The Role of Trans-Sialidases from Trypanosoma Congolense in Nagana Disease

刚果锥虫转唾液酸酶在纳加纳病中的作用

• 批准号: 252602372
• 负责人: Professor Dr. Sörge Kelm
• 金额: --
• 依托单位: Nigerian Institute for Trypanosomiasis and Onchocerciasis Research
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/252602372?language=en
• 关键词: Role; Trans; Sialidases; Trypanosoma; Congolense

African trypanosomiasis, also known as sleeping sickness in humans and Nagana in cattle, is a disease that is resurgent in Africa and occurs in 37 countries, extending to over 10 million square kilometres, which is about a third of the continent and 50 million cattle (about 30% of Africa's total cattle population) are exposed to the risk of infection. Compared to other diseases, sleeping sick­ness and Nagana have attracted relatively little attention and have been listed among the most neglected tropical diseases (e.g. by WHO, MSF and DNDi). Animals suffering Nagana develop fever, weight loss and progressively become weak, unproductive and infertile.Trypanosoma congolense is one of the most prominent pathogens causing Nagana. Unable to synthesise Sia, trypanosomes use the enzyme trans-sialidase (TS) to scavenge the monosaccharides from host glycoconjugate and sialylate acceptor molecules present on the surface of the parasite membrane. Based on the results of the first project phase, in which TS from T. congolense (TconTS) were characterised and observed that these enzymes are expressed in parasites also in those life cycle phases of transmission, the overall goal of the project is to test the hypothesis that TconTS and related proteins can be used as targets in strategies to control the spread of the disease Nagana. This is based on their essential roles in the lifecycle of T. congolense. In accor­dance with this goal, the aim of the second phase of the project is dedicated to address four aspects:The role of trans-sialylation for the parasite colonisation in tsetse flies.The characterisation of the activities of TconTSx towards natural substrates.The potential of DNA- and bionanoparticle-based vaccines against TconTSx proteins.The potential of sialidases in tsetse midgut to suppress colonisation with T. congolense.To achieve these objectives work packages for the partners in Nigeria and the Ubiverrsity Bremen in Germany have been developed. In addition the exchange program will foster capacity building at both partner institutions, the Ahmadu Bello University in Zaria and the Nigerian Institut for Trypanosomiasis Research in Kaduna.

非洲锥虫病，也被称为人类昏睡病和牛Nagana，是一种在非洲死灰复燃的疾病，在37个国家发生，面积超过1000万平方公里，约占非洲大陆的三分之一，5000万头牛（约占非洲总牛群的30%）面临感染风险。与其他疾病相比，昏睡病和长痛病引起的关注相对较少，并被列为最被忽视的热带疾病之一（如世界卫生组织，无国界医生组织和DNDi）。患有长角线虫病的动物会出现发热、体重减轻，并逐渐变得虚弱、不生产和不育。刚果锥虫是引起长角线虫病的最主要病原体之一。由于不能合成Sia，锥虫使用转唾液酸酶（TS）从寄生虫膜表面上存在的宿主糖缀合物和唾液酸受体分子中除去单糖。在第一阶段研究的基础上，利用T.刚果（TconTS）的特点，并观察到这些酶在寄生虫中表达，也在传播的生命周期阶段，该项目的总体目标是测试的假设，TconTS和相关蛋白质可以作为目标的战略，以控制疾病Nagana的传播。这是基于它们在T生命周期中的重要作用。刚果语。根据这一目标，该项目的第二阶段的目标致力于解决四个方面：转唾液酸化在采采蝇中寄生虫定殖中的作用; TconTSx对天然底物的活性的表征;针对TconTSx蛋白的DNA和生物纳米颗粒疫苗的潜力;采采蝇中肠中唾液酸酶抑制TconTSx定殖的潜力。为实现这些目标，为尼日利亚和德国的普遍性不莱梅的合作伙伴制定了一揽子工作计划。此外，该交流计划还将促进两个合作机构的能力建设，即扎里亚的艾哈迈迪贝洛大学和卡杜纳的尼日利亚锥虫病研究所。