Take The Advantages of Whole Genome Sequencing in Mycobacterium Tuberculosis Research

Whole Genome Sequencing (WGS) refers to a research technology that uses high-throughput sequencing technology to sequence individuals or populations of species, analyze the obtained genome maps, and identify their differences, in order to explore the evolution of species and screen functional genes at the entire genome level. It has the advantages of comprehensive, accurate, high-throughput, and high-resolution information acquisition, Currently, more and more researchers are applying it to the epidemiological study of microorganisms such as bacteria.

The advantages of whole genome sequencing technology

  1. It can quickly and comprehensively detect all relevant drug resistance sites, which is conducive to clinicians' timely and reasonable selection of treatment options
  2. The technology is simple to operate, more practical, and easier to promote
  3. Compared with traditional drug sensitivity tests, the price is more economical and more conducive to patient acceptance.

Predicting Bacterial Resistance to Antibiotics through Whole Genome Sequencing

In the diagnosis of drug-resistant tuberculosis, rapid detection of drug resistance of Mycobacterium tuberculosis is essential to improve the treatment effect of patients and reduce the spread of bacteria. Whole-genome sequencing (WGS) has shown tremendous potential in rapid diagnosis of drug-resistant tuberculosis (TB). Researchers performed WGS on drug-resistant Mycobacterium tuberculosis isolates obtained from Shanghai (n= 137) and Russia (n=78). Furthermore, drug sensitivity testing and genome-wide sequencing techniques were used to simultaneously detect the resistance of all strains to seven anti-tuberculosis drugs (isoniazid, rifampicin, streptomycin, ethambutol, ofloxacin, amikacin, and capreomycin). The predicted drug resistance results of genome-wide sequencing were compared with the results of phenotypic drug sensitivity testing to determine the sensitivity and specificity of genome-wide sequencing prediction. The results showed that WGS could predict 82.07% of phenotypically drug-resistant domestic strains.This study demonstrates that genome wide sequencing technology has a high sensitivity in predicting the drug resistance phenotype of anti-tuberculosis drugs.

Whole-genome phylogeny of the 215 M. tuberculosis isolates.

Whole genome sequencing reveals pre-resistance in Mycobacterium tuberculosis

Recent advances in bacterial whole-genome sequencing have resulted in a comprehensive catalog of antibiotic resistance genomic signatures in Mycobacterium tuberculosis. Researchers have sequenced the whole genome of more than 3000 tuberculosis samples and tracked the tuberculosis infection of patients in the past 20 years for reconstructing the family tree of TB bacteria, known as phylogenetic numbers, researchers then used computer analysis to identify the ancestral genetic code of the bacteria (which subsequently leads to drug resistance). By analyzing the branches of the family tree, researchers identified key changes related to MTB resistance, thereby understanding which factors are most likely to cause MTB resistance. This study described loci and genomic polymorphisms associated with a higher risk of resistance acquisition. Identifying markers of future antibiotic resistance could enable targeted therapy to prevent resistance emergence in M. tuberculosis and other pathogens by whole genome sequencing. Mycobacterium tuberculosis whole genome sequencing data can provide insights into temporal and geographical trends in resistance acquisition and inform public health interventions. Recent research has used a large number of clinically collected Mycobacterium tuberculosis genome-wide sequencing data and phenotypic drug resistance testing data to study when, where, and how M. tuberculosis acquired drug resistance worldwide. These studies demonstrate that whole genome sequencing has promoted the research of M. tuberculosis.

Genome-Wide association study (GWAS) results.

Whole genome sequencing technology has been widely used in the research of Mycobacterium tuberculosis, including lineage identification, microevolution, drug resistance prediction, transmission monitoring, and diagnosis of mixed infections. It is expected to rapidly and better prevent, control and diagnose tuberculosis, and conduct detailed and real-time epidemiological research on tuberculosis outbreaks. From the perspective of accuracy, convenience, and economy, it is undoubtedly of greater value to use whole genome sequencing technology to diagnose multidrug-resistant and even extensively resistant pulmonary tuberculosis in the future.

References:

  1. Torres Ortiz, Arturo et al. "Genomic signatures of pre-resistance in Mycobacterium tuberculosis." Nature communications vol. 12,1 7312. 15 Dec. 2021
  2. Wang, Luqi et al. "Whole-genome sequencing of Mycobacterium tuberculosis for prediction of drug resistance." Epidemiology and infection vol. 150 e22. 7 Jan. 2022
  3. Ektefaie, Yasha et al. "Globally diverse Mycobacterium tuberculosis resistance acquisition: a retrospective geographical and temporal analysis of whole genome sequences." The Lancet. Microbe vol. 2,3 (2021): e96-e104.
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