Molecular Pathogens, 2025, Vol.16, No.4, 182-192 http://microbescipublisher.com/index.php/mp 187 Eurasian grapes after infection. The results show that a large number of defense-related genes in disease-resistant hairy grapes are rapidly upregulated, including genes encoding PR proteins, antibacterial enzymes, signaling molecule synthases, and these genes in the Eurasian species of sensory disease respond weakly. For example, genes such as PAD4 and EDS1 associated with the SA pathway are strongly induced in disease-resistant grapes, indicating that SA signaling dominates the resistance response. At the same time, some genes related to cell wall reinforcement and phenylagen metabolism (such as resin alcohol synthase STS) are also highly expressed, promoting the establishment of physical and chemical barriers. Transcriptome comparisons can also reveal new candidate regulators. For example, studies have found significant changes in the expression of multiple long-chain non-coding RNA (lncRNA) in grapes that are resistant to downy mildew. Bhatia et al. reported a batch of specific lncRNA molecules that are upregulated when grapes are infected with downy mildew and powdery mildew, which may participate in resistance responses by regulating gene expression (Bhatia and Upadhyay, 2021). These lncRNAs have a co-expression relationship with defense genes, and some can also serve as precursors of miRNAs, thereby indirectly affecting the resistance-related gene network. 5.2 Application of proteome and metabolomic group in the analysis of resistance mechanism In addition to information at the gene expression level, the realization of disease resistance also involves levels such as protein functional modification and metabolites accumulation. In terms of proteomics, researchers compared the proteome differences between disease-resistant and sensory grapes during infection through quantitative techniques such as bidirectional electrophoresis combined with mass spectrometry identification or iTRAQ. Some studies have found that some defense-related enzymes (such as peroxidase POD and polyphenol oxidase PPO) in anti-downer disease grapes have significantly higher activity than those of the susceptible varieties after infection, while the activity differences between the antioxidant enzymes SOD and CAT are not obvious. Among them, POD activity is positively correlated with resistance, which can be used as an auxiliary indicator for identifying disease resistance of varieties. Metabolomics research focuses on changes in plant metabolites. Grapes accumulate a variety of secondary metabolites during downy mildew infection, some of which are considered chemical barriers to disease resistance. For example, resveratrol and its derived acetylation products are an important class of antimicrobial phytoalens (Phytoalexins) that significantly increase in the content of disease-resistant grapes when they are infected with downy mildew (Figueiredo et al., 2015). 5.3 Examples of integrated omics in research on anti-disease mechanism With the accumulation of omics data at all levels, how to integrate them to comprehensively analyze the anti-disease mechanism has become a new research trend. A representative case is the Variety Super Pangenome Study. The study sequenced and assembled high-quality genomes of 72 Varieties representative germplasm (including 25 wild species and 47 cultivars) to construct a pan-genome framework. At the same time, 113 of the grapes were sequenced under downy mildew infection, and a correlation study was conducted in combination with phenotype disease resistance score and structural variation (SV) analysis. Through this grand integrated analysis, the research team identified 63 structural variants and their candidate genes significantly related to downy mildew resistance, among which the resistance regulator represented by VvLHT8, a gene encoding a lysine-histidine transporter, is particularly prominent (Guo et al., 2024). Functional studies have shown that different variants of VvLHT8 will affect the accumulation level of salicylic acid in the grape body, thereby regulating disease resistance. This result is a model for multiomic data fusion: genomic SV provides information on genetic diversity, transcriptome reveals the expression patterns of genes during disease resistance, and phenotypic associations link the two to identify key genes. 6 Resistance Case Study: Molecular and Genetic Insights of Typical Grape Germplasm 6.1 Comparison of resistance between European grapes (Vitisvinifera) and wild grape species During the domestication process, European grape cultivation mainly pursues fruit flavor and yield, and does not undergo strict selection for disease resistance. Therefore, most Eurasian varieties lack effective resistance to downy mildew. However, in the wild germplasm of the Variety, especially those native to the Americas and Asia, tend to show significant downy mildew resistance, a result of long-term coexistence with pathogens. Comparative
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