Deal with superbugs! Chinese scientists have designed and modified an antibacterial peptide

The invention of antibiotics has extended the lifespan of human beings by a large margin. However, the extensive use or abuse of broad-spectrum antibiotics and antimicrobials has led to the emergence of various drug-resistant bacteria or fungi. In February 2017, the World Health Organization released a list of bacteria in urgent need of new antibiotics. Drug-resistant Acinetobacter baumannii (Ab bacteria) and P. aeruginosa are the top two on the list.

According to statistics, nearly 1 million people die every year worldwide from bacterial infections that cannot be treated with ordinary antibiotics. At the same time, due to the insufficient research and development capacity of new antibacterial drugs, the resistance genes of various bacteria themselves can be spread horizontally, which greatly reduces the therapeutic effect of existing antibiotics, and human beings may face the advent of the post-antibiotic era without effective antibiotics.

The team led by researcher Lai Ling of the Kunming Institute of Zoology of the Chinese Academy of Sciences has identified more than 1,000 antimicrobial peptides in recent years, and on this basis, the structural function of antimicrobial peptides has been modified to improve antibacterial activity, reduce toxicity and cost.

Antimicrobial peptides are a class of polypeptide small molecules with antibacterial activity, which have attracted worldwide attention because of their rapid sterilization and difficulty in leading to microbial resistance, and can be used for the research and development of new antibacterial drug candidate molecules.

ZY4 is an antimicrobial peptide recently designed and modified by the team, which has strong antibacterial activity, high stability and low toxicity. ZY4 showed high and rapid bactericidal activity against drug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, while ZY4 also had a significant clearance effect on the biofilms and persister cells of these two bacteria, and its comprehensive antibacterial effect was significantly better than that of traditional antibiotics such as tobramycin, levofloxacin, kanamycin and cefotetan.

In addition, the long-term use of ZY4 is not easy to produce drug resistance, and after 60 generations of continuous action between ZY4 and Acinetobacter baumannii and Pseudomonas aeruginosa, the bacteriostatic effect of ZY4 on these two types of bacteria has not changed significantly.

Subsequent animal experiments have also shown that ZY4 can significantly inhibit the spread of Acinetobacter baumannii and Pseudomonas aeruginosa in vivo and lung infections and inflammation caused by Pseudomonas aeruginosa.

This study provides a good drug candidate molecule for coping with the current increasingly serious problems of transmission and infection of drug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, and also provides a reference new strategy for the design of highly efficient and low-toxic antimicrobial peptides.

Recently, the above research results were published online in the top academic journal "Proceedings of the National Academy of Sciences" (PANS). James Mwangi, phD student at Kunming Institute of Zoology, Chinese Academy of Sciences, Master student Yin Yizhu, assistant researcher Wang Gan and master student Yang Min are the co-first authors of the paper, and researcher Lai Ling and associate researcher Zhang Zhiye are the co-corresponding authors of the paper.