Nucleoside decoys - a novel pathogen strategy to infect plants

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.