Folate Metabolism Interferes with Plant Immunity through 1C Methionine Synthase-Directed Genome-wide DNA Methylation Enhancement

Plants rely on primary metabolism for flexible adaptation to environmental changes. Here, through a combination of chemical genetics and forward genetic studies in Arabidopsis plants, we identified that the essential folate metabolic pathway exerts a salicylic acid-independent negative control on plant immunity. Disruption of the folate pathway promotes enhanced resistance to Pseudomonas syringae DC3000 via activation of a primed immune state in plants, whereas its implementation results in enhanced susceptibility. Comparative proteomics analysis using immune-defective mutants identified a methionine synthase (METS1), in charge of the synthesis of Met through the folate-dependent 1C metabolism, acting as a nexus between the folate pathway and plant immunity. Overexpression of METS1 represses plant immunity and is accompanied by genome-wide global increase in DNA methylation, revealing that imposing a methylation pressure at the genomic level compromises plant immunity. Take together, these results indicate that the folate pathway represents a new layer of complexity in the regulation of plant defense responses.