[Analysis on Drug Resistance-associated Mutations of Multi-drug Resistant Based on Whole-genome Sequencing in China]

To analyze the resistance mutational profiles of multi-drug resistant in China and the correlation between major mutation types and genotypes based on the whole-genome sequencing data. Search and download of the genome-wide sequencing data of published in China by August 2019 on NCBI database were conducted. Mutation frequency of drug resistance-related gene loci based on whole-genome sequencing was used to predict the molecular susceptibility of strains, and the correlation between mutation types and genotypes was analyzed. According to the results of molecular resistance and susceptibility profiles, 1 024 MDR strains were identified from 2 019 strains. The major mutation types of resistance-related genes to common drugs were S315T (73.2%, isoniazid), S450L (63.1%, rifampicin), K43R (70.0%, streptomycin), M306V (37.4%, ethambutol), _promoter T (-11)C (7.9%, pyrazinamide), A90V (32.3%, fluoroquinolones), A1401G (67.7%, second-line injection drugs), _promoter C (-15) T (87.0%, Ethionamide), I43T (30.4%, P-aminosalicylic acid). Among them, the frequencies of S315T, M306V, K43R, A90V in lineage 2 were significantly higher than those in lineage 4, and I43T was only found in lineage 2. The proportion of S315T was significantly higher in the ancient Beijing genotype compared to the modern genotype, in contrast, the proportion of K43R was significantly higher in modern Beijing genotype, the differences were significant (all <0.05). The results showed the main mutation types of resistance-related genes of MDR strains to many commonly used anti-tuberculosis drugs in China based on whole-genome sequencing, providing a basis for the development of sensitive and specific rapid molecular detection methods. At the same time, it was also found that the major mutation types of MDR-related genes were related to the genotype of the strains.