Life at the margins: modulation of attachment proteins in Helicobacter pylori

Abstract

Helicobacter pylori is the primary cause of peptic ulcer disease and is estimated to account for about 60% of all cases of gastric cancer, the second most common cause of cancer death worldwide. Among the H. pylori virulence factors associated with disease, in addition to the well-known cag pathogenicity island, is the BabA adhesin, an outer membrane protein that binds with high affinity to fucosylated glycans on the gastric epithelium, such as Lewis B (Le(b)) and related terminal fucose residues found on the blood group O (H antigen), A and B antigens. BabA-mediated attachment to the gastric mucosa promotes chronic inflammation and gastric pathology, which from the bacterial perspective carries both risks and benefits. We recently described modulation in expression of BabA and related outer membrane proteins that occurs during colonization of experimental animals. Here we put these findings into a broader context, and speculate on their implications for the host-pathogen relationship.

Figure 1

Schematic diagram of the ecology of H. pylori. As H. pylori moves through the mucus layer toward the epithelial surface, it encounters a gradient of decreased acid and increased nutrients, which promote viability and bacterial cell growth. A proportion of bacterial cells attach to the epithelium via BabA, SabA and probably other adhesins that bind their cognate glycan receptors. Attachment to the epithelium permits injection of the CagA oncoprotein via the type IV secretion system (T4SS), disruption of cell signalling and polarity and loss of tight junctions. These inflammatory changes further increase nutrient availability but at the cost of encountering toxic reactive oxygen species. Epithelial cells and the mucus layer are continuously shed into the lumen, carrying attached H. pylori cells, which will be lost into the lumen and expelled unless binding is inhibited. Modulation of attachment proteins gives H. pylori the flexibility to regulate its exposure to these “physicochemical facts of life”, and promote chronic infection.