Comparative transcriptomics has identified several candidate genes contributing to the resistance of Cucumis metuliferus against Meloidogyne incognita. The Southern root-knot nematode (Meloidogyne incognita) is a significant threat to Cucurbitaceae crops. The African horned melon (Cucumis metuliferus), a wild relative, exhibits high resistance to this nematode. To explore the resistance mechanism, phenotypic analyses were conducted on a susceptible inbred line (CM27) and a resistant inbred line (CM3). CM3 exhibited enhanced root biomass and significantly higher resistance compared to CM27, with poor nematode development observed in CM3 roots. Transcriptomic profiling at multiple post-infection time points revealed 2243 and 3700 differentially expressed genes (DEGs) in CM3 and CM27, respectively. Among these, the top ten DEGs upregulated exclusively in CM3 were functionally analyzed using virus-induced gene silencing (VIGS). Silencing of EVM0019904 or EVM0017058 in CM3 led to susceptibility to M. incognita. These findings provide novel insights into the resistance mechanisms of M. incognita in C. metuliferus and offer potential resources for breeding nematode-resistant Cucurbitaceae crops.
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