Patterns of rpoC mutations in drug-resistant mycobacterium tuberculosis isolated from patients in South Korea

Yeo Jun Yun, Jong Seok Lee, Je Chul Yoo, Eunjin Cho, Dahee Park, Yoon-Hoh Kook, Keun Hwa Lee

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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.

Original languageEnglish
Pages (from-to)222-227
Number of pages6
JournalTuberculosis and Respiratory Diseases
Volume81
Issue number3
DOIs
StatePublished - 1 Jul 2018

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Multidrug-Resistant Tuberculosis
Republic of Korea
Mycobacterium tuberculosis
Mutation
Rifampin
Pharmaceutical Preparations
Isoniazid
Combination Drug Therapy
Codon

Keywords

  • Beta' subunit of RNA polymerase
  • Drug resistance
  • Multiple
  • Mutation
  • Mycobacterium tuberculosis

Cite this

Yun, Yeo Jun ; Lee, Jong Seok ; Yoo, Je Chul ; Cho, Eunjin ; Park, Dahee ; Kook, Yoon-Hoh ; Lee, Keun Hwa. / Patterns of rpoC mutations in drug-resistant mycobacterium tuberculosis isolated from patients in South Korea. In: Tuberculosis and Respiratory Diseases. 2018 ; Vol. 81, No. 3. pp. 222-227.
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title = "Patterns of rpoC mutations in drug-resistant mycobacterium tuberculosis isolated from patients in South 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.",
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Patterns of rpoC mutations in drug-resistant mycobacterium tuberculosis isolated from patients in South Korea. / Yun, Yeo Jun; Lee, Jong Seok; Yoo, Je Chul; Cho, Eunjin; Park, Dahee; Kook, Yoon-Hoh; Lee, Keun Hwa.

In: Tuberculosis and Respiratory Diseases, Vol. 81, No. 3, 01.07.2018, p. 222-227.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Patterns of rpoC mutations in drug-resistant mycobacterium tuberculosis isolated from patients in South Korea

AU - Yun, Yeo Jun

AU - Lee, Jong Seok

AU - Yoo, Je Chul

AU - Cho, Eunjin

AU - Park, Dahee

AU - Kook, Yoon-Hoh

AU - Lee, Keun Hwa

PY - 2018/7/1

Y1 - 2018/7/1

N2 - 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.

AB - 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.

KW - Beta' subunit of RNA polymerase

KW - Drug resistance

KW - Multiple

KW - Mutation

KW - Mycobacterium tuberculosis

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DO - 10.4046/trd.2017.0042

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