P-137 - Manipulation of plant NAD+ metabolism by bacterial TIR domain effectors

Nicotinamide adenine dinucleotide (NAD⁺) is a universal co-factor and redox carrier involved in various metabolic processes in cells across kingdoms. Recently, it was discovered that Toll/interleukin-1 receptor (TIR) domains of proteins, which are often associated with intracellular immune receptors in plants, function as NAD⁺ hydrolyzing enzymes and produce specific NAD⁺-derived products that subsequently activate immune signaling. This discovery links NAD⁺ metabolism and degradation to immune signaling. Interestingly, pathogens produce host-manipulating effectors that can also hydrolyze NAD⁺. Our recent analysis on the pangenome of Pseudomonas syringae revealed 13 type III secreted effector families that contain five different NAD⁺ hydrolase domains. In particular, two effector families employ TIR-like domains to promote disease. Here, we will report on the functional characterizations of the TIR effectors, including their particular NAD⁺ hydrolysis products during infection and immune suppression activities. The study uncovers novel virulence mechanisms and provides insight into a newly emerged host-pathogen arms race centered on manipulation of immune signaling by NAD⁺-derived small molecules.