Study on Mutation and Its Characteristics of Mycobacterium Tuberculosis Multidrug Resistance Genes Based on Whole-genome Sequencing

Objective: The increase in the development of resistance to multiple drugs in mycobacterium tuberculosis(MTB) poses a substantial obstacle to the prevention and management of tuberculosis(TB). A thorough investigation of the genotypes linked to multidrug resistance is crucial for comprehending the mechanisms underlying drug resistance. The objective of this research was to assess the attributes of gene mutations associated with multidrug resistance in clinical isolates of mycobacterium tuberculosis through the utilization of whole-genome sequencing. Methods: A total of 124 strains of drug-resistant mycobacterium tuberculosis were collected, and the genomic DNA of both multidrug-resistant and rifampin-resistant strains were extracted and sequenced. Bioinformatics was used to analyze and compare multidrug resistance-related gene sequences in order to detect the variation of multidrug resistance genes. Results: The results revealed that the resistance spectrum of XDR-TB group was much wider than that of the other three groups, with the RR-TB group having the most limited resistance spectrum.Within the MDR-TB strains, fabG1 exhibited the highest frequency of mutations, while RRS, gyrA, and rpoB were identified as the predominant mutation bases in XDR-TB strains. Additionally, rpoB emerged as the primary mutation base in MDR-TB and RR-TB strains. Notably, the fabG1 mutation was found to be closely associated with PDR-TB. Furthermore, the correlation between the mutation rate of rpoB and multidrug resistance was deemed to be of secondary importance. Conclusion: Various strains of MTB exhibited distinct mechanisms of drug resistance, with the gene mutations of fabG1,RRS, gyrA, and rpoB potentially playing a pivotal role in the development of drug resistance. However, the primary genes responsible for drug resistance mutations varied among different strains of TB.