Understanding innate immunity in fungi

项目总结 这项探索性工作的目标是为理解先天免疫防御奠定基础。 毛霉菌，特别关注触发细胞程序性死亡(PCD)的机制。 我们预计这些过程将成为未来控制毛霉病的目标，毛霉病是人类的 由毛霉菌引起的感染。毛霉菌病日益频繁，破坏性极强，通常 对免疫功能受损的人来说是致命的。 毛霉菌的一些临床分离株含有内共生菌(EB)，可分离和 独立种植的。我们最近的工作对真菌对这种孤立的EB的反应产生了洞察力 被真菌视为互助者与拮抗者。在互惠作用中，细菌进入真菌细胞并 操纵放任宿主的细胞过程。在拮抗作用中，非宿主真菌的细菌感染是 被真菌反应所阻断，类似于动植物的先天免疫。在动物和植物中， 先天免疫机制防止细菌入侵细胞环境并抑制这些入侵 通过启动PCD。 为了实现我们的目标，解开毛霉菌天然免疫的新机制，我们将使用 分离的EB作为一种诱导真菌防御反应的工具。我们将测试毛霉菌是否能够：(I) 感知微生物，(Iii)部署防御模块以防止细菌进入，以及(Iii)面对细菌 能够突破这些主要防御，触发PCD以消除入侵者。为了检验这些假设， 我们将解决以下具体目标：(1)确定候选天然免疫感受器在 非宿主菌株的细菌感染和(2)识别负责消除细菌的新基因 感染，包括控制防御和PCD模块的基因。 除了它们对健康的深远影响外，毛霉菌还提供了一个非常方便的研究系统 用于阐明多菌疾病中真菌和细菌的相互作用。项目的预期结果 包括真菌先天免疫和PCD的分子基础的测定，这在未来可能是 旨在根除毛霉菌感染。

PROJECT SUMMARY The goal of this exploratory work is to develop foundations for understanding innate immunity defenses in Mucoromycotina fungi, with a particular focus on the mechanisms triggering programmed cell death (PCD). We expect that these processes will become future targets for controlling mucormycoses, which are human infections caused by Mucoromycotina. Mucormycoses are increasingly frequent, highly destructive, and often fatal in immune-compromised individuals. Some clinical isolates of Mucoromycotina harbor endosymbiotic bacteria (EB) that can be isolated and cultivated independently. Our recent work generated insights into fungal responses to such isolated EB that were perceived by fungi as mutualists versus antagonists. In mutualisms, bacteria enter fungal cells and manipulate cellular processes of permissive hosts. In antagonisms, bacterial infections of non-host fungi are blocked by fungal responses that resemble innate immunity of animals and plants. In animals and plants, innate immunity mechanisms prevent bacterial invasions of cellular environment and suppress those invasions by initiating PCD. To accomplish our goal of unraveling novel mechanisms of innate immunity in Mucoromycotina, we will use isolated EB as a tool to elicit fungal defense responses. We will test whether Mucoromycotina are able to: (i) sense microbes, (iii) deploy defense modules that prevent bacterial entry, and (iii) when faced with bacteria capable of breaching these primary defenses, trigger PCD to eliminates intruders. To test these hypotheses, we will address the following specific aims: (1) determine the roles of candidate innate immunity sensors in bacterial infection of non-host strains and (2) identify novel genes responsible for elimination of bacterial infections, including genes that control defense and PCD modules. In addition to their profound health impacts, Mucoromycotina present a remarkably convenient study system for elucidating fungal-bacterial interactions in polymicrobial disorders. Expected outcomes of the project include determination of the molecular bases of fungal innate immunity and PCD, which, in the future, could be targeted to eradicate Mucoromycotina infections.