Abstract
Bacterial wilt, caused by Ralstonia solanacearum, is a devastating disease that limits global tobacco production. To decipher the molecular basis of resistance, we conducted an integrated multiomics analysis of a susceptible cultivar, Honghua Dajinyuan (HD), and a moderately resistant cultivar, Yanyan 97 (YY), leveraging LC‒MS-based metabolomics and RNA-seq transcriptomics. The resistant YY cultivar exhibited coordinated multitiered defense, characterized by the accumulation of resistance-related metabolites (e.g., prenol lipids and organooxygen compounds) and the enrichment of plant hormone signaling pathways. Transcriptomic analysis revealed 818 differentially expressed genes (DEGs) involved in cell wall modification and stress responses. Crucially, the integration of weighted gene coexpression network analysis (WGCNA) with prior QTL mapping pinpointed Nta17g05760 within the qBWR17b locus as a core candidate gene. Our study systematically elucidates a defense network involving hormone signaling, cell wall reinforcement, and antimicrobial synthesis and provides a key candidate gene and theoretical foundation for the molecular breeding of wilt-resistant tobacco.