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Host Defense Peptide Mimicking Peptide Polymer Exerting Fast, Broad Spectrum, and Potent Activities toward Clinically Isolated Multidrug-Resistant Bacteria.
ACS Infectious Diseases ( IF 4.0 ) Pub Date : 2020-01-23 , DOI: 10.1021/acsinfecdis.9b00410
Sheng Chen 1, 2 , Xiaoyan Shao 2 , Ximian Xiao 1 , Yidong Dai 2 , Yun Wang 2 , Jiayang Xie 1 , Weinan Jiang 1 , Yun Sun 2 , Zihao Cong 1 , Zhongqian Qiao 1 , Haodong Zhang 1 , Longqiang Liu 1 , Qiang Zhang 1 , Wenjing Zhang 1 , Liang Zheng 3 , Bingran Yu 3 , Minzhang Chen 1 , Wenguo Cui 4 , Jian Fei 5 , Runhui Liu 1
Affiliation  

Multidrug-resistant (MDR) bacteria have emerged quickly and have caused serious nosocomial infections. It is urgent to develop novel antimicrobial agents for treating MDR bacterial infections. In this study, we isolated 45 strains of bacteria from hospital patients and found shockingly that most of these strains were MDR to antimicrobial drugs. This inspired us to explore antimicrobial peptide polymers as synthetic mimics of host defense peptides in combating drug-resistant bacteria and the formidable antimicrobial challenge. We found that peptide polymer 80:20 DM:Bu (where DM is a hydrophilic/cationic subunit and Bu is a hydrophobic subunit) displayed fast bacterial killing, broad spectrum, and potent activity against clinically isolated strains of MDR bacteria. Moreover, peptide polymer 80:20 DM:Bu displayed potent in vivo antibacterial efficacy, comparable to the performance of polymyxin B, in a Pseudomonas aeruginosa (P. aeruginosa) infected rat full-thickness wound model. The peptide polymer can be easily synthesized from ring-opening polymerization with remarkable reproducibility in structural properties and biological activities. The peptide polymer's potent and broad spectrum antimicrobial activities against MDR bacteria in vitro and in vivo, resistance to proteolysis, and high structural diversity altogether imply a great potential of peptide polymer 80:20 DM:Bu in antimicrobial applications as synthetic mimics of host defense peptides.

中文翻译:

模仿肽聚合物的宿主防御肽,对临床分离的耐多药细菌具有快速,广谱和有效的活性。

耐多药(MDR)细菌迅速出现,并引起了严重的医院感染。迫切需要开发用于治疗MDR细菌感染的新型抗菌剂。在这项研究中,我们从住院患者中分离出45株细菌,令人震惊地发现,这些菌株大多数是抗微生物药物的MDR。这激发了我们探索抗菌肽聚合物作为宿主防御肽的合成模拟物的作用,以对抗耐药细菌和强大的抗菌挑战。我们发现,肽聚合物80:20 DM:Bu(其中DM是亲水/阳离子亚基,Bu是疏水亚基)显示出快速的细菌杀灭力,广谱性和针对临床分离的MDR细菌株的有效活性。此外,多肽聚合物80:20 DM:Bu表现出强大的体内抗菌功效,在铜绿假单胞菌(P. aeruginosa)感染的大鼠全层伤口模型中,其性能与多粘菌素B相当。该肽聚合物可以容易地从开环聚合反应合成,在结构特性和生物活性方面具有显着的可重复性。该肽聚合物在体外和体内对MDR细菌的有效和广谱抗菌活性,对蛋白水解的抵抗力以及高结构多样性共同暗示着肽聚合物80:20 DM:Bu在抗微生物应用中作为宿主防御肽的合成模拟物具有巨大潜力。该肽聚合物可以容易地从开环聚合反应合成,在结构特性和生物活性方面具有显着的可重复性。该肽聚合物在体外和体内对MDR细菌的有效和广谱抗菌活性,对蛋白水解的抵抗力以及高结构多样性共同暗示着肽聚合物80:20 DM:Bu在抗微生物应用中作为宿主防御肽的合成模拟物具有巨大潜力。该肽聚合物可以容易地从开环聚合反应合成,在结构特性和生物活性方面具有显着的可重复性。该肽聚合物在体外和体内对MDR细菌的有效和广谱抗菌活性,对蛋白水解的抵抗力以及高结构多样性共同暗示着肽聚合物80:20 DM:Bu在抗微生物应用中作为宿主防御肽的合成模拟物具有巨大潜力。
更新日期:2020-01-23
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