Hopeaphenol targets histidine kinase signaling across kingdoms to suppress bacterial virulence and potentiate plant immunity
Small molecules can control plant disease either by disarming the pathogen or by priming host immunity, but single compounds that do both are rare and mechanistically unexplained. Here we show that hopeaphenol (HP), a resveratrol tetramer from stilbene producing plants, acts on histidine kinase (HK) signaling on both sides of the Arabidopsis-Pseudomonas interaction. In Pseudomonas syringae pv. tomato DC3000, HP represses the type III secretion regulon and motility genes, restricts surface motility independently of effector delivery, and binds a defined subset of virulence-associated sensor kinases while reducing their autophosphorylation; comparable engagement occurs in Pectobacterium atrosepticum. Binding and inhibition depend on the tetrameric scaffold rather than the resveratrol monomer. In the host, HP binds the CHASE domains of the cytokinin receptors AHK2, AHK3 and AHK4 and elicits an immune-associated, rather than canonical cytokinin, transcriptional output. HP-dependent potentiation of PTI and ETI responses and early restriction of bacterial growth require AHK3 and AHK4. HP thus coordinates opposing outputs from divergent HK systems across kingdoms.