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Identification and Characterization of the Rhoptry Neck Protein 2 in Babesia divergens and B. microti

机译:巴氏杆菌和微小芽孢杆菌Rhoptry颈蛋白2的鉴定与表征

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Apicomplexan parasites include those of the genera Plasmodium, Cryptosporidium, and Toxoplasma and those of the relatively understudied zoonotic genus Babesia. In humans, babesiosis, particularly transfusion-transmitted babesiosis, has been emerging as a major threat to public health. Like malaria, the disease pathology is a consequence of the parasitemia which develops through cyclical replication of Babesia parasites in host erythrocytes. However, there are no exoerythrocytic stages in Babesia, so targeting of the blood stage and associated proteins to directly prevent parasite invasion is the most desirable option for effective disease control. Especially promising among such molecules are the rhoptry neck proteins (RONs), whose homologs have been identified in many apicomplexan parasites. RONs are involved in the formation of the moving junction, along with AMA1, but no RON has been identified and characterized in any Babesia spp. Here we identify the RON2 proteins of Babesia divergens (BdRON2) and B. microti (BmRON2) and show that they are localized apically and that anti-BdRON2 antibodies are significant inhibitors of parasite invasion in vitro. Neither protein is immunodominant, as both proteins react only marginally with sera from infected animals. Further characterization of the direct role of both BdRON2 and BmRON2 in parasite invasion is required, but knowledge of the level of conformity of RON2 proteins within the apicomplexan phylum, particularly that of the AMA1-RON2 complex at the moving junction, along with the availability of an animal model for B. microti studies, provides a key to target this complex with a goal of preventing the erythrocytic invasion of these parasites and to further our understanding of the role of these conserved ligands in invasion.
机译:蚜虫寄生虫包括疟原虫,隐孢子虫和弓形虫属的寄生虫,以及人畜共患病巴贝斯虫属相对未被充分研究的寄生虫。在人类中,杆状杆菌病,特别是输血传播的杆状杆菌病,已成为对公共卫生的主要威胁。像疟疾一样,疾病病理是寄生虫病的结果,寄生虫病是通过宿主红细胞中巴贝虫寄生虫的周期性复制而形成的。但是,在巴贝虫病中没有外红细胞生成阶段,因此,针对血液阶段和相关蛋白以直接预防寄生虫入侵是有效控制疾病的最理想选择。在这类分子中特别有前途的是rhoptry颈部蛋白(RON),其同系物已在许多apicomplexan寄生虫中鉴定出。 RON与AMA1一起参与了活动结的形成,但在任何巴贝斯虫属中均未鉴定到RON。在这里,我们鉴定了巴氏杆菌(BdRON2)和微小芽孢杆菌(BmRON2)的RON2蛋白,并显示它们位于根尖,并且抗BdRON2抗体是体外寄生虫入侵的重要抑制剂。这两种蛋白质都不具有免疫优势,因为这两种蛋白质仅与感染动物的血清发生少量反应。需要进一步表征BdRON2和BmRON2在寄生虫侵袭中的直接作用,但需要了解apicomplexan门内RON2蛋白(尤其是移动连接处的AMA1-RON2复合物)中RON2蛋白的整合水平,以及一种用于B. microti研究的动物模型,为靶向这种复合物提供了关键,目的是防止这些寄生虫的红细胞入侵,并进一步使我们了解这些保守配体在入侵中的作用。

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