Broad-spectrum bacteriophages
Synthetic bacteriophages with programmable specificity have been created
"Weekly PHARMACY" based on the materials of World Pharma News: Synthetic phages with programmable specificity.
Bacteriophages are viruses that infect bacteria. Bacteriophages are very specific to the host and usually infect and kill only individual species or even subspecies of bacteria. Compared to conventional antibiotics, bacteriophages do not cause collateral damage to the "beneficial" bacteria inhabiting the intestine. The ability to target the destruction of pathogenic bacteria has led to the fact that bacteriophages have become regarded as potential "magic bullets" in the fight against bacterial infections, especially those bacteria that have developed resistance to antibiotics.
However, the high specificity of bacteriophages is also their disadvantage. Clinicians should prescribe various combinations of bacteriophages to increase the likelihood that one of them will be specific to infection. This approach significantly limits the possibilities of turning bacteriophage therapy into a standardized treatment option.
Until now, bacteriophages had to be isolated from their natural environment first, tested for their effectiveness against the bacterial strain(s) and, most importantly, sequenced their genomes to ensure they were safe for use in humans.
Genetically modified bacteriophages
Under the leadership of Samuel Kilcher, a researcher at Ambizione, researchers from the Institute of Food, Nutrition and Health, Switzerland, genetically reprogrammed bacteriophages to produce synthetic bacteriophages with the ability to recognize and attack a wider range of bacterial strains outside their natural host. The researchers reported their findings in the journal Cell Reports (Reprogramming Bacteriophage Host Range through Structure-Guided Design of Chimeric Receptor Binding Proteins).
Based on the tails of bacteriophages, there are specialized receptor-binding proteins that recognize specific receptors on the open cell walls of the target bacterium.
"Using X-ray crystallography, we cracked the atomic structure of the first receptor-binding protein of bacteriophages specific to Listeria. Thus, we have provided a block diagram for the reengineering of our bacteriophages," said the study's lead author Matthew Dunne.
Similar to the Lego constructor, the researchers assembled new receptor-binding proteins by combining protein components derived from different bacteriophages to provide broader specificity. Finally, the researchers genetically modified Listeria-specific bacteriophages with their designer receptor binding proteins. As a result, the modified bacteriophages were able to identify and destroy new, initially nonspecific strains of target bacteria.
The long way forward
There are still many obstacles that need to be overcome before treatments using genetically modified bacteriophages enter clinical practice. In this study, bacteriophages that are specific only to Listeria were studied. This bacterium can cause severe infections in people with weak immune systems.
Currently, researchers are planning to create artificial bacteriophages to fight other pathogenic microorganisms, which, as a result of antibiotic resistance, are often difficult to influence with conventional therapy. Examples of such pathogens are Staphylococcus aureus, Klebsiella pneumoniae and Enterococcus species. Methods for constructing such bacteriophages have not yet been developed.
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