Integrated Multi-Omics Analysis Unveils Mediagenic acid and Progesterone in Malus sieversii Resistance Against Cytospora mali

Background Apple canker disease, caused by the necrotrophic fungus Cytospora mali , poses a significant global threat to apple production, necessitating the development of eco-friendly control strategies. Results Multi-omics analysis of C. mali -infected Malus sieversii (wild apple) revealed coordinated transcriptional-metabolic reprogramming associated with the biosynthesis of antifungal specialized metabolites. The C. mali infection triggered reactive oxygen species (ROS) accumulation and upregulation of pathogenesis-related ( PR ) genes, indicative of active plant immunity. We identified 1382 differentially accumulated metabolites, predominantly terpenoids, flavonoids, and phenolic acids. Terpenoid accumulation correlated with the upregulation of key transcription factors (AP2/ERF, WRKY) regulating their biosynthesis. Antifungal assays demonstrated that two terpenoids, mediagenic acid (MA) and progesterone (PROG), significantly inhibited C. mali growth. Pre-infection application of MA or PROG significantly reduced lesion length and the biomass of C. mali in M. sieversii . PROG exhibited superior efficacy compared to MA in inducing resistance, correlating with stronger differential regulation of PR genes in plants. Conclusions This study elucidates molecular mechanisms underlying canker resistance and provides potential practical solutions for disease management in orchards and natural ecosystems.