Salicylic acid biosynthesis (isochorismate route) and NPR1-dependent defence signalling

After pathogen attack Arabidopsis makes most of its salicylic acid (SA) from chorismate through isochorismate. In the chloroplast stroma, isochorismate synthase 1 (ICS1, also SID2/EDS16) isomerizes chorismate to isochorismate; this is the committed, pathogen-induced step, and its paralog ICS2 contributes little. The MATE transporter EDS5 exports isochorismate to the cytosol, where the GH3 amidotransferase PBS3 conjugates it with glutamate to isochorismate-9-glutamate, which decomposes, spontaneously or with the help of the acyltransferase EPS1, into SA. SA is perceived by the NPR protein family: the paralogs NPR3 and NPR4 bind SA with high affinity and act as CUL3-ligase adaptors that control NPR1 turnover, while NPR1 itself has been reported to bind SA more weakly, although the relative roles of NPR1 and NPR3/NPR4 as SA receptors are debated. SA-induced changes in cellular redox reduce cytoplasmic NPR1 oligomers to monomers that enter the nucleus, where NPR1 acts as a transcription coregulator. Sumoylated NPR1 switches from WRKY repressors to TGA transcription factors and activates defence genes such as PR1, and NPR1 directly induces a set of WRKY transcription factor genes. One of these, WRKY70, is a sequence-specific transcription factor that promotes SA-induced pathogenesis-related gene expression, represses jasmonate-responsive genes and, together with WRKY54, restrains SA biosynthesis, forming a negative feedback loop. Together these steps drive local resistance and systemic acquired resistance (SAR) against biotrophic pathogens.

Boundary. The module runs from chorismate in the plastid to NPR1-dependent transcription of SA defence genes, including the NPR1-induced transcription factor WRKY70. It ends at transcription of pathogenesis-related genes; the antimicrobial activities of PR proteins, SA catabolism and conjugation (SA glucosides, methyl salicylate, 2,3- and 2,5-DHBA), and the N-hydroxypipecolic acid (NHP) branch of systemic acquired resistance (ALD1, SARD4, FMO1) are outside it. The phenylalanine ammonia-lyase route to SA, which supplies a minor share of pathogen-induced SA in Arabidopsis, is not modelled. SA-JA antagonism is recorded only as the WRKY70 repression of JA-responsive genes; the jasmonate pathway itself is MODULE:jasmonate_coi1_jaz_signaling. EDS1 and PAD4 are upstream inputs, not parts. EDS1 and PAD4 are required for pathogen-induced SA accumulation and amplify SA-dependent defence (PMID:11574472), and both gene reviews give GO:0009862 among their core processes. They do not catalyse any SA biosynthetic step and are not part of NPR1-dependent transcription: they act upstream, as the ligand-responsive EDS1-PAD4 adaptor complex that receives TIR-NLR-derived nucleotide signals and promotes ICS1 expression and SA accumulation. That activity (signaling adaptor activity, GO:0035591, the core molecular function in both gene reviews) is already modelled as the EDS1-PAD4-ADR1 variant of part 3 of MODULE:plant_nlr_resistosome_signaling (annoton eds1_pad4_receptor). Repeating it here would duplicate that annoton, so the link is recorded in prose; EDS1-PAD4 feeds this module at the level of ICS1 induction. Their transcriptional route to ICS1 (via SARD1 and CBP60g) is not modelled because those regulators have no gene reviews here. RPM1 and RPS2 are NLR receptors whose activation leads to SA accumulation; they belong to effector-triggered immunity (MODULE:plant_nlr_resistosome_signaling) and are not parts here. FLS2, EFR and other surface pattern recognition receptors also induce SA; their early signalling is a separate pattern-triggered immunity module (FLS2/EFR-BAK1), not part of this one. Biosynthesis steps without gene reviews. EDS5 (isochorismate export), PBS3 (isochorismate-9-glutamate synthesis) and EPS1 (acceleration of IC-9-Glu breakdown) are established pathway members (PMID:31371615) but have no gene reviews in this repository, so they are named in the description and the biosynthesis part description, not grounded as annotons. Isochorismate also feeds phylloquinone biosynthesis (ICS1 review second core function), which is outside this module. SA perception. NPR3 and NPR4 bind SA with high affinity and act as CUL3 E3-ligase adaptors controlling NPR1 turnover (PMID:22699612); NPR1 binds SA comparatively weakly in the assays of PMID:32788727, although reported NPR1 SA-binding affinities vary between studies and the competing model in which NPR1 is the principal SA receptor (with NPR3/NPR4 as co-repressors) is still argued in the field. The module therefore treats SA perception as unresolved between NPR1 and NPR3/NPR4, and the NPR1 review does not assert SA binding or receptor activity for NPR1. NPR3/NPR4 and the TGA transcription factors (TGA2, TGA3, TGA5, TGA6) have no gene reviews here, so the SA-perception step and the TGA partners are named in prose and the NPR1 annoton carries only the transcription coregulator activity from its review. WRKY70. WRKY70 is placed downstream of NPR1: its full SA induction needs NPR1, epistasis puts it downstream of NPR1, and NPR1 directly induces WRKY genes. The WRKY70 review asserts DNA-binding transcription factor activity with positive regulation of SA-mediated signalling as its core process. Saleh et al. 2015 instead describe WRKY70 as a transcriptional repressor that unmodified NPR1 associates with. PMID:17096590 reports a dual role for WRKY70 and WRKY54: wrky70 and wrky54 wrky70 mutants over-accumulate ICS1 transcript and SA without constitutive PR gene expression, so WRKY70 represses SA biosynthesis while positively transducing the SA signal. This is recorded as a negative-regulation connection from the WRKY70 step back to the ICS1 step. The dual-role finding partly reconciles the activator and repressor framings, but the direct targets remain undefined (see knowledge gaps). Grounding. Gene reviews ground ICS1, NPR1 and WRKY70 (ARATH); EDS1 and PAD4 are cited in notes. No PANTHER family ids are asserted. No production GO-CAM in gocams/index.tsv contains these proteins. Curation follow-ups (not knowledge gaps). Review EDS5, PBS3, EPS1, NPR3, NPR4, TGA2/TGA3, SARD1 and CBP60g, then add them as members (biosynthesis steps 2-3, the SA-perception step, the TGA partners of NPR1, and the transcriptional induction of ICS1). A separate NHP biosynthesis module (ALD1, SARD4, FMO1) would complete systemic acquired resistance.