바로가기메뉴

본문 바로가기 주메뉴 바로가기

Patterns of rpoC Mutations in Drug-Resistant Mycobacterium tuberculosis Isolated from Patients in South Korea

Tuberculosis & Respiratory Diseases / Tuberculosis & Respiratory Diseases,
2018, v.81 no.3, pp.222-227







  • Downloaded
  • Viewed

Abstract

Background: Rifampicin (RFP) is one of the principal first-line drugs used in combination chemotherapies against Mycobacterium tuberculosis , and its use has greatly shortened the duration of chemotherapy for the successful treatment of drug-susceptible tuberculosis. Compensatory mutations have been identified in rpoC that restore the fitness of RFPresistant M. tuberculosis strains with mutations in rpoB . To investigate rpoC mutation patterns, we analyzed 93 clinical M. tuberculosis isolates from patients in South Korea. Methods: Drug-resistant mycobacterial isolates were cultured to determine their susceptibility to anti-tubercular agents. Mutations in rpoC were identified by sequencing and compared with the relevant wild-type DNA sequence. Results: In total, 93 M. tuberculosis clinical isolates were successfully cultured and tested for drug susceptibilities. They included 75 drug-resistant tuberculosis species, of which 66 were RFP-resistant strains. rpoC mutations were found in 24 of the 66 RFP-resistant isolates (36.4%). Fifteen different types of mutations, including single mutations (22/24, 91.7%) and multiple mutations (2/24, 8.3%), were identified, and 12 of these mutations are reported for the first time in this study. The most frequent mutation involved a substitution at codon 452 (nt 1356) resulting in amino acid change F452L. Conclusion: Fifteen different types of mutations were identified and were predominantly single-nucleotide substitutions (91.7%). Mutations were found only in dual isoniazid- and RFP-resistant isolates of M. tuberculosis . No mutations were identified in any of the drug-susceptible strains.

keywords
Mycobacterium tuberculosis, Drug Resistance, Multiple, Beta' Subunit of RNA Polymerase, Mutation

Reference

1.

Gandhi NR, Nunn P, Dheda K, Schaaf HS, Zignol M, van Soolingen D, et al. Multidrug-resistant and extensively drug-resistant tuberculosis: a threat to global control of tuberculosis. Lancet 2010;375:1830-43.

2.

World Health Organization. Global tuberculosis report 2015. Geneva: World Health Organization; 2015.

3.

Abate D, Tedla Y, Meressa D, Ameni G. Isoniazid and rifampicin resistance mutations and their effect on second-line antituberculosis treatment. Int J Tuberc Lung Dis 2014;18:946-51.

4.

Jeon D. Medical management of drug-resistant tuberculosis. Tuberc Respir Dis 2015;78:168-74.

5.

Park JS. Issues related to the updated 2014 Korean guidelines for tuberculosis. Tuberc Respir Dis 2016;79:1-4.

6.

Islam T, Hiatt T, Hennig C, Nishikiori N. Drug-resistant tuberculosis in the WHO Western Pacific Region. Western Pac Surveill Response J 2014;5:34-46.

7.

Yun YJ, Lee KH, Haihua L, Ryu YJ, Kim BJ, Lee YH, et al. De- tection and identification of Mycobacterium tuberculosis in joint biopsy specimens by rpoB PCR cloning and sequencing. J Clin Microbiol 2005;43:174-8.

8.

Yue J, Shi W, Xie J, Li Y, Zeng E, Wang H. Mutations in the rpoB gene of multidrug-resistant Mycobacterium tuberculosis isolates from China. J Clin Microbiol 2003;41:2209-12.

9.

Cavusoglu C, Hilmioglu S, Guneri S, Bilgic A. Characterization of rpoB mutations in rifampin-resistant clinical isolates of Mycobacterium tuberculosis from Turkey by DNA sequencing and line probe assay. J Clin Microbiol 2002;40:4435-8.

10.

de Vos M, Muller B, Borrell S, Black PA, van Helden PD, War- ren RM, et al. Putative compensatory mutations in the rpoC gene of rifampin-resistant Mycobacterium tuberculosis are associated with ongoing transmission. Antimicrob Agents Chemother 2013;57:827-32.

11.

Comas I, Borrell S, Roetzer A, Rose G, Malla B, Kato-Maeda M, et al. Whole-genome sequencing of rifampicin-resistant Mycobacterium tuberculosis strains identifies compensatory mutations in RNA polymerase genes. Nat Genet 2011;44:106- 10.

12.

Wayne LG. Simple pyrazinamidase and urease tests for routine identification of mycobacteria. Am Rev Respir Dis 1974;109:147-51.

Tuberculosis & Respiratory Diseases