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

Tuberculosis and Respiratory Diseases

article

Yeo Jun Yun¹  Jong Seok Lee²  Je Chul Yoo³  Eunjin Cho²  Dahee Park³  Yoon-Hoh Kook⁴  Keun Hwa Lee³ 

[1] Ewha Medical Research Institute, Ewha Womans University;International Tuberculosis Research Center;Department of Microbiology and Immunology, Jeju National University College of Medicine;Department of Microbiology and Immunology, Seoul National University College of Medicine

关键词: Mycobacterium tuberculosis;    Drug Resistance;    Multiple;    Beta' Subunit of RNA Polymerase;    Mutation;   

DOI  :  10.4046/trd.2017.0042

学科分类：医学（综合）

来源: The Korean Academy of Tuberculosis and Respiratory Diseases

【 摘 要 】

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 RFP-resistant 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.

【 授权许可】

CC BY-NC