Remodelling autoactive NLRs for broad-spectrum immunity in plants

Junzhu Wang, Tianyuan Chen, Zhendong Zhang, Mengjie Song, Tianxin Shen, Xin Wang, Xiyin Zheng, Yan Wang, Ke Song, Xiaoyang Ge, Kai Xu, Tiancong Qi, Fuguang Li, Yiguo Hong and Yule Liu ()
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Junzhu Wang: Tsinghua University
Tianyuan Chen: Tsinghua University
Zhendong Zhang: Tsinghua University
Mengjie Song: Tsinghua University
Tianxin Shen: Tsinghua University
Xin Wang: Tsinghua University
Xiyin Zheng: Tsinghua University
Yan Wang: Tsinghua University
Ke Song: Tsinghua University
Xiaoyang Ge: Chinese Academy of Agricultural Sciences
Kai Xu: Nanjing Normal University
Tiancong Qi: Tsinghua University
Fuguang Li: Chinese Academy of Agricultural Sciences
Yiguo Hong: Hebei Agricultural University
Yule Liu: Tsinghua University

Nature, 2025, vol. 645, issue 8081, 737-745

Abstract: Abstract Remodelling plant immune receptors has become a vital strategy for creating new disease resistance traits to combat the growing threat of plant pathogens to global food security and environmental sustainability1–17. However, current methods are constrained by the rapid evolution of plant pathogens and often lack broad-spectrum and durable protection. Here we report an innovative strategy to engineer broad-spectrum, durable and complete disease resistance in plants through expression of a chimeric protein containing a flexible polypeptide coupled with a single or dual conserved pathogen-originated protease cleavage site fused in frame to the N terminus of an autoactive nucleotide-binding and leucine-rich-repeat immune receptor (NLR) containing a coiled-coil or RESISTANCE TO POWDERY MILDEW 8-like coiled-coil domain. Following invasion, pathogen-originated specific proteases cleave the inactive chimeric protein to form free autoactive NLR, triggering broad-spectrum plant disease resistance. We demonstrate that a single engineered NLR can confer broad-spectrum and complete resistance against multiple potyviruses. Given that many pathogenic organisms across kingdoms encode proteases, this strategy has the potential to be exploited to control viruses, bacteria, oomycetes, fungi, nematodes and pests in plants.

Date: 2025
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DOI: 10.1038/s41586-025-09252-z

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