Liu Runhui, Professor of East China University of science and technology research group: fast, efficient and broad-spectrum antibacterial β - peptide polymer simulating host defense peptide

Author: as the main drug to treat microbial infection, Zhang Qiang, a master's student, has been playing an important role in the field of medical and health since it was found However, the emergence of drug-resistant microorganisms leads to less and less antibiotics available in clinical practice, and some bacteria are even "incurable" Therefore, it is urgent to develop new antimicrobial agents that can effectively resist resistant microorganisms The host defense peptides (HDPs), which exist naturally, are expected to be a powerful weapon to solve drug-resistant microbial infection because of their destructive antibacterial mechanism However, the poor stability and high cost of HDPs greatly limit its application in real life In order to make up for its shortcomings, Liu Runhui, Professor of East China University of science and technology, recently developed a kind of β - polypeptide polymer with rapid, efficient and broad-spectrum antibacterial activity by simulating HDPs, which can effectively kill resistant bacteria and not easily make them resistant This achievement was recently published on Biomaterials Science (DOI: 10.1039/c9bm00248k) In order to overcome the inherent shortcomings of traditional antibiotics, Professor Liu Runhui and others paid close attention to and studied the natural host defense peptide and its analogues in vivo, and made preliminary results In this study, researchers synthesized a series of HDP mimic β - polypeptide polymers with different hydrophobic and hydrophilic / cationic subunits The skeleton structure of these β - polypeptide polymers is similar to that of natural HDPs, and they have excellent biocompatibility However, β - polypeptide polymers are composed of non natural β - amino acids, so they have excellent enzyme stability In addition, researchers prepared β - polypeptide polymers by ring opening polymerization of β - lactam The cost of synthesis is much lower than that of natural HDPs and it is easy to prepare in large quantities In this study, β - polypeptide polymer with the best comprehensive evaluation of biological activity has high efficiency, broad-spectrum (including drug-resistant bacteria) bactericidal activity and low hemolysis and cytotoxicity Time sterilization test results show that the optimal β - polypeptide polymer can kill more than 98% of Staphylococcus aureus and Pseudomonas aeruginosa in 5 minutes at the concentration of 2 × mic, realizing rapid sterilization The results of drug resistance test (Fig 2) showed that under the stimulation of continuous use of β - polypeptide polymer, bacterial reproduction over 1000 generations did not show drug resistance As a control, Pseudomonas aeruginosa was 32 times resistant to antibiotics, while Staphylococcus aureus was 512 times resistant to antibiotics These results all show the potential of β - polypeptide polymer in the treatment of drug-resistant bacterial infection and in solving the challenge of microbial resistance In addition, the study of membrane activity shows that β - polypeptide polymer has a strong membrane destruction effect on bacterial cell membrane The broad-spectrum antibacterial activity, rapid bactericidal characteristics, membrane damage effect and SEM characterization of β - polypeptide polymer consistently show the antibacterial mechanism of membrane destruction of the antibacterial compound (Fig 3) Fig 1 Time sterilization curve of β - polypeptide polymer (a) S aureus (a USA300); (b) P aeruginosa (source: Biomaterials Science) Fig 2 Resistance test of β - polypeptide polymer 20:80 Bu: DM and antibiotics to (a) S aureus and (b) P aeruginosa (source: Fig 3 Schematic diagram of the antibacterial action of HDP simulated β - polypeptide polymer (source: Biomaterials Science) Zhang Qiang, a postgraduate of East China University of science and technology, is the first author and main finisher of the achievement, and Professor Liu Runhui is the corresponding author The research was supported by NSFC and the Ministry of science and technology.