Research Highlights

Bacterial infection: Short and sweet

Sialyl Lewis X structure. Click here for a key to the symbols.

Infection by Helicobacter pylori is a prime cause of gastric cancer; however, despite H. pylori prevalence being high, the number of infected people developing this cancer is low. This is because genetic preconditions, the diet, and bacterial virulence factors have been shown to play a role in gastric cancerogenesis. Among the virulence factors is the cytotoxin-associated gene pathogenicity island (cagPAI) which is present in the genome of only a small subgroup of high-pathogenicity H. pylori (high-Hp) strains. The cagPAI encodes a secretion system that directly interferes with host cell metabolism via the CagA and CagE proteins. Cancer is also more likely to develop when changes in host cell surface glycosylation occur during a persistent H. pylori infection. At the chronic stage of infection gastric cell surface glycolipids carry short sialyl-Lewis X (sLeX) tetrasaccharides that act as ligands for the adhesion of sialic acid-binding H. pylori. Research by Marcos et al. published in the Journal of Clinical Investigation now shows a mechanism by which high-Hp infection induces the expression of sLeX.

Marcos et al. compared gastric cell gene expression profiles and found that the expression of genes promoting inflammatory and immune responses — such as the tumor necrosis factor- (TNF-) — was significantly increased with high-Hp infection but not with low-pathogenicity H. pylori. Importantly, when Marcos et al. used the Consortium for Functional Glycomics (CFG) microarray to screen glycogene expression, they found that high-Hp infection also altered glycosyltransferase transcription in gastric cells. The N-acetylglucosamine transferase 3GnT5, which initiates the synthesis of sLeX glycans, was upregulated, whereas the glycosyltransferase iGnT, which elongates glycolipid glycans by polylactosamines, was downregulated.

Next, Marcos et al. observed that incubating gastric cells with TNF- enhanced 3GnT5 expression. The final link between infection and glycan changes was discovered by bacterial mutant screening — only H. pylori strains expressing both CagA and CagE increased 3GnT5 expression in infected host cells. These findings indicate that infection by high-Hp strains facilitates bacterial attachment by changing the gastric cell surface glycans, which promotes persistent infection and bacterial access to host cell metabolites. This study reveals a novel aspect of the H. pylori–host cell interaction that could potentially be used as a target for antibacterial drug development.

Author: Mirko von Elstermann