Mycobacterium another antibiotic9. Autophagy is a complex process involving

Mycobacterium tuberculosi can cause a dangerous disease called Tuberculosis (TB). This
microbacteria can attack various organs, but mostly it attacks the lungs. The
TB infection can spread from coughing or sneezing which allows Mycobacterium tuberculosi to enter the
body along with dusts or droplets19. There are 6 countries with the world’s largest TB disease spread:
South Africa, Nigeria, China, Pakistan, India and Indonesia. Mycobacterium tuberculosi can evolve its
resistance against antimicrobial drugs. There is a type of TB called
Multidrug-resistant TB (MDR-TB) which cannot be treated by at least with two of
the potent first line anti-TB drugs like isoniazid
and rifampicin. To improve detection
of the case and treatment for MDR-TB, any further development is needed. There
are 300,000 cases of MDR-TB patients that were estimated in 2013. Around 45%
cases from them were detected among all pulmonary TB in the world while around
5% of cases of MDR-TB that are not detected or not managed outside the national
TB programs were not reported25.


Comparative genomic analyses drug resistance on MTB can be caused by 3
things, they are chromosonal mutations that required for the action of
antibiotics, gene that encodes the protein targets of drugs applied, or enzymes
that are required to activate pro-drug. The target of antibiotics is important
to cell function. Resistant mutations encodes gene target will affect
pathogenesis15. In every 106 to 108 replications, wild strains
of MTB will undergo spontaneous mutations that confer resistance to a single

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Table 1.Mutations in antibiotic19


mutation rate


2.56 x 10-6


2.25x 10-10


1 x 10-7


2.95 x 10-8


1 x 10-3



TB therapy with fast onset needs Rifampicin
(RIF) as critical component of first-line therapy3. Almost 90% of RIF resistant strains are also resist to isoniazid. RIF
resistant is used as subtitution marker for detecting MDR TB2. RIF resistant is caused by mutation of a single
nucleotide-substitution on rpoB region. In this mutation process, the gene
encodes the ?-subunit of RNA polymerase into DNA-dependent (RNAP) (ilse du).
Transcription of the RNAP from the mutations of rpo in the gene has some
effects toward physiology of the MTB. Mutations in this site can cause
secondary mutations which lead resistance to another antibiotic9.


Autophagy is a complex process involving multiple protein that consist
of complex formation and initiation of double membrane development phagophore
as nucleation, elongation of the membrane and completion of autophagosome
vesicles surround the cargo, and then they will fuse with lysosom. Lysosom
contain hydrolase that can degrade and dispose component18. MTB persist and mutiply within
infected macrophage, where it resides in host-derived phagosome which fails to
fuse with lysosom10. Autophagy caused by metabolic and immune signals consists of
recognition of pathogen and stimulation by pro-inflammatory cytokines.
Autophagy trigger microtubule-associated proteins 1B light chain 3B
(MAP1LC3B/LC3), a protein encoded by the gene MAP1LC3B in humans25. LC3 was first identified as a
protein co-purified with microtubule-associated protein 1A and 1B from rat brains.
This protein is derived from 28% of amino acids with Apg8/Aut7p who plays a
role in autophagy in yeast, undergoes complex C-terminal proteolitic and lipid
(phosphathydil ethanolamine) modifications, which is translocates from cytosol
to the autophagosomal membrane12.