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February 19, 2026Pathogens0 citationsOpen Access

Investigation of Gene Regions Responsible for Drug Resistance in Clinical Isolates of Mycobacterium tuberculosis Complex Resistant to at Least Two First-Line Anti-Tuberculosis Drugs

MÜMahmut ÜlgerNBNurcihan BİLTEKİNSUSeda Tezcan Ulger

Key Points

  • The study aims to investigate mutations related to drug resistance in Mycobacterium tuberculosis complex isolates resistant to multiple first-line drugs.
  • Analyzed 23 clinical isolates for drug susceptibility using BACTEC MGIT 960 system.
  • Identified point mutations through DNA sequence analysis and comparison with GenBank reference sequences.
  • Focused on drug resistance-associated gene regions like rpsL, katG, and inhA.
  • Identified an AAG → AGG mutation at rpsL codon 43 in 7 isolates and codon 88 in 1 isolate.
  • Detected a novel GAG → GCG mutation at rpsL codon 70 in 2 isolates.
  • Most frequent mutation was AGC → ACC at katG codon 315 in 10 isolates.
  • Found a C → T mutation at inhA promoter position −15 in 4 isolates.

Abstract

Early and rapid diagnosis of drug resistance in tuberculosis (TB) plays a key role in reducing the spread of resistance and enabling effective treatment. The aim of this study was to investigate mutations in drug resistance-associated gene regions of Mycobacterium tuberculosis complex (MTBC) isolates resistant to at least two first-line anti-tuberculosis drugs through sequence analysis, in order to characterize the core molecular features of these strains in the region and to identify previously unreported, geographically distinct novel mutation sites. The drug susceptibility of 23 clinical isolates was assessed using the BACTEC MGIT 960 system, and resistance-associated point mutations were identified through DNA sequence analysis and comparison with GenBank reference sequences. AAG → AGG mutation was detected in the rpsL gene region at codon 43 (n = 7) and codon 88 (n = 1). Additionally, GAG → GCG point mutation was identified at codon 70 (n = 2), representing a new region not previously reported in the literature. The most frequent mutation was AGC → ACC at katG codon 315 (n = 10), followed by a C → T substitution at position −15 of the inhA promoter region (n = 4). Additionally, TCG → TTG at rpoB codon 531 (n = 4) and ATG → GTG at embB codon 306 (n = 1) were detected. The detection of resistance-associated mutations is essential for controlling drug-resistant tuberculosis. In this study, a novel rpsL mutation (GAG → GCG) at codon 70 and a previously unreported codon 88 mutation in our country were identified, contributing to the understanding of molecular resistance mechanisms and epidemiology.

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Cite This Study

Ülger et al. (2026) studied this question.

synapsesocial.com/papers/6996a7b5ecb39a600b3edab9https://doi.org/10.3390/pathogens15020222
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