Enterohemorrhagic Escherichia coli Targets Annexin A6 and ATG16L1 to Inhibit Autophagy and Induce Inflammation

Here, we reveal how EHEC’s effector EspF collaborates with host Annexin A6 (ANXA6) to suppress autophagy and drive inflammation. CRISPR/Cas9-mediated ANXA6 knockout in intestinal epithelial cells reversed EHEC-induced autophagic inhibition, as evidenced by elevated LC3B-II levels and reduced p62 accumulation.

Mechanistically, EspF stabilizes ANXA6 to disrupt PI3K/mTOR signaling and impair autophagosome formation, whereas ANXA6 suppresses the expression of ATG16L1, a key autophagy regulator. EHEC infection triggered IL-1β hypersecretion in macrophages, which was coupled with NF-κB pathway hyperactivation via IκBα/p65 phosphorylation. In vivo, EHEC infection upregulated intestinal ANXA6 expression, correlating with mucosal inflammation and barrier dysfunction.