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  1. The crisis of resistant bacteria needs to be resolved

  2. Ideal substitute for traditional antibiotics

  3. Development prospect

Abstract:

Since the 1920s and 1930s, the discovery and application of antibiotics have saved countless lives. If people have benefited from it before, now the world has to work to solve the consequences of antibiotic abuse - the emergence and spread of resistant bacteria.

In September this year, 193 member states attending the UN General Assembly signed a declaration promising to strengthen the control of antibiotics. As countries take actions to promote the reduction of antibiotic use, scientists are also actively looking for alternatives to develop antibiotics.

The crisis of resistant bacteria needs to be resolved

Besides "super bacteria", there are "super bacteria"! A few days ago, South China Agricultural University found a kind of "super bacteria". According to reports, the drug-resistant bacteria carry a heterozygous particle and are resistant to carbapenems and myxomycetes at the same time. Among them, the latter has been regarded as the "last line of defense" for human resistance to drug-resistant bacteria.

With the discovery of "super bacteria", the lineup of drug-resistant bacteria has become more and more complete and powerful. Countries around the world have gradually realized that the abuse of antibiotics and the emergence of drug-resistant bacteria are becoming a major global crisis.

Especially since this year, this issue has attracted unprecedented attention. In September this year, the G20 communique in Hangzhou promised to "promote the prudent use of antibiotics"; in the same month, 193 member states attending the UN General Assembly signed a declaration promising to strengthen the control of antibiotics. In August, China's health and Family Planning Commission jointly issued an appeal to the whole society to take joint action to curb the development of drug resistance.

In addition to strengthening supervision in policy, looking for alternatives is also a way to reduce the use of antibiotics. At present, the development of antibiotic substitutes is becoming a priority topic in the field of biomedicine, in which antimicrobial peptides become the "star of hope" of antibiotic substitutes because of their broad-spectrum and high-efficiency bactericidal activity to bacteria, and they are not easy to produce drug resistance.

According to the data, in 1980, Swedish scientists first induced polypeptides with antibacterial activity in silkworm chrysalis. Since then, scientists have discovered and isolated peptides with antibacterial activity from bacteria, fungi, amphibians, insects, higher plants, mammals and even human body.

Ideal substitute for traditional antibiotics

Years ago, the discovery of hyphomycin was a bright spot. In 2005, scientists isolated a kind of defensin mycelium from saprophytic ascomycetes growing on the surface of Nordic pine forest for the first time. It can prevent the growth of bacteria by blocking the synthesis of bacterial cell wall, and has a strong defensive effect on Gram-positive bacteria (such as Staphylococcus, Streptococcus, pneumococcus, etc.).

Nz2114, a derivative of hyphomycin, is a better derivative peptide obtained by high-throughput mutation than the parent peptide. Its antibacterial activity against Staphylococcus aureus is significantly increased, which is more than 30 times higher than the parent peptide. In order to further enhance the antibacterial activity of nz2114 against Staphylococcus aureus (hereinafter referred to as Staphylococcus aureus), especially against methicillin resistant Staphylococcus aureus (hereinafter referred to as MRSA), Wang Jianhua's team further modified nz2114 and obtained mutant mp1102.

The results showed that the antibacterial activity of MRSA of mp1102 was 15 times that of nz2114. For example, if mp1102 is used to treat mice infected with Staphylococcus aureus at concentrations of 5mg / kg, 10mg / kg and 20mg / kg, 90% of Staphylococcus aureus can be killed within 12 hours.

At the same time, mp1102 has antibacterial activity against Clostridium perfringens, which can cause gas gangrene, food poisoning and other diseases. "Mechanism study shows that mp1102 has double bactericidal mechanism of destroying cell membrane and interfering with DNA in Clostridium perfringens." Wang Jianhua said that the antibacterial activity of mp1102 against Clostridium perfringens was better than that of mycelium, nz2114 or other antibiotics such as bacitracin zinc, aureomycin and Virginia mycin.

Since then, the team has introduced net positive charge and hydrophobic amino acids into the mycelium mycomycin sequence, and designed the antibacterial peptide mp1106, so that its anti Staphylococcus aureus activity is nearly 40 times higher than the parent peptide. In order to improve the bactericidal targeting of Staphylococcus aureus, the research team connected Staphylococcus aureus pheromone to mycelium to construct Staphylococcus aureus targeted antimicrobial peptide. The results showed that the target peptide had specific bactericidal effect on the target bacteria, but had no bacteriostatic activity on other probiotics such as bacillus, Streptococcus lactis and Enterococcus faecalis.

Development prospect

Antibacterial peptide has the function of promoting growth and treating diseases for livestock and poultry. It is a non-toxic, harmless and residue free green product and is expected to become a substitute for antibiotics. The industrialization of antimicrobial peptide feed additive and its application in pig, chicken, fish and other feeds are of great significance to reduce the use of traditional feed antibiotics and curb the generation of drug resistance of pathogenic bacteria.

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Chengdu Shengnuo Biotechnology Co., Ltd. has "Chengdu polypeptide drug engineering technology research center" in Chengdu, mainly engaged in polypeptide, polypeptide drug and beauty peptide research. Our zero defect has passed the FDA certification, and now it has become the first-class professional peptide drug and product development, technology transfer, technical service and peptide drug industry in the scale production and export of China's parks.

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