Host Defense Peptide Mimicking Peptide Polymer Exerting Fast, Broad Spectrum, and Potent Activities toward Clinically Isolated Multidrug-Resistant Bacteria

Host Defense Peptide Mimicking Peptide Polymer Exerting Fast, Broad Spectrum, and Potent Activities toward Clinically Isolated Multidrug-Resistant Bacteria
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宿主防御肽模拟肽聚合物对临床分离的多重耐药细菌发挥快速、广谱和有效的活性。

DOI:
10.1021/acsinfecdis.9b00410
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发表时间:
2020-03-13
影响因子:
5.3
通讯作者:
Liu, Runhui
Liu, Runhui
中科院分区:
医学2区
文献类型:
--
作者:
Chen, Sheng;Shao, Xiaoyan;Liu, Runhui

文献摘要

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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.