Durable rust resistance in wheat conferred by engineering host protein TaHRLI to evade recognition by the virulence...

Endoplasmic reticulum (ER) stress and the hypersensitive response (HR) are recognized as cornerstones of plant immunity; however, the mechanistic synergy and the strategies pathogens employ to dismantle this alliance remain elusive. Here, we identify a virulence effector, PstCRT (calreticulin), from Puccinia striiformis f. sp. tritici (Pst), that suppresses host immune responses by disrupting ER stress-mediated HR. PstCRT directly targets the HR-like lesion-inducing protein (TaHRLI) in wheat and obstructs its ER translocation. Within the ER lumen, TaHRLI interacts with wheat calreticulin (TaCRT), triggering Ca²⁺ efflux and activating the unfolded protein response (UPR) to induce cell death and disease resistance. Pathogen-derived PstCRT structurally mimics TaCRT to sequester TaHRLI to the plasma membrane via competitive interaction, thereby effectively suppressing ER stress-induced HR initiation. Crucially, we found that CRT secretion represents a conserved virulence strategy across different rust genera. AlphaFold-guided engineering of TaHRLI in wheat generated the TaHRLI^Mut variant that evades PstCRT recognition. Overexpressing TaHRLI^Mut in wheat conferred broad-spectrum resistance against Pst in biennial field trials, effectively mitigating pathogen-induced yield losses while preserving essential agronomic traits. Collectively, this study elucidates a molecular mechanism underlying pathogen disruption of ER stress-induced HR to promote infection and proposes an innovative strategy for engineering durable crop protection.