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Investigating microbial predation as a driver of endosymbiosis and phagocyte evasion

研究微生物捕食作为内共生和吞噬细胞逃避的驱动因素

基本信息

批准号：
BB/W002760/1
负责人：
Elizabeth Ballou
金额：
$ 101.66万
依托单位：
UNIVERSITY OF EXETER
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2022
资助国家：
英国
起止时间：
2022 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FW002760%2F1
关键词：
Investigating microbial predation driver endosymbiosis

项目摘要

Microbes in the soil are in an arms race, surrounded by friends and foes, that has been going on for millennia. The evidence of this is recorded on their genomes: individual organisms have evolved genetic tools to resist their enemies. But there is also evidence of long-standing partnerships between microbes known as endosymbiosis, where bacteria live inside fungal cells. Partnerships between bacteria and fungi can allow them to escape amoebae that prey on them in the environment. We have shown that, together, a bacterial endosymbiont and its fungal host can make a powerful toxin that blocks amoebae from swallowing the fungus. The bacteria also changes how the fungus can use its genes to respond to different kinds of stress. This is important because amoebae are very similar to the cells in the human immune system that are the first line of defense against infection. The ancient fight going on in the soil is therefore a training ground for when endosymbionts and their fungal hosts infect humans. However, we know very little about how these partnerships arise in the first place, or how they alter how each species behaves. This project brings together three groups with unique expertise in endosymbiosis, fungal pathogenesis, and amoeba biology to investigate three questions: 1) How often do bacteria and fungi collaborate to avoid amoebae?2) What are the mechanisms for this?3) How do these partnerships impact the long-term evolution of the individual members, and the team? To answer these questions, we will look at bacterial-fungal partnerships across a wide range of species, looking for differences and commonalities in their shared genomes. We will also watch these partners interact with amoebae in the lab using sophisticated microscopy and mutant analysis to identify the different strategies they can take to evade their ancient enemy. Finally, we will closely examine one of these pairs in depth to understand the mechanisms that allow these partnerships to exist at the molecular level.

土壤中的微生物正在进行一场军备竞赛，被朋友和敌人所包围，这种情况已经持续了数千年。这方面的证据记录在它们的基因组上：个体生物进化出了抵抗敌人的遗传工具。但也有证据表明，微生物之间存在长期的伙伴关系，称为内共生，细菌生活在真菌细胞内。细菌和真菌之间的伙伴关系可以使它们逃脱环境中捕食它们的变形虫。我们已经证明，细菌内共生体和它的真菌宿主可以一起产生一种强大的毒素，阻止阿米巴吞噬真菌。这种细菌还改变了真菌如何利用其基因来应对不同种类的压力。这一点很重要，因为阿米巴原虫与人类免疫系统中作为抗感染第一道防线的细胞非常相似。因此，当内共生菌和它们的真菌宿主感染人类时，土壤中进行的古老斗争是一个训练场。然而，我们对这些伙伴关系最初是如何产生的，或者它们如何改变每个物种的行为方式知之甚少。该项目汇集了三个在内共生，真菌发病机制和阿米巴生物学方面具有独特专业知识的小组，以研究三个问题：1）细菌和真菌多久合作一次以避免阿米巴？2)其机制是什么？3)这些伙伴关系如何影响个人成员和团队的长期发展？为了回答这些问题，我们将研究各种物种的细菌-真菌伙伴关系，寻找它们共享基因组的差异和共性。我们还将观察这些伙伴在实验室中使用复杂的显微镜和突变分析与变形虫互动，以确定它们可以采取的不同策略来逃避它们的古老敌人。最后，我们将深入研究其中一对，以了解允许这些伙伴关系在分子水平上存在的机制。