Human cells also use "detergents"

Human cells also use "detergents"

Protein helps cells destroy bacteria autonomously

Human cells also use "detergents" Human cells also use "detergents"proteins to help cells destroy bacteria autonomously Proteins help cells to destroy bacteria autonomously Proteins help cells to destroy bacteria autonomously

Before Salmonella can be killed, the detergent-like protein APOL3 must pass through the bacterial outer membrane
.

Image source: Howard Hughes Medical Institute

Like many people, cells also use "cleaning products" to fight off bacteria
.

This cell "detergent" is actually a kind of protein.
Most tissues of the human body can produce this molecule.
It can remove invading bacteria, just like detergent for cleaning oil stains
.

The team of John MacMicking, a researcher at the Howard Hughes Medical Institute in the United States, discovered that this protein called APOL3 prevents infection by dissolving the cell membrane of bacteria
.

The researchers tested the protein on Salmonella and other similar microorganisms that can cause food poisoning, and said that this work provides a new perspective on how human cells can resist infection

On July 16, related papers were published in "Science"
.

How much do you know about immune weapons

How much do you know about immune weapons

When a virus invades animal cells, the protein that initially receives this "intelligence" will send a signal to the next protein, interlocking, and ultimately activating the natural immune response
.

Animal cells use multiple such natural immune pathways to mediate immune responses

In fact, when it comes to protecting the human body, the special cells of the immune system are like a bunch of "bodyguards
.

" But the alarm signals that mobilize these cells can also activate "ordinary citizens

Moreover, in the "arms race" between pathogens and hosts, infected microorganisms often evade extracellular defense mechanisms and use the rich nutrient environment within the cells as a niche for replication
.

As a result, the researchers infected some non-immune cells with a salmonella bacteria that can invade the water lining of the cells
.

Salmonella belongs to a type of bacteria surrounded by two layers of membranes.

Scientists have discovered that the interferon gamma warning signal can prevent Salmonella from "taking over" human cells, but they don't know which protein saved human cells
.

Who will save the cells

Who will save the cells

The MacMicking team screened the genes of more than 19,000 human cells, looking for genes that might encode protective proteins
.

This work prompted the researchers to discover APOL3

The researchers said that APOL3 is a host defense protein stimulated by IFN-g, which has evolved a powerful "detergent-like" activity to provide bactericidal protection in the cytoplasm of human cells
.

"Most apolipoproteins transport lipids in the extracellular fluid, while APOL3 works in the cell to dissolve pathogen membrane lipids in the host cytoplasm
.

This is unexpected, especially since the body must prevent membrane lytic proteins from attacking the host.

In fact, APOL3 also got the help of the second molecule GBP1
.

Using high-resolution microscopy and other techniques, the team revealed the combination of its work: GBP1 destroys the outer membrane of bacteria and allows APOL3 to pass through, thereby breaking the inner membrane of bacteria-this is a "fatal blow" to kill bacteria

Just like washing powder, part of APOL3 is attracted by water and part is attracted by grease
.

Of course, what these ingredients remove is not the dirt on the cloth, but the large bacterial inner membrane, which is composed of grease molecules
.

MacMicking said that this process is highly selective because APOL3 needs to avoid attacking the cell membrane of human cells themselves
.
The research team found that APOL3 avoids cholesterol, the main component of cell membranes, and instead selects special lipids that bacteria prefer
.

This process is also called cellular autoimmunity by researchers
.
Autonomous cell immunity involves all nucleated cells in the host defense response to infection, not limited to cells of the immune system
.
"In this study, we found that epithelial cells, fibroblasts and endothelial cells can limit infections and even kill bacteria when activated by immune cytokines
.
" MacMicking said
.

Natural antibiotics

Natural antibiotics

MacMicking said that there are other human proteins that can kill pathogens in cells, but APOL3 is the first intracellular "detergent-like" protein found in human cells
.
"This is an example of humans making antibiotics in the form of proteins.
In other words, it is a natural antibiotic
.
" MacMicking hopes that these findings will one day help develop new infection treatments
.

On the other hand, scientists believe that APOL3 can provide extensive protection for the human body because it is in the "toolbox" of many cells
.
For example, researchers found that it can protect blood vessels and cells in the intestine
.

The discovery of this detergent-like molecule in non-immune cells "provides more evidence for the idea that any cell in the body can be part of the immune system.
" The scientist Carl Nathan said, "This also adds a new example of how creatures'kill' each other
.
"

Whether it's perforating, poisoning, or starving to a pathogen, the immune system has developed several methods to kill "hostile" cells
.
Nathan believes that the use of APOL3 for membranes is one of the most deadly known
.

"All microbial pathogens have membranes.
These membranes are difficult to repair and change because they are not encoded in the genome or plasmids like proteins or nucleic acids
.
This means that it is difficult for bacteria to produce new APOL3 resistant species through mutations.
Mutations
.
Therefore,
liposoluble proteins are unlikely to be'bypassed ' by bacterial escape mutants .
" MacMicking said
.

For example, APOL3 can attack the double membrane of Gram-negative bacteria in a multi-pronged approach with interferon-stimulating genes.
The latter is a strong barrier that can be resistant to many types of antibiotics
.

But to apply this discovery to infection treatment, researchers still have a long way to go
.
"At present, we are still a long way from human treatment, but in the future, APOL3 chemical mimics can be used to kill antibiotic-resistant Salmonella and other intracellular bacteria
.
"

Moreover, deciphering the body’s defense system can provide scientists with new tools to fight against microorganisms-these microorganisms are constantly evolving to fight against traditional antibiotics
.
"For example, the use of
cell'detergents ' and other mechanisms by which the human body kills bacteria can help supplement the natural immune response .
" MacMicking said, "Next, we will continue to explore which important human pathogens APOL3 can kill or limit to.
Inside the human cell
.
" (Source: China Science News Tang Feng)

Related paper information: https://doi.
org/10.
1126/science.
abf8113

https://doi.
org/10.
1126/science.
abf8113 https://doi.
org/10.
1126/science.
abf8113