The Helicobacter heilmannii hofE and hofF Genes are Essential for Colonization of the Gastric Mucosa and Play a Role in IL-1β-Induced Gastric MUC13 Expression.

Abstract

Helicobacter heilmannii is a zoonotic bacterium associated with gastric disease in humans. We recently showed that H. heilmannii binds to human gastric mucins and epithelial cells and highlighted a potential role for the murine Muc13 mucin in gastric Helicobacter colonization. The aims of this study were to investigate the role of the H. heilmannii hof gene locus encoding HofH/F/E/G/C/D in adhesion to the gastric mucosa and induction of increased gastric Muc13 expression. Bacterial hof gene and host gene expression experiments, Helicobacter binding assays and experimental infection studies in mice were performed. H. pylori and its ΔhofF mutant were included for comparison. Helicobacter heilmannii strains lacking HofE or HofF showed a clear decrease in binding to gastric mucins and epithelial cells as well as a lower gastric colonization level in the stomach of Balb/c mice at 4 and 9 weeks post-infection compared to the H. heilmannii wildtype strain. Interestingly, H. heilmannii ΔhofE and ΔhofF and H. pylori ΔhofF did not induce an increased expression of MUC13 in human gastric epithelial cells and of Muc13 in the stomach of mice. Finally, we demonstrated that IL-1β is induced in the stomach as a response to Helicobacter colonization which on its turn is involved in the expression of MUC13/Muc13 in the gastric epithelium. These novel results in Helicobacter research identified H. heilmannii HofE and HofF as adhesins and suggest an important role of H. heilmannii HofE and HofF and H. pylori HofF in IL-1β-induced gastric MUC13/Muc13 expression.