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Susceptibility of microbial cells to the modified PIP2-binding sequence of gelsolin anchored on the surface of magnetic nanoparticles
Journal of Nanobiotechnology ( IF 10.6 ) Pub Date : 2019-07-08 , DOI: 10.1186/s12951-019-0511-1
Robert Bucki , Katarzyna Niemirowicz-Laskowska , Piotr Deptuła , Agnieszka Z. Wilczewska , Paweł Misiak , Bonita Durnaś , Krzysztof Fiedoruk , Ewelina Piktel , Joanna Mystkowska , Paul A. Janmey

Magnetic nanoparticles (MNPs) are characterized by unique physicochemical and biological properties that allow their employment as highly biocompatible drug carriers. Gelsolin (GSN) is a multifunctional actin-binding protein involved in cytoskeleton remodeling and free circulating actin sequestering. It was reported that a gelsolin derived phosphoinositide binding domain GSN 160–169, (PBP10 peptide) coupled with rhodamine B, exerts strong bactericidal activity. In this study, we synthesized a new antibacterial and antifungal nanosystem composed of MNPs and a PBP10 peptide attached to the surface. The physicochemical properties of these nanosystems were analyzed by spectroscopy, calorimetry, electron microscopy, and X-ray studies. Using luminescence based techniques and a standard killing assay against representative strains of Gram-positive (Staphylococcus aureus MRSA Xen 30) and Gram-negative (Pseudomonas aeruginosa Xen 5) bacteria and against fungal cells (Candida spp.) we demonstrated that magnetic nanoparticles significantly enhance the effect of PBP10 peptides through a membrane-based mode of action, involving attachment and interaction with cell wall components, disruption of microbial membrane and increased uptake of peptide. Our results also indicate that treatment of both planktonic and biofilm forms of pathogens by PBP10-based nanosystems is more effective than therapy with either of these agents alone. The results show that magnetic nanoparticles enhance the antimicrobial activity of the phosphoinositide-binding domain of gelsolin, modulate its mode of action and strengthen the idea of its employment for developing the new treatment methods of infections.

中文翻译:

微生物对锚固在磁性纳米颗粒表面的凝溶胶蛋白的修饰的PIP 2结合序列的敏感性

磁性纳米颗粒(MNP)具有独特的物理化学和生物学特性,可作为高度生物相容的药物载体使用。凝溶胶蛋白(GSN)是一种多功能肌动蛋白结合蛋白,参与细胞骨架重塑和游离循环肌动蛋白螯合。据报道,凝溶胶蛋白衍生的磷酸肌醇结合结构域GSN 160-169(PBP10肽)与若丹明B偶联,具有很强的杀菌活性。在这项研究中,我们合成了一个新的抗菌和抗真菌纳米系统,该系统由MNP和附着在表面的PBP10肽组成。这些纳米系统的理化性质通过光谱学,量热法,电子显微镜和X射线研究进行了分析。使用基于发光的技术和针对革兰氏阳性菌(金黄色葡萄球菌MRSA Xen 30)和革兰氏阴性菌(铜绿假单胞菌Xen 5)的代表性菌株以及对真菌细胞(Candida spp。)的标准杀灭实验,我们证明了磁性纳米颗粒可以显着增强PBP10肽通过基于膜的作用方式的作用,包括与细胞壁成分的附着和相互作用,微生物膜的破坏和肽摄取的增加。我们的研究结果还表明,使用基于PBP10的纳米系统治疗浮游生物和生物膜形式的病原体比单独使用这两种药物进行治疗更为有效。结果表明,磁性纳米颗粒增强了凝溶胶蛋白的磷酸肌醇结合域的抗菌活性,
更新日期:2019-07-08
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