Mycobacterium treated by at least with two of

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
drug.

 

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. 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.