Pattern of InhA and KatG mutations in isoniazid monoresistant Mycobacterium tuberculosis isolates

Abstract

Aims and Objectives: The aim of the study is to detect the pattern of genetic mutation, i.e., Inh A or Kat G or both ( Inh A and kat G) in isoniazid (INH) monoresistant mycobacteria and to correlate with the pattern in multidrug-resistant (MDR) isolates. Materials and Methods: In this study, a quantitative research approach was used. The research design was descriptive observational study. The study was conducted at the Department of Respiratory Medicine, JLN Medical College, Ajmer, Rajasthan, and Intermediate Referral Laboratory, State TB Demonstration Centre, Ajmer. A total of 298 samples found to have resistant strains of Mycobacterium tuberculosis were enrolled with purposive sampling. Results: The mean age of patients was 40.27 ± 13.82 years. There were 250 (83.9%) males, while 48 (16.1%) were females. One hundred ninety-two (64.4%) were resistant for INH only, while the rest were resistant to both INH as well as rifampicin (MDR-tuberculosis). The most common mutation in INH monoresistance was kat G (125; 65.1%) as compared to inh A (54; 28.1%) and both inh A and kat G (13; 6.7%). Among kat G mutations, the most common gene pattern was the absence of WT (S315T) and the presence of MUT1 (S315T1). Conclusion: Knowledge about mutation patterns of different INH resistant strains is important in the present era where there is a provision of separate regimens for INH monoresistant TB. Since these mutations are very closely related to high- or low-degree resistance to INH, the therapeutic regimens cannot be generalized.

Molecular Characterization of katG and inhA Mutations by Genotype MTBDRplus Line Probe Assay To Guide Isoniazid and Ethionamide Use for Drug-Resistant Tuberculosis

“…INH mono-resistance forms a major chunk of drug-resistant TB. In our study, resistance to RIF and INH was observed to be 9.6%, while INH monoresistance was found in 6.6% of samples, consistent with previous Indian studies[15][16][17]. The highest resistance to INH was seen in the age groups of 16-35 years.…”

“…Although INH resistance is associated with resistance-conferring mutations in multiple genes, katG and inhA account for ~90% of resistance detected by phenotypic DST. INH resistance due to katG gene mutation was documented in 71.9% of INH-resistant study samples, which agrees with previous studies[15,20]. S315T1 mutation was the most common (96.2%) mutation responsible for high-level INH resistance.…”

“…The highest resistance to INH was seen in the age groups of 16-35 years. A higher positivity rate was seen in males, which has also been noted in previous studies[15]. This emergence of INH mono-resistance can be attributed to many factors, like previous tuberculosis treatment, HIV coinfection, and the confounding effect of INH preventive therapy[18,19].…”

Effectiveness of Xpert MTB/RIF and the Line Probe Assay tests for the rapid detection of drug-resistant tuberculosis in the Central African Republic

“…For the inhA gene, the only observed mutation was Mut1, i.e. Cys15Thr, generally associated with an amino acid substitution on codon 15 of the gene [ 23 ].…”

Comparative Study on Tuberculosis Drug Resistance and Molecular Detection Methods Among Different Mycobacterium Tuberculosis Lineages

“… 33 Previous studies have shown that the most common causes of RIF resistance in M.tb are mutations in the katG gene (50–70%) and mabA-inhA promoter region (20–50%). 34 Through WGS, it was determined that the major RIF resistance gene mutations were primarily located in the katG gene (61.11%, 11/18) and fabG1 gene (27.78%, 5/18). All lineages exhibited the katG p.Ser315Thr and fabG1 c.-15C>T mutations, but no mutations were detected in the inhA gene.…”