DETECTION OF DRUG RESISTANCE MUTATIONS IN rpoB, katG, inhA, gyrA GENES OF Mycobacterium tuberculosis TO RIFAMPICIN, ISONIAZID, FLUOROQUINOLONE

The emergence of resistant strains of Mycobacterium tuberculosis significantly complicates control of disease spread. Multi-drug resistance is often the result of patients' non-compliance with the treatment regimen, very rarely - spontaneous point mutations in the genes of the microorganism. The emergence of resistance in strains of M. tuberculosis with multi-drug resistance to fluoroquinolones indicates the formation of a genotype with pre-extensive drug resistance. The most frequent mutations associated with rifampicin resistance are mutations in the rpoB (Ser531Leu, Asp516Val, His526Asp, His526Tyr) gene. Mutations determining resistance to isoniazid are located in the katG (Ser315Thr) gene with the highest detection frequency and in the promoter region of the inhA (C(-15)T; T(-8)A/C) with the lowest detection frequency. The mutations that cause resistance to fluoroquinolones are most often detected in the gyrA (Asp94Asn, Asp94Gly, Asp94His) genes. According to our study, the majority of cases M. tuberculosis resistance to rifampicin, isoniazid, fluoroquinolones was due to alterations in rpoB (Ser- 531Leu), katG (Ser315Thr), gyrA (Asp94Gly). It is important to understand that as one of the measures to prevent the spread of resistant M. tuberculosis strains is rapid molecular genetic methods that identify the pathogen’s DNA in the biomaterial and determine its resistance profile to the main anti-tuberculosis drugs in just 1-2 days. Cultural diagnostic methods take weeks, there is a chance that before obtaining the results of the drug sensitivity test, the patient can undergo treatment with drugs to which the bacteria are resistant, that will contribute to the development of resistance to other anti-tuberculosis drugs and further spread of resistant strains.