BBSRC-NSF/BIO: Investigating microbial predation as a driver of endosymbiosis and phagocyte evasion

BBSRC-NSF/BIO：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：
2202410
负责人：
Jessie Uehling
金额：
$ 59.15万
依托单位：
Oregon State University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-15 至 2025-03-31
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2202410&HistoricalAwards=false
关键词：
BBSRC NSF BIO Investigating microbial

项目摘要

Soil microbes compete. As a result they evolved tools to resist their enemies. However, there is also evidence of collaboration between microbes (endosymbiosis), where bacteria live inside fungal cells. We have shown that, together, a bacterial endosymbiont and its fungal host create a holobiont that can make a powerful toxin that blocks soil-dwelling amoebae from engulfing the fungus. This endosymbiotic bacterium also changes how the fungus controls its own gene expression to fight different kinds of stress. This project examines how frequently fungi and endosymbionts evade amoebae; the implications for fungal housing of endosymbionts; and whether these symbioses lead to co-evolution. 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 record reactions of wild-type and mutant fungal-bacterial endosymbionts with amoebae in the lab to identify the different strategies they can take to evade amoebae engulfment. Finally, we will examine one endosymbiont pair in depth to understand the mechanisms that allow these partnerships to exist. Amoebae are very similar to the cells in the human immune system that are the first line of defense against infection. Thus, this study can help our understanding of immunity. Additional broader impacts of this proposal include developing fungal biological education modules and teaching resources in the K-6 classrooms, develop mushroom grow kits for children, and participation in science podcasts. Identifying how environmental fungi developed traits to evade immune cells is critical to understanding the causes of opportunistic fungal infections in nature and in humans. Mucoromycota are primarily soil-associated fungi, some of which are also opportunistic mammalian pathogens. We recently identified an endosymbiosis between Betaproteobacteria Ralstonia (bacterium) and Mucoromycota Rhizopus (fungus), a symbiosis that blocks engulfment and killing of the fungus by the soil-dwelling amoeba Dictyostelium and also confers virulence in animals. Endosymbioses between Betaproteobacteria and Mucoromycota are environmentally ubiquitous. Endosymbionts are also observed in approximately half of clinical Rhizopus isolates, where phagocyte-related deficiencies are a major predictor of susceptibility. We hypothesize that interactions between bacterium-fungus holobionts and soil amoeba drive their evolutionary trajectories and opportunistic virulence in mammals. We will use phenotypic, genomic, and molecular tools to dissect the holobiont-phagocyte interaction and investigate host-pathogen interactions at two levels: 1) interactions between bacteria and their fungal hosts, and 2) the effect of endosymbionts on phagocyte evasion and opportunistic virulence. We will take both an unbiased approach to survey bacterial-fungal-amoebal interactions across the genus and a directed approach to investigate the molecular mechanisms for specific bacterial-fungal isolates alone and with amoeba. These mechanistic studies will be coupled to comparative genomics analyses to reveal how evolutionary pressures exerted by amoebae drive endosymbiosis and immune evasion. This collaborative US/UK project is supported by the US National Science Foundation and the UK Biotechnology and Biological Sciences Research Council.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

土壤微生物竞争。结果，他们发展了抵抗敌人的工具。但是，也有迹象表明，微生物（内共生）之间的合作，在真菌细胞内生活。我们已经表明，一个细菌内共生菌及其真菌宿主共同创造了一种霍洛比昂，可以产生强大的毒素，从而阻止土壤居住的变形虫吞没真菌。这种内共生细菌还改变了真菌如何控制自己的基因表达以抵抗不同种类的压力。该项目研究了真菌和内共生膜逃避变态的频率；对内共生体的真菌外壳的影响；这些共生是否导致共同进化。为了回答这些问题，我们将研究各种物种之间的细菌 - 真菌伙伴关系，以寻找共享基因组的差异和共同点。我们还将记录实验室中野生型和突变真菌 - 细菌 - 细菌内共生菌的反应，以确定他们可以采取的不同策略来逃避变形虫吞噬。最后，我们将深入研究一个内共生对，以了解允许这些伙伴关系存在的机制。 Amoebae与人类免疫系统中的细胞非常相似，该细胞是针对感染的第一道防线。因此，这项研究可以帮助我们理解免疫力。该建议的其他更广泛的影响包括在K-6教室中开发真菌生物学教育模块和教授资源，开发蘑菇种植套件，并参与科学播客。确定环境真菌如何发展为逃避免疫细胞的特征对于理解自然界和人类的机会性真菌感染的原因至关重要。粘膜瘤主要是与土壤相关的真菌，其中一些也是机会主义的哺乳动物病原体。我们最近确定了蛋白核细菌RALSTONIA（细菌）和粘膜瘤性根瘤菌（真菌）之间的内共生，这是一种共生的共生，可阻止土壤居住的Amoeba dictyostelium吞噬并杀死真菌，并使动物中的毒死。贝氏蛋白酶和粘膜瘤之间的内共生性在环境上无处不在。在大约一半的临床根茎分离株中还观察到内共生体，其中与吞噬细胞相关的缺陷是易感性的主要预测指标。我们假设细菌 - 脉量霍洛皮群岛和土壤变形虫之间的相互作用驱动其进化轨迹和哺乳动物的机会性毒力。我们将使用表型，基因组和分子工具来剖析Holobiont-Phagococyte相互作用，并研究两个级别的宿主 - 病原体相互作用：1）细菌与其真菌宿主之间的相互作用，以及2）内共生菌对吞噬细胞反射和机会性毒素的影响。我们将采用一种无偏的方法来调查整个属的细菌 - 真菌 - 摩托巴相互作用，也可以采用一种指示方法来研究单独的特定细菌 - 恋爱分离株的分子机制，并使用变形虫。这些机械研究将耦合到比较基因组学分析，以揭示大羊角驱动内共生和免疫逃避施加的进化压力。美国国家科学基金会和英国生物技术和生物科学研究委员会的支持。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子和更广泛影响的评估审查标准的评估来支持的。