ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Infectious Agents and Disease
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1669327
This article is part of the Research TopicAdvancements in Diversity and Drug Resistance Mechanisms in Mycobacterial DiseasesView all 14 articles
Molecular insights of drug-resistant tuberculosis: genetic mutations and their profile
Provisionally accepted
- 1Baba Raghav Das Medical College, Gorakhpur, India
- 2Deen Dayal Upadhyaya Gorakhpur University, Gorakhpur, India
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Introduction: Drug-resistant tuberculosis (DR-TB) poses a significant public health threat, with molecular diagnostics playing a pivotal role in understanding the genetic basis of resistance. This study focused on the genetic mutational patterns observed in DR-TB cases, aiming to identify key mutations associated with resistance to rifampicin (RIF) and isoniazid (INH) . Methodology: A total of 6954 non-duplicate clinical samples from individuals from all age groups, recognizing TB and DR-TB in TB cases were collected from 7 linked districts between June 2022 to May 2024. Samples were transported under cold chain conditions to the Intermediate Reference Laboratory. TB confirmation was performed using fluorescence microscopy staining. Further 1998 sputum positive samples were analyzed by Line Probe Assay for characterization of genetic mutations. Results: Among the analyzed cases, a total of 136 cases of DR-TB were identified. This includes 57 (41.92%) cases of multidrug-resistant TB, 73 (53.68%) cases of isoniazid mono-resistance, and 6 (4.4%) cases of rifampicin mono-resistance. The analysis revealed a high prevalence of rpoBMUT3 (S531L) mutations in 52 (82.25%) cases which is associated with rifampicin resistance. In high–level isoniazid (katG gene mutation) resistance, katG MUT1 (S315T1) was predominantly present in 83 (63.35%) cases while in low-level isoniazid resistance (inhA gene mutation), inhAMUT1 (C-15T) mutations was present in 29 (22.13%) cases. Maharajganj and Deoria reported the highest prevalence of rpoBMUT3 (S531L) mutations while Kushinagar and Sant Kabirnagar exhibited higher rates of katGMUT1 (S315T1) mutations. Other regions showed notable distributions of rpoB, katG and inhA genes mutations. Conclusion: The high prevalence of mutations such as rpoBMUT3 (S531L) and katGMUT1 (S315T1) highlights the need for integrating molecular tools into routine workflows in identifying genetic mutations. District-specific mutations emphasize the influence of local epidemiological factors on resistance patterns, necessitating region-specific interventions. Continuing research into regional resistance trends are vital to addressing the global DR-TB burden effectively.
Keywords: Drug resistance tuberculosis, genetic mutation pattern, Line probe assay, Isoniazid resistance, Rifampicin resistance, Molecular diagnostics
Received: 19 Jul 2025; Accepted: 15 Sep 2025.
Copyright: © 2025 Singh, SINGH, Kumar, Mishra and Singh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Amresh Kumar Singh, amresh.sgpgi@gmail.com
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