Molecular insights of drug-resistant tuberculosis: genetic mutations and their profile

Introduction Drug-resistant tuberculosis (DR-TB) poses a significant public health threat, with molecular diagnostics playing a pivotal role in understanding the genetic mechanisms of resistance. This study focuses on the patterns of genetic mutations observed in DR-TB cases, with the aim to identify key mutations associated with resistance to rifampicin (RIF) and isoniazid (INH). Methodology A total of 6,954 non-duplicate clinical samples were obtained from individuals of all age groups, categorized as TB and DR-TB, from seven linked districts between June 2022 and May 2024. The samples were transported under cold chain conditions to an intermediate reference laboratory. TB was confirmed using fluorescence microscopy, and 1,998 sputum-positive samples were analyzed using line probe assay for characterization of genetic mutations. Results Among the analyzed cases, a total of 136 cases of DR-TB were identified. This included 57 cases (41.92%) of multidrug-resistant TB (MDR-TB), 73 cases (53.68%) of INH monoresistance, and 6 cases (4.4%) of RIF monoresistance. The analysis revealed a high prevalence of rpo B MUT3 (S531L) mutations in 52 cases (82.25%), which is associated with RIF resistance. In high-level INH ( kat G gene mutation) resistance noted in 83 (63.35%) cases, kat G MUT1 (S315T1) was predominant, while low-level INH resistance ( inh A gene mutation), inh A MUT1 (C-15T) mutation, was found in 29 (22.13%) cases. Maharajganj and Deoria reported the highest prevalence of rpo B MUT3 (S531L) mutations, while Kushinagar and Sant Kabir Nagar exhibited higher rates of kat G MUT1 (S315T1) mutations. Other regions showed notable distribution of rpo B, kat G, and inh A gene mutations. Conclusion The high prevalence of mutations such as rpo B MUT3 (S531L) and kat G MUT1 (S315T1) highlights the need for integrating molecular tools into routine workflows to identify 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.