Exploring TrpB in the pathogenesis of cryptosporidiosis

探索 TrpB 在隐孢子虫病发病机制中的作用

基本信息

  • 批准号:
    9532418
  • 负责人:
  • 金额:
    $ 5.08万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-08-01 至 2018-05-31
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): Cryptosporidiosis is a diarrheal disease that disproportionately affects children and immunocompromised adults. The WHO estimates that in 2010, diarrheal disease accounted for 10.5% of deaths in children under the age of five, with the majority of childhood deaths occurring in Africa and Southeast Asia. In developing countries, malnutrition exacerbates diarrheal episodes and prolongs infection. These prolonged childhood infections are known to cause destructive, permanent effects, such as stunted growth, developmental delay, and cognitive deficiency. Of the known diarrheal diseases, cryptosporidiosis appears to one of the most deadly. Tryptophan synthesis enables intracellular bacteria such as Mycobacterium tuberculosis and Chlamydia trachomatis to evade a key mechanism of host innate immunity, IFN-γ induced tryptophan catabolism. Through horizontal gene transfer, Cryptosporidium has acquired a bacterial tryptophan synthase gene, tryptophan synthase beta (CpTrpB), and we believe that this gene acquisition was a crucial step to adaptation to the mammalian intestine. We will evaluate the role of CpTrpB in Cryptosporidium metabolism, growth, and survival during host tryptophan catabolism. In this project we propose to 1) define the metabolic activity of CpTrpB during host tryptophan catabolism, both in vitro and in vivo, and 2) determine the impact of CpTrpB gene loss on Cryptosporidium parvum through genetic analysis. The unique tryptophan metabolism in Cryptosporidium is an attractive target for drug development and pathogen attenuation, and studying CpTrpB offers the opportunity to explore the biology of a novel parasite pathogenesis factor.
 描述(申请人提供):隐孢子虫病是一种腹泻性疾病,对儿童和免疫功能低下的成年人影响不成比例。世界卫生组织估计,2010年,腹泻疾病占五岁以下儿童死亡的10.5%,其中大部分儿童死亡发生在非洲和东南亚。在发展中国家,营养不良会加剧腹泻发作并延长感染时间。众所周知,这些长期的童年感染会造成破坏性的永久性影响,如发育迟缓、发育迟缓和认知缺陷。在已知的腹泻疾病中,隐孢子虫病似乎是最致命的疾病之一。色氨酸合成使结核分枝杆菌和沙眼衣原体等胞内细菌逃避宿主天然免疫的一个关键机制,即干扰素-γ诱导色氨酸分解代谢。通过水平基因转移,隐孢子虫获得了细菌色氨酸合成酶基因,色氨酸合成酶β(CpTrpB),我们认为这一基因的获得是适应哺乳动物肠道的关键一步。我们将评估CpTrpB在隐孢子虫在宿主色氨酸分解代谢过程中的代谢、生长和存活中的作用。在本项目中,我们建议1)确定CpTrpB在宿主体内和体外色氨酸分解代谢过程中的代谢活性;2)通过遗传分析确定CpTrpB基因缺失对微小隐孢子虫的影响。隐孢子虫独特的色氨酸代谢是药物开发和病原菌减毒的重要靶点,对CpTrpB的研究为探索一种新的寄生虫致病因子的生物学机制提供了机会。

项目成果

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Adam Sateriale其他文献

Adam Sateriale的其他文献

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{{ truncateString('Adam Sateriale', 18)}}的其他基金

Investigation of subtelomeric gene families in Cryptosporidium
隐孢子虫亚端粒基因家族的研究
  • 批准号:
    9505635
  • 财政年份:
    2018
  • 资助金额:
    $ 5.08万
  • 项目类别:

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