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GENETIC MONITORING AND CONTROL OF DRUG-RESISTANT M.
TUBERCULOSIS STRAINS IN THE REGION
Saifutdinov Zayniddin Asamutdinovich
Department of Microbiology, Immunology and
Fundamentals of Molecular Genetics
Parpieva Nargiza Nusratovna
director of the republican scientific and practical medical center of phthisiology
and pulmonology, chief phthisiologist of the republic, head of the department of
phthisiology of the TMA, doctor of medical sciences, professor
https://doi.org/10.5281/zenodo.15473701
Abstract
This study focuses on the genetic monitoring of drug-resistant
Mycobacterium tuberculosis (MDR/XDR-TB) strains in a high-burden region of
Central Asia. A total of 360 clinical isolates were collected and analyzed using
whole-genome sequencing (WGS) to detect resistance-associated mutations and
determine the genetic structure of circulating strains. The most common
mutations were found in katG, rpoB, gyrA, and Rv0678. The study revealed high
regional prevalence of the Beijing lineage (58%). Genomic data enabled
identification of transmission clusters and geographic resistance patterns. These
findings provide a foundation for molecular surveillance and targeted
interventions in tuberculosis control programs across the region.
Keywords:
Mycobacterium tuberculosis, genetic monitoring, drug resistance, WGS,
Beijing lineage, Central Asia, transmission, TB control.
Relevance
The global spread of multidrug-resistant and extensively drug-resistant
tuberculosis (MDR/XDR-TB) poses a critical challenge for public health systems,
particularly in high-burden regions like Central Asia. Conventional diagnostic
methods are time-consuming and often ineffective in rapidly detecting
resistance, leading to treatment delays and ongoing transmission. Genetic
monitoring using whole-genome sequencing (WGS) offers a transformative
approach to TB control by enabling fast, comprehensive, and accurate detection
of resistance mutations and identifying patterns of strain circulation. Such
molecular tools can uncover hidden transmission links, reveal regional
distribution of high-risk genotypes (e.g., Beijing lineage), and help predict
outbreaks. By integrating genetic surveillance into national TB programs, health
authorities can implement timely interventions, adjust treatment protocols, and
monitor the effectiveness of control measures. This study provides a model for
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establishing genomic surveillance systems in the region and supports the shift
toward precision public health strategies for combating drug-resistant
tuberculosis.
Objective:
To evaluate the genetic profiles and transmission dynamics of drug-resistant M.
tuberculosis strains in the region using whole-genome sequencing and to inform
regional TB control strategies.
Materials and Methods
The study included 360 M. tuberculosis isolates from MDR and XDR-TB
patients across five provinces of Central Asia, collected between 2021 and 2024.
Whole-genome sequencing was performed using the Illumina MiSeq platform.
Resistance mutations in katG, inhA, rpoB, gyrA, rrl, and Rv0678 were identified
through TBProfiler. Phylogenetic classification was based on SNP analysis and
lineage assignment. Transmission clusters were reconstructed using pairwise
SNP distances (≤12 SNPs). Epidemiological metadata were integrated to map
strain distribution and identify geographic hotspots. Data analysis involved R
v4.3 and BioNumerics software for cluster visualization and statistical
comparisons across regions.
Results
Among the 360 isolates, 58% belonged to the Beijing lineage, 22% to LAM,
and 13% to CAS. The most prevalent resistance mutations were katG S315T
(80%), rpoB S450L (74%), gyrA D94G (39%), and Rv0678 A63P (33%). WGS
revealed 17 distinct transmission clusters, with the largest cluster (n=42)
detected in two bordering provinces. Geographic mapping identified three high-
transmission zones. Phylogenetic analysis showed close genomic relationships
between strains in cross-border regions, suggesting ongoing regional
transmission. The results confirmed WGS as a critical tool for identifying
outbreaks, tracking drug-resistant clones, and designing targeted public health
responses based on genetic evidence.
Conclusion
Genetic monitoring through WGS has proven essential for understanding
the structure and transmission dynamics of drug-resistant M. tuberculosis
strains in Central Asia. The identification of dominant genotypes, common
resistance mutations, and regional transmission clusters enables public health
authorities to make data-driven decisions. The Beijing lineage continues to play
a central role in the spread of MDR/XDR-TB in the region. Integration of WGS
into TB control programs supports early detection of outbreaks, improves
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treatment strategies, and enhances surveillance capacity. This study provides a
foundation for developing regional genomic monitoring systems and advancing
precision TB control through molecular epidemiology.
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