Undermining effector-targeted susceptibility factors to provide late blight resistance

破坏效应子靶向的易感因子以提供晚疫病抗性

• 批准号: BB/N009967/1
• 负责人: Paul Birch
• 金额: $ 77.31万
• 依托单位: University of Dundee
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FN009967%2F1
• 关键词: Undermining; effector; targeted; susceptibility; factors

An increasing world population and impacts of climate change place ever-greater demands on the world food supply. A major constraint to global food security is crop loss due to plant pests and diseases. With the increasing stringency of conditions under which chemicals are approved for agriculture, the choice of effective fungicides and pesticides will become more limited in the near future. Furthermore, as introgressed host resistance genes are rapidly defeated by pathogens and pests in the field, there is an urgent need to explore the development of novel, durable and sustainable means to combat crop diseases.Plants face a barrage of microbial threats and defend themselves by employing two layers of inducible defence responses. The first involves recognition by cell surface receptors of essential, widely conserved molecules (called PAMPs) that are exposed by pathogens during infection. Successful (adapted) pathogens secrete and deliver proteins called effectors to suppress these defences. The second defence layer involves recognition of effectors by immune receptors, resistance proteins, to evoke effector-triggered immunity. This project focusses on the late blight pathogen Phytophthora infestans, the major pathogen of potato and tomato, two of the world's main food crops. Amongst the weapons P. infestans has to subjugate its hosts are RXLR effectors which are delivered inside plant cells to promote susceptibility. RXLR effectors have been shown to target and suppress positive regulators of immunity. In contrast, here we present considerable unpublished information revealing the discovery of two RXLR effectors that target host susceptibility (S) factors; proteins whose activity promotes disease. One effector interacts with isoforms of plant protein phosphatase 1 (PP1), forming holoenzymes that may dephosphorylate host proteins to activate or inactivate them. The other effector interacts with NRL, member of a family of plasma membrane-associated regulators of light signalling. NRL promotes susceptibility by suppressing immunity triggered by perception of a P. infestans PAMP. S factors present very attractive opportunities to undermine infection effectively and durably. For example, whereas a resistance protein imposes a selection pressure on a pathogen to alter or lose the cognate avirulence gene to evade detection, modification or conditional removal of an S factor imposes a far more challenging selection pressure, in that the associated host protein activity is required for infection. Critically, reducing endogenous levels of these S factors (PP1c isoforms and NRL) attenuates P. infestans infection, suggesting that combined reduction of both S factors may provide a durable strategy to combat late blight.Little is understood about how S factors promote disease. It is an emerging, exciting area of plant disease research, making our proposal timely. We will provide detailed understanding of 1) the virulence targets dephosphorylated by effector-PP1c holoenzymes, and the mechanistic consequences of dephosphorylation (objective 1); and 2) the means by which NRL suppresses PAMP-triggered immunity (objective 2). It will also reveal whether natural variants exist of these S factors that cannot be targeted by the associated effectors (objective 3C), implicating evolution of S factors to evade effector-mediated exploitation. These studies will provide novel insights into negative regulation of plant immunity. They also provide novel means with which to combat plant disease, and potato blight specifically.Industry is keen to exploit understanding of S factors as a durable means to provide disease resistance. This project, with industrial partner JR Simplot, will deliver novel approaches for pathogen-inducible removal of S factors to provide late blight resistance (objectives 3A; 3B).

世界人口的增加和气候变化的影响对世界粮食供应提出了越来越大的需求。全球粮食安全的一个主要制约因素是植物病虫害造成的农作物损失。随着批准用于农业的化学品的条件越来越严格，在不久的将来，有效的杀菌剂和杀虫剂的选择将变得更加有限。此外，由于导入的寄主抗性基因在田间迅速被病原体和害虫击败，迫切需要探索新的、持久的和可持续的方法来抗击作物病害。植物面临着大量的微生物威胁，并通过两层诱导防御反应来防御自己。第一个涉及细胞表面受体对基本的、广泛保守的分子(称为PAMP)的识别，这些分子在感染期间被病原体暴露。成功的(适应的)病原体分泌和传递被称为效应器的蛋白质来抑制这些防御。第二层防御层涉及免疫受体识别效应器，即抗性蛋白，以唤起效应器触发的免疫。该项目的重点是晚疫病菌，马铃薯和番茄这两种世界主要粮食作物的主要病原菌。在致病疫霉必须征服其宿主的武器中，RXLR效应器是在植物细胞内传递的，以促进敏感性。RXLR效应器已被证明可以靶向和抑制积极的免疫调节因子。相反，我们在这里展示了大量未发表的信息，揭示了两个针对宿主易感性因子(S)的RXLR效应器的发现；这些蛋白质的活性促进了疾病的发生。一个效应器与植物蛋白磷酸酶1(PP1)的异构体相互作用，形成全酶，可以使宿主蛋白去磷酸化，激活或灭活它们。另一个效应器与NRL相互作用，NRL是与质膜相关的光信号调节家族的成员。NRL通过抑制对致病疫霉PAMP的感知而触发的免疫增强易感性。S因子提供了非常有吸引力的机会，可以有效和持久地削弱感染。例如，抗性蛋白对病原菌施加选择压力以改变或丢失同源无毒基因以逃避检测、修饰或有条件地移除S因子施加更具挑战性的选择压力，因为相关的宿主蛋白活性是感染所必需的。关键是，降低这些S因子(PP1c亚型和NRL)的内源水平可以减轻致病疫霉的侵染，这表明联合减少两种S因子可能提供抗晚疫病的持久策略。关于S因子如何促进疾病尚不清楚。这是一个新兴的、令人兴奋的植物病害研究领域，使我们的建议来得及时。我们将详细了解1)由效应器-PP1c全酶去磷酸化的毒力靶标，以及去磷酸化的机制后果(目标1)；以及2)NRL抑制PAMP触发的免疫(目标2)的方法。它还将揭示这些S因子是否存在不能被相关效应器靶向的自然变体(目标3C)，暗示S因子的进化以逃避效应器介导的利用。这些研究将为植物免疫的负调控提供新的见解。它们还提供了对抗植物病害，特别是马铃薯枯萎病的新方法。工业界热衷于利用对S因素的了解，作为提供抗病能力的持久手段。该项目与工业合作伙伴JR Simplot合作，将提供病原体诱导去除S因子的新方法，以提供对晚疫病的抗性(目标3A；3B)。

项目成果

Message in a Bubble: Shuttling Small RNAs and Proteins Between Cells and Interacting Organisms Using Extracellular Vesicles.

气泡中的消息：使用细胞外囊泡在细胞和相互作用的生物之间穿梭小RNA和蛋白质。

• DOI: 10.1146/annurev-arplant-081720-010616
• 发表时间: 2021-06-17
• 期刊: Annual review of plant biology
• 影响因子: 23.9
• 作者: Cai Q;He B;Wang S;Fletcher S;Niu D;Mitter N;Birch PRJ;Jin H
• 通讯作者: Jin H

Opening the Effector Protein Toolbox for Plant-Parasitic Cyst Nematode Interactions.

• DOI: 10.1016/j.molp.2016.09.008
• 发表时间: 2016-11-07
• 期刊: MOLECULAR PLANT
• 影响因子: 27.5
• 作者: Eves-van den Akker, Sebastian;Birch, Paul R. J.
• 通讯作者: Birch, Paul R. J.

All Roads Lead to Susceptibility: The Many Modes of Action of Fungal and Oomycete Intracellular Effectors.

所有道路都会引起敏感性：真菌和卵菌的细胞内效应子的许多作用方式。

• DOI: 10.1016/j.xplc.2020.100050
• 发表时间: 2020-07-13
• 期刊: Plant communications
• 影响因子: 10.5
• 作者: He Q;McLellan H;Boevink PC;Birch PRJ
• 通讯作者: Birch PRJ

Devastating intimacy: the cell biology of plant-Phytophthora interactions.

• DOI: 10.1111/nph.16650
• 发表时间: 2020-10
• 期刊: The New phytologist
• 作者: Boevink PC;Birch PRJ;Turnbull D;Whisson SC
• 通讯作者: Whisson SC

Plant pathogen effector utilizes host susceptibility factor NRL1 to degrade the immune regulator SWAP70.

• DOI: 10.1073/pnas.1808585115
• 发表时间: 2018-08-14
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: He Q;Naqvi S;McLellan H;Boevink PC;Champouret N;Hein I;Birch PRJ
• 通讯作者: Birch PRJ