08 February 2018

We will produce the virus according to the customer's sketch

Bacteriophages are viruses capable of hunting and destroying individual bacteria. They are widespread in nature. Each individual type of bacteriophages corresponds to a specific type of bacteria. It is this fact that gives researchers hope to use them after modification to fight dangerous bacterial infections.

Bakteriophages.jpg
Bacteriophages and E.coli bacteria.

Bacteriophages are already being used in the food industry to destroy pathogens in food by natural methods.

The process of genetic modification of phages is laborious and complex. It is especially difficult to "tune" them to gram-positive bacteria, for example, staphylococci: the introduction of the phage genome into bacteria is quite problematic, because their cell wall is very dense.

A group of researchers from the Swiss Higher Technical School of Zurich, led by Professor Martin Loessner, has developed a new technology that will allow scientists to "tune" the genome of bacteriophages to impart new functions and multiply them in a bacterial "bioreactor" – microbes of the genus Listeria with a weak cell wall, but capable of developing (L-forms of bacteria).

The new tool for setting up bacteriophages works very quickly, it is built on a modular principle: it can be used to modify almost any bacteriophage for various purposes and with a wide variety of functions.

Thus, if earlier it was necessary to study a large number of bacteriophages to find one suitable for fighting bacteria, now it is possible to reprogram any bacteriophage for a specific purpose.

The researchers used synthetic biology techniques to plan the phage genome and assemble it from DNA fragments. The technique allows you to exclude unnecessary genes (for example, those responsible for the synthesis of toxins) and add the necessary ones (for example, those responsible for the production of enzymes that dissolve the cell wall).

To activate a bacteriophage from synthetic DNA, its genome is placed in an L-form bacterium. These bacteria then produce all the components of the phage according to the genetic plan and ensure the correct assembly of the virus. Thus, they are practically a universal incubator for bacteriophages.

After the end of the process of "assembling" the bacteriophage, the incubator cell is placed in a medium that dissolves its shell. The released bacteriophages can be collected and further multiplied to the required amount.

The key condition for the new technique of creating bacteriophages is the inability of their genome to integrate into the host genome. Otherwise, the phage will cease to be useful for fighting the bacterium. However, using a new method, it is possible to reprogram the bacteriophage in such a way that it becomes dangerous for bacteria again.

The advantage of the authors is the absence of the problem of the formation of resistance of bacteria to phages: even if this happens, the phage can be reprogrammed to overcome resistance and successfully fight the pathogen.

The method of creating synthetic bacteriophages is an important element in the fight against dangerous bacteria. In addition, it can be used for diagnostic purposes and in the food industry.

The authors of the article have applied for a patent of the method developed by them. The application is under consideration.

Article by Kilcher et al. Cross-genus rebooting of custom-made, synthetic bacteriophage genomes in L-form bacteria is published in the journal PNAS.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of ETH Zurich: Workbench for virus design


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