Host Cell Contact Induces Fur‐dependent Expression of Virulence Factors CagA and VacA in Helicobacter pylori

Abstract Background Helicobacter pylori , a gram negative bacterium, colonizes the stomach in a majority of the world population. The two major virulence factors of H. pylori V ac A and C ag A , thought to be associated with chronic inflammation and disease, have been extensively studied, but the regulation of the expression of these virulence genes in H. pylori remains poorly understood. Methods qRT ‐PCR was performed to quantify gene expression in unadhered and AGS ‐adhered H. pylori . Δ fur mutant was constructed by splicing by overlap extension PCR and allelic exchange. Results Adherence of H. pylori to the gastric epithelial cell line AGS strongly induces the expression of both cagA and vacA . Induction of cagA and vacA in the AGS cell‐adhered H. pylori Δ fur mutant strain was consistently lower than in the adhered parent strain. However, expression of the genes was similar between the wild‐type and Δ fur mutant strains in the unadhered state, suggesting that F ur has a role in the upregulation of cagA and vacA expression, especially in AGS ‐adhered H. pylori . Consistent with these results, microscopic observations revealed that infection of AGS cells with H. pylori Δ fur mutant strain produced much less damage as compared to that produced by the wild‐type H. pylori strain. Conclusions These results suggested that cagA and vacA gene expression is upregulated in H. pylori, especially by host cell contact, and F ur has a role in the upregulation.