Specificity in host carbohydrate-apicomplexan recognition

宿主碳水化合物-apicomplexan 识别的特异性

• 批准号: BB/E02520X/1
• 负责人: Steve Matthews
• 金额: $ 51.45万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE02520X%2F1
• 关键词: Specificity; host; carbohydrate; apicomplexan; recognition

The phylum Apicomplexa contains some of the most widespread protozoan parasites of humans and animals. Key members include Plasmodium spp., Eimeria spp., Neospora caninium and Toxoplasma gondii. Not only has T. gondii emerged as the principal model for the study of other apicomplexa parasites it is an important pathogen in its own right, causing severe disseminated disease. Eimeria are a group of highly successful intracellular protozoan parasites that develop within enterocytes. They are the cause of intestinal Coccidiosis in chickens, which is one of the economically most important diseases in modern poultry farming. Neospora caninum has emerged as global pathogen of major significance in cattle and dogs. N. caninum is recognised as the major diagnosed cause of reproductive failure in dairy cattle and infected cattle are up to seven times more likely to abort. Infection by apicomplexans is established in the host by rapid and forced invasion of host cells. Proteins secreted at the first stage of this process, participate in apical attachment to host cell surfaces and the formation of a connection with the parasite actinomyosin system, thereby providing the platform from which to drive invasion - these are called microneme proteins (MICs). We have identified a novel region within this family of proteins that interacts with host carbohydrates and is present in MICs from Eimeria and N. caninum. We have named this the 'Micronemal Adhesive Repeat Regions' (MARRs). We plan to investigate some fundamental aspects of how MICs discriminate host ligands, which will provide new information on how the parasite works at the molecular level. Our specific objectives are to determine the structures of MARRs from three different apicomplexans in complex with cognate ligands. The structural information provided by our studies will allow us to make new hypotheses about how they discriminate between different cell types. We will then design new experiments to test these hypotheses. Our work should provide a foundation that may reveal new pathways to the development of antimicrobial strategies.

顶复门包含一些最广泛的原生动物寄生虫的人类和动物。主要成员包括疟原虫属，艾美球虫属，犬新孢子虫和刚地弓形虫。不仅是T。刚地虫是研究其他顶复门寄生虫的主要模型，它本身就是一种重要的病原体，可引起严重的传播性疾病。艾美耳球虫是一组在肠上皮细胞内发育的非常成功的细胞内原生动物寄生虫。它们是鸡肠道球虫病的原因，这是现代家禽养殖中经济上最重要的疾病之一。犬新孢子虫已成为牛和犬的重要全球性病原体。n.犬瘟热被认为是奶牛繁殖失败的主要诊断原因，受感染的牛流产的可能性高达7倍。顶复门的感染是通过快速和强制侵入宿主细胞而在宿主中建立的。在这个过程的第一阶段分泌的蛋白质参与顶端附着到宿主细胞表面，并与寄生虫放线菌球蛋白系统形成连接，从而提供驱动入侵的平台-这些被称为微线蛋白（MIC）。我们已经确定了一个新的区域，在这个家庭的蛋白质，与宿主的碳水化合物相互作用，并存在于MIC从艾美耳球虫和N。犬的我们将其命名为“双股粘合剂重复区”（MARR）。我们计划研究MIC如何区分宿主配体的一些基本方面，这将为寄生虫如何在分子水平上工作提供新的信息。我们的具体目标是确定结构的MARR从三个不同的apicomplexans在复杂的同源配体。我们的研究提供的结构信息将使我们能够对它们如何区分不同的细胞类型做出新的假设。然后，我们将设计新的实验来验证这些假设。我们的工作应该提供一个基础，可以揭示新的途径，抗菌策略的发展。

项目成果

Toxoplasma gondii-induced activation of EGFR prevents autophagy protein-mediated killing of the parasite.

• DOI: 10.1371/journal.ppat.1003809
• 发表时间: 2013
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Muniz-Feliciano L;Van Grol J;Portillo JA;Liew L;Liu B;Carlin CR;Carruthers VB;Matthews S;Subauste CS
• 通讯作者: Subauste CS

Toxoplasma gondii immune mapped protein 1 is anchored to the inner leaflet of the plasma membrane and adopts a novel protein fold.

• DOI: 10.1016/j.bbapap.2016.11.010
• 发表时间: 2017-03
• 期刊: Biochimica et biophysica acta. Proteins and proteomics
• 作者: Jia Y;Benjamin S;Liu Q;Xu Y;Dogga SK;Liu J;Matthews S;Soldati-Favre D
• 通讯作者: Soldati-Favre D

The role of sialyl glycan recognition in host tissue tropism of the avian parasite Eimeria tenella.

• DOI: 10.1371/journal.ppat.1002296
• 发表时间: 2011-10
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Lai L;Bumstead J;Liu Y;Garnett J;Campanero-Rhodes MA;Blake DP;Palma AS;Chai W;Ferguson DJ;Simpson P;Feizi T;Tomley FM;Matthews S
• 通讯作者: Matthews S

Sialic acids: key determinants for invasion by the Apicomplexa.

唾液酸：顶复门入侵的关键决定因素。

• DOI: 10.1016/j.ijpara.2010.04.007
• 发表时间: 2010
• 期刊: International journal for parasitology
• 影响因子: 4
• 作者: Friedrich N