Prevalence and Patterns of Gene Mutations Associated with <i>M. tuberculosis</i> Resistance to Isoniazid and Rifampicin in Patients with Different Clinical Manifestations of Tuberculosis

Abstract

The objective: to study prevalence and patterns of mutations in the katG, inhA, ahpC, rpoB genes associated with Mycobacterium tuberculosis (MTB) resistance to isoniazid (H) and rifampicin (R) in patients with various clinical manifestations of pulmonary tuberculosis (TB).Subjects and Methods. 441 sputum samples collected in tuberculosis patients were tested using biological microchips. Tests were carried out in Group 1 - patients with confirmed bacterial excretion (n = 256) and in Group 2 (n = 185) - patients without bacterial excretion. The same patients were enrolled in Group 3 - patients with acute progressing tuberculosis (n = 52) and Group 4 (n = 99) - patients with localized tuberculosis.Results. In Group 1, DNA of Mycobacterium tuberculosis was found in 79.3% of patients, in Group 2 - in 57.8%. Among all samples, mutations in the genes encoding resistance to isoniazid were detected in 15.5%, resistance to rifampicin - in 58.1%. Resistance to isoniazid was more often caused by mutations in the katG gene (49%) versus the inhA (29%) and ahpC (4.2%) genes. We found 13 most common types of mutations in the rpoB gene associated with resistance to rifampicin. The dominant mutations in both groups were Seu531->Leu mutations - 19.7% in Group 1 and 24.3% in Group 2. In Group 1, mutations in the katG gene (53.7%) were observed more often than mutations in the inhA gene (27.7%). In Group 3, mutations in the katG gene were registered in 30.8%, in the inhA gene - in 25%. There were no statistically significant differences in patterns of mutations in the katG, inhA, ahpC, rpoB genes between Groups 1, 2 and 3, 4. Thus, patients without bacterial excretion and patients with localized tuberculosis are a hidden dangerous reservoir of tuberculous mycobacteria with multiple drug resistance to rifampicin and drug resistance to isoniazid.