A typical NLR recognizes a family of structurally conserved effectors to confer plant resistance against adapted and non-adapted Phytophthora pathogens.

Plants possess remarkably durable resistance against non-adapted pathogens in nature. However, the underlying molecular mechanisms remain poorly understood, and it is unclear how the resistance is maintained without coevolution between hosts and non-adapted pathogens. In this study, we used Phytophthora sojae (Ps), a non-adapted pathogen of Nicotiana benthamiana (Nb), as a model and identified an RXLR effector that determines Nb incompatibility to Ps. Knockout of this RXLR effector in Ps enables successful infection of Nb, leading us to name it AvrNb (Avirulence gene in Nb). A systematic screening of Nb NLR genes further revealed that NbPrf, previously reported to be a receptor of bacterial avirulence proteins, is the NLR protein responsible for mediating AvrNb recognition and initiating the hypersensitive response (HR). Mutation in NbPrf makes Nb completely compatible to Ps. We found that AvrNb is structurally conserved among multiple Phytophthora pathogens, and its homologs also induce NbPrf-dependent HR. Remarkably, further inoculation assay showed that NbPrf is also involved in plant immunity to two adapted Phytophthora pathogens, Phytophthora infestans and Phytophthora capsici. Our findings suggest that NbPrf represents a promising resource for breeding resistance to Phytophthora pathogens and implicate that the conserved effectors present in both adapted and non-adapted pathogens may provide sufficient selective pressure to maintain the remarkably durable incompatibility between plants and non-adapted pathogens.