Globally, tuberculosis is the most common infectious bacterial disease leading to death. The pathogen responsible for tuberculosis, Mycobacterium tuberculosis, has a number of peculiarities. The first is that it grows very slowly. While other typical pathogens, such as pneumococcus and pseudomonads, can already be identified by their growth in the microbiological laboratory during the first 72 hours, it usually takes several weeks for the TB bacteria to settle. develop in the laboratory. Thus, it often takes one to two months before the effectiveness of individual drugs can be tested.
However, these efficacy tests are essential for the effective treatment of multidrug-resistant tuberculosis (MDR-TB), which is becoming more and more common. In these cases, the pathogen has become resistant, i.e. unresponsive, to the best anti-tuberculosis drugs, rifampicin and isoniazid. This is due to changes in the genome, called mutations, which almost always occur at the same points in the genome. Treatment for MDR-TB is long, expensive, and frequently associated with side effects.
For the selection of antibiotics in combination therapy, doctors have so far relied on the results of the drug test after culture. “Currently, 15 drugs are available for second-line treatment, of which at least four are used in combination,” explains Prof. Christoph Lange, coordinator of the clinical study at the Borstel Research Center.
In order to speed up the choice of the most effective antibiotics, scientists from the DZIF of the Borstel Research Center, headed by Prof. Stefan Niemann, have created a catalog of mutations in the genetic material of tuberculosis bacteria that can predict resistance antibiotics from bacteria against all drugs. Unlike many other bacteria, the genetic material of TB bacteria does not change much over time. The genome of tuberculosis bacteria contains approximately 4.4 million building blocks (base pairs) that store information for approximately 4,000 genes.
Hans-Peter Grobbel, medical student and DZIF undergraduate fellow in Christoph Lange’s team, supported by fellow student Niklas Köhler, Professor Matthias Merker, Dr Sönke Andres and Dr Harald Hoffmans, reviewed the results of the resistance predictions antibiotics through global genome analyzes. Using tuberculosis bacteria from 70 MDR-TB patients treated at Borstel’s medical department, the researchers compared the molecular prediction of antibiotic resistance with actual results from culture tests. They were provided by Professor Florian Maurer, head of the national reference laboratory for tuberculosis bacteria in Borstel. Scientists also examined whether reliable combinations of drugs for the treatment of MDR-TB could be compiled based on the prediction of the bacteria’s genetic material.
“Ninety-nine percent of all drugs in the combination therapies that we have assembled based on the results of molecular predictions of the genetic material of tuberculosis bacteria are also effective according to traditional microbiological tests for resistance to antibiotics. », Explains Grobbel. Today, molecular methods are both cheap and fast. Ideally, patients can already receive personalized MDR-TB treatment within the first week of their TB diagnosis.
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Material provided by German Infection Research Center. Note: Content can be changed for style and length.