Willcox M D P, Hume E B H, Aliwarga Y, Kumar N, Cole N
Institute for Eye Research, The University of New South Wales (UNSW), Sydney, NSW, Australia.
J Appl Microbiol. 2008 Dec;105(6):1817-25. doi: 10.1111/j.1365-2672.2008.03942.x. Epub 2008 Nov 1.
To develop an antimicrobial peptide with broad spectrum activity against bacteria implicated in biomaterial infection of low toxicity to mammalian cells and retaining its antimicrobial activity when covalently bound to a biomaterial surface.
A synthetic peptide (melimine) was produced by combining portions of the antimicrobial cationic peptides mellitin and protamine. In contrast to the parent peptide melittin which lysed sheep red blood cells at >10 microg ml(-1), melimine lysed sheep red blood cells only at concentrations >2500 microg ml(-1), well above bactericidal concentrations. Additionally, melimine was found to be stable to heat sterilization. Evaluation by electron microscopy showed that exposure of both Pseudomonas aeruginosa and Staphylococcus aureus to melimine at the minimal inhibitory concentration (MIC) produced changes in the structure of the bacterial membranes. Further, repeated passage of these bacteria in sub-MIC concentrations of melimine did not result in an increase in the MIC. Melimine was tested for its ability to reduce bacterial adhesion to contact lenses when adsorbed or covalently attached. Approximately 80% reduction in viable bacteria was seen against both P. aeruginosa and S. aureus for 500 microg per lens adsorbed melimine. Covalently linked melimine (18 +/- 4 microg per lens) showed >70% reduction of these bacteria to the lens.
We have designed and tested a synthetic peptide melimine incorporating active regions of protamine and mellitin which may represent a good candidate for development as an antimicrobial coating for biomaterials.
Infection associated with the use of biomaterials remains a major barrier to the long-term use of medical devices. The antimicrobial peptide melimine is an excellent candidate for development as an antimicrobial coating for such devices.
开发一种具有广谱抗菌活性的抗菌肽,对与生物材料感染相关的细菌具有活性,对哺乳动物细胞毒性低,并在与生物材料表面共价结合时保留其抗菌活性。
通过结合抗菌阳离子肽蜂毒素和鱼精蛋白的部分区域,制备了一种合成肽(蜂毒明肽)。与在浓度>10μg/ml时能裂解绵羊红细胞的亲本肽蜂毒素不同,蜂毒明肽仅在浓度>2500μg/ml时才会裂解绵羊红细胞,该浓度远高于杀菌浓度。此外,发现蜂毒明肽对热灭菌稳定。电子显微镜评估显示,将铜绿假单胞菌和金黄色葡萄球菌暴露于最低抑菌浓度(MIC)的蜂毒明肽下,会使细菌膜结构发生变化。此外,这些细菌在低于MIC浓度的蜂毒明肽中反复传代,MIC并未增加。测试了蜂毒明肽在吸附或共价连接时减少细菌黏附到隐形眼镜上的能力。对于每片吸附500μg蜂毒明肽的情况,对铜绿假单胞菌和金黄色葡萄球菌的活菌数减少了约80%。共价连接的蜂毒明肽(每片18±4μg)使这些细菌在隐形眼镜上的黏附减少>70%。
我们设计并测试了一种包含鱼精蛋白和蜂毒素活性区域的合成肽蜂毒明肽,它可能是开发生物材料抗菌涂层的良好候选物。
与生物材料使用相关的感染仍然是医疗器械长期使用的主要障碍。抗菌肽蜂毒明肽是开发此类器械抗菌涂层的优秀候选物。