Whole Genome Sequencing For Tuberculosis Bacteria Has Improved Diagnosis And Treatment Outcomes. Here’s How

The complete genomic sequence of Mycobacterium tuberculosis, the causative organism of tuberculosis, was first obtained in 1998, by Cole et al. The DNA sequence data for the entire Mycobacterium tuberculosis genome was obtained through whole genome sequencing. The whole genome has served as an extremely important resource to understand tuberculosis. 

With the information obtained from the Mycobacterium tuberculosis genome, researchers have performed extensive research on tuberculosis and its epidemiology, and made efforts towards improving diagnostic and treatment outcomes. 

How whole genome sequencing for tuberculosis has been a boon for patients as well as researchers

Whole genome sequencing of Mycobacterium tuberculosis is a boon for molecular biology researchers and tuberculosis patients because scientists can predict antibacterial susceptibility, analyse individual outbreaks and historical trends of epidemics,try to improve the efficacy of the Bacille Calmette-Guérin (BCG) vaccine, and find suitable targets for novel drugs against tuberculosis, according to an October 2023 study published in The Journal of Clinical Investigation.

Scientists perform whole genome sequencing of past Mycobacterium tuberculosis isolates retrospectively (analyse genomic data sequenced in the past), and that of new isolates prospectively (analyse genomic data of new isolates to find out how harmful those strains could become in the future). 

The Centers for Disease Control and Prevention (CDC) uses such data to identify mutations in new strains and detect possible drug resistance, among other applications. 

Whole genome sequencing is used for therapeutic innovations, including the newest generation of antitubercular drugs, to identify therapeutic targets, and track resistance mechanisms. 

Diagnostic advancements have also been possible because of the data obtained from the entire genome of Mycobacterium tuberculosis. 

There are many understudied variants of Mycobacterium tuberculosis, and through whole genome sequencing of these isolates, scientists can obtain relevant information about bacterial factors that promote host infection. 

There are several instances of whole genome sequencing having helped scientists identify pre-existing drug resistance and susceptibility to tuberculosis infection in certain populations. 

Also, studying the human genome and the reference genome of Mycobacterium tuberculosis can help scientists understand how the pathogen and human immune systems affect one another. 

The most widely used Mycobacterium tuberculosis strain is H37Rv. Globally, scientists use the genome of H37Rv as a reference sequence.

The different ways in which the use of whole genome sequencing for Mycobacterium tuberculosis has improved diagnostic and treatment outcomes include improved strain typing (microbial characterisation to differentiate between different strains of a particular bacterial species) and transmission tracking, enhanced drug resistance detection, prediction of treatment outcomes, detection of mixed infections, identification of novel drug targets, and optimisation of public health interventions, Dr Ajit Baviskar, a specialist in critical care and medical quality at White Lotus International Hospital, Maharashtra, told ABP Live. 

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Tracing the source of infections, and identifying mutations leading to drug resistance

By analysing genetic variations between strains, health authorities can identify outbreaks, trace the source of infections, and implement targeted control measures more effectively, he explained. 

A large number of tuberculosis patients fail to respond to standard treatment because they are resistant to key first-line drugs such as rifampicin and isoniazid, said Dr Aparna Bhanushali, Head, Growth and Scientific Support, HaystackAnalytics. This is a health-tech company in the Indian Institute of Technology Bombay (IIT) that creates clinical genomic products.

She explained that whole genome sequencing has significantly improved treatment outcomes by comprehensively identifying drug resistance profiles in the case of multidrug-resistant tuberculosis. “It is a revolutionary molecular diagnostic tool that helps trace the mutations responsible for drug resistance. This allows for the identification of the most effective treatment.”

In other words, since genetic mutations associated with drug resistance can be analysed through whole genome sequencing, clinicians can identify drug-resistant strains more accurately, and design treatment regimens accordingly.

This helps improve patient outcomes and prevent further transmission of resistant strains.

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Detecting mixed infections and identifying novel drug targets

Whole genome sequencing can detect mixed infections with different strains or subpopulations of tuberculosis bacteria within a single patient. This insight is crucial for selecting appropriate treatment regimens and monitoring treatment responses effectively, according to Dr Baviskar.

He also said that whole genome sequencing can analyse genetic markers associated with virulence and drug resistance, helping predict treatment outcomes more accurately, and aiding clinicians in selecting the most effective treatment options for individual patients. This reduces the risk of treatment failure and relapse. 

Whole genome sequencing can reveal genetic vulnerabilities in different strains of Mycobacterium tuberculosis, facilitating the identification of novel drug targets. 

Information on genetic vulnerabilities will allow scientists to develop new drugs and treatment strategies, particularly for drug-resistant tuberculosis strains that are challenging to treat with existing antibiotics, Dr Baviskar explained. 

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Predicting resistance profiles of anti-tuberculosis drugs

With the help of whole genome sequencing, the resistance profiles of all anti-tuberculosis drugs can be predicted reliably in a single run, according to Dr Bhanushali. She said that globally, several countries have highlighted the utility and impact of whole genome sequencing on treatment outcomes, and have also shown that underdiagnosis due to inefficient diagnostic tools results in inappropriate treatment, and subsequently, mortality. 

“Whole genome sequencing data can inform public health interventions by providing insights into tuberculosis transmission dynamics, population structure, and drug resistance patterns. This information helps health authorities prioritise resources, implement targeted control measures, and monitor the effectiveness of tuberculosis control programmes more efficiently,” he said.

Therefore, as experts have explained, whole genome sequencing has improved scientists’ understanding of tuberculosis epidemiology, pathogenesis, and treatment response, and such rich genomic data helps healthcare professionals deliver personalised and effective therapies to tuberculosis patients, and contribute towards global efforts to eliminate the disease.

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