The human body produces many peptides that help the immune system resist attacks from pathogens. And, as it turned out, there are candidates for the role of powerful antimicrobial drugs among them.
In the new work, researchers at the Massachusetts Institute of Technology, together with Italian colleagues, were looking for compounds that could serve as the basis for a new generation of antibiotics that will defeat superbugs. Recall that many existing drugs are losing their strength: microorganisms have already developed resistance to most of them.
Previous work shows that looking for new weapons is worth looking to nature. Effective compounds have been found, for example, in the milk of the platypus, in the glands of rattlesnakes, and in tobacco.
But not only organisms of animals and plants repel the attacks of a huge number of pathogenic bacteria. The human body is also experiencing constant raids of pathogens, and it is not surprising that this "house" has developed its own system of defense against threats.
Specialists have focused on the gastrointestinal tract, since its bacterial composition is the most diverse and numerous. The team looked for compounds that are involved in defense mechanisms. Most often, this role is assumed by digestive enzymes and peptides. While many of these are not strong enough to be used as antibiotics, they can provide clues to researchers and indicate what "tweaks" are needed for new drugs.
“These peptides really are a great template for engineering. The idea is to use synthetic biology and modify them further, to make them more powerful,”explains one of the leading authors of the new work, Cesar de la Fuente-Nunez (Cesar de la Fuente-Nunez).
Together with his colleagues, he discovered almost two thousand promising compounds. Then they were tested using a special algorithm that reveals similarities with already known antimicrobial peptides.
“This is a data mining method that makes it easy to find peptides that have not been previously studied. We have models that we know are associated with classical antimicrobial peptides, and the search engine finds samples through the database that are similar to those that kill bacteria,”says the researcher.
The program helped to select 800 suitable peptides, and experts are already betting on one of them. This compound is called pepsinogen. It is produced in the stomach and is involved in the digestion of food.
Some fragments of this peptide, which are a by-product of the digestion process, have been labeled by the algorithm as "potentially antimicrobial." Their function had not previously been studied, so the experts had a new direction to work with.
To test how potent these indicated pepsinogen fragments could be, the researchers ran laboratory tests in a petri dish. They used several "diverse" pathogens - Salmonella, E. coli and Pseudomonas aeruginosa.
It turned out that the peptide effectively destroys these bacteria not only in an acidic environment (as in the stomach), but also at a neutral acidity level.
Tests in mice have also shown that pepsinogen fragments are able to kill skin infections caused by Pseudomonas aeruginosa.
At the next stage of the work, scientists will have to figure out the mechanism of action of the peptide and find a way to make it even more powerful. In addition, they will continue to check other connections chosen by the algorithm.
A scientific article on the results of the current work was published in the ACS Synthetic Biology.