Aizezi, Y.; Bi, Y.; Zhang, H.; Kim, J.-G.; Chaudhary, A.; Trinh, C. S.; Shen, Q. J.; Xu, S.-L.; Mudgett, M. B.; Wang, Z.-Y.

Interaction with microbes can reprogram metabolism and alter nutrient availability in plant cells. How metabolic cues modulate immune responses remains unknown. Here, we show that sugar-sensing O-glycosylation of immune-signaling kinases mediates metabolic regulation of immunity. Under sugar-replete conditions, the MAP kinase kinases (MKK4 and MKK5), key components of pattern-triggered immunity (PTI), are glycosylated by O-GlcNAc and O-fucose in their activation loops and thus cannot be activated by upstream kinases, thereby restricting PTI. Pathogen infection or sugar starvation reduces O-glycosylation of MKK4/5 and enhances immune signaling; these effects are reversed by GDP-fucose treatment, demonstrating that reduced sugar availability decreases O-fucosylation and enhances immune signaling in infected cells. Chemical inhibition of O-fucosylation enhances immunity and pathogen resistance in both Arabidopsis and tomato. Our findings establish O-glycosylation of MKKs as a metabolic rheostat that fine-tunes immune responses according to sugar availability during plant-microbe interactions, providing a new strategy for improving crop health.