Downy mildew is a major disease that significantly impacts the yield and quality of Brassica rapa. While histone deacetylase (HDAC) family members are implicated in stress responses, their role in regulating downy mildew resistance in B. rapa remains unclear. Herein, we treated the susceptible B. rapa line R32 with Trichostatin A (TSA), a potent HDAC inhibitor. Notably, TSA application significantly enhanced the susceptibility of B. rapa seedlings to downy mildew infection, demonstrating that HDAC plays a crucial role in mediating resistance against this pathogen. Subsequently, we conducted phylogenetic analysis of HDAC family members and performed high-throughput sequencing to assess HDAC gene expression patterns in the resistant (R31) and susceptible (R32) lines following downy mildew inoculation. Notably, the expression of BrHDA6 was significantly higher in the resistant line R31 compared to the susceptible line R32, suggesting its potential role in disease resistance. Using a genetic transformation system, we generated stable transgenic B. rapa plants overexpressing or silenced for BrHDA6. Inoculation with the downy mildew pathogen revealed that BrHDA6 positively regulates disease resistance. Modification omics and parallel reaction monitoring analysis demonstrated that BrHDA6 directly reduces the acetylation level of sulphotransferase 12 (BrSOT12), which likely enhances sulfotransferase activity, consequently boosting salicylic acid production during downy mildew infection. Interaction between BrHDA6 and BrSOT12 was further validated through yeast two-hybrid and dual-luciferase assays. Our study reveals that BrHDA6 confers downy mildew resistance in B. rapa through nonhistone protein deacetylation of BrSOT12, uncovering a novel regulatory mechanism in plant–pathogen interactions.

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