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

Abstract

BackgroundRifampicin (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.MethodsDrug-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.ResultsIn 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.ConclusionFifteen 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.

Low-Level Rifampin Resistance and rpoB Mutations in Mycobacterium tuberculosis: an Analysis of Whole-Genome Sequencing and Drug Susceptibility Test Data in New York

“…This link between compensatory mutations and strains with rpoB Ser450Leu has been well established (23,25,54,(57)(58)(59)(60). A majority of rpoC mutations identified in our study have been described in previous reports (54,(57)(58)(59)(60)(61)(62)(63)(64)(65)(66). Many of these mutations are located between codons 431 and 527, a particular region identified as harboring mutations that may compensate for the fitness cost of rpoB resistance mutations (53).…”

Identification and Characterization of Genetic Determinants of Isoniazid and Rifampicin Resistance in Mycobacterium tuberculosis in Southern India

“…A more recent study by Yun et al . (2018) reported the presence of rpoC mutations in 25.8% of the total isolates 60 . In our study, we found that 8/24 resistant isolates had mutations in rpoC , of which 7 had the S450L dominant mutation.…”

A precision overview of genomic resistance screening in isolates ofMycobacterium tuberculosisusing web-based bioinformatics tools

“…In addition, we identified compensatory mutations that are associated with MDR transmission, such as W848G and I491V in the rpoC gene and T187A in the rpoA gene. (3,(58)(59)(60)(61).…”