Phytophthora infestans RXLR Effectors Target Parallel Steps in an Immune Signal Transduction Pathway

The potato (Solanum tuberosum) blight pathogen Phytophthora infestans delivers Arg-X-Leu-Arg (RXLR) effector proteins into host cells to subvert plant immune responses and promote colonization. We show that transient expression and stable transgenic expression of the RXLR effector Pi22926 in Nicotiana benthamiana promotes leaf colonization by P. infestans. Pi22926 suppresses cell death triggered by coexpression of the Cladosporium fulvum avirulence protein Avr4 and the tomato (Solanum lycopersicum) resistance protein Cf4. Pi22926 interacts with a potato mitogen-activated protein kinase kinase kinase, StMAP3K beta 2, in the nucleoplasm. Virus-induced gene silencing (VIGS) of the ortholog NbMAP3K beta 2 in N. benthamiana enhances P. infestans colonization and attenuates Cf4/Avr4-induced cell death, indicating that this host protein is a positive regulator of immunity. Cell death induced by Cf4/ Avr4 is dependent on NbMAP3K epsilon and NbMAP3K beta 2, indicating that these MAP3Ks function in the same signaling pathway. VIGS of NbMAP3K beta 2 does not compromise cell death triggered by overexpression of MAP3K epsilon. Similarly, VIGS of NbMAP3K epsilon does not attenuate cell death triggered by MAP3K beta 2, demonstrating that these MAP3K proteins function in parallel. In agreement, Pi22926 or another RXLR effector, PexRD2, only suppresses cell death triggered by expression of StMAP3K beta 2 or StMAP3K epsilon, respectively. Our data reveal that two P. infestans effectors, PexRD2 and Pi22926, promote P. infestans colonization by targeting MAP3K proteins that act in parallel in the same signal transduction pathway.