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

非洲锥虫病，也被称为人类昏睡病和牛那加纳病，是一种在非洲死灰复燃的疾病，在37个国家发生，蔓延范围超过1000万平方公里，约占非洲大陆的三分之一，5000万头牛（约占非洲牛总数的30%）面临感染风险。与其他疾病相比，昏睡病和长眠病引起的关注相对较少，被列为最被忽视的热带病（例如世卫组织、无国界医生组织和世界疾病诊断组织）。患那迦那病的动物会发烧、体重减轻，并逐渐变得虚弱、不能生育和不育。刚果锥虫是引起那加纳病的最主要病原体之一。由于无法合成Sia，锥虫利用反式唾液酸酶（TS）清除寄生膜表面的糖缀合物和唾液酸受体分子中的单糖。第一个项目阶段对刚果热锥虫的TS进行了表征，并观察到这些酶在寄生虫中也在传播的生命周期阶段表达，根据第一阶段的结果，该项目的总体目标是检验这样一种假设，即刚果热锥虫和相关蛋白质可以作为控制长老病传播战略的目标。这是基于它们在刚果锥虫生命周期中的重要作用。根据这一目标，该项目的第二阶段致力于解决四个方面的问题：反式唾液化对采采蝇中寄生虫定植的作用。TconTSx对天然底物活性的表征。基于DNA和生物纳米颗粒的TconTSx蛋白疫苗的潜力。采采中肠唾液酸酶抑制刚果锥虫定殖的潜力。为实现这些目标，为尼日利亚合作伙伴和德国不莱梅大学制定了一揽子工作方案。此外，该交流项目将促进两个伙伴机构的能力建设，即位于扎里亚的阿赫迈杜·贝罗大学和位于卡杜纳的尼日利亚锥虫病研究所。

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.