Analysis of Tuberculosis Cases with a Different Range of Mutations in Pathogen Genes Associated with Resistance to Isoniazid and Rifampicin

The objective: to analyze cases of tuberculosis with a different range of mutations in the M. tuberculosis genes associated with resistance to isoniazid and rifampicin, to determine prevalence of such mutations, clinical significance and molecular genetic characteristics of pathogens. The cases detected in Saratov Oblast were included in the analysis. Subjects and Methods. A total of 437 sputum samples obtained from HIV-negative tuberculosis patients in 2006-2020 living in Saratov Oblast were examined by biological microarray method. The range of mutations was studied in katG, inhA, ahpC genes associated with drug resistance to isoniazid and in rpoB gene associated with drug resistance to rifampicin. Results. DNA of M. tuberculosis was isolated from 70.9% of samples, of which 53.8% had mutations. Single-nucleotide substitutions in one of katG, inhA, ahpC, rpoB genes were found in 36.1%, double mutations were found in 10.9%, and multiple mutations (substitutions of three or more nucleotides) were found in 6.8%. The largest number of double and multiple mutations was registered in rpoB gene - 8.9% and 10.2%, respectively. The largest number of combined mutations in different genes was observed in the combination katG + rpoB – 23.4% and katG + inhA + rpoB – 19.2% 17 (5.48%) samples with simultaneous multiple and combined mutations in different genes katG , inhA , ahpC were identified. Of these, 14 (82.3%) people had multiple mutations in katG , inhA , ahpC genes combined with multiple mutations in rpoB gene, of which 57.2% had severe forms of tuberculosis with destruction and positive results of sputum tests. Thus in Saratov Oblast among patients with pulmonary tuberculosis, a group was identified in which M. tuberculosis had multiple mutations in katG , inhA , ahpC genes in combination with multiple mutations in rpoB gene.