A Newly Discovered Part of the Immune System: A Treasure Trove for Natural Antibiotics

Scientists have discovered a previously unknown aspect of our immune system and suggest it contains natural antibiotics that could transform the fight against antibiotic resistance.

The Proteasome: From Recycling Center to Weapons Factory

The discovery centers on a small cellular structure, the proteasome , which normally breaks down old proteins for recycling. New research shows that it does more than recycle: it can also produce defensive chemicals against bacterial infection.

On March 5, 2025, Nature published a study showing that when the proteasome detects bacterial infection in a cell, it changes its structure and releases lethal peptides. These destroy bacteria by disrupting their outer membranes.

The article's lead author, Prof. Yifat Merbl of the Weizmann Institute of Science, said, "This discovery is truly exciting because we did not know this was happening. We have discovered a new aspect of our immune system and realized that every cell in our body contains a mechanism producing natural antibiotics."

Figure 1: The image shows the proteasome recycling proteins under normal conditions (a, an uninfected cell) and, during infection, producing antimicrobial peptides through the PSME3 protein to disrupt bacterial membranes (b, an infected cell).

The following points are emphasized:

• In an uninfected cell, the proteasome only breaks down proteins.
• During infection, PSME3 binds to the proteasome, leading to production of specialized defensive peptides.
• These positively charged peptides disrupt bacterial membranes and destroy bacteria.

Strong Effects in Laboratory and Animal Experiments

The researchers tested these natural antibiotics against bacteria in the laboratory and in mice with pneumonia and sepsis, or blood poisoning. Results showed effectiveness comparable to certain existing antibiotics. Disabling proteasome function in the laboratory also made cells more vulnerable to bacteria.

This discovery changes our understanding of how the body fights infection. There is an entirely unexplored process within our cells that produces microbe-fighting molecules. It is an important and surprising development. More research is needed, however, to determine whether this mechanism can serve as a source of new antibiotics.

New Hope for Antibiotics?

Each year, approximately one million peopleworldwide die from infections caused by antibiotic-resistant bacteria. Meanwhile, development of new antibiotics has slowed substantially in recent years.

This discovery offers scientists an alternative source for producing new antibiotics, potentially a treasure trove. In the past, soil samples were examined to discover antibiotics; now, a source already within our bodies may have been identified. Because these peptides are naturally produced in the human body, researchers also anticipate fewer safety problems during drug development than might otherwise arise.

Conclusion: The Immune System's Hidden Power

This study shows that the proteasome not only recycles old proteins but also forms an important part of the body's natural defenses. If the mechanism can successfully be translated into medications, it could mark major progress against antibiotic resistance.

Experts caution that further research is needed to understand how these natural antibiotics work in humans and that clinical applications will take time. Nevertheless, revealing this previously unknown aspect of immunity may open new possibilities for fighting infection.