XDR and MDR-TB genetic markers of M. tuberculosis strains circulating in Kyrgyz Republic

In Kyrgyz Republic multidrug-resistant tuberculosis (MDR-TB) is a real public health problem. For treatment of MDR-TB the second-line drug fluoroquinolone (FQ) is used. The use of this drug has led to the emergence of fluoroquinolone-resistant M.Tuberculosis (M.tb). Aim: The aim of this study was to asses the fluroquinolone resistance in MDR-TB cases and to reveal the main mutations of gyrA gene associated with FQ resistance in Kyrgyz Republic. Materials and methods: DNA samples of M. tb were collected from 70 adult patients with primary MDR-TB. From all samples the 33 sputum samples were taken from patients from the penitentiary system and 37 sputum samples were taken from patients from the civilian sector. The resistance to rifampicin, isoniazid and fluoroquinolone were analyzed by biochip assay. Results: 70 selected samples of M.tb strains carried mutations leading to MDR and including 5 cases with FQ resistance. The most prevalent mutations of gyrA gene was Asp94Gly, the second was Ala90Val. One case had the combination of both mutations Asp94Gly and Ala90Val of gyrA gene. These mutations of gyrA gene were coexisting in the same samples with Ser531Leu mutation of rpoB, Ser315Thr of katG and inhA T_15 mutation of inhA gene. Conclusion: In XDR-TB cases mutations of gyrA gene leading to FQ resistance of M.tuberculosis are mostly associated with presence of Ser531Leu mutation of rpoB, Ser315Thr mutation of katG gene and inhA T_15 mutation of inhA gene.