[Bedaquiline susceptibility and molecular mutation characteristics of Mycobacterium tuberculosis in Guizhou Province].

Objective

To detect the drug resistance of Mycobacterium tuberculosis (MTB) to the new drug bedaquiline (Bdq) and the mutations of drug resistance-related genes, and to analyze the correlation between drug resistance gene mutation types and drug resistance phenotypes.

Methods

From January 2020 to December 2022, 521 strains of MTB identified by Guiyang Public Health Clinical Center were collected, including 253 drug-susceptible tuberculosis (DS-TB) strains and 268 multi-drug resistant tuberculosis (MDR-TB) strains. The conventional drug sensitivity of Mycobacterium tuberculosis and the minimum inhibitory concentration (MIC) of Bdq were detected by microplate method. At the same time, Sanger sequencing was used to identify the mutations of Bdq resistance-related genes Rv0678, atpE and pepQ in all strains, and the whole genome sequencing of Bdq-resistant strains was performed to analyze their drug resistance and molecular mutation characteristics.

Results

The Bdq MIC of 521 clinical strains was mainly concentrated in the range of 0.016-0.12 mg/L. Bdq-resistant strains were only detected in MDR strains, with a drug resistance rate of 4.1% (11/268). Known Bdq resistance gene mutations were detected in 11 Bdq phenotype resistant strains, of which 10 were Rv0678 gene mutations, 1 was Rv0678 and pepQ gene mutations, and no atpE gene mutation was detected. There were 8 types of mutations in the Rv0678 gene, including C151T (3/11), 19delG (2/11), G404A (1/11), T284C (1/11), C305T (1/11), G149A (1/11), T95C (1/11) and 201delG (1/11). Our survey found that only one of the 11 patients with Bdq resistance had a history of Bdq medication; moreover, the whole genome sequence analysis of Bdq-resistant strains found that 3 strains were clustered strains, suggesting that transmission is an important cause of Bdq resistance.

Conclusions

Bdq had a strong antibacterial activity in the Guizhou region. Mutations in the Rv0678 gene served as the primary determinant of Bdq resistance; and transmission played a significant role in the dissemination of Bdq-resistant strains. The findings highlight the need for Bdq resistance-associated genetic screening and transmission chain surveillance in the control of multidrug-resistant tuberculosis.