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抗自溶素特异性 IgG 片段的被动免疫治疗:抗生素治疗对耐甲氧西林金黄色葡萄球菌感染的类似保护作用。

Passive immunotherapy with specific IgG fraction against autolysin: Analogous protectivity in the MRSA infection with antibiotic therapy.

机构信息

Department of Biotechnology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

Department of Microbiology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

出版信息

Immunol Lett. 2019 Aug;212:125-131. doi: 10.1016/j.imlet.2018.11.010. Epub 2018 Nov 26.

Abstract

Staphylococcus aureus is a leading infectious cause of life-threatening diseases in human beings, with no effective vaccine available to date against this bacterium. Treatment of methicillin-resistant S. aureus (MRSA) infections has become increasingly difficult because of the emergence of multidrug-resistant isolates. Immunotherapy represents a potential approach to prevent S. aureus-related infections. Autolysin is one of the virulence factors, which controls the growth, cell lysis, daughter-cell separation, and biofilm formation. Our study focused on passive immunization against MRSA infection. Herein, rabbit polyclonal IgG was produced following the preparation of r-autolysin. Specificity of IgG against r-autolysin was investigated by ELISA and western blotting assays. IgG fraction was prepared using sulfate ammonium precipitation, and the ability of antiserum to promote phagocytosis of bacteria was assessed by opsonophagocytosis assay. Then, passive immunization of mice was carried out with polyclonal IgG fraction and, mice were sacrificed three days after challenge and their kidneys, liver, and spleen were collected. Results exhibited that the passive immunization with rabbit polyclonal anti-IgG fraction tremendously improved survival rates of mice challenged by S. aureus as well as vancomycin treatment compared with the negative control groups. In addition, a remarkable decrease in bacterial numbers was observed in mice treated with rabbit polyclonal anti-IgG. Importantly, our findings demonstrated that passive immunotherapy and antibiotic therapy lead to decreased histopathological damage in mice infected by S. aureus as compared with control groups. Our results suggested that the passive immunization may result in the introduction of excellent strategies to control infections caused by MRSA, like antibiotic therapy.

摘要

金黄色葡萄球菌是导致人类生命威胁性疾病的主要感染源,目前针对这种细菌还没有有效的疫苗。由于多药耐药株的出现,耐甲氧西林金黄色葡萄球菌(MRSA)感染的治疗变得越来越困难。免疫疗法代表了预防金黄色葡萄球菌相关感染的一种潜在方法。自溶素是一种毒力因子,它控制着细菌的生长、细胞裂解、子细胞分离和生物膜形成。我们的研究集中在针对 MRSA 感染的被动免疫上。在此,通过制备 r-自溶素,产生了兔多克隆 IgG。通过 ELISA 和 Western blot 分析来研究 IgG 针对 r-自溶素的特异性。使用硫酸铵沉淀法制备 IgG 部分,并通过调理吞噬作用测定法评估抗血清促进细菌吞噬的能力。然后,用多克隆 IgG 部分对小鼠进行被动免疫,在攻毒后 3 天处死小鼠,并收集其肾脏、肝脏和脾脏。结果表明,与阴性对照组相比,兔多克隆抗 IgG 部分的被动免疫大大提高了金黄色葡萄球菌攻毒和万古霉素治疗后小鼠的存活率。此外,在接受兔多克隆抗 IgG 治疗的小鼠中,细菌数量显著减少。重要的是,我们的研究结果表明,与对照组相比,被动免疫疗法和抗生素治疗可导致感染金黄色葡萄球菌的小鼠的组织病理学损伤减少。我们的研究结果表明,被动免疫可能会为控制 MRSA 引起的感染提供优秀的策略,如抗生素治疗。

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