Investigations on mutations in katG gene and inhA promoter region associated with isoniazid resistance in the clinical isolates of mycobacterium tuberculosis from Tehran, Iran

BACKGROUND: Isoniazid (INH) is one of the first-line drugs used for the treatment of Mycobacterium tuberculosis (Mtb). This study aimed to determine the mutations in katG and inhA promoter regions associated with INH resistance in clinical isolates of Mtb from Tehran, Iran. METHODS: This descriptive cross-sectional study was conducted in the tuberculosis (TB) center of Tehran in 2020. 50 samples obtained from these patients were cultured on Löwenstein-Jensen medium (LJ), then, INH-resistant strains and their minimum inhibitory concentration (MIC) were determined using the proportional method. To determine the INH-resistance mutations, sequencing was performed following the amplification of both katG and inhA genes using real-time polymerase chain reaction (PCR). The genetic relationships were determined based on each strain's genetic pattern using the primers related to enterobacterial repetitive intergenic consensus PCR (ERIC-PCR), which is a proper tool used for typing Mtb strains. In this study, the phylogenetic tree was plotted using NTSYS software. RESULTS: Five INH-resistant Mtb strains were isolated from 50 patients with TB in Tehran. All the studied resistant strains (100%) showed a mutation in codon 315 of the katG gene; none of them exhibited any mutation in the promoter. I335T mutation was observed in one INH-resistant strain (20%). The phylogenetic tree of the strains indicated seven clusters as well as 31 patterns in the strains. The strain with two mutations in 335 and 315 had MIC > 8. CONCLUSION: KatG mutation could result in a high level of INH resistance. Therefore, routine identification of this mutation can help in determining the INH resistance, thereby preventing further propagation of these strains.