Type: Process Essays
Sample donated: Randy Gonzalez
Last updated: August 13, 2019
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. 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 TBtherapy 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 resistantis used as subtitution marker for detecting MDR TB2.RIF resistant is caused by mutation of a single nucleotide-substitution on rpoBregion. In this mutation process, the gene encodes the ?-subunit of RNApolymerase into DNA-dependent (RNAP) (ilse du). Transcription of the RNAP fromthe 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 toanother antibiotic9.