Identification and Characterization of the Rhoptry Neck Protein 2 in Babesia divergens and B. microti.
Identification and Characterization of the Rhoptry Neck Protein 2 in Babesia divergens and B. microti.
复制标题
分歧巴贝斯虫和田鼠巴贝斯虫中棒状体颈蛋白 2 的鉴定和表征。
DOI：
10.1128/iai.00107-16
复制
发表时间：
2016
影响因子：
3.1
通讯作者：
Lobo,CherylA
中科院分区：
文献类型：
--
作者：
Ord,RosalynnL;Rodriguez,Marilis;Cursino-Santos,JenyR;Hong,Hyunryung;Singh,Manpreet;Gray,Jeremy;Lobo,CherylA
顶复门寄生虫包括疟原虫属、隐孢子虫属和弓形虫属，以及研究相对不足的人畜共患巴贝虫属。在人类中，巴贝斯虫病，特别是输血传播的巴贝斯虫病，已成为对公共卫生的主要威胁。与疟疾一样，该疾病的病理学是寄生虫血症的结果，寄生虫血症是通过巴氏疟原虫在宿主红细胞中的周期性复制而发展的。然而，在巴氏疟原虫中没有红细胞外期，因此靶向血液期和相关蛋白以直接防止寄生虫入侵是有效控制疾病的最理想选择。在这些分子中特别有前途的是棒状体颈蛋白（RON），其同系物已在许多顶复门寄生虫中被鉴定。RON与AMA 1一起沿着参与移动连接的形成，但在任何巴贝属中均未鉴定和表征罗恩。在这里，我们确定的RON 2蛋白的巴氏divergens（BdRON 2）和B。microti（BmRON 2），并显示它们位于顶端，抗BdRON 2抗体是体外寄生虫入侵的重要抑制剂。这两种蛋白质都不是免疫显性的，因为这两种蛋白质都只与感染动物的血清发生轻微反应。需要进一步表征BdRON 2和BmRON 2在寄生虫入侵中的直接作用，但是需要了解RON 2蛋白在顶复门中的一致性水平，特别是在移动连接处的AMA 1-RON 2复合物的一致性水平，沿着B的动物模型的可用性。Microti的研究提供了一个关键的目标，以防止这些寄生虫的红细胞入侵，并进一步了解这些保守的配体在入侵中的作用。
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 invasionin 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.