The health system faces a huge problem: pathogenic bacteria are becoming increasingly resistant to antibiotics. One possible approach on which many hopes rest is the use of natural enemies of bacteria: phages are specific viruses that infect and destroy bacteria.
Researchers led by Samuel Kilcher of ETH Zurich have taken an important step to use phages therapeutically, as the university reported on Monday. Scientists could reprogram them so that they would no longer only attack their specific "victim" bacteria for which they specialized, but also others. They report in Cell Reports.
The key to attacking bacteria
Phages recognize "their" bacteria using surface structures. Phages carry proteins that specifically land on the bacterial surface (receptor), such as a lock key. Only if the phage key matches the bacterial castle can the phage attack and kill the bacterium.
The team around Kilcher focused on Listeriaphages, phages that infect Listeria and each specializes in different listerienstmme. Using X-ray crystallography, researchers were able to describe in detail the structure of the "key" of listerafafagen or receptor-binding protein.
Based on this, the researchers then designed new receptor-binding proteins that can be assembled on a modular basis and fit into various other bacterial receptors. Genetic instructions for the construction of these proteins have been reintroduced by scientists in Listeriaphagen, programming them as "contract killers" against various Listeriaaphagen tribes.
Reduced effort and cost
A mix of such designer phages could be used for therapy to combat a wide range of bacterial strains, ETH wrote. Until now, researchers have had to isolate phages for this purpose from the environment and characterize them as consumption.
However, such therapies are difficult to standardize so far, the statement said. It is different with design phages: they can be much more deliberately developed, produced and customized. This reduces effort and costs.
However, it will probably take some time to put it into practice. Researchers are now looking to develop designer phages, especially against pathogens, which are otherwise difficult to deal with antibiotic resistance. However, methods have not yet been developed to produce appropriate phages in the laboratory, ETH wrote.
Although cases of experimental phage therapies have already been isolated, large clinical trials and the approval of such therapies are still lacking.