Molecular interactions between parasites and microbes in the intestine

肠道寄生虫和微生物之间的分子相互作用

• 批准号: RGPIN-2017-03801
• 负责人: Reynolds, Lisa
• 金额: $ 2.26万
• 依托单位: University of Victoria
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=744222
• 关键词: Molecular; interactions; between; parasites; microbes

The intestinal tract of mammals is home to trillions of bacterial microbes, and can also be colonised by parasites, such as worms. Despite belonging to different kingdoms of life, bacteria and parasitic worms face similar challenges in the intestine. Both must compete for limited nutritional and spatial resources, and both need to evade expulsion by the host immune system. Recent evidence reveals that bacteria and parasitic worms can influence each other's presence in the intestines. Our research is centred on understanding the mechanisms of interaction between parasitic worms and bacterial microbes in the intestinal tract. Our work will have a broad impact and importance. Firstly, it is of importance to the livestock industry. Evidence from animal models suggests that animals that are colonised by worms are at increased risk of infection by pathogenic bacteria. Given that the resistance to drugs against parasitic worms is increasing in the livestock industry, it is critical to understand how worms promote colonisation by pathogenic bacteria, so that interventions can be designed to protect against bacterial infection. Secondly, understanding how cross-kingdom interactions between parasitic worms and bacteria occur will influence research on co-evolution, microbiology, immunology and parasitology. It is clear that the presence of worms promotes the ability of select bacterial species to persist in the mammalian intestinal tract. However, little is understood of the mechanisms by which this occurs. Work from myself and others has shown that parasitic worms alter the availability of products released during metabolism (metabolites) in the intestines. Our work aims to understand exactly how worms alter the intestinal metabolic environment, and how these changes in metabolites act on certain bacteria to promote their ability to colonise the intestines. We will examine interactions between worms and bacteria in mice, as in this model system both parasite and microbe populations in the intestine can be readily manipulated and tracked. We expect to identify the types of metabolites that are altered by the presence of parasitic worms, how exposure to these metabolites alters bacterial gene expression, how alterations in bacterial gene expression affect the ability of bacteria to survive in the intestine, and the types of bacteria that are affected by the presence of worms. Undertaking this research will require methods from several research disciplines, including microbiology, parasitology and biochemistry. Trainees completing this research will therefore be highly skilled in a breath of techniques that are in demand in both academic and biotech settings, including cell culture, metabolite identification, mouse husbandry and experimental use, as well as critical thinking, writing, and project management skills, which will prepare them well for productive future careers.

哺乳动物的肠道是数万亿细菌微生物的家园，也可能被寄生虫（如蠕虫）定植。尽管细菌和寄生虫属于不同的生命王国，但它们在肠道中面临着类似的挑战。两者都必须竞争有限的营养和空间资源，并且都需要避免被宿主免疫系统驱逐。最近的证据表明，细菌和寄生虫可以相互影响对方在肠道中的存在。我们的研究集中在了解寄生虫和肠道细菌微生物之间相互作用的机制。我们的工作将具有广泛的影响和重要性。首先，它对畜牧业很重要。来自动物模型的证据表明，被蠕虫定植的动物被致病菌感染的风险增加。鉴于畜牧业对寄生虫药物的耐药性正在增加，了解蠕虫如何促进致病菌的定植是至关重要的，这样就可以设计干预措施来防止细菌感染。其次，了解寄生虫和细菌之间的跨界相互作用如何发生，将影响共同进化、微生物学、免疫学和寄生虫学的研究。很明显，蠕虫的存在促进了选择细菌物种在哺乳动物肠道中持续存在的能力。然而，人们对这种现象发生的机制知之甚少。我和其他人的研究表明，寄生虫改变了肠道代谢过程中释放的产物（代谢物）的可用性。我们的工作旨在确切了解蠕虫如何改变肠道代谢环境，以及代谢物的这些变化如何作用于某些细菌，以促进它们在肠道内定居的能力。我们将研究小鼠体内蠕虫和细菌之间的相互作用，因为在这个模型系统中，肠道内的寄生虫和微生物种群都可以很容易地操纵和跟踪。我们希望确定寄生蠕虫的存在改变了代谢物的类型，暴露于这些代谢物如何改变细菌基因表达，细菌基因表达的改变如何影响细菌在肠道中的生存能力，以及受蠕虫存在影响的细菌类型。开展这项研究将需要几个研究学科的方法，包括微生物学、寄生虫学和生物化学。因此，完成这项研究的学员将在学术和生物技术环境中都有很高的技能，包括细胞培养、代谢物鉴定、老鼠饲养和实验使用，以及批判性思维、写作和项目管理技能，这将为他们未来的职业生涯做好准备。