Classic and current views of plant-microbe interactions. (a) The 'gene-for-gene' model proposed by HH Flor in 1946 is illustrated by the interaction of P. syringae AvrPtoB and tomato Pto, which is guarded by the resistance (R) gene Prf. A plant cultivar expressing a given R gene is resistant to a pathogen strain delivering a cognate avirulence (Avr) gene. This host-pathogen incompatibility is typically accompanied by the hypersensitive response (HR). If either component of the Avr/R gene pair is missing, the plant-microbe interaction becomes compatible and disease occurs. (b) The 'zigzag' model proposed by Jonathan Jones and Jeffery Dangl in 2006. The perception of PAMPs (for example, flg22) by a cognate pattern recognition receptor (for example, FLS2) mediates PAMP-triggered immunity (PTI). Pathogens secrete effectors (for example, AvrPtoB N-ter) that suppress PAMP signaling and PAMP-triggered immunity, and thus confer disease in the absence of R protein activation. In resistant tomato plants, Prf recognizes AvrPtoB N-ter via Fen and induces a reinforcement of defense termed effector-triggered immunity (ETI). To counteract this, P. syringae has acquired a new function for AvrPtoB by the addition of a carboxy-terminal E3 ligase domain that targets Fen for degradation. In turn, tomato plants have evolved Pto that resists AvrPtoB-mediated degradation and triggers strong ETI involving the HR. Compared with the gene-for-gene relationship, this model integrates the multilayered/stacked plant immune responses of different amplitudes and highlights the constant evolutionary adaptation in plant-microbe interactions. Components of plant immunity are shown in green, pathogen-derived molecules are depicted in red.