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- Drug resource: the "devourer" of bacteria will make a revolution in tuberculosis therapy
Drug resource: the "devourer" of bacteria will make a revolution in tuberculosis therapy
Scientists have discovered and described a new virus capable of destroying mycobacteria, including pathogens of such dangerous diseases as tuberculosis and leprosy. The discovered virus, mycobacteriophage Vic9, is the first to be isolated in Russia. This is an important scientific achievement that can initiate the creation of a new drug against tuberculosis, the Gabrichevsky Research Institute of Epidemiology and Microbiology told Izvestia. However, scientists still have a lot of work to do to create an effective drug.
How bacteriophages kill pathogens
Scientists from the Federal Scientific and Clinical Center of Physico-Chemical Medicine named after Academician Y.M. Lopukhin of the Federal Medical and Biological Agency and colleagues have discovered and described a new bacterial virus, mycobacteriophage Vic9. According to them, bacterial infections are one of the most common causes of death worldwide. At the same time, antibiotic-resistant varieties are increasingly found among the pathogens. For some forms of multidrug-resistant tuberculosis, the probability of successful treatment today is no more than 68%. Phage therapy, a method in which dangerous bacteria are infected with special viruses called bacteriophages, can become an alternative or supplement to traditional antibiotic treatment.
Phages penetrate bacterial cells, destroy them from the inside, simultaneously multiplying and forming a new generation of viruses. However, they usually target a single bacterial species or even a strain of the pathogen (a strain is a variant with special properties). This makes the phages safe for the patient and his normal microflora. However, to select an effective treatment, it is important to have an extensive collection of well-studied bacteriophages. At the same time, it is necessary to know how their life cycle works and which bacteria they infect.
Researchers isolated Vic9 from soil samples using the bacterium Mycobacterium smegmatis. This microorganism is often used in research because it is genetically close to tuberculosis bacillus, but it is safe for humans. To obtain the bacteriophage, the researchers used the method of cumulative cultures: a selected culture was added to a solution containing virus particles from nature, but purified from all microorganisms. This allowed only phages targeting this bacterium to multiply, among which was Vic9.
— In addition to Vic9, we identified about 20 more phages, including those that demonstrate high activity against tuberculosis bacillus. We plan to use the developed system of methods, including life cycle analysis, for their detailed research and replenishment of our collection. In addition, the mechanism by which mycobacteria evade the immune response requires attention. They can survive inside macrophages, immune cells designed to destroy them. Tuberculosis pathogens are also capable of becoming resistant to standard therapy. We want to investigate how phages will affect mycobacteria in such protected conditions," said Egor Shitikov, a participant in the study and head of the Laboratory of Molecular Genetics of Microorganisms at the Lopukhin National Research Center for Physico—Chemical Medicine of the Russian Academy of Medical Sciences.
How the new phage will help fight tuberculosis
Using an electron microscope, the scientists determined that Vic9 is arranged like a typical mycobacteriophage with a head containing genetic material and a long tail, which it uses to attach to the bacterium. The authors also studied the phage's life cycle and its ability to kill various mycobacteria.
The authors decoded the Vic9 genome and compared it with the genetic sequences of other bacteriophages. The results showed that he is included in one of the earlier described groups of mycobacterium viruses. At the same time, Vic9 turned out to be the first representative of this group found in Eurasia. Other similar bacteriophages have previously been isolated only in the USA and Brazil. In addition, scientists have identified several unique genes in the genome that other similar phages do not have. These features will help us understand how phages evolve to adapt to new hosts and how they interact with bacteria. The authors plan to study the discovered genes in more detail to determine which proteins they are responsible for producing and what advantages this gives to the bacteriophage.
The researchers plan to replenish the collection of described phages, which in the future will allow phage therapy to be considered as an alternative method of treating tuberculosis and other dangerous diseases caused by mycobacteria.
Bacteriophages are special viruses that infect and destroy bacteria. They are created by nature itself and are widespread on our planet. Their special properties have been used in medicine for many years as an addition or, in some cases, an alternative to antibacterial drugs, Alexey Vorobyev, head of the Laboratory of Clinical Microbiology and Biotechnology of Bacteriophages at the Moscow Research Institute of Epidemiology and Microbiology named after G.N. Gabrichevsky of Rospotrebnadzor, told Izvestia.
— Against the background of the problem of antibiotic resistance, the search for new ways to combat bacterial infections is an extremely relevant area. Bacteriophages have proven themselves to be effective antimicrobial agents, not only active against antibiotic-resistant bacterial strains, but also safe for humans. Isolation of the Vic9 bacteriophage may become a "starting point" in the creation of a new bacteriophage—based drug for the treatment of tuberculosis, the expert said.
Isolation of the bacteriophage Vic9 is an important scientific achievement, the expert emphasized. The research team has yet to conduct a significant set of tests to obtain scientific data that can be used in the isolation of new mycobacterium bacteriophages and the development of drugs based on them.
Mycobacteria, and tuberculosis in particular, are quite tricky bacteria, said Mikhail Bolkov, a researcher at the Institute for the Study of Aging at the Russian State Scientific and Clinical Center of the Pirogov Russian National Research Medical University of the Russian Ministry of Health. In fact, they can live inside immune cells in the focus of infection, doubly protecting themselves from the immune system. In addition, the long history of tuberculosis treatment with various antibiotics has led to the selection of resistant forms of bacteria.
— Nowadays, little attention is paid to bacteriophages due to the fact that bacteria also know how to develop resistance to them, this is a well-known CRISPR/Cas mechanism that has been used in genetic engineering. But phages themselves are not useless, and if they are used correctly, it can be an effective addition to tuberculosis chemotherapy," the expert noted.
Research results, supported by a grant from the Russian Science Foundation (RSF), опубликованы in the journal Frontiers in Microbiology.
Переведено сервисом «Яндекс Переводчик»
