Effect of co-culture with ETBF in NOZ cell line on gene expreesion difference

Enterotoxigenic bacteroides fragilis (ETBF), a strain of B.fragilis is enriched in gallbladder cancer (GBC), but its causative role and translational implications in GBC remain unclear. Here, we demonstrate that ETBF promotes GBC cell proliferation and metastasis both in vitro and in vivo. Mechanistically, ETBF adheres to GBC cells through its surface protein, Membrane-bound lytic murein transglycosylase D precursor (MltD precursor), which binds to the TMPRSS13 receptor on GBC cells, leading to the activation of JAK2-STAT3 signaling pathway. Blockade of the MltD precursor-TMPRSS13 interaction abolishes ETBF-driven protumorigenic effects and JAK2 and STAT3 phosphorylation. Additionally, ETBF secretes the metalloprotease, B. fragilis toxin-1 (BFT-1), which accelerates GBC progression via activating NF-κB signaling to increase secretion of the cytokine CXCL1 and recruit myeloid-derived suppressor cells (MDSCs) into tumors for angiogenesis. Collectively, our study elucidates an oncogenic mechanism driven by ETBF and identifies that the MltD precursor-TMPRSS13 interaction as a potential therapeutic target for GBC.