Tuberc Respir Dis.  2018 Jul;81(3):222-227. 10.4046/trd.2017.0042.

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

Affiliations
  • 1Ewha Medical Research Institute, Ewha Womans University, Seoul, Korea.
  • 2International Tuberculosis Research Center, Masan, Korea.
  • 3Department of Microbiology and Immunology, Jeju National University College of Medicine, Jeju, Korea. yomust7@jejunu.ac.kr
  • 4Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Korea.

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.

Keyword

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

MeSH Terms

Base Sequence
Codon
Drug Resistance, Multiple
Drug Therapy
Drug Therapy, Combination
Humans
Korea*
Mycobacterium tuberculosis*
Mycobacterium*
Rifampin
Tuberculosis
Tuberculosis, Multidrug-Resistant
Codon
Rifampin
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