Genetic markers of multi-drug and extensive drug resistant M. tuberculosis in Kyrgyz Republic

Tuberculosis (TB) is still a major cause of morbidity and mortality worldwide and also in Kyrgyz Republic. Decades of tuberculosis treatment failures in Kyrgyz Republic led to acquired resistance to the first-line antituberculous drugs, isoniazid (INH) and rifampicin (RIF), resulting in multidrug resistant tuberculosis (MDR-TB) (300-400 cases per year). Switch to second line drugs lead to acquisition of resistance to them and spread of XDR-TB. XDR tuberculosis cases represent about 3 to 10% of MDR cases in the countries like Kyrgyz Republic. The aim of this study is the identification of mutation in rpoB, katG, inhA, ahpC and gyrA genes in MDR-Tb cases in Kyrgyz Republic. Materials and methods. DNA samples of M. tuberculosis (M.Tb) were collected from 99 sputum samples from adult patients with primary MDR-TB. Mutations associated with resistance to rifampicin, isoniazid and fluoroquinolone were analyzed by biochip assay. Results. We have demonstrated that in the rpoB gene of MDR M.tb strains the prevalent point mutation was Ser531Leu (59%). Among strains resistant to isoniasid the mutations of katG gene were found in 91% (inhA gene – 7% and ahpC gene -2%, respectively). The most frequent mutations in katG was Ser315Thr (91% of cases). The frequent mutations of gyrA gene were Asp94Gly and Ala90Val. Conclusion: In Kyrgyz Republic the main cases of M.Tb resistance to rifampicin is Ser531Leu mutation in rpoB gene, to isoniazid – Ser315Thr mutation of katG gene. The cause of resistance to fluoroquinolone are gyrA gene – Asp94Gly and Ala90Val.