Caenorhabditis elegans avoids epigallocatechin gallate (EGCG) through SRXA-7 G-protein coupled receptor

Flavonoids are plant-derived polyphenols that influence nematode behavior, yet their neuronal and molecular targets remain poorly understood. Here, we show that the free-living nematode Caenorhabditis elegans detects and avoids a green tea catechin epigallocatechin gallate (EGCG) via the SRXA-7 Gprotein coupled receptor (GPCR) in the ASH nociceptive neurons. EGCG and epicatechin gallate (ECG), both containing a galloyl group, trigger strong avoidance, unlike other green tea catechins lacking this moiety. EGCG avoidance behavior displays species- and strain-specific differences among Caenorhabditis species and wild C. elegans isolates. Moreover, it is dynamically modulated by prior experience and feeding state. The ASH chemosensory neurons are required for EGCG detection, with avoidance mediated through canonical GPCR signaling components including GRK-2, GPA-3, ODR-3, and TRPV channels OCR-2 and OSM-9. A targeted GPCR screen revealed that srxa-7 mutants exhibited specific defects in EGCG avoidance. EGCG-evoked calcium responses in ASH are reduced in srxa-7 mutants and restored by ASH-specific expression of srxa-7 cDNA. These findings indicate that SRXA-7 is a sensory receptor for galloylated polyphenols, uncovering the neuronal and molecular basis of adaptive aversive responses to dietary plant compounds in nematodes. [BMB Reports 2026; 59(8): 384-390].