For more than 200 years, the plant hormone salicylic acid (SA) has been studied for its medicinal use in humans. However, its extensive signaling role in plants, particularly in defense against pathogens, has only become evident during the past 20 years. This review surveys how SA in plants regulates both local disease resistance mechanisms, including host cell death and defense gene expression, and systemic acquired resistance (SAR). Genetic studies reveal an increasingly complex network of proteins required for SA-mediated defense signaling, and this process is amplified by several regulatory feedback loops. The interaction between the SA signaling pathway and those regulated by other plant hormones and/or defense signals is also discussed.

Summary: Systemic immunity triggered by local plant–microbe interactions is studied as systemic acquired resistance (SAR) or induced systemic resistance (ISR) depending on the site of induction and the lifestyle of the inducing microorganism. SAR is induced by pathogens interacting with leaves, whereas ISR is induced by beneficial microbes interacting with roots. Although salicylic acid (SA) is a central component of SAR, additional signals exclusively promote systemic and not local immunity. These signals cooperate in SAR‐ and possibly also ISR‐associated signaling networks that regulate systemic immunity. The non‐SA SAR pathway is driven by pipecolic acid or its presumed bioactive derivative N‐hydroxy‐pipecolic acid. This pathway further regulates inter‐plant defense propagation through volatile organic compounds that are emitted by SAR‐induced plants and recognized as defense cues by neighboring plants. Both SAR and ISR influence phytohormone crosstalk towards enhanced defense against pathogens, which at the same time affects the composition of the plant microbiome. This potentially leads to further changes in plant defense, plant–microbe, and plant–plant interactions. Therefore, we propose that such inter‐organismic interactions could be combined in potentially highly effective plant protection strategies.

Infection of Arabidopsis thaliana with avirulent Pseudomonas syringae induces camphene and α- and β-pinene emissions contributing to systemic resistance inducti

• Enhanced Disease Susceptibility1 (EDS1) is an important regulator of plant basal and receptor‐triggered immunity. Arabidopsis EDS1 interacts with two related proteins, Phytoalexin Deficient4 (PAD4) and Senescence Associated Gene101 (SAG101), whose combined activities are essential for defense signaling. The different sizes and intracellular distributions of EDS1–PAD4 and EDS1–SAG101 complexes in Arabidopsis leaf tissues suggest that they perform nonredundant functions. • The nature and biological relevance of EDS1 interactions with PAD4 and SAG101 were explored using yeast three‐hybrid assays, in vitro analysis of recombinant proteins purified from Escherichia coli, and characterization of Arabidopsis transgenic plants expressing an eds1 mutant (eds1^L262P) protein which no longer binds PAD4 but retains interaction with SAG101. • EDS1 forms molecularly distinct complexes with PAD4 or SAG101 without additional plant factors. Loss of interaction with EDS1 reduces PAD4 post‐transcriptional accumulation, consistent with the EDS1 physical association stabilizing PAD4. The dissociated forms of EDS1 and PAD4 are fully competent in signaling receptor‐triggered localized cell death at infection foci. By contrast, an EDS1–PAD4 complex is necessary for basal resistance involving transcriptional up‐regulation of PAD4 itself and mobilization of salicylic acid defenses. • Different EDS1 and PAD4 molecular configurations have distinct and separable functions in the plant innate immune response.