New Insight into the Molecular Mechanism of the FUT2 Regulating Escherichia coli F18 Resistance in Weaned Piglets

Escherichia coli (E. coli) F18 is the main pathogen responsible for post-weaning diarrhea (PWD) in piglets. Resistance to E. coli F18 depends on the expression of the cognate receptors in the intestinal epithelial cells. However, the molecular mechanism of E. coli F18 resistance in weaned piglets remains unclear. Here, we performed a comparative transcriptome study of the duodenal tissue from Sutai E. coli F18 sensitive and resistant pigs by RNA-seq, and pig α(1,2) fucosyltransferase 2 (FUT2) was identified as a host differentially expressed gene controlling the E. coli F18 infection. Function analysis showed that the FUT2 expression was high in the duodenum and jejunum, with higher levels detected in sensitive individuals than in resistant individuals (p < 0.01). Expression levels of FUT2 were upregulated in IPEC-J2 cells after lipopolysaccharide (LPS)-induction or E. coli stimulation. FUT2 knockdown decreased the adhesion of E. coli F18 to IPEC-J2 cells (p < 0.05). FUT2 overexpression markedly increased the adhesion of E. coli F18 to IPEC-J2 cells (p < 0.05 or p < 0.01). Furthermore, the FUT2 mRNA levels correlated with methylation levels of the mC-22 site in the specificity protein 1 (Sp1) transcription factor (p < 0.05). Electrophoretic mobility shift assays (EMSA) showed that Sp1 interacts with the wild-type FUT2 promoter DNA, but not with methylated DNA. Our data suggested that FUT2 methylation at the mC-22 site inhibits Sp1 binding to the FUT2 promoter, thereby reducing FUT2 expression and enhancing E. coli F18 resistance in weaned piglets. These observations highlight FUT2 as a promising new target for combating E. coli F18 susceptibility in weaned piglets.