State Key Laboratory of Bioreactor Engineering, Key Laboratory for Ultrafine Materials of Ministry of Education, Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, China.
Biomater Sci. 2019 Apr 23;7(5):2144-2151. doi: 10.1039/c9bm00248k.
Microbial infections have always been serious challenges to human health considering that antibiotics almost inevitably induce microbial resistance. Therefore, it is urgent to develop a new antibacterial agent that is active against drug-resistant bacteria and is less susceptible to microbial resistance. In this work, a series of host defense peptide (HDP) mimicking antibacterial poly-β-peptides were synthesized, characterized and evaluated for their biological activities. The best poly-β-peptide within this study (20 : 80 Bu : DM) displays potent and broad spectrum antibacterial activity against antibiotic-resistant super bugs and low toxicity toward mammalian cells. Moreover, these poly-β-peptides are bactericidal and kill bacteria very fast within 5 min. An antimicrobial resistance test demonstrated that bacteria develop no resistance toward the selected poly-β-peptides even over 1000 generations. Our studies demonstrate that random copolymers of heterochiral poly-β-peptides, without the need for defined secondary structures, can mimic the antimicrobial HDP. These results imply the potential application of these poly-β-peptides as new antimicrobial agents to tackle drug resistant antimicrobial infections.
考虑到抗生素几乎不可避免地会诱导微生物产生耐药性，微生物感染一直是人类健康的严重挑战。因此，迫切需要开发一种新的抗菌剂，它对耐药菌具有活性，并且不易产生微生物耐药性。在这项工作中，合成了一系列模拟宿主防御肽（HDP）的抗菌聚-β-肽，并对其生物学活性进行了表征和评价。在这项研究中，最好的聚-β-肽（20:80 Bu:DM）对具有抗药性的超级细菌具有强大且广谱的抗菌活性，对哺乳动物细胞的毒性较低。此外，这些聚-β-肽具有杀菌作用，能在 5 分钟内快速杀死细菌。抗菌耐药性测试表明，即使经过 1000 多代，细菌也不会对所选聚-β-肽产生耐药性。我们的研究表明，无需定义二级结构的杂手性聚-β-肽的随机共聚物可以模拟抗菌 HDP。这些结果表明，这些聚-β-肽有可能作为新的抗菌剂应用于解决耐药性抗菌感染。
