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Customers of the School of Life Sciences, Sichuan University published high-scoring papers using Foregene’s products, with an impact factor of 17.848

Recently, the Song Xu team from the School of Life Sciences of Sichuan University published a cover paper entitled Coagulation factors VII, IX and X are antibacterial proteins against drug-resistant Gram-negative Bacteria in Cell Research.

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Cell Research is an international journal jointly published by the Chinese Academy of Sciences and the British Nature Publishing Group, which is quite authoritative in the academic world.

Once this article was published, it immediately caused a sensation in academia. So far, the research results have been received by dozens of media such as Xinhua News Agency, World Wide Web, Phoenix Net, Southern Metropolis Daily, Biological Valley, British Daily Mail, American Daily Science, EurekAlert1!, Springer Nature, Phys.org, etc. , BioMedCentral and other well-known journals have extensive reports, and the global attention to this research result is still growing.

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The article pointed out that the three coagulation factors VII, IX and X that play a role in the initiation of the coagulation cascade are a new type of endogenous host antibacterial protein, that is, coagulation factors VII, IX and X have important roles in the coagulation process. It may also be able to fight against Gram-negative bacteria, including highly resistant “super bacteria” such as Pseudomonas aeruginosa and Acinetobacter baumannii.

Song Xu, the corresponding author of this article, said: “In the past, it was generally believed that coagulation factors can cause thrombosis, but this study revealed that coagulation factors also have the special effect of sterilization. This is the first discovery at home and abroad.”

Research Background

As we all know, bacterial resistance has become a serious public health problem worldwide. Relevant data point out that nearly 1 million people die from drug-resistant bacteria infections worldwide every year. If there is no better solution, the number of deaths each year from 2050 will be 10 million.

The abuse of antibiotics, coupled with the excellent evolutionary ability of bacteria, has made some pathogenic bacteria that could have been killed by antibacterial drugs become drug-resistant, becoming almost indestructible “super bacteria”.

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In addition, compared with Gram-positive bacteria (Gram+), negative bacteria (Gram-) are more difficult to kill due to the presence of the outer membrane (the main component is LPS, alias endotoxin, lipopolysaccharide). The outer membrane is an envelope composed of an inner cell membrane, a thin cell wall and an outer cell membrane.

Research history

 

Song Xu’s team had been studying the effect of coagulation factors on the treatment of malignant tumors, but in 2009, it was unexpectedly discovered that coagulation factors can kill bacteria. In order to explain the bactericidal mechanism of coagulation factors, the project has been 10 years from the beginning of the research to the publication of the paper.

Accidentally found

In 2009, researchers accidentally discovered that coagulation factor VII can fight against Escherichia coli among more than a dozen coagulation factors.

Escherichia coli belongs to Gram-negative bacteria in bacteria. This type of bacteria is difficult to deal with, because their cells have an inner cell membrane, a thin cell wall and an outer cell membrane. The envelope can keep the drugs out and protect the bacteria from “intrusion.”

Propose assumption

Coagulation factors are a group of proteins in the blood that are involved in blood clotting. When human body injury causes bleeding, various coagulation factors are activated step by step to form fibrin filaments, which seal the wound together with platelets. If one or several coagulation factors are lacking, coagulation disorders will occur.

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Scientists have noticed that patients with coagulopathy are often prone to bacterial diseases such as sepsis and pneumonia. This connection led them to speculate that coagulation factors may not only play an important role in the coagulation process, but may also have an anti-infection effect.

In-depth study

In order to investigate whether coagulation factors can deal with a wider range of Gram-negative bacteria, researchers began to study its antibacterial mechanism in depth. They found that coagulation factor VII and structurally similar factors IX and factor X, these three proteins can break through the solid envelope of gram-negative bacteria.

Many existing antibacterial substances target cell metabolism or cell membranes, but these three coagulation factors have different modes of action. They can hydrolyze LPS, the main component of bacterial outer membrane. Losing LPS makes it difficult for Gram-negative bacteria to survive.

Go further

The research team further explored the mechanism and found that the coagulation factor protein acts on bacteria through its light chain component, while the heavy chain component has no antibacterial effect.

In the laboratory culture environment, the researchers clearly observed that after adding the coagulation factor or its light chain components, the bacterial cell envelope was damaged first, and then within 4 hours, the entire bacterial cell was almost completely destroyed.

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Add the factor VII light chain component to the cultured Escherichia coli,

Bacterial outer membrane components are damaged, cells are destroyed

 

Not only Escherichia coli, but some other Gram-negative bacteria tested were also “conquered”, including Pseudomonas aeruginosa and Acinetobacter baumannii. Both of these bacteria are listed by the World Health Organization (WHO) as the 12 most threatening bacteria to human health because of their drug resistance.

Experimental verification

The following animal experiments further verified the effectiveness of clotting factors against super bacteria.

The researchers inoculated mice with a large number of drug-resistant Pseudomonas aeruginosa or Acinetobacter baumannii. After injecting high doses of factor VII light chain, the mice survived; while the mice in the control group injected with normal saline were 24 All died of infection after hours.

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After infection with super bacteria, infusion of factor VII light chain

Can play a protective role and significantly improve the survival rate of mice

Significance

Currently, no antibacterial substance is known to be effective by hydrolyzing LPS.

Clarifying the antibacterial mechanism based on LPS hydrolysis and the antibacterial characteristics of coagulation factors, combined with the ability to produce these coagulation factors on a large scale at a lower cost, may provide a cost-effective new strategy to combat drug-resistant Gram-negative bacteria An emergency public health crisis triggered.

In addition, this work also has broad application prospects in clinical practice. At present, no known antibacterial drugs play an effect by hydrolyzing LPS. Combining the antibacterial properties of FVII, FIX, and FX against LPS and low-cost large-scale production, it is expected to develop new drugs against “super bacteria” infections.

Topic extension

Although people are more familiar with the name “super bacteria”, their accurate term should be “multi-drug resistant bacteria”, which refers to a type of bacteria that are resistant to multiple antibiotics.

As mentioned earlier, the current increasing resistance of bacteria is mainly due to the unreasonable use or even abuse of antibiotics. For example, the high-frequency use of broad-spectrum antibiotics in the treatment of respiratory tract infections.

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Respiratory tract infection is a disease we are all familiar with. According to statistics, each child is infected about 6 to 9 times a year, and adolescents and adults are infected about 2 to 4 times a year.

Because respiratory tract infections are often emergency departments, the biggest difficulty for emergency doctors when facing patients is that they cannot obtain pathogenic information in a short time. Therefore, the lag of pathogenic examinations makes clinicians have to resort to broad-spectrum antibiotics (which can be effective). For many kinds of bacteria).

It is this “spreading a big net” method of medication that has led to an increasingly serious problem of bacterial acquired drug resistance. Because when the majority of sensitive strains are continuously killed, drug-resistant strains will multiply to replace the sensitive strains, and the bacteria’s resistance rate to the drug will continue to increase.

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Therefore, if an accurate pathogen detection report can be obtained in a short period of time to guide doctors in prescribing the right medicine, the use of broad-spectrum antibiotics can be greatly reduced, thereby alleviating the problem of bacterial resistance.

Faced with this practical problem, the Fuji scientific research team set out to develop a 15-item respiratory pathogen detection kit.

This kit adopts the combination of Direct PCR and multiplex PCR technology, which can detect Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, Haemophilus influenzae and other 15 common lower respiratory tracts in the sputum in about 1 hour. Pathogenic bacteria can effectively distinguish between colonizing bacteria (normal bacteria) and pathogenic bacteria. I believe it will be expected to be an effective tool to assist clinicians in the precise medication use.

In the face of the “super bacteria”, the public enemy of the whole people, mankind has never taken it lightly. In the field of life sciences, there are still many researchers like Song Xu’s team who are working hard to explore and work silently on the road to find “super bacteria” solutions.

Here, on behalf of the biological peers and the beneficiaries, Fortune Biotech would like to express its highest respect to all the scientists who have devoted their efforts and sweat to this, and also pray that human beings can defeat the “super bacteria” as soon as possible and have a safer and healthier life. surroundings.

 


Post time: Jun-25-2021