylate shunt. The need for the
ICL gene for M. tuberculosis survival during late-stage infection
 indicates that due to changing environment bacteria requires
to switch its diet dependency from carbohydrate to lipid source.
Furthermore, as M. tuberculosis enters into persistence stage
within the host, TB starts depending solely on the lipid-rich hostcell
debris in evolving granulomas. Hence, it is more obvious
that in the absence of an external supply of carbohydrates (as
diet) in this new environment, the glyoxylate shunt may supply
the sugar precursors required for assembly of the carbohydraterich
mycobacterial cell envelope, as well as an alternative energy
source. However, it is still an unknown phenomenon to understand
the mechanism by which fatty acids generated in the host which
may be utilized by TB cells during dormant stage.
M. tuberculosis are obligate aerobe, and it has also been well
known that M. tuberculosis encounter hypoxic environments
in acute diseases as well as in latent infection . The Wayne
model has established a link between starvation for oxygen and
drug resistance. Under low oxygen tension the bacilli terminates
growth and enters into a non-replicating or dormant stage, dormant
TB adapts anaerobiosis and maintains viability for extended period of time while waiting for the weakening of the host immune
system to produce diseases, moreover, the dormant form of TB
was found to be resistant to all conventional antimycobacterial
Bacilli that were disrupted for their respiratory nitrate
reductase  and isocitrate lyase (ICL), an enzyme of glyoxalate
pathway and implicated in the metabolic adaptation to anaerobiosis
 showed reduced virulence in mice. It is proposed that under
hypoxic growth, M. tuberculosis starts synthesizing triglycerides
as a reserve energy source and could use it during and after the
dormancy period. However, there is not much known about these
mechanisms and we propose to verify this hypothesis by using
in vitro hypoxic model and also by using Triolein and Lipolytic
protein  that we presume their involvement in the synthesis of
TG and could be an important for TG synthesis in M. tuberculosis
while going into dormancy.
We thank Dr. Rajesh S. Gokhale for making this work possible.
The authors acknowledge financial support from GAP0092 and
OLP1121 of the Department of Science and Technology and
Council of Scientific & Industrial Research.
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