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探索新型抗菌脂肽 Battacin 作为抗菌涂层的潜力的可行性研究。

Feasibility Study Exploring the Potential of Novel Battacin Lipopeptides as Antimicrobial Coatings.

机构信息

School of Chemical Sciences, The University of Auckland , Private Bag 92019, Auckland, New Zealand.

出版信息

ACS Appl Mater Interfaces. 2017 Jan 18;9(2):1373-1383. doi: 10.1021/acsami.6b15859. Epub 2017 Jan 4.

Abstract

Colonization of medical implant surfaces by pathogenic microorganisms causes implant failure and undermines their clinical applicability. Alarming increase in multidrug-resistant bacteria poses serious concerns with the use of medical implants. Antimicrobial peptides (AMPs) that form part of the innate immune system in all forms of life are attractive alternatives to conventional antibiotics to treat multidrug-resistant bacterial biofilms. The aim of this study was to assess the in vitro antibacterial potency of our recently discovered lipopeptides from the battacin family upon immobilization to various surfaces. To achieve this, glass, silicon, and titanium surfaces were functionalized through silanization followed by addition of the heterobifunctional cross-linker, succinimidyl-[N-maleimidopropionamido]-poly(ethylene glycol) ester to generate maleimide-functionalized surfaces. The lipopeptide, GZ3.27, with an added N-terminal cysteine was covalently coupled to the surfaces via a thioether bond through a Michael-type addition between the cysteine sulfhydryl group and the maleimide moiety. Success of surface immobilization and antimicrobial activity of the coated surfaces was assessed using water contact angle measurements, X-ray photoelectron spectroscopy, ellipsometry, scanning electron microscopy, colony forming unit assays and biofilm analysis. The lipopeptide-coated surfaces caused significant damage to the cellular envelop of Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli (E. coli) upon contact and prevented surface colonization by P. aeruginosa and E. coli biofilms. The lipopeptides investigated in this study were not hemolytic to mouse blood cells in solution. Findings from this study indicate that these lipopeptides have the potential to be developed as promising antimicrobial coatings on medical implants.

摘要

医用植入物表面被致病微生物定植会导致植入物失效,并降低其临床适用性。多重耐药菌的惊人增长对医用植入物的使用提出了严重的担忧。抗菌肽(AMPs)是所有生命形式固有免疫系统的一部分,是治疗多重耐药菌生物膜的传统抗生素的替代品。本研究旨在评估我们最近发现的来自 battacin 家族的脂肽在固定到各种表面时的体外抗菌效力。为此,通过硅烷化对玻璃、硅和钛表面进行功能化,然后添加双功能交联剂琥珀酰亚胺-[N-马来酰亚胺丙酰胺基]-聚乙二醇酯,生成马来酰亚胺功能化表面。带有 N 端半胱氨酸的脂肽 GZ3.27 通过迈克尔型加成反应通过硫醚键共价偶联到表面,半胱氨酸巯基与马来酰亚胺部分之间发生加成反应。通过水接触角测量、X 射线光电子能谱、椭圆光度法、扫描电子显微镜、集落形成单位测定和生物膜分析评估表面固定化的成功和涂层表面的抗菌活性。脂肽涂层表面与铜绿假单胞菌(P. aeruginosa)和大肠杆菌(E. coli)接触时会对其细胞包膜造成严重损伤,并阻止 P. aeruginosa 和 E. coli 生物膜在表面定植。研究中研究的脂肽在溶液中对小鼠血细胞没有溶血作用。本研究的结果表明,这些脂肽有可能被开发为医用植入物的有前途的抗菌涂层。

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