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。在历史上，寄主与寄生虫、病原体和共生体之间的成对相互作用主要是作为孤立的成对相互作用来研究的。现在，越来越多的人认识到宿主就是生态系统。一种单独的植物或动物容纳了数百种甚至数千种微生物，它们直接或间接地通过共享的宿主相互竞争或促进。因此，人们正在形成共识，即生态框架对于理解与宿主相关的群落的组装和功能至关重要。共享同一宿主的微生物会影响彼此的定植成功。这些模式扩大到整个与宿主相关的微生物群落。微生物组操作表明，寄生虫改变了微生物组的组成，而微生物组反过来又可以影响宿主的寄生虫负载或微生物共生体的定植成功。共生微生物之间的串扰通常表现为优先效应，即早期与一种微生物的接触会影响宿主对后来的定殖者的反应。被寄生虫或病原体感染的植物表现出更强、更快的反应。在与寄主相关的社区中，优先效应无处不在。然而，相对于多寄生虫或多共生体系统，共生共生体和寄生虫之间的优先效应仍未得到充分研究。伍德实验室最近发现，在豆科植物紫花苜蓿中，较早到达的寄生线虫通过较晚到达的固氮根瘤菌抑制结瘤，而较早到达的根瘤菌促进根瘤的形成。换句话说，在共生的宿主中，寄生虫抑制了共生，而共生体增加了对寄生虫感染的易感性。这一结果具有生物学意义，因为它几乎肯定是不适应宿主的。紫花苜蓿-根瘤菌-线虫系统是一个易于处理的实验系统，在其中区分基于资源和基于防御的机制对与宿主相关的群落中竞争的相对贡献。对非共生宿主进行控制接种很简单，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，在该系统中，植物的根系统被分成两个独立操纵的花盆，以分离局部和系统的反应。因此，在这个建议中，我们将使用遗传学、生理学和细胞生物学的方法来检验优先效应通过宿主防御反应或替代地通过宿主资源分配来调节的假设。

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.