Based on this information, the researchers then designed novel receptor binding proteins with different host specificities that could be assembled according to the Lego principle of different protein components. Finally, Listeriaphages are genetically engineered to encode such proteins that bind to receptor designers and therefore recognize, infect and kill new strains of the target bacterium. Although these different design phages attack new hosts, they have the same structural framework.
Fago cocktail as a form of therapy
A mixture of such phage variants can now be used for therapy. "We can cover a wide range of hosts by delivering several synthetically generated phages in one cocktail," Kilcher explains. The difference with wild type bass cocktails is that they could be synthetically much more purposefully developed, produced and adapted. Growing artificial phages in pure culture is neither expensive nor time consuming. "We can program them for almost any purpose."
In addition to therapeutic applications, researchers could use synthetic phages, for example, they can also be used as diagnostic markers for specific molecular structures, for example to identify exactly one strain in a mixed bacterial population.
The path to therapy
Until genetically modified phage therapy arrives at the clinic, there are still many obstacles to overcome. This study is just a proof of concept. Refers to the model system Listeria, This bacterium is found in food and can cause severe infections in weakened people.
Researchers now plan to create artificial phages against other pathogens, with conventional therapy often difficult due to antibiotic resistance. They include, for example Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa and EnterobacterHowever, methods for producing such phages in the laboratory have yet to be developed. "Each phage and each host organism has its own particular challenges," points out Professor Eur from Zurich Martin Loessner, co-author of the study and head of the Laboratory for Food Microbiology at IFNH. He thinks, however, that it is only a matter of time until a job is developed for such pathogens.
Much hope rests on phage therapies. In one case, genetically modified phages were already used therapeutically. A few months ago, US researchers reported in the journal Nature Medicine that a 15-year-old cystic fibrosis man had been assigned phages to cure a severe infection caused by mycobacteria. It worked. However, there is still a lack of extensive clinical trials required to approve phage therapies.