22-BBSRC/NSF-BIO Hidden costs of infection: mechanisms by which parasites disrupt host-microbe symbioses and alter development

宿主-微生物相互作用领域正在经历一场范式转变。历史上，宿主与其寄生虫、病原体和共生体之间的成对相互作用主要作为孤立的成对相互作用进行研究。现在，人们越来越认识到宿主是生态系统。单个植物或动物体内有数百甚至数千种微生物，它们通过共同的宿主直接或间接地相互竞争或促进。因此，正在形成的共识是，生态框架是至关重要的了解主机相关社区的组装和功能。共享同一宿主的微生物影响彼此的定殖成功。这些模式扩展到整个宿主相关的微生物群落。微生物组操纵表明，寄生虫改变微生物组组成，并且微生物组反过来可以影响宿主的寄生虫负荷或微生物共生体的定殖成功。共定殖微生物之间的串扰通常表现为优先效应，其中与一种微生物的早期遭遇影响宿主对后来的定殖者的反应。被寄生虫或病原体引发的植物表现出更强和更快的反应。优先效应普遍存在于宿主相关的群落中。然而，相对于多寄生虫或多共生体系统，共定殖共生体和寄生虫之间的优先效应仍然研究不足。伍德实验室最近发现，在豆科苜蓿中，早到的寄生线虫抑制晚到的固氮根瘤菌的生长，而早到的根瘤菌促进虫瘿的形成。换句话说，在共同定殖的宿主中，寄生虫抑制共生，而共生体增加对寄生虫感染的易感性。这一结果是生物学意义，因为它几乎可以肯定是不适应的host.The苜蓿-根瘤菌-线虫系统是一个易于处理的实验系统，其中区分资源和防御为基础的机制，在主机相关的社区竞争的相对贡献。控制接种到非共生宿主上是简单的，因为根瘤菌和线虫都是水平传播的。我们将使用分根培养系统，其中植物的根系被分成两个独立操作的盆，以解开局部和系统的反应。因此，在本提案中，我们将使用遗传，生理和细胞生物学的方法来测试的假设，优先级的影响是由宿主防御反应或宿主资源分配介导的。

The field of host-microbe interactions is undergoing a paradigm shift. Historically, pairwise interactions between hosts and their parasites, pathogens, and symbionts were primarily studied as isolated pairwise interactions. Now, there is increasing recognition that hosts are ecosystems. An individual plant or animal houses hundreds or even thousands of species of microorganisms that compete with or facilitate each other, either directly or indirectly via their shared host. As a result, consensus is emerging that an ecological framework is critical to understand the assembly and function of host-associated communities. Microorganisms that share the same host affect each other's colonization success. These patterns scale up to entire host-associated microbial communities. Microbiome manipulations show that parasites alter microbiome composition, and that the microbiome in turn can affect a host's parasite load or the colonization success of microbial symbionts. Crosstalk between co-colonizing microorganisms often manifests as a priority effect, in which an early encounter with one microorganism impacts the host's response to later colonizers. Plants that are primed by an encounter with a parasite or pathogen exhibit stronger and more rapid responses. Priority effects are ubiquitous in host-associated communities. Yet, relative to multiparasite or multi-symbiont systems, priority effects between co-colonizing symbionts and parasites remain understudied. The Wood lab recently found that in the legume Medicago, early arriving parasitic nematodes inhibit nodulation by later-arriving nitrogen-fixing rhizobia, while early arriving rhizobia facilitate gall formation. In other words, in co-colonized hosts, the parasite inhibits symbiosis, while the symbiont increases susceptibility to parasite infection. This result is biologically significant because it is almost certainly maladaptive for the host.The Medicago-rhizobia-nematode system is a tractable experimental system in which to discriminate between the relative contribution of resource- and defence-based mechanisms to competition in host-associated communities. Controlled inoculations onto aposymbiotic hosts is straightforward because both rhizobia and nematodes are horizontally transmitted. We will use split-root culture system, in which a plant's root system is split into two pots that are independently manipulated, to disentangle local and systemic responses. Thus, in this proposal we will use genetic, physiological and cell biological approaches to test the hypotheses that priority effects are mediated by host defence responses or alternatively by host resource allocation.