Tuberculosis study identifies genetic causes of drug resistance

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Researchers have identified genetic causes of drug resistance to tuberculosis (TB) treatment.

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The team created a dataset that was used to measure how changes in the genetic code on M. tuberculosis kill these bacteria that cause TB.

It harnessed two new advances – a new test for drug resistance and a new approach that identifies all genetic changes in a sample of drug-resistant TB bacteria.

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The researchers say these innovations, along with ongoing work in the field, will improve the way TB patients are treated in the future.

This innovative, large-scale, international collaboration has enabled us to create perhaps the most comprehensive map of the genetic alterations responsible for drug resistance in tuberculosis.

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The Comprehensive Resistance Prediction for Tuberculosis International Consortium (CRyPTIC) research project has led to the development of clinical M. The largest global dataset of tuberculosis samples collected to date included 15,211 samples from 27 countries across five continents.

Researchers suggest that the infection kills more people each year than any other bacteria, virus or parasite except Covid-19.

Although it is treatable, drug resistance has emerged as a major problem over the past 30 years.

Testing for mutations in the M. tuberculosis genome to determine which drugs will give the patient the best chance of cure is the most realistic way to get drug resistance testing for every patient, scientists say .

Genome is the complete set of genetic information in an organism.

Dr. Derrick Crook, Professor of Microbiology, University of Oxford Said: “This innovative, large-scale, international collaboration has enabled us to produce possibly the most comprehensive map of the genetic changes responsible for drug resistance in tuberculosis.”

Through nine new pre-prints that have not yet been peer-reviewed, the researchers uncovered several findings.

They included how new drug resistance tests should be interpreted, and how a massive citizen science project helped solve this problem.

Our ultimate goal is to obtain sufficiently accurate genetic prediction of resistance to most anti-tuberculosis drugs, so that whole genome sequencing can replace culture-based DST for TB.

The research also revealed how a new approach to detect and describe genetic changes in the whole TB genome sequence improved the way we detect genetic changes that drive drug resistance.

This further indicates how individual mutations, and combinations of mutations, may be related to even minor changes in the way a drug kills an infection, thereby reducing the effectiveness of treatments, as well as for treating tuberculosis. Particular attention is paid to the two novel compounds used.

The research also revealed how artificial intelligence can predict drug resistance, and how the data contributed to the first catalog of drug resistance mutations in the TB genome, which was supported for global use. World Health Organization (WHO).

It is hoped that the findings will help improve the control of TB and facilitate WHO’s final TB strategy through better, faster and more targeted treatment of drug-resistant tuberculosis, and the need for universal drug susceptibility testing (DST). Will pave the way in that direction.

Prof Kruk said: “Our ultimate goal is to obtain sufficiently accurate genetic prediction of resistance to most anti-tuberculosis drugs, so that whole genome sequencing can replace culture-based DST for TB.

“This will enable rapid changes to near-patient assays to revolutionize the detection and management of MDR-TB.”

This project is funded by the MRC Newton Fund, Welcome Trust and the Bill & Melinda Gates Foundation, and the work of Prof. Crook’s team is supported through the NIHR Oxford Biomedical Research Center’s Antimicrobial Resistance and Microbiology Theme.

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