Mechanisms of pathogen suppression of NLR-mediated immunity
Lead Research Organisation:
University of East Anglia
Department Name: Sainsbury Laboratory
Abstract
Just like humans, plants get sick. They can be infected by parasites as diverse as oomycetes, fungi, bacteria, viruses, nematode worms and insects. But, also like humans, plants have an immune system that helps them defend against disease. Their first line of defence are disease resistance genes. Many of these genes encode so-called immune receptors, which are proteins that detect parasites and kick-off the immune response.
Plant genomes may encode anywhere between 50 and 1000 immune receptors; some of which work solo as singletons, while others operate in pairs or as complex networks. One driving force behind the evolution of immune receptors is gene duplication. Receptor genes duplicate and afterwards the two copies can evolve in different ways. The original immune receptors are multi-tasking proteins that detect parasites and trigger the immune response. Following gene duplication, evolution has led immune receptors to specialize. Some receptors became dedicated to pathogen detection and lost the ability to trigger a defence response on their own, whereas others operate in concert with these sensor receptors to trigger the immune response.
This project will study how a plant pathogen counteract an immune receptor network of its host plant. We will focus on the potato blight pathogen Phytophthora infestans and determine the mechanism by which it suppresses the function of the subset of immune receptors that trigger the immune response. Understanding the interplay between plant pathogens and their host's immune receptors would generate fundamental knowledge about the functioning principles that determine the outcomes of these interactions, which in turn would set the stage for researchers to be able to use them to protect agricultural crops from disease.
A better understanding of how these complex interactions between pathogens and plant immune receptor operate should set the stage for breeding crop plants that are better able to resist diseases. Our long-term aim is to understand the dynamics of plant-pathogen interactions in sufficient detail to improve our capacity to protect plants against crop diseases.
Plant genomes may encode anywhere between 50 and 1000 immune receptors; some of which work solo as singletons, while others operate in pairs or as complex networks. One driving force behind the evolution of immune receptors is gene duplication. Receptor genes duplicate and afterwards the two copies can evolve in different ways. The original immune receptors are multi-tasking proteins that detect parasites and trigger the immune response. Following gene duplication, evolution has led immune receptors to specialize. Some receptors became dedicated to pathogen detection and lost the ability to trigger a defence response on their own, whereas others operate in concert with these sensor receptors to trigger the immune response.
This project will study how a plant pathogen counteract an immune receptor network of its host plant. We will focus on the potato blight pathogen Phytophthora infestans and determine the mechanism by which it suppresses the function of the subset of immune receptors that trigger the immune response. Understanding the interplay between plant pathogens and their host's immune receptors would generate fundamental knowledge about the functioning principles that determine the outcomes of these interactions, which in turn would set the stage for researchers to be able to use them to protect agricultural crops from disease.
A better understanding of how these complex interactions between pathogens and plant immune receptor operate should set the stage for breeding crop plants that are better able to resist diseases. Our long-term aim is to understand the dynamics of plant-pathogen interactions in sufficient detail to improve our capacity to protect plants against crop diseases.
Technical Summary
The aim of this project is to determine how a plant pathogen effector counteracts an immune receptor network of its host plant. We will investigate how the RXLR-WY/LWY type effector AVRcap1b of the potato blight pathogen Phytophthora infestans suppresses the activity of NRC immune receptors to counteract effector-triggered immunity and overcome disease resistance. The mechanisms by which plant pathogen effectors suppress this form of immunity are poorly understood in contrast to the widely studied suppression of pathogen-associated molecular patterns (PAMP)-triggered immunity (PTI).
NRC proteins are central nodes in a large bow-tie NLR immune network of solanaceous plants. They function downstream of classical R proteins as executors (helper NLRs) of the hypersensitive cell death immune response. NRCs belong to the MADA-NLR class of immune receptors, which are thought to cause hypersensitive cell death following a conformational switch and translocation of a resistosome structure into the plant plasma. We found that AVRcap1b suppresses the functions of autoimmune NRCs without binding these proteins and, therefore, acts downstream of these hypersensitive cell death executors. Therefore, understanding the mechanism by which AVRcap1b suppresses NRCs has the unique potential of revealing the signalling elements downstream of activated MADA-NLRs, and therefore provide original insights into how the resistosome functions.
We will investigate members of the membrane trafficking ENTH-GAT domain protein family that we identified as the host targets of AVRcap1b and found to be necessary for NRC-mediated hypersensitive cell death.
Understanding the interplay between AVRcap1b, ENTH-GAT and NRCs will significantly advance our understanding of the functioning principles that determine the outcome of complex pathogen-host interactions.
NRC proteins are central nodes in a large bow-tie NLR immune network of solanaceous plants. They function downstream of classical R proteins as executors (helper NLRs) of the hypersensitive cell death immune response. NRCs belong to the MADA-NLR class of immune receptors, which are thought to cause hypersensitive cell death following a conformational switch and translocation of a resistosome structure into the plant plasma. We found that AVRcap1b suppresses the functions of autoimmune NRCs without binding these proteins and, therefore, acts downstream of these hypersensitive cell death executors. Therefore, understanding the mechanism by which AVRcap1b suppresses NRCs has the unique potential of revealing the signalling elements downstream of activated MADA-NLRs, and therefore provide original insights into how the resistosome functions.
We will investigate members of the membrane trafficking ENTH-GAT domain protein family that we identified as the host targets of AVRcap1b and found to be necessary for NRC-mediated hypersensitive cell death.
Understanding the interplay between AVRcap1b, ENTH-GAT and NRCs will significantly advance our understanding of the functioning principles that determine the outcome of complex pathogen-host interactions.
Planned Impact
This project addresses fundamental aspects of plant-pathogen interactions and plant immunity with important perspectives for exploiting newly disovered functioning principles towards breeding resilient crops and producing safe and nutritious food.
Plant diseases are a recurring threat to the production of safe and sufficient food leading the United Nations to declare 2020 as the International Year of Plant Health (IYPH). This project impacts the agricultural and biotechnology sectors and fits firmly within the remit of BBSRC food security agenda. Food insecurity-the incapacity to access a safe and nutritious diet-is not just an affliction of developing countries but also affects millions of people in the UK and other Western societies. There is currently an appetite in the UK to revisit the issue of GM crops, notably blight resistant potatoes. Therefore, this research project is timely and relevant to broader societal issues.
We anticipate that our research outcomes will significantly impact:
Agricultural biotechnology industry
The AgBio industry will acquire insights into the mechanistic functioning of plant pathogen effectors and plant disease resistance genes. Our fundamental advances will ultimately reveal and resurrect R genes that are currently defeated (suppressed) by pathogen effectors. The PI and TSL have had long-standing interactions with industry to develop and deploy solutions. Indeed, the PI currently collaborates with industrial partners to exploit R gene networks to help breed disease resistant vegetable and field crops.
Plant breeders
Knowledge gained from understanding the dynamics and functional principles of an R gene network will help identify new approaches for breeding disease resistance to maximize crop protection. Given that six potato late blight R genes are members of the NRC network, this project will also have a direct impact on current multi-disciplinary projects supported by BBSRC programmes, such as the Horticulture and Potato Initiative (HAPI). In addition, The NRC network operates against major classes of plant pathogens, i.e. oomycetes, bacteria, viruses, nematodes, and insects, and therefore has potential for technology and knowledge transferred beyond the potato blight pathosystem.
Public
Our ultimate aim is to provide affordable and nutritious food for all. This project fits within that long-term aim. The great majority of UK food and agriculture research funding is devoted to field crops despite the importance of vegetable crops in meeting the UK government guidelines for a healthy diet. About four million UK children are estimated to suffer from malnutrition and cannot afford vegetables to meet the 5-a-day guidelines for a nutritious diet.
The environment
Improving crop genetic resistance will help reduce chemical use for disease management. This will positively influence the environment as excessive use of agrochemicals can be harmful to natural ecosystems and will contribute to the sustainable production of food.
Plant diseases are a recurring threat to the production of safe and sufficient food leading the United Nations to declare 2020 as the International Year of Plant Health (IYPH). This project impacts the agricultural and biotechnology sectors and fits firmly within the remit of BBSRC food security agenda. Food insecurity-the incapacity to access a safe and nutritious diet-is not just an affliction of developing countries but also affects millions of people in the UK and other Western societies. There is currently an appetite in the UK to revisit the issue of GM crops, notably blight resistant potatoes. Therefore, this research project is timely and relevant to broader societal issues.
We anticipate that our research outcomes will significantly impact:
Agricultural biotechnology industry
The AgBio industry will acquire insights into the mechanistic functioning of plant pathogen effectors and plant disease resistance genes. Our fundamental advances will ultimately reveal and resurrect R genes that are currently defeated (suppressed) by pathogen effectors. The PI and TSL have had long-standing interactions with industry to develop and deploy solutions. Indeed, the PI currently collaborates with industrial partners to exploit R gene networks to help breed disease resistant vegetable and field crops.
Plant breeders
Knowledge gained from understanding the dynamics and functional principles of an R gene network will help identify new approaches for breeding disease resistance to maximize crop protection. Given that six potato late blight R genes are members of the NRC network, this project will also have a direct impact on current multi-disciplinary projects supported by BBSRC programmes, such as the Horticulture and Potato Initiative (HAPI). In addition, The NRC network operates against major classes of plant pathogens, i.e. oomycetes, bacteria, viruses, nematodes, and insects, and therefore has potential for technology and knowledge transferred beyond the potato blight pathosystem.
Public
Our ultimate aim is to provide affordable and nutritious food for all. This project fits within that long-term aim. The great majority of UK food and agriculture research funding is devoted to field crops despite the importance of vegetable crops in meeting the UK government guidelines for a healthy diet. About four million UK children are estimated to suffer from malnutrition and cannot afford vegetables to meet the 5-a-day guidelines for a nutritious diet.
The environment
Improving crop genetic resistance will help reduce chemical use for disease management. This will positively influence the environment as excessive use of agrochemicals can be harmful to natural ecosystems and will contribute to the sustainable production of food.
Organisations
Publications
Marchal C
(2022)
Emerging principles in the design of bioengineered made-to-order plant immune receptors.
in Current opinion in plant biology
Contreras MP
(2023)
NLR receptors in plant immunity: making sense of the alphabet soup.
in EMBO reports
Adachi H
(2022)
NLR receptor networks in plants.
in Essays in biochemistry
Bentley AR
(2022)
Near- to long-term measures to stabilize global wheat supplies and food security.
in Nature food
Harant A
(2022)
A vector system for fast-forward studies of the HOPZ-ACTIVATED RESISTANCE1 (ZAR1) resistosome in the model plant Nicotiana benthamiana.
in Plant physiology
Kourelis J
(2021)
RefPlantNLR is a comprehensive collection of experimentally validated plant disease resistance proteins from the NLR family.
in PLoS biology
Derevnina L
(2021)
Plant pathogens convergently evolved to counteract redundant nodes of an NLR immune receptor network.
in PLoS biology
Kourelis J
(2022)
The helper NLR immune protein NRC3 mediates the hypersensitive cell death caused by the cell-surface receptor Cf-4
in PLOS Genetics
De La Concepcion JC
(2022)
A blast fungus zinc-finger fold effector binds to a hydrophobic pocket in host Exo70 proteins to modulate immune recognition in rice.
in Proceedings of the National Academy of Sciences of the United States of America
| Description | Parasites are organisms that live in or on another organism, called a host, and can cause harm. Hosts have an immune system to protect themselves from parasites, but parasites can sometimes suppress the host's immune response. Helper NLR proteins are important molecules in the immune system that help to recognize and fight parasites. Researchers have found that parasites can counteract the host's immune response by suppressing these helper NLR proteins. By studying how parasites suppress the immune system, researchers can develop strategies to make crops more resistant to diseases. In this study, researchers found that a parasite called a cyst nematode produces a molecule that binds to and inhibits a helper NLR protein called NRC2. This prevents NRC2 from activating other immune molecules and fighting the parasite. However, the researchers also discovered that a single change in the amino acid sequence of NRC2 can prevent the parasite's molecule from binding to it. This means that the immune system can still recognize and fight the parasite, even in the presence of the parasite's suppressive molecule. This finding suggests a new approach to developing disease-resistant crops. By identifying and modifying the amino acid sequences of helper NLR proteins, it may be possible to make crops more resistant to parasites and other diseases. |
| Exploitation Route | Start-up |
| Sectors | Manufacturing, including Industrial Biotechology |
| Description | Contributed to a start-up Resurrect Bio |
| First Year Of Impact | 2022 |
| Sector | Manufacturing, including Industrial Biotechology |
| Impact Types | Economic |