Scientists will overcome the resistance of tuberculosis to antibiotics
Polit.<url> based on the materials of Science: Emma Hiolski, Biological version of malware reverses antibiotic resistance in TB
According to the World Health Organization, in 2015, 10.4 million people contracted tuberculosis, and about two million died from this disease. Almost half of the new patients were infected with strains of Mycobacterium tuberculosis with multidrug resistance, therefore, most of the anti-tuberculosis drugs will not help them.
A group of scientists from France, Sweden, Belgium, Switzerland and South Korea has found a way to make Mycobacterium tuberculosis susceptible to one of the existing drugs again. This is ethionamide, which now serves as a second-line anti-tuberculosis antibiotic. The use of ethionamide is strongly limited by its side effects, in particular its harmful effects on the digestive organs, liver and thyroid gland, but if the discovery is confirmed, then this disadvantage will be overcome, since smaller doses will be needed for treatment.
Ethionamide is a prodrug, that is, it passes into its active form already in the body under the influence of one of the mycobacterium proteins – ethA. But many mycobacteria had a mutation in the gene responsible for the production of this protein, which made them completely resistant to ethionamide. The researchers found another gene (ethA2) in the causative agent of tuberculosis, which is usually inactive, so they did not have time to develop resistance to this gene. In combination with the low molecular weight substance SMARt-420, the activity of this gene increases significantly, which makes the mycobacterium vulnerable to ethionamide.
Experiments in bacterial cultures and on laboratory mice have shown the high efficiency of the proposed method against a wide range of M.tuberculosis strains, both sensitive to ethionamide and resistant. In mice treated with a combination of ethionamide and SMARt-420, the number of bacteria in the lungs decreased by almost 40,000 times. Since SMARt-420 significantly increases the effectiveness of the drug, it can be used in small doses, avoiding severe side effects.
To reduce the chances of bacteria to acquire a mutation in the ethA2 gene and become resistant to this treatment, the researchers suggest using SMARt-420 in therapy occasionally to destroy those bacteria that have a mutation in the ethA gene. Ethionamide will cope with other bacteria alone.
The researchers hope to begin clinical trials in 18 months.
Article by Blondiaux et al. The reversal of antibiotic resistance in Mycobacterium tuberculosis by spirosoxazoline SMARt-420 is published in the journal Science.
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17.03.2017