Metabolic Reprogramming of a Phenolic Acid by a Plant P450 Monooxygenase Reverses Bacterial Immunosuppression

Soil acidification often exacerbates plant diseases caused by soil-borne pathogens like Ralstonia solanacearum, but the underlying molecular mechanisms remain elusive. This study unveils a sophisticated metabolic game in the tobacco-R. solanacearum pathosystem, where the pathogen manipulates host metabolism to suppress immunity, and the plant counteracts by enzymatically reprogramming a key metabolic signal. Using multi-omics approaches, we discovered that R. solanacearum infection induces a significant accumulation of veratric acid (VA) in tobacco. We demonstrated that VA acts as a potent immunosuppressant rather than a nutrient for the pathogen. It broadly inhibits plant pattern-triggered immunity, including flg22-induced ROS burst, and transcriptionally represses a suite of nucleotide-binding leucine-rich repeat (NLR) receptors, crucially including NtG28897 (NtTAO1). Silencing of NtTAO1 confirmed its pivotal role in resistance against Tobacco Mosaic Virus (TMV). Facing this metabolic sabotage, tobacco engages a counter-defence mechanism. We identified a specific cytochrome P450 monooxygenase (CYP86A22) that catalyses the conversion of the disease-promoting VA into vanillic acid (VanA). Transient overexpression of this P450 in Nicotiana benthamiana enhanced the in vivo conversion of VA to VanA. Crucially, this enzymatic conversion conferred strong resistance against TMV, whereas the P450 or VA alone did not. Our findings reveal a novel plant immune strategy 'metabolic signal reprogramming' where a P450 enzyme detoxifies a susceptibility metabolite into a defensive compound. This work provides a new paradigm for plant-pathogen interactions and identifies promising targets for metabolic engineering or green chemical strategies to achieve sustainable disease control.