Prevalence and molecular characterization of 1 fluoroquinolone - resistant Mycobacterium tuberculosis isolates in

26 China is one of the countries with the highest multidrug-resistant (MDR) 27 and fluroquinolone (FQ)-resistant TB burden country globally. 28 Nevertheless, knowledge on the prevalence and molecular 29 characterization of FQ-resistant Mycobacterium tuberculosis (M. 30 tuberculosis) isolates from this region remains not numerous. In this study, 31 by utilizing agar proportion susceptibility method, the 138 ofloxacin 32 (OFX)-resistant M. tuberculosis isolates were enrolled from the national 33 drug resistance survey of China. All these M. tuberculosis strains were 34 tested for drug susceptibility to ofloxacin, levofloxacin, moxifloxacin, 35 gatifloxacin and sparfloxacin using the liquid Middlebrook 7H9 medium. 36 The entire gyrA and gyrB genes conferring FQ resistance were sequenced, 37 and the spoligotyping was performed to distinguish different genotypes. 38 Overall, the prevalence of FQ resistance in China was highest for 39 ofloxacin (3.76%), intermediate for levofloxacin (3.18%) and 40 moxifloxacin (3.12%), and lowest for sparfloxacin (1.91%) and 41 gatifloxacin (1.33%). Mutations in gyrA gene were observed in 89 42 (64.5%) out of 138 OFX-resistant M. tuberculosis strains. Position 94 and 43 90 was the most frequent mutation site conferring FQ resistance in these 44 on July 9, 2017 by gest httpaac.asm .rg/ D ow nladed fom strains, accounting for high-level FQ resistance. Furthermore, Beijing 45 genotype showed no association with high-level FQ resistance and 46 distribution in hot spots in QRDR of gyrA. Our findings will provide 47 essential implications into the feasibility of genotypic tests relying on 48 detecting mutations in the QRDR of gyrA and the shorter first-line 49 treatment regimens based on FQs in China. 50