Science, published online 18 October 2012; doi:10.1126/science.1226743

Effector-triggered immunity (ETI) in plants is initiated when pathogens produce effector molecules that target the plant's defense pathways and the plant responds with resistance proteins (R-proteins) that 'guard' the target from the effector. However, in the case of Cochliobolus victoriae, a fungus that infects Arabidopsis thaliana, the small-molecule effector victorin collaborates with an R-protein to enhance rather than reduce susceptibility to infection. Previous studies had shown that thioredoxin TRX-h5 and the R-protein LOV1 are required for victorin-mediated susceptibility. Lorang et al. now show that victorin acts by covalently modifying TRX-h5 to hijack ETI. Mutational analysis and MS revealed that Cys39 of TRX-h5, a residue previously linked to LOV1 activation, becomes modified with the natural product in victorin-treated Arabidopsis. Victorin modification inhibited TRX-h5 activity and dampened plant defense gene activation mediated by one of its substrates, the NPR1 transcription factor. In contrast, LOV1 activation was dependent on the presence of TRX-h5 and victorin, and imaging and yeast two-hybrid experiments confirmed a physical interaction between LOV1 and TRX-h5 in the plasma membrane. Together, these data may support a general pathway in which an R-protein, tasked with guarding a particular defense protein, can be redirected by effectors to aid pathogenic infection.