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Characterization of rpoB and katG: study of RIF resistance to the subunit-�Ž�² RNA polymerase and INH resistance in katG gene in patients with TB in Jayapura-Papua Province, Indonesia | Abstract
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Abstract

Characterization of rpoB and katG: study of RIF resistance to the subunit-�Ž�² RNA polymerase and INH resistance in katG gene in patients with TB in Jayapura-Papua Province, Indonesia

Author(s): Hendrikus M. B. Bolly and Yohanis Ngili

The main problem that continues to increase in the treatment and control of TB in the province of Papua is multidrug-resistant of M. tuberculosis (MDR-TB) isolates, which is defined by the World Health Organization, WHO as M. tuberculosis isolates were resistant to RIF and INH. Treatment of TB patients are usually performed by administering three types of anti-tuberculosis medicines with primary choice is rifampin (RIF) and isoniazid (INH), then accompanied with streptomycin or pyrazinamide. RIF resistance due to mutations in the rpoB gene, the gene that produces RNA polymerase β-subunit and INH resistance is largely due to mutations in the gene katG. With the increasing number of people with HIV/AIDS cause TB disease WHO categorizes as a re-emerging disease. Objectives of this study was to obtain information MDR-TB relations with the relevant genes, as well as information combined genotype of M. tuberculosis. Here, we showed that the majority of MDR-TB isolates are resistant to other anti-tuberculosis drugs, and the frequency of mutations rpoB526 and rpoB531 almost the same but katG315 mutation is only found in 16 isolates. This study success to detect mutations in addition to codon rpoB526 or rpoB531 which has never been published, among them the mutation C1307T (Asp516Gly), T1374A and A1376C (Ser539Thr), and C1413T (Pro552Ser). Their C1363A nucleotide changes (Pro535His) in M. tuberculosis sensitive six anti-tuberculosis drugs showed entire rpoB mutations causing resistance properties. On the basis of this phenomenon, it can be suggested that the formation mechanism of MDR-TB strains begins with rpoB mutations followed by mutation katG. This study shows that the mechanism of resistance to an anti-tuberculosis drug that only affects a single gene, such as rifampin affecting rpoB, will be more easily controlled than anti-TB drugs that affect multiple genes, for example isoniazid affecting other genes other than katG.