Molecular Pathogens, 2025, Vol.16, No.4, 182-192 http://microbescipublisher.com/index.php/mp 186 PTI usually manifests as a series of basic defenses such as reactive oxygen outbreak, cell wall thickening, and antibacterial substance synthesis. Some studies have pointed out that PTI responses in disease-resistant grapes are rapid and strong, and can curb their expansion in the early stages of pathogen invasion. However, obligate parasites such as downy mildew bacteria often evolve effector proteins to inhibit or avoid PTI. For example, a class of RxLR effector secreted by Downy bacteria into cells can interfere with host kinase signals and block PTI-related immune output. When these pathogenic effectors enter the host cell, if the grape variety carries a specific disease-resistant R gene, the presence of the effector can be directly or indirectly recognized, thereby stimulating a stronger second immune line, namely ETI. There is also a synergistic relationship between PTI and ETI: strong ETI responses often involve reinforcing the PTI pathway and early warning of adjacent cells to enter a defensive state through excitor induction (Goyal et al., 2020). 4.2 Regulatory role of key signaling molecules (SA, JA, ET, etc.) in resistance The initiation and transmission of plant disease-resistant reactions cannot be separated from the regulation of various signal molecules in the body. Among them, salicylic acid (SA) is considered to be one of the core signaling molecules in response to biological stress such as grape downy mildew. When grapes are infected with downy mildew bacteria, the SA signaling pathway is often activated quickly, thereby inducing a large number of downstream defense gene expression, including genes encoding disease course-related proteins (PR proteins). Studies have shown that downy mildew-resistant grape lines accumulate significantly high levels of SA and its glucosidized derivatives early in the infection, which is positively correlated with their high resistance traits. In disease-resistant signaling networks, signaling molecules such as jasmonic acid (JA) and ethylene (ET) are more related to anti-worm or anti-necrotic pathogens. However, JA/ET signal also plays a role in grapes' resistance to downy mildew. There have been reports that increased JA levels and upregulation of JA response genes were detected in grape-down mildew interactions, which may be related to enhanced cell wall defense and secondary metabolism. As a hormone that regulates aging and defense response, ethylene has a relatively complex role and is speculated to play an auxiliary regulatory role in downy mildew resistance. 4.3 Molecular function verification of typical resistance genes In grape anti-downermic disease research, multiple resistance-related genes have been cloned and their functions have been verified by molecular means. Functional verification mainly relies on methods such as transgene overexpression or gene knockout to observe changes in plant disease-resistant traits to confirm the role of candidate genes in the disease-resistant process. A successful case is the disease-resistant protein 10.1 gene (VpPR10.1). VpPR10.1 is derived from disease-resistant wild grapes and belongs to the PR protein family. The team of China Agricultural University cloned the VaHAESA gene and overexpressed it in Arabidopsis. It was found that the transgenic plants have increased resistance to downy mildew-related pathogens, indicating that VaHAESA, as a membrane receptor, plays a positive regulatory function in disease resistance signals (Ma et al., 2018). The above examples reflect the mechanism of action of different types of resistance genes in the fight against downy mildew: some are direct antibacterial, some are signal perception, and some are metabolic regulation. In addition to gene overexpression verification, gene editing technology has also been used in the study of grape resistance mechanism in recent years. Li Mengyuan et al. of Northwest A&F University (2020) used CRISPR/Cas9 to knock out one of the grapes' own PR4b genes, and found that the mutant plants had reduced resistance to powdery mildew and downy mildew, proving the importance of this gene to fight disease (Li et al., 2020). 5 Application of Multiomics Research in The Analysis of Downy Mildew Resistance 5.1 Transcriptomics reveals expression patterns of resistance-related genes The development of transcriptomics (RNA-seq) technology provides a possibility to fully understand the changes in gene expression in grapes under downy mildew infection. By comparing the transcriptional expression profiles of disease-resistant and sensory varieties during bacterial infestation, researchers can identify key genes and regulatory networks related to resistance. The researchers used transcriptome sequencing to analyze the differences in gene expression between wild hairy grapes that are resistant to downy mildew and susceptible
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