METTL3 enhances E. coli F18 resistance by targeting IKBKG/NF-κB signaling via an m⁶A-YTHDF1–dependent manner in IPEC-J2 cells

Post-weaning diarrhea caused by enterotoxigenic E. coli F18 introduces enormous losses to the porcine industry. N⁶-methyladenosine (m⁶A) is a ubiquitous epitranscriptomic biomarker that modulates host cell resistance to pathogen infection, however, its significance in E. coli F18-treated IPEC-J2 cells remains unexplored. Herein, we revealed that m⁶A and associated modulators strongly controlled E. coli F18 susceptibility. The data indicated an enhancement of METTL3 contents in E. coli F18-treated IPEC-J2 cells. METTL3 is known to be a major modulator of E. coli F18 adhesion within IPEC-J2 cells. As expected, METTL3 deficiency was observed to reduce m⁶A content at the IKBKG 5′-UTR, leading to critical suppression of YTHDF1-dependent IKBKG translation. Therefore, the activation of the NF-κB axis was observed, which enhanced IPEC-J2 resistance to E. coli F18 infection. Taken together, these findings uncover a potential mechanism underlying the m⁶A-mediated control of E. coli F18 susceptibility. This information may contribute to the establishment of new approaches for combating bacteria-induced diarrhea in piglets.