宿主防御肽模拟聚合物与蛋白酶K联用抗生物被膜  

Combination of Host Defense Peptide Mimicking Peptide Polymer and Proteinase K against Biofilms

作　　者：毕玉芳 武月铭 刘士琦 钱宇芯 刘润辉[1] BI Yufang;WU Yueming;LIU Shiqi;QIAN Yuxin;LIU Runhui(Engineering Research Center for Biomedical Materials of Ministry of Education,School of Materials Science and Engineering,East China University of Science and Technology,Shanghai 200237,China)

机构地区：[1]华东理工大学材料科学与工程学院,教育部医用生物材料工程研究中心,上海200237

出　　处：《功能高分子学报》2022年第3期261-269,共9页Journal of Functional Polymers

基　　金：国家自然科学基金(22075078,21861162010);上海市自然科学基金(18ZR1410300);上海市优秀青年学术带头人(20XD1421400)。

摘　　要：采用双(三甲基硅基)胺基锂(LiHMDS)引发的α-氨基酸N-羧酸酐(NCA)快速开环聚合方法合成宿主防御肽模拟聚合物,该聚合物呈现窄分子量分布。抗菌实验结果表明,该聚合物对耐甲氧西林金黄色葡萄球菌(MRSA)浮游菌和持留菌有高杀菌活性,且遵循破膜杀菌机制。实验证明,1.25 U/mL的蛋白酶K在人工尿液环境中可分散MRSA成熟生物被膜。蛋白酶K与聚合物协同作用实现了人工尿液中成熟生物被膜的清除。Staphylococcus aureus(S.aureus)is one of the main pathogens causing urinary catheter-related infections,and its biofilm has strong resistance to immune clearance and antibiotics.Effective measures should be taken to solve catheter biofilm-related infections fundamentally.In this study,the host defense peptide mimicking peptide polymer was synthesized by rapid ring-opening polymerization ofα-amino acid N-carboxyanhydride(NCA),which was initiated by lithium bis(trimethylsilyl)amide(LiHMDS).The resulting polymer showed a narrow molecular weight distribution.Antimicrobial experiment showed that this peptide polymer had a high bactericidal activity against the planktonic and persister cells of methicillin-resistant Staphylococcus aureus(MRSA).Bactericidal mechanism showed that this peptide polymer killed MRSA by destroying the integrity of bacterial cell membrane.Protein is one of the basic components of extracellular polymeric matrix(EPS),which plays an important role in bacterial colonization and biofilm development.The dispersing effect of proteinase K on EPS is beneficial to the penetration of antimicrobial agents into biofilms.1.25 U/mL proteinase K dispersed mature MRSA biofilms in artificial urine,and the remaining cell viability was about 55%of the control group.The combination of proteinase K and polymer further eradicated mature MRSA biofilms in artificial urine,which confirmed the potential of synergism in eradicating the biofilms inside urinary catheter.The optimal combination reduced the cell viability within biofilms to about 10%of the control group.

关 键 词：多肽聚合物 蛋白酶K 生物被膜 持留菌 药物协同 

分 类 号：R318.08[医药卫生—生物医学工程]