探索atp结合盒(ABC)转运蛋白抗原作为抗

Salma Abdallah, Mervat A. Kassem, Nelly M. Mohamed, M. Bahey-El-Din
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引用次数: 0

摘要

目的:鲍曼不动杆菌多重耐药菌株的出现和有限的可用治疗方案,导致世界卫生组织将这种病原体列为迫切需要开发新的治疗方案的微生物之一。本研究旨在首次探索外排相关蛋白,atp结合盒(ABC)转运体底物结合蛋白作为鲍曼不动杆菌感染候选疫苗的潜力。已知ABC转运蛋白底物结合蛋白在鲍曼不动杆菌的铁获取途径中发挥作用。它利用ATP水解释放的能量,将铁结合的铁载体运输穿过质膜进入细胞。方法:将ABC转运蛋白底物结合蛋白的相关基因克隆到pQE31质粒载体中,在大肠杆菌中进行表达。用金属亲和层析纯化该蛋白。纯化后的抗原与卡介苗(BCG)和明矾纳米粒作为佐剂联合给药。在小鼠感染模型中评估了免疫参数,并在细菌攻击后测试了保护作用。结果:末次免疫2周后,检测血清样品抗原特异性IgG抗体反应,免疫小鼠与阴性对照组相比,抗原特异性IgG抗体反应极显著。用鲍曼不动杆菌攻毒小鼠后,只获得持续24小时的短暂保护。结论:鲍曼不动杆菌毒力因子的多样性,包括多种铁获取机制,可能需要设计多组分疫苗来产生有效的保护作用。此外,免疫方案、使用的佐剂和给药途径是值得进一步研究的关键因素,以实现完全的持久保护。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Exploration of the Potential of the ATP-Binding Cassette (ABC) Transporter Antigen as a Vaccine Candidate Against
Objectives: The emerging multidrug-resistant strains of Acinetobacter baumannii and the limited available treatment options, have led the World Health Organization to enlist this pathogen among the microorganisms with critical priority demanding the development of novel treatment alternatives. This study aimed at exploring, for the first time, the potential of an efflux-related protein, the ATP-binding cassette (ABC) transporter substrate-binding protein, as a vaccine candidate against A. baumannii infections. The ABC transporter substrate-binding protein is known to play a role in the iron acquisition pathway of A. baumannii . It utilizes the energy released from the hydrolysis of ATP in the transportation of the iron-bound siderophore across the plasma membrane into the cell. Methods: In this work, the ABC transporter substrate-binding protein was expressed in Escherichia coli after cloning its respective gene into pQE31 plasmid vector. The protein was purified using metal affinity chromatography. The purified antigen was administered to mice in combination with Bacillus Calmette–Guérin (BCG) and alum nanoparticles as adjuvants. Immunological parameters were assessed, and protection was tested following bacterial challenge in a murine infection model. Results: Two weeks after the last immunization dose, serum samples were tested for antigen-specific IgG antibody response which was extremely significant in immunized mice when compared with negative control mice. Following challenge of mice with A. baumannii , only a short-lived protection lasting for 24 hours was obtained. Conclusion: The diversity of the virulence factors exhibited by A. baumannii including several iron acquisition mechanisms might necessitate the design of a multi-component vaccine to elicit effective protection. Furthermore, the immunization regimen, the used adjuvant, and the route of administration are critical factors which are worthy of further investigation to fulfill complete long-lasting protection.
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