Scientists have found a new resource for antibiotics — it «hid» in the human body

Researchers from the Weizmann Institute of Science have discovered that structural fragments of human cells — proteasomes are capable of producing natural antibiotics from parts of damaged proteins.

For a long time, it was believed that the key function of proteasomes was to break down damaged proteins and transfer their components to T cells to enhance the immune response to dangerous bacteria. However, researchers have found that, among other things, proteasomes are able to detect dangerous bacteria in cells and develop defense mechanisms to prevent their development and spread.

The researchers note that proteasomes are able to produce so-called «protective peptides» from protein fragments that break bacterial membranes and stop infectious processes even before the immune system begins to respond. Proteasomes are found in every cell in the human body and break down old or damaged proteins, allowing their structural components to be reused. After a cell becomes infected, proteasomes undergo a transformation and begin not only to break down proteins, but also to create antibacterial peptides that break through the membranes of bacterial cells.

In their experiments, the researchers forced the proteasome in human cells to confront Salmonella bacteria. The proteasome released tiny peptides that stopped the growth of Salmonella. Using the technology of mass spectrometry analysis of proteasome products, the researchers found that out of more than 50 thousand peptides secreted by the proteasome, more than a thousand had the necessary size and chemical composition to fight dangerous microbes.

Scientists have selected 10 most promising peptides to test them against bacteria — Escherichia coli (E. coli), Pseudomonas aeruginosa, Micrococcus luteus (Micrococcus luteus) and others, most of which were vulnerable to the new peptides. At the same time, the peptides did not demonstrate toxic effects on cells.

The researchers paid special attention to a peptide derived from the PPP1CB protein, which is associated with the regulation of phosphatase— enzymes of the hydrolase class that catalyze the hydrolysis of phosphoric acid esters in living organisms. In laboratory conditions, this enzyme not only destroyed all dangerous bacteria, but also reduced the number of bacteria in infected mice and even increased survival among mice with sepsis compared to standard antibiotic treatment protocols.

The resistance of a number of dangerous bacteria to antibiotics remains one of the key challenges facing the modern healthcare system. The further adaptation of bacteria causing such dangerous infections as urinary tract infections, pneumonia, and sepsis to available antibiotics makes them even more dangerous.

According to a report by the UK National Health Service, 7.6 thousand people die every year due to antibiotic resistance of dangerous bacteria. Globally, these figures amount to more than 1 million deaths annually and continue to grow.

Since these antimicrobial peptides come from our own cells, this is also an advantage in terms of safety. Medicines derived from them may be less likely to cause harmful immune reactions. Daniel Davies, an immunologist at Imperial College London, notes that the new peptides still have to undergo a number of tests before they can become a breakthrough in the creation of a new generation of antibiotics.

The results of the study were published in the journal Nature

Source: ZME Science