Scientists Discover New Function of Cells in Our Immune System
Scientists knew about the proteasome, but they didn't know they could do this.
Hiya!
I used to think we’d discovered everything we needed to know. Then I learned we have no idea how much we don’t know. Even when we think we know everything about something, a new discovery inevitably changes everything we thought we knew.
For instance, we understand our immune system pretty well, but scientists just discovered a new role for the trash bins of our cells: the proteasome. This finding could revolutionize the medical field by providing a new source of antibiotics while also potentially solving our growing global antimicrobial drug resistance problem.
The Proteasome
The research we’re discussing today focuses on the proteasome — a structure inside every cell within a body — which takes up about 1 to 2 percent of a cell’s protein content.
Nicknamed our cellular trash bins, proteasomes are made of protein complexes that chop dead and aging proteins into smaller pieces, called peptides, which can be recycled into new proteins. All in all, proteasomes are responsible for breaking down about 70 percent of cellular proteins.
However, in the 1990s, researchers discovered peptides on the surface of cells that help the immune system identify threats, aka an infected cell. However, no one realized the extent of this responsibility until more recently thanks to technological advancements.
Several years ago, Professor Yifat Merbl and her colleagues at the Weizmann Institute of Science in Israel created an innovative technique using CRISPR technology that allowed them to investigate proteasomes in cells to reveal information about a cell’s function that is not otherwise seen.
(Fun fact: The Weizmann Institute of Science is a public research university established fourteen years before the State of Israel was founded.)
The team’s official name for their technique is Mass spectrometry Analysis of Proteolytic Peptides (MAPP). However, unofficially, they refer to it as “dumpster diving,” since they’re essentially rummaging through the body’s trash to look for information.
Using this method, the researchers tracked how proteasomes respond to various diseases, like cancer and lupus, while accumulating peptide degradation data.
It was then, Merbl explained in a news release by the Weizmann Institute, that:
“We took a broad look at all the data and asked ourselves: Could the products of the degradation play an additional role, beyond being presented to the immune system?”
According to their dumpster diving efforts, the team was surprised to learn that many of the degraded peptides matched ones previously identified as antimicrobial peptides — the body’s first line of defense against pathogens and a critical immune system component.
According to the World Health Organization,
“Antimicrobials – including antibiotics, antivirals, antifungals, and antiparasitics – are medicines used to prevent and treat infectious diseases in humans, animals and plants.”
For years, experts thought such antimicrobial peptides were made by protein-chopping enzymes called proteases. If proteasomes are responsible for breaking down protein structures into smaller pieces called peptides, proteases break down the peptides into their chemical components, like amino acids. However, Merbl and her team’s new findings suggest something else.
New Study
For the new study, published on March 10, 2025, in Nature, an international team of researchers led by Merbl and the Weizmann Institute of Science was involved in a series of experiments aimed at investigating additional possible tasks of proteasomes.
They discovered that the proteasome produced the antimicrobial peptides, once thought to be products of the proteases process.
Further, the researchers found that the proteasome produces these peptides regularly but ramps up production significantly during bacterial infections.
First Round of Experiments
In one of the experiments, the researchers inhibited the proteasomes within one group of human cells while leaving another group untouched. Then, they infected all the cells with salmonella to see how the differing groups would respond.
The team discovered that the invading salmonella bacteria thrived in the cells with inhibited proteasomes.
In a similar experiment, the bacteria flourished when the cell’s proteasome functioned, but the peptides it produced were destroyed.
In the news release, Merbl said:
“Before now, we knew nothing about the connection between proteasome outcomes and the production of these peptides. In light of our findings, we conducted an extensive series of experiments demonstrating that the proteasomes are key to this defense system.”
To investigate further, the team involved mice.
Second Round of Experiments
After their initial results, the team devised experiments involving mice infected with bacteria that develop sepsis and pneumonia and then studied how the mice’s proteasomes responded.
The researchers discovered that the peptides created by the proteasome successfully and significantly decreased the number of harmful bacteria in the mice. The peptides also reduced tissue damage caused by the bacteria and improved the mice’s survival rates.
So, basically, the team’s experiments show that proteasomes can detect when bacteria have infected a cell. Then, they change their structure and roles to transform old proteins into weapons that kill bacteria and aid in healing the host.
The results stunned the team for a couple of reasons. For one thing, the experiments demonstrated how, when administered in large quantities, peptides that the body naturally creates can effectively fight against life-threatening infections.
Secondly, the success of this natural yet previously unidentified process was comparable to the results of using strong antibiotics to fight off a similar infection.
Considering such remarkable results, the researchers wondered how many other unidentified antimicrobial peptides are hiding within our proteins.
Third Round of Experiments
So, in the next series of experiments, the researchers utilized an algorithm to analyze all of the proteins created by the human body and then searched for peptides containing any potential antimicrobial properties.
And they found them in an astonishing 92 percent of human proteins.
More specifically, the algorithm identified more than 270,000 previously unknown antimicrobial peptides produced by the proteasome, which is a massive untapped reservoir of naturally created antimicrobial sources that future scientists might be able to use to develop new antibiotic treatments.
New Source for Antibiotics
The potential for scientists to create new antibiotics is particularly exciting because they are desperately needed. Among the many health concerns we have today, a significant but underreported one is that our rate of antimicrobial resistance is growing, which is causing a substantial global health challenge that millions of people die from every year.
Antimicrobial resistance happens when bacteria, fungi, parasites, and viruses stop responding to medicine, essentially making the medicine ineffective and the diseases more challenging, if not impossible, to treat. Without treatment, the resulting disease, disability, or illness caused by the microbial invasion is more likely to increase and spread if it’s contagious.
So, the possibility that our own bodies contain a treasure trove of new potential antibiotic sources changes everything. Merbl told James Gallagher of BBC News:
"This is really exciting, because we never knew that this was happening. We discovered a novel mechanism of immunity that is allowing us to have a defence against bacterial infection. It's happening throughout our body in all the cells, and generates a whole new class of potential natural antibiotics."
In the news release, she adds:
“This peptide database opens a new frontier for developing personalized treatments against infections and other medical conditions.”
For example, the peptides Merbl and her team found could potentially be altered to improve a person’s immunity, such as cancer patients or organ transplant recipients whose immune systems are weaker.
Such a discovery could even revolutionize medicine and maybe solve our antibiotic resistance challenge if scientists can utilize this new source to develop innovative therapies. Lindsey Edwards, a senior lecturer in microbiology at King's College London, explained to James Gallagher of BBC News,
"It's a potential goldmine for new antibiotics, that's quite exciting. In previous years it's been digging up soil [to find new antibiotics], it is wild that it's something we have within us, but comes down to having the technology to be able to detect these things."
In addition to a brand new source of antibiotics, Edwards points out that the safety side of developing them into medicines might be a lot easier since they’re already products of the human body, which means our bodies may be less likely to reject them.
Meanwhile, Daniel Davis, an immunologist at Imperial College London, told Gallagher that Merbl’s research is "extremely provocative and very interesting" because it changes our understanding of how our immune system works. Davis said:
"What's really exciting about this, is it's a totally undiscovered process by which anti-germ molecules are made inside our cells, it feels profoundly important and surprising."
Still, Davis cautioned against jumping into developing new antimicrobial drugs using this newfound source just yet. He believes experts should be patient and that the entire concept needs more testing, which will take time.
Perspective Shift
See what I mean? For all this time, we thought proteasomes were just trash recyclers for cells, like a janitor. Yet, now we know they also moonlight as warriors, chopping up and unleashing antimicrobial weaponry against invaders.
Yet, this discovery is merely one of countless others that wouldn’t have been possible without technological advancements that allow scientists to peer deeper and study even the tiniest details of our world — and sometimes, it’s the small things that have the biggest potential to change everything.
Fascinating. And good news! Thanks