Scientists engineer plant immune receptors to fight devastating cereal blast fungus

A devastating fungal pathogen that destroys enough rice each year to feed 60 million people may finally face a serious technological counterattack. Researchers at the John Innes Centre in the United Kingdom, working in association with scientists at Kobe University in Japan, have shown how a recently discovered class of plant immune receptors can be re-engineered at the molecular level to recognise a broader range of attacks from the blast fungus, Magnaporthe oryzae. The study, published in Science Advances, offers a proof of principle that could reshape how breeders defend wheat, barley and rice against one of agriculture’s most destructive diseases.

The blast fungus is the most serious disease of cultivated rice, and its reach is expanding. First detected in wheat in Brazil in the 1980s, the pathogen has since spread to parts of Asia and Africa, where it now threatens cereal harvests that millions of people depend upon. Although blast is not currently present in the United Kingdom, researchers caution that a changing climate could eventually allow it to threaten cereal production in northern Europe as well. That combination of global spread and environmental change is precisely why the John Innes Centre team describes their work as a potential intervention against what they call the worst fungal disease of cereals.

To understand why the new findings matter, it helps to look at how the pathogen attacks. Like many plant pathogens, Magnaporthe oryzae inserts small proteins known as effectors into the cells of leaves and stems. Once inside, these effectors manipulate the host’s cellular machinery to suppress defences and promote disease. Plants, in turn, have evolved intracellular immune receptors that can detect these foreign molecules and trigger an immune response. That response typically involves localised cell death around the site of infection, a dramatic but effective sacrifice that cuts off the pathogen’s route to spreading through the rest of the plant.

For more than three decades, the dominant characters in this molecular arms race have been a class of receptors called nucleotide-binding and leucine-rich repeat receptors, or NLRs. A considerable body of research has placed NLRs at the forefront of our understanding of how plants mount immune responses to blast and other diseases. But in recent years, scientists studying cereal crops have increasingly turned their attention to a second, newer class of intracellular immune receptors known as tandem kinase proteins, or TKPs. These receptors, first characterised in cereals, appear to operate differently from NLRs, and their full potential has only begun to be explored.

What caught the attention of Professor Mark Banfield, a group leader at the John Innes Centre and an author of the study, was a structural feature that some TKPs share with certain NLRs: an integrated Heavy Metal Associated domain, abbreviated HMA. Previous research had shown that these HMA domains are important for recognising pathogen effectors and for mounting an immune response. If the domain acts as the molecular docking site for effectors, Banfield reasoned, then deliberately altering the amino acids at that binding interface could create novel recognition specificities, effectively reprogramming the receptor to catch effectors it would never notice naturally. That, he suggests, could open a new frontline for plant defence.

To test that idea, the team turned to structural biology. Using biophysical analysis and crystallography, they resolved at high resolution the structural interaction between HMA domains and effectors from the blast pathogen. The structures revealed that HMA domains function as biological baits within TKPs, luring pathogen effectors into a binding interaction. When the effector takes the bait, the receptor is activated and the plant’s immune response follows. Seeing the interface in atomic detail gave the researchers exactly the map they needed: they could see which residues on the HMA domain contact the effector and therefore which positions to target when engineering new binding properties.

The engineering itself delivered the study’s most striking result. Guided by the structural knowledge, the researchers successfully modified TKP immune receptors so that they acquired dual specificity, binding to effectors associated with infection of both wheat and barley. Such broad recognition rarely occurs in nature, where receptors tend to be tuned to particular pathogen molecules. Demonstrating that a cereal immune receptor can be redesigned to respond to multiple effectors simultaneously is a powerful indication that TKPs are amenable to bioengineering, and it sets the stage for work on the many TKPs that have recently been discovered in diverse cereal crops. In principle, the approach could allow scientists to custom-engineer disease resistance receptors that respond to several effectors at once, making it much harder for the pathogen to escape detection.

It is important to note that these proof of principle experiments were carried out in protoplasts, individual wheat cells used as surrogates for whole plant tissue. The next stage for the group is to translate the findings from these surrogate assays into glasshouse plants, where the engineered receptors must function within intact immune systems and provide genuine protection against infection. Dr Daniel Yu, the first author of the study, said the work shows that this new class of resistance proteins is amenable to engineering purposes, and that tools previously used to engineer NLR receptors may also work with this new class. That continuity with established methods could accelerate progress considerably, since the plant science community already has decades of experience in manipulating NLRs.

The structural understanding of effector-receptor binding may also be amplified by other emerging technologies. Precision breeding and artificial intelligence approaches could help researchers design novel specificities into HMA domains more rapidly and accurately than trial-and-error screening would allow. Machine learning tools trained on protein structures are increasingly capable of predicting how changes at a binding interface will alter molecular recognition, and combining such predictions with the crystallographic data from this study could compress the design cycle for new disease resistance genes from years to months.

Perhaps the most strategically significant aspect of the work lies in the relationship between the two receptor classes. Professor Banfield noted that NLRs and TKPs are probably activated in different ways, which opens the possibility of more robust immunity in the field because breeders would not be putting all their eggs in one basket. Further down the road, he suggested, techniques may allow genes encoding TKPs and NLRs to be stacked together against the same disease, producing what he described as a super-resistant crop. Because the two receptor classes would trigger immunity through different mechanisms, it is likely to be substantially more difficult for the pathogen to evolve around the combined defence. For a fungus that already claims enough rice each year to feed 60 million people and is steadily extending its range into wheat and barley, that kind of layered, engineered resistance may be exactly the intervention global food security requires.

Subject of Research: Bioengineering of tandem kinase plant immune receptors to broaden recognition of cereal blast fungus effectors

Article Title: Can this biotech innovation halt the destructive march of a cereal killer?

Article References: Can this biotech innovation halt the destructive march of a cereal killer?. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: blast fungus, Magnaporthe oryzae, tandem kinase proteins, NLR receptors, HMA domain, plant immunity, wheat, rice, barley, effector recognition, bioengineering, food security