Patterns of rpoC Mutations in Drug-Resistant Mycobacterium tuberculosis Isolated from Patients in South Korea.
- Author:
Yeo Jun YUN
1
;
Jong Seok LEE
;
Je Chul YOO
;
Eunjin CHO
;
Dahee PARK
;
Yoon Hoh KOOK
;
Keun Hwa LEE
Author Information
- Publication Type:Original Article
- Keywords: Mycobacterium tuberculosis; Drug Resistance, Multiple; Beta' Subunit of RNA Polymerase; Mutation
- MeSH: Base Sequence; Codon; Drug Resistance, Multiple; Drug Therapy; Drug Therapy, Combination; Humans; Korea*; Mycobacterium tuberculosis*; Mycobacterium*; Rifampin; Tuberculosis; Tuberculosis, Multidrug-Resistant
- From:Tuberculosis and Respiratory Diseases 2018;81(3):222-227
- CountryRepublic of Korea
- Language:English
- 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 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.