Grapevine protection against Plasmopara viticola by a natural extract involves a signaling cascade common to Rpv locus-mediated defense responses

The cultivation of Vitis vinifera is severely constrained by fungal and oomycete diseases that negatively impact yield and fruit quality. Although phytosanitary products remain central to disease control, their intensive use raises major concerns related to pathogen resistance, environmental impact, human health, and increasingly strict regulatory constraints. Consequently, sustainable and integrated disease management strategies that reduce chemical inputs while maintaining high production standards are urgently needed. In this context, a plant-derived natural extract (LL017) has been developed as a sustainable plant protection product, demonstrating good field efficacy with a reduction of downy mildew ( Plasmopara viticola ) severity when applied in combination with only 30% of the standard fungicide dose. This highlights its strong potential for integration into reduced-input protection strategies. To support the rational deployment of biologicals and to generate new mechanistic knowledge, we investigated the molecular mode of action underlying LL017-induced resistance in grapevine. LL017 did not directly affect pathogen viability but instead activated host-mediated defence responses, inducing coordinated early and late immune mechanisms comparable to those controlled by well-characterized grapevine resistance loci. Deep metatranscriptomic analyses and gene co-expression network inference identified an early signalling cascade converging on stilbene synthase regulation as a key component of LL017-mediated resistance. In parallel, LL017 modulated primary metabolism–related genes, suggesting a broader transcriptional reprogramming associated with enhanced grapevine fitness. Overall, this study provides new fundamental insights into the molecular networks underlying robust defence responses in grapevine while supporting the optimized use of biologicals in sustainable disease management strategies.