Velcro antibiotics are here! Hug bacteria before killing them?

Produced by: Science Popularization China

Author: Ouyang Haomiao (Institute of Microbiology, Chinese Academy of Sciences)

Producer: China Science Expo

Antibiotics are an important weapon in modern medicine. When some bacteria in our body pose a threat to our health, we need antibiotics to kill the bacteria until we recover.

When it comes to antibiotics, everyone will think of "drug resistance". Due to the abuse of antibiotics and the rapid mutation of bacteria, some bacteria can resist antibiotics, making antibiotics ineffective.

So, is there an antibiotic that can break through the limitations of "drug resistance" and better help us achieve health?

(Photo source: veer photo gallery)

How do antibiotics work?

There are many bacteria in our body. They are tiny organisms. Some bacteria are beneficial to the body, such as probiotics; however, some "bad" bacteria can pose a threat to our body, making us feel uncomfortable and causing colds, fevers, etc. At this time, antibiotics are needed.

Antibiotics are like a "cannon" in an army that specifically targets these bacteria. When they find the enemy - bacteria, they will start to attack the bacteria. Some antibiotics can directly destroy the cell wall or cell membrane of bacteria, thereby killing the "bad" bacteria; some antibiotics are like snipers, which can enter the bacteria and accurately hit its key parts; and some antibiotics are like agents, lurking inside the bacteria, destroying their living environment, making the "bad" bacteria weak and finally defeated by our immune system. When antibiotics start fighting bacteria, they will continue to attack bacteria until all the bacteria are killed, so that we can recover quickly.

(Photo source: veer photo gallery)

New antibiotics: Clinging to bacteria like Velcro

From the principle of antibiotic action, we can find that destroying the bacterial cell wall is a very effective way to kill bacteria. Scientists have also conducted a lot of research in this direction, including blocking the synthesis of cell walls, destroying the structure of cell walls, etc. So, in addition to the above methods, are there any other means?

Recently, researchers from Utrecht University in the Netherlands published their latest discovery in Nature Microbiology, that a small molecule antibiotic called plectasin can be assembled into a larger structure and locked onto the surface of bacterial cells, just like the hooks and loops on both sides of Velcro are tightly glued together, making it impossible for bacteria to escape and thus continue to infect body cells. This exciting discovery may bring breakthrough progress to the development of antibiotics and is of great significance to the development of new antibiotics that can fight drug-resistant bacteria.

This plectasin is a class of enzymes with antibacterial activity produced by fungal mycelium, such as the antibacterial mycelium Plectasin from truffles. The uniqueness of this antibiotic is that it does not just inhibit bacteria through simple chemical binding, but enhances its antibacterial activity through an ingenious self-assembly mechanism , which is the "Velcro mechanism" of antibiotic mycelial enzymes.

Simply put, this small molecule antibiotic can assemble into larger structures and lock onto the surface of bacterial cells, just like the hooks and loops on both sides of Velcro stick together, making it impossible for the bacteria to escape and continue to infect body cells.

Taking Plectasin as an example, in order to form a "Velcro" that can kill bacteria, antibiotic mycelial enzymes need to go through the following steps:

1. Calcium ion-triggered self-assembly

In the presence of calcium ions, the mycelial enzyme Plectasin undergoes conformational changes, enabling it to self-assemble, thereby effectively self-assembling on the bacterial surface.

2. Targeting bacterial cell wall precursor lipid II

Once the hyphal enzymes Plectasin undergo conformational changes, they can efficiently and selectively recognize and bind to the bacterial cell wall precursor lipid II, a process similar to inserting a key into a lock. Since lipid II is an indispensable precursor in the synthesis of bacterial cell walls, this binding is also a key step in the self-assembly process.

3. Self-assembly to form supramolecular structures

On the surface of bacterial cells, the hyphae enzyme Plectasin molecules further interact with each other to form dense supramolecular structures. These structures are firmly attached to the bacterial membrane through multi-point binding. This self-assembly forms a dense supramolecular structure similar to "Velcro" that is firmly locked on the bacterial surface. This multi-point binding not only enhances the stability of the enzyme molecules on the bacterial surface, but also improves its antibacterial effect.

4. Inhibit bacterial cell wall synthesis

When these supramolecular structures are formed, they act like tiny "hooks" attached to the bacterial "rings", hooking their target lipid II, thereby preventing lipid II from synthesizing new cell walls , and eventually causing the bacteria to lose their structural integrity and function, thus dying. In this process, even if a lipid II breaks free from the "hook", the bacteria are still locked in a large number of "hooks" and cannot escape, and cannot cause further infection.

Schematic diagram of "Velcro"

(Image source: Nature Microbiology)

Through its unique "Velcro" mechanism of action, the mycelial enzyme Plectasin has the potential to deal with multi-drug resistant bacteria, which also makes it an important research direction in the current antibiotic resistance crisis.

New ideas for antibiotic design: Focus on drug self-assembly efficiency

In addition to Plectasin, scientists have also discovered that many antibiotics may use a similar self-assembly "Velcro mechanism" to enhance their antibacterial activity. This discovery also provides a new idea for the design of antibiotics: not only should the ability of the drug to bind to the target be considered, but also the efficiency of drug self-assembly should be taken into account . By learning from this mechanism, it may be possible to develop drugs that can fight bacterial infections more effectively in the future, thereby addressing the increasingly serious problem of antibiotic resistance.

In addition, scientists have also studied the efficacy and safety of the antibiotic mycelial enzyme in the human body. The results show that this antibiotic can resist infections caused by Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa in animal experiments. The next step will be to further evaluate its application prospects in humans through clinical trials.

Antibiotic resistance is a major challenge facing healthcare systems around the world. The emergence of drug-resistant bacteria has rendered many traditional antibiotics ineffective. The study of the "Velcro mechanism" of antibiotic hyphal enzymes has opened up new avenues for the research and development of antibiotics. By understanding and utilizing the self-assembly mechanism of drugs, scientists can design more effective antibacterial drugs, which provides valuable ideas for future antibacterial treatments. This can not only extend the service life of existing antibiotics, but also may develop new weapons to fight drug-resistant bacteria.

It is hoped that this discovery will inspire more research and usher in a new era of antibiotic development to protect human health from the threat of bacterial infections.