Investigating microbial predation as a driver of endosymbiosis and phagocyte evasion

土壤中的微生物正在进行一场被敌人和朋友包围的军备竞赛，这场竞赛已经持续了数千年。这一点的证据被记录在它们的基因组中：单个有机体进化出了抵抗敌人的遗传工具。但也有证据表明，被称为内共生的微生物之间存在长期的合作关系，即细菌生活在真菌细胞内。细菌和真菌之间的合作可以让它们逃脱在环境中捕食它们的阿米巴。我们已经证明，细菌内共生菌和它的真菌宿主一起可以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利用其基因对不同类型的压力做出反应的方式。这一点很重要，因为阿米巴与人类免疫系统中的细胞非常相似，后者是抵御感染的第一道防线。因此，当内共生体及其真菌宿主感染人类时，土壤中正在进行的古老战斗是一个训练场。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。这个项目汇集了三个在内生共生、真菌致病和阿米巴生物学方面具有独特专业知识的团队来调查三个问题：1)细菌和真菌多久合作一次以避免阿米巴？2)这种合作的机制是什么？3)这些伙伴关系如何影响个体成员和团队的长期进化？为了回答这些问题，我们将研究广泛物种中的细菌-真菌伙伴关系，寻找它们共享的基因组中的差异和共同点。我们还将观察这些伙伴在实验室中使用先进的显微镜和突变分析与阿米巴相互作用，以确定他们可以采取的不同策略来躲避他们古老的敌人。最后，我们将深入研究其中的一对，以了解允许这些伙伴关系在分子水平上存在的机制。

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.