Nucleoside decoys - a novel pathogen strategy to infect plants

植物抗病（R）基因被广泛应用于植物育种，以帮助减轻全球作物因害虫和病原体造成的损失超过30%。不幸的是，随着病原体进化出部署多功能“效应器”的复杂方法，抗性往往被克服，这些“效应器”是病原体军械库的关键要素，它们共同工作以避免检测和抑制宿主免疫力。尽管25年前克隆了R蛋白，但我们对这些蛋白在植物中如何发挥作用的知识仍然有限。R蛋白有两种类型，TNL和CNL，两者都含有共同的关键功能结构域，即中央核苷酸结合（N）结构域和羧基末端“富含亮氨酸重复”（L）区域。最近显示，“T“NL疾病抗性蛋白的氨基末端TIR（Toll白细胞介素1）结构域二聚化以产生能够切割细胞的关键能量源NADH或NADPH的复合物。重要的是，这种“NADase”活性对于激活抗病性至关重要。值得注意的是，虽然动物和细菌TIR结构域具有相似的酶活性，但产物似乎不同。植物和细菌产生一种叫做v-cADPR（变异环腺苷二磷酸核糖）的化合物。我们现在已经鉴定出第二种“v-cADPR”，我们称之为540。值得注意的是，这是由有毒细菌引起的。这就提出了一个假设，即病原体可以产生代谢诱饵来干扰R蛋白信号传导，从而抑制植物免疫。该项目旨在使用基因编辑，化学和生物化学的组合来测试这一假设。

Plant disease resistance (R) genes are widely deployed in plant breeding to help mitigate global crop losses to pests and pathogens which exceed 30%. Unfortunately, resistance is often overcome in the field as pathogens evolve ever sophisticated methods of deploying multi-functional "effectors" - key elements of the pathogens armoury the work collectively to avoid detection and suppress host immunity.Despite having cloned R proteins more than 25 years ago we still have limited knowledge on how these function in planta. R proteins come in two flavours, TNLs and CNLs, both containing common key functional domains, the central nucleotide binding (N) domain and carboxyl terminal "leucine rich repeat" (L) region. It was recently shown that the amino terminal TIR, (Toll Interleukin 1) domain of "T"NL disease resistance proteins dimerises to generate a complex capable of cleaving NADH or NADPH, key energy sources for cells. Critically, this "NADase" activity was essential to activate disease resistance. Notably, although animal and bacteria TIR domains have similar enzymatic activities, the products appear to differ. Plants and bacteria produce a compound called v-cADPR (variant cyclic ADP Ribose).We have now identified a second "v-cADPR" that we call 540. Remarkably this is induced by virulent bacteria. This raises the hypothesis that pathogens can generate metabolic decoys to interfere with R proteins signalling and hence suppress plant immunity. This project seeks to test that hypothesis using a combination of gene editing, chemistry and biochemistry.