Transport pathways of host-derived iron in schistosomes parasites

血吸虫寄生虫中宿主来源铁的转运途径

• 批准号: nhmrc : 442910
• 负责人: Prof Alexander Loukas
• 金额: $ 21.48万
• 依托单位: Queensland Institute of Medical Research
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/transport-pathways-host-schistosomes-parasites/81878
• 关键词: Transport; pathways; host; derived; iron

This project will identify the diversity and biological roles of receptors for metabolic iron expressed on the body surface of the parasitic blood flukes (schistosomes) of humans. Schistosomes are a major health problem in many tropical countries and are responsible for significant human morbidity and lost productivity. Adult worms feed on human blood, from which derive amino acids for the production of many hundreds of eggs released per day into the human blood stream. The intense cellular response induced by parasite eggs trapped in body organs is the major cause of chronic human disease. We have discovered two intriguing phenomena of iron metabolism in schistosomes. Firstly, schistosomes have a greater reliance on iron than many other organisms, storing a surfeit in cells that produce the protein-rich egg shell. Secondly, a major transmembrane iron transporter of the parasites, thought to be involved in the uptake of iron, is found on the parasite external body surface and not in the parasite intestine. The extensive nutritional dependence of these worms on iron and the surface location of mediators of iron uptake raise the exciting possibility that we have uncovered a novel system that might be exploited for vaccine or drug-mediated control of these significant human parasites. If we can dissect the pathways schistosomes use to derive iron from their hosts, we may be able to generate vaccines to block this nutritional pathway, or use drugs to block embryogenesis. This project is a fact-finding mission that asks if the host-interactive tegument of these parasites is a major source of metabolic iron. Molecules we demonstrate to be present on the surface will be tested as vaccine candidates in mouse vaccine trials

该项目将确定人类寄生血吸虫（寄生虫体）体表表达的代谢铁受体的多样性和生物学作用。血吸虫病是许多热带国家的一个主要健康问题，是造成重大人类发病率和生产力损失的原因。蠕虫以人类血液为食，从中提取氨基酸，每天释放数百个卵进入人体血液。寄生虫卵被困在人体器官中引起的强烈细胞反应是人类慢性疾病的主要原因。我们发现了两个有趣的现象，铁代谢的染色体。首先，与许多其他生物相比，卵小体对铁的依赖性更大，将过量的铁储存在产生富含蛋白质的蛋壳的细胞中。其次，寄生虫的一个主要的跨膜铁转运蛋白，被认为是参与铁的吸收，发现在寄生虫的外部身体表面，而不是在寄生虫的肠道。这些蠕虫对铁的广泛营养依赖性和铁吸收介质的表面位置提高了令人兴奋的可能性，我们已经发现了一种新的系统，可能被利用疫苗或药物介导的控制这些重要的人类寄生虫。如果我们能够剖析铁小体从宿主体内获取铁的途径，我们就有可能生产出阻断这种营养途径的疫苗，或者使用药物来阻断胚胎发生。这个项目是一个事实调查的使命，询问这些寄生虫的宿主相互作用的外皮是否是代谢铁的主要来源。我们证明存在于表面上的分子将在小鼠疫苗试验中作为候选疫苗进行测试