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

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.