Insight into Population Structure and Drug Resistance of Pediatric Tuberculosis Strains from China and Russia Gained through Whole-Genome Sequencing

Int J Mol Sci. 2023 Jun 18;24(12):10302. doi: 10.3390/ijms241210302.

Abstract

This study aimed to determine phenotypic and genotypic drug resistance patterns of Mycobacterium tuberculosis strains from children with tuberculosis (TB) in China and Russia, two high-burden countries for multi/extensively-drug resistant (MDR/XDR) TB. Whole-genome sequencing data of M. tuberculosis isolates from China (n = 137) and Russia (n = 60) were analyzed for phylogenetic markers and drug-resistance mutations, followed by comparison with phenotypic susceptibility data. The Beijing genotype was detected in 126 Chinese and 50 Russian isolates. The Euro-American lineage was detected in 10 Russian and 11 Chinese isolates. In the Russian collection, the Beijing genotype and Beijing B0/W148-cluster were dominated by MDR strains (68% and 94%, respectively). Ninety percent of B0/W148 strains were phenotypically pre-XDR. In the Chinese collection, neither of the Beijing sublineages was associated with MDR/pre-XDR status. MDR was mostly caused by low fitness cost mutations (rpoB S450L, katG S315T, rpsL K43R). Chinese rifampicin-resistant strains demonstrated a higher diversity of resistance mutations than Russian isolates (p = 0.003). The rifampicin and isoniazid resistance compensatory mutations were detected in some MDR strains, but they were not widespread. The molecular mechanisms of M. tuberculosis adaptation to anti-TB treatment are not unique to the pediatric strains, but they reflect the general situation with TB in Russia and China.

Keywords: China; Mycobacterium tuberculosis; Russia; drug resistance; pediatric tuberculosis.

MeSH terms

  • Antitubercular Agents / pharmacology
  • Antitubercular Agents / therapeutic use
  • Child
  • China / epidemiology
  • Drug Resistance
  • Drug Resistance, Multiple, Bacterial / genetics
  • Genotype
  • Humans
  • Mutation
  • Mycobacterium tuberculosis* / genetics
  • Phylogeny
  • Rifampin
  • Russia / epidemiology
  • Tuberculosis* / drug therapy
  • Tuberculosis* / epidemiology
  • Tuberculosis, Multidrug-Resistant* / drug therapy
  • Tuberculosis, Multidrug-Resistant* / epidemiology
  • Tuberculosis, Multidrug-Resistant* / genetics

Substances

  • Antitubercular Agents
  • Rifampin