Mutations that cause most resistance to tuberculosis are currently identified

Until the advent of SARS-CoV-2, the most destructive pathogens on earth Mycobacterium tuberculosis, A bug that causes tuberculosis. In 2020, the organism shortened the lives of 1.5 million people, according to the latest report from the World Health Organization released on October 14. This is a health system primarily caused by covid-19. People whose immune system has been destroyed by HIV are at particular risk. Approximately 200,000 of the 680,000 AIDS deaths annually are the result of secondary TB infection.

More than 12 antibiotics and other medications are used to treat tuberculosis. However, Mycobacterium tuberculosis One or more of these unaffected ones are emerging and spreading at an alarming rate. For example, of the 10 million tuberculosis patients in 2019, nearly 500,000 were drug resistant. However, on October 19, good news came out when the Comprehensive Resistance Prediction (CRyPTIC for short) of the International Cooperation Agency for Tuberculosis, an international cooperation agency that has been searching for a method to quickly diagnose resistant bacteria, announced the results. .. The consortium’s analysis of more than 15,000 samples from patients in 27 countries is a way to detect any resistance-induced mutations in the genome of a particular bacterium.

At this time, it is difficult to determine if the strain causing a particular case of tuberculosis is resistant to a particular drug. One of the common approaches, now over 100 years old, is to incubate microorganisms from sputum samples in Petri dishes until they are large enough to form visible plaques. Then sprinkle the plaque with one or more medications to see if the bacteria stop growing.However Mycobacterium tuberculosis The more notorious it is in laboratory conditions, the slower it reproduces. It takes 2 to 6 weeks to grow sufficiently for the test, and up to 3 more weeks for the test to produce results. Still, the results may not be easy to interpret. The answer to whether the drug worked is literally in the eyes of the viewer — and different eye pairs often see different answers.

But about 15 years ago, researchers using new gene sequencing technology Mycobacterium tuberculosisGenome. Therefore, a test called the polymerase chain reaction (PCR) was used to search for samples for these mutations. The PCR test requires only a small amount of bacteria and can be completed within hours. Therefore, PCR testing is now widely used to identify mutations that confer resistance to one of the most effective anti-tuberculosis drugs, rifampicin.

CRyPTIC researchers identify all possible combinations of mutations that confer resistance to any combination of drugs, and evaluate mutation-related resistance levels to different doses of the drug for PCR testing. Proposed to expand the range. Participating laboratories used 96-well culture plates instead of Petri dishes to grow the bacteria. The well contained various amounts of 13 tuberculosis drugs. The plate was photographed after the drug had time to act. The image was then entered into the database for inspection.

But that part of the process still needed a human eye. These were provided by 9,000 crowdsourced “citizen scientists” and each plate was individually inspected by about 15 such volunteers. By comparing the results of these tests to the entire genomic sequence of each sample, CRyPTIC researchers can discover which combination of genetic alterations correlated with which form of drug resistance. Some of their findings are surprising (for example, it turns out that a mutation that gives resistance can co-exist with another mutation that counteracts its effect). However, they are fairly convinced that they have identified almost all combinations of important mutations.

We hope that the resulting catalog will be used to design better PCR tests. It also identifies drug combinations that are most likely to treat a particular patient as rapid whole-genome sequences become increasingly available. This allows for individualized treatment of tuberculosis.

In addition, the CRyPTIC approach may serve as a template for investigating drug resistance of other pathogens. This may help prevent the spread of such resistance with the indiscriminate and sloppy use of antibiotics around the world. If accurate diagnosis can prevent this spread, CRyPTIC results will affect not only personal health but also public health. ■■

Mutations that cause most resistance to tuberculosis are currently identified

Source link Mutations that cause most resistance to tuberculosis are currently identified

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