Investigating the Mutations in atpE and Rv۰۶۷۸ Genes in Mycobacterium Tuberculosis Clinical Isolates

Introduction: Tuberculosis (TB) caused by the bacterium Mycobacterium tuberculosis remains a critical global public health concern due to the high morbidity and mortality rates. Mutation in atpE and Rv۰۶۷۸ genes contributes to drug resistance in M. tuberculosis. This study investigates the antibiotic resistance patterns and mutations in atpE and Rv۰۶۷۸ genes in ۲۲ M. tuberculosis clinical isolates. Methods: Drug susceptibility testing (DST) for rifampin, isoniazid, streptomycin, capreomycin, ofloxacin, kanamycin, and ethambutol was conducted using the proportional method. This was followed by determining the minimum inhibitory concentration (MIC) for bedaquiline (BDQ) via the microplate Alamar blue assay (MABA). Genomic regions encompassing atpE and Rv۰۶۷۸ genes were amplified and sequenced for mutation analysis. Data analysis was performed using SPSS software to interpret mutation patterns concerning drug susceptibility profiles. Results: Of ۲۲ isolates, ۵ (۲۷.۸%) were extensively drug-resistant tuberculosis (XDR-TB), and ۱۳ (۷۲.۲%) were multi-drug resistant tuberculosis (MDR-TB). Resistance rates to kanamycin, ofloxacin, capreomycin, and streptomycin were ۴۰.۶%, ۴۶.۳%, ۸۵%, and ۷۴.۶%, respectively. Additionally, phenotypic resistance to bedaquiline was observed in ۱۲ (۵۴.۵%) isolates. Sequencing revealed no resistance-conferring mutations in the atpE or Rv۰۶۷۸ genes among the isolates. Conclusion: Our findings showed substantial resistance to first- and second-line drugs in M. tuberculosis clinical isolates. This highlights the necessity for ongoing, comprehensive studies to elucidate the evolving drug resistance patterns and understand the underlying mechanisms in clinical isolates.

Keywords:

Mycobacterium tuberculosis , DST , atpE , Rv۰۶۷۸ , Bedaquiline , Extensively drug-resistant tuberculosis (XDR-TB) , Multi-drug resistant tuberculosis (MDR-TB)