Mycobacterium another antibiotic9. Autophagy is a complex process involving

Mycobacterium tuberculosi can cause a dangerous disease called Tuberculosis (TB).

Thismicrobacteria can attack various organs, but mostly it attacks the lungs. TheTB infection can spread from coughing or sneezing which allows Mycobacterium tuberculosi to enter thebody 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 itsresistance against antimicrobial drugs. There is a type of TB calledMultidrug-resistant TB (MDR-TB) which cannot be treated by at least with two ofthe potent first line anti-TB drugs like isoniazidand rifampicin. To improve detectionof the case and treatment for MDR-TB, any further development is needed. Thereare 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 around5% of cases of MDR-TB that are not detected or not managed outside the nationalTB programs were not reported25.

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 Comparative genomic analyses drug resistance on MTB can be caused by 3things, they are chromosonal mutations that required for the action ofantibiotics, gene that encodes the protein targets of drugs applied, or enzymesthat are required to activate pro-drug. The target of antibiotics is importantto cell function. Resistant mutations encodes gene target will affectpathogenesis15. In every 106 to 108 replications, wild strainsof MTB will undergo spontaneous mutations that confer resistance to a singledrug. Table 1.

Mutations in antibiotic19 Drug Average mutation rate Isoniazid 2.56 x 10-6 Rifampicin 2.25x 10-10 Ethambutol 1 x 10-7 Streptomycin 2.95 x 10-8 Pyrazinamide 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. RIFresistant is used as subtitution marker for detecting MDR TB2. RIF resistant is caused by mutation of a singlenucleotide-substitution on rpoB region. In this mutation process, the geneencodes the ?-subunit of RNA polymerase into DNA-dependent (RNAP) (ilse du).

Transcription of the RNAP from the mutations of rpo in the gene has someeffects toward physiology of the MTB. Mutations in this site can causesecondary mutations which lead resistance to another antibiotic9. Autophagy is a complex process involving multiple protein that consistof complex formation and initiation of double membrane development phagophoreas nucleation, elongation of the membrane and completion of autophagosomevesicles surround the cargo, and then they will fuse with lysosom. Lysosomcontain hydrolase that can degrade and dispose component18. MTB persist and mutiply withininfected macrophage, where it resides in host-derived phagosome which fails tofuse with lysosom10.

Autophagy caused by metabolic and immune signals consists ofrecognition 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 aprotein 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 arole in autophagy in yeast, undergoes complex C-terminal proteolitic and lipid(phosphathydil ethanolamine) modifications, which is translocates from cytosolto the autophagosomal membrane12.