1 Young Researchers and Elites Club, North Tehran Branch, Islamic Azad University, Tehran, Iran

2 Department of Microbiology, Kerman Branch, Islamic Azad University, Kerman, Iran

3 Biotechnology Research Center, venom & Biotherapeutics Molecules Lab., Pasteur Institute of Iran, Tehran, Iran


Objective: The Rifampicin resistance and susceptibility of Mycobacterium tuberculosis are caused by mutations in the 81-base pair region of the rpoB gene encoding the b-subunit of RNA polymerase. Methods: Isoniazid resistance of M. tuberculosis is related to mutations in inha , oxyR and ahpC genes which 30 to 90 percent of Isoniazid resistance is occurred in 3015 codons of katg gene. The rpoB and katG sequences of 30 isolates were analyzed to identify the mutations and compare the mutations with their related susceptibilities. Results: In this research, we investigated the location and type of rpoB and katG mutations in Mycobacterium tuberculosis which had been achieved from Pasteur Institute of Tehran. PCR Amplification and DNA sequencing methods were performed. In this assay, from 507 to 537 codons and 315 codons of rpoB and katG genes were sequenced and also mutations were analyzed, respectively.


Main Subjects

Abal, A.T., Ahmad, S.,Mokaddas, E. (2002). Variations in the occurrence of the S315T mutation within the katG gene in isoniazid-resistant clinical
Mycobacterium tuberculosis isolates from Kuwait. Microb Drug Resist, 8: 99-105.
Ahmad, S., Araj, G.F., Akbar, P.K., Fares, E., Chugh, T.D.,Mustafa, A.S. (2000). Characterization of rpoB mutations in rifampin-resistant Mycobacterium
tuberculosis isolates from the Middle East. Diagn Microbiol Infect Dis, 38(4): 227-232.
Ahmad, S.,Mokaddas, E. (2005). The occurrence of rare rpoB mutations in rifampicin-resistant clinical Mycobacterium tuberculosis isolates from Kuwait.
Int. J. Antimicrob. Agents, 26(3): 205-212.
Ahmad, S., Mokaddas, E.,Fares, E. (2002).
Characterization of rpomutations in rifampin
resistant clinical Mycobacterium tuberculosis
isolates from Kuwait and Dubai. Diagn Microbiol Infect Dis, 44(3): 245-252.
Aktas, E., Durmaz, R., Yang, D., Yang, Z.(2005). Molecular characterization of isoniazid and rifampin resistance of Mycobacterium tuberculosis
clinical isolates from Malatya, Turkey. Microb Drug Resist ,11(2):94-99.
Billington, O.J., McHugh, T.D.,Gillespie, S.H. (1999).
Physiological cost of rifampin resistance induced in vitro in Mycobacterium tuberculosis. Antimicrobial Agents Chemother, 43: 1866-1869.
Borrel, S.,Gagneux, S. (2009). Infectiousness, reproductive fitness and evolution of drugresistant Mycobacterium tuberculosis. Int J Tuberc Lung Dis,
13: 1456-1466.
Burman, W.J.,Jones, B.E. (2001). Treatment of HIVrelated tuberculosis in the era of effective antiretroviral therapy. Am. J. Respir. Crit. Care, 164:7-12.
Davies, G.R., Cerri, S.,Richeldi, L. (2010). Rifabutin
for Treating Pulmonary Tuberculosis (Review). Ltd, The Cochrane Collaboration.
Feuerriegel, S., Oberhauser, B., George, A.G., Dafae, F., Richter, E., R¸sch-Gerdes, S.,Niemann, S. (2012). Sequence analysis for detection of first-line drug resistance in Mycobacterium tuberculosis strains from a high-incidence setting. BMC Microbiology, 90(12): 1-10.
Figueiredo, R., Ramos, D.F., Moiteiro, C., Medeiros, M.A., Marcelo Curto, M.J., Cardoso de Menezes, J., Pando, R.H., Silva, P.E.A.,Costa, M.d.C. (2012). Pharmacophore insights into rpoB gene mutations in Mycobacterium tuberculosis rifampicin resistant isolates. Eur. J. Med. Chem, 47(0): 186-193.
Gagneux, S., Burgos, M.V., DeRiemer, K., Enciso, A., MuÒoz, S., Hopewell, P.C., Small, P.M.,Pym, A.S. (2006). Impact of bacterial genetics on the
transmission of isoniazid-resistant Mycobacterium tuberculosis. PLoS Pathog, 2: 61.
Herrera, L., Valverde, A., Saiz, P., Saez, J.A., Portero, J.L., Jimenez, M.S. (2004). Molecular characterization of isoniazidresistant Mycobacterium tuberculosis clinical strains isolated in the Philippines. Int J Antimicrob Agents, 23:572-576.
Huang, W.L., Chen, H.Y., Kuo, Y.M.,Jou, R. (2009). Performance Assessment of the GenoType MTBDRplus Test and DNA Sequencing in Detection of Multidrug-Resistant Mycobacterium tuberculosis. J Clin Microbiol, 47(8): 2520-2524.
King, L., Munsiff, S.S.,Ahuja, S.D. (2010). Achieving international targets for tuberculosis treatment success among HIV-positive patients in New York
City. Int. J. Tuberc. Lung Dis, 12(4): 1613-1620.
Lin, Y.-H., Tai, C.-H., Li, C.-R., Lin, C.-F.,Shi, Z.-Y. (2013). Resistance profiles and rpoB gene mutations of Mycobacterium tuberculosis isolates in
Taiwan. JMII, 46(4): 266-270.
Pym, A.S., Saint-Joanis, B.,Cole, S.T. (2002). Effect of katG mutations on the virulence of Mycobacterium tuberculosis and the implication for transmission in humans. Infect Immun, 70: 4955-4960.
Simon, A. W., Stuart, M. W., Malcolm, D. Y., Francis, A. D. (1998). Comparison of Three Molecular Assays for Rapid Detection of Rifampin Resistance in
Spies, F.S., von Groll, A., Ribeiro, A.W., Ramos, D.F., Ribeiro, M.O., Dalla Costa, E.R., Martin, A., Palomino, J.C., Rossetti, M.L., Zaha, A.,da Silva, P.E.A. (2013). Biological cost in Mycobacterium tuberculosis with mutations in the rpsL, rrs, rpoB, and katG genes. Tuberculosis, 93(2): 150-154.
Van Soolingen, D. (2001). Molecular epidemiology of tuberculosis and other mycobacterial infections: main methodologies and achievements. J Intern
Med, 249: 1-26.