A built-in brake for plant immunity: Resistance (R) protein-mediated immunity is fine-tuned by <i>R</i> gene analogs.

Abstract

Potato late blight caused by <i>Phytophthora infestans</i> threatens global food security. Unlike the fact that most race-specific resistance to <i>P. infestans</i> (<i>Rpi</i>) genes is rapidly overcome by evolving pathogen populations, the <i>R8</i> gene from <i>Solanum demissum</i> has conferred durable, quantitative resistance for nearly a century despite encoding a canonical coiled-coil-type nucleotide-binding, leucine-rich repeat (NLR) protein. We identified specific <i>R8</i> gene analogs that act as negative modulators of <i>R8</i>-mediated immunity. These <i>R8</i> gene analogs lack independent resistance functions but perturb the recognition of avirulence effector Avr8 by R8 and interfere with oligomerization and plasma membrane association of NRC2, a helper NLR essential for the R8 signaling pathway. Stable overexpression of such RGAs effectively compromises <i>R8</i>-mediated resistance in both potato and <i>Nicotiana benthamiana</i>. We propose that this endogenous regulation balances the intensity of <i>R8</i>-mediated immunity, likely reducing selection pressure on the pathogen population and prolonging resistance durability. Our findings reveal a regulatory layer where genetically linked RGAs control resistance (R) protein-mediated immunity, providing a conceptual framework for durable resistance breeding.