文献类型：期刊文献

英文题名：Quaternary Ammonium Salt Derivatives of Hyperbranched Polylysine with Enhanced Antibacterial Activity against Multidrug-Resistant Gram-Negative Bacteria

作者：Chen, Guohao[1,2];Liu, Xiao[1,3];Liu, Hui[1,3];Liang, Shuhan[4];Sun, Shuhong[5];Han, Miaomiao[1];Ji, Shengxiang[1,3]

机构：[1]Chinese Acad Sci, Changchun Inst Appl Chem, Key Lab Polymer Ecomat, Changchun 130022, Jilin, Peoples R China;[2]East China Univ Sci & Technol, Shanghai 200237, Peoples R China;[3]Univ Sci & Technol China, Hefei 230026, Peoples R China;[4]Xian Jiaotong Liverpool Univ, Suzhou 215123, Peoples R China;[5]Delegate Off Changchun, Changchun 130041, Peoples R China

年份：2024

卷号：7

期号：11

起止页码：7444

外文期刊名：ACS APPLIED BIO MATERIALS

收录：EI(收录号：20244517337420);WOS:【ESCI(收录号:WOS:001348523800001)】；

基金：This work was financially supported by the National Key Research and Development Program (2022YFC2603500 and 2022YFC2603504) and Jilin Province Science Technology Development Plan Project (20230508114RC).

语种：英文

外文关键词：Hyperbranched polylysine; Quaternary ammonium salts; Multidrug-resistant Gram-negativebacteria; Antibacterialactivity; Antimicrobial mechanism

摘要：Multidrug-resistant (MDR) Gram-negative bacteria infections have gradually become a more serious health problem recently, and antibacterial drugs are urgently needed to tackle MDR Gram-negative bacteria. Herein, we synthesized a series of quaternary ammonium salt derivatives of hyperbranched polylysine (HPL-Cm-n) with different alkyl chain lengths (m = 4, 8, 12, 16) and grafting ratios (n = 5.8-21.0) of alkyl quaternary ammonium salts (Cm). HPL-Cm-ns exhibited excellent antibacterial activities against drug-sensitive E. coli and P. aeruginosa, and specifically, HPL-C12-ns were also highly active against MDR E. coli and P. aeruginosa. The cytotoxicity and hemolytic activity of HPL-Cm-ns increased with the increase in the alkyl chain length and the grafting ratio of Cm. The killing study proved that HPL-C12-9.5 had fast killing kinetics and was bactericidal toward both drug-sensitive and MDR E. coli. The mechanistic studies showed that, similar to hyperbranched polylysine (HPL), HPL-C12-9.5 killed bacteria by disrupting the cell membranes and causing leakage of the cytoplasmic contents. HPL-C12-ns might have potential as an antibacterial agent to combat MDR Gram-negative bacteria.