A Profile of Drug-Resistant Mutations in Mycobacterium tuberculosis Isolates from Guangdong Province, China

Guangdong Province, China’s largest economy, has a high incidence of tuberculosis (TB). At present, there are few reports on the distribution, transmission and drug resistance of Mycobacterium tuberculosis (Mtb) strains in this region. In this study, we performed minimum inhibitory concentration testing for 14 anti-TB drugs and whole-genome sequencing of 713 clinical Mtb isolates from 20,662 sputum culture-positive tuberculosis patients registered at 31 tuberculosis drug resistance surveillance sites covering 20 cities in Guangdong Province from 2016 to 2018. Moreover, we evaluated genome-wide associations between mutations and drug resistance, and further investigated the differences in the MICs of mutations. The epidemiology, drug-resistant phenotypes and whole genome sequencing data of 713 clinical Mtb isolates were analyzed, revealing the lineage distribution and drug-resistant gene profiles in Guangdong Province. WGS combined with quantitative MIC measurements identified several novel loci associated with resistance, of which 16 loci were found to be related to resistance to more than one drug. This study analyzed the lineage distribution, prevalence characteristics and resistance-corresponding gene profiles of Mtb isolates in Guangdong province, and provided a theoretical basis for the formulation of tuberculosis prevention and control policy in the province.