Molecular characteristics and in vitro susceptibility to bedaquiline of Mycobacterium tuberculosis isolates circulating in Shaanxi, China

Abstract Objective This study aimed to investigated the molecular characteristics and in vitro susceptibility to bedaquiline of Mycobacterium tuberculosis (MTB) isolates from Shaanxi, China. Methods MIC of bedaquiline was determined using microplate alamarblue assay for 518 MTB isolates from Shaanxi. The isolates with MIC values of bedaquiline greater than or equal to 0.12 μg/ml were sequenced for atpE, Rv0678 and pepQ genes. Drug susceptibility test and spoligotyping were also conducted for all strains. Results Ten (1.93%) bedaquiline-resistant strains isolated from 518 tuberculosis patients and the resistance rate of bedaquiline was not correlate to gender, age, treatment history, region and genotype. Five bedaquiline-resistant isolates and one bedaquiline-susceptible isolate carrying Rv0678 mutations, identified six mutation types, including G5T, A263 G, C185 T, G19deletion, C265 T and T323C. No mutation within the atpE and pepQ genes were observed. Conclusion Bedaquiline showed a strong in vitro antibacterial activity against MTB isolates and the Rv0678 gene serves as the major mechanism contributing bedaquiline resistance among MTB isolates from Shaanxi, China. Three novel mutation types (G19deletion, C265 T and T323C) of Rv0678 gene were associated with resistance to bedaquiline. Furthermore, in addition to the current three resistance-associated genes (atpE, Rv0678 and pepQ), other resistance mechanisms of bedaquiline may exist that need further study.