Peptide polymer displaying potent activity against clinically isolated multidrug resistant Pseudomonas aeruginosa in vitro and in vivo
Peptide polymer displaying potent activity against clinically isolated multidrug resistant Pseudomonas aeruginosa in vitro and in vivo
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肽聚合物在体外和体内对临床分离的多重耐药铜绿假单胞菌表现出有效的活性
DOI：
10.1039/c9bm01726g
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发表时间：
2020-01-21
影响因子：
6.6
通讯作者：
Liu, Runhui
中科院分区：
文献类型：
--
作者：
Jiang, Weinan;Xiao, Ximian;Liu, Runhui
多药耐药(MDR)铜绿假单胞菌因其较高的内在耐药率和对常用抗生素的获得性而导致严重的医院感染。迫切需要开发针对多药耐药铜绿假单胞菌的抗菌药物。在这里，我们报告了一种27肽聚合物90：10Dll：BLG，作为一种宿主防御肽的合成模拟物，它在体外和体内对多种临床分离的耐多药铜绿假单胞菌具有很强的活性，在我们的研究中表现出比抗生素更好的表现。这种多肽聚合物还表现出可忽略不计的溶血和低细胞毒性，以及快速杀菌效果。多肽聚合物的结构多样性、由六甲基二硅氮化锂引发的快速N-羧酸酐聚合反应的简便性以及其化学结构和生物学特性的良好重现性，这些都表明多肽聚合物作为宿主防御肽的合成模拟物具有巨大的抗菌应用潜力。
Multidrug resistant (MDR) Pseudomonas aeruginosa has caused serious nosocomial infections owing to its high intrinsic resistance and ease of acquiring resistance to common antibiotics. There is an urgent need to develop antimicrobial agents against MDR Pseudomonas aeruginosa. Here we report a 27-mer peptide polymer 90 : 10 DLL : BLG, as a synthetic mimic of a host defense peptide, that displayed potent in vitro and in vivo activities against multiple strains of clinically isolated MDR Pseudomonas aeruginosa, performing even better than antibiotics within our study. This peptide polymer also showed negligible hemolysis and low cytotoxicity, as well as quick bacterial killing efficacy. The structural diversity of peptide polymers, their easy synthesis from lithium hexamethyldisilazide-initiated fast N-carboxyanhydride polymerization, and the excellent reproducibility of their chemical structure and biological profiles altogether suggested great potential for antimicrobial applications of peptide polymers as synthetic mimics of host defense peptides.