LAUSR

Significance Plant nonhost resistance (NHR) prevents infection by all members of most microbial species, but its molecular mechanisms are not well understood. We found that effector proteins from the potato blight pathogen Phytophthora infestans, which enhance infection in host plants, fail to enhance susceptibility in nonhost Arabidopsis. These P. infestans effectors often failed to interact with Arabidopsis orthologs of their potato target proteins, whereas many interactions were detected between these Arabidopsis orthologs and effectors from its adapted pathogen Hyaloperonospora arabidopsidis. Thus, breakdown in effector–target interactions in distantly related nonhost plants is likely a key component of NHR. Importantly, we demonstrate that exploiting this breakdown and expressing nonhost target orthologs in host plants provide a strategy to prevent crop disease.