H. pylori bacteria infect the gastric mucosa and can lead to cancer. They show increasing resistance to antibiotics, but BabA and SabA proteins may be able to step in as potential components of a gastric cancer vaccine.
Helicobacter pylori infects the gastric mucosa of more than half of all people worldwide, and infection with these bacteria is an early risk factor for gastric cancer. Both H. pylori and the host inflammatory response that it elicits are believed to contribute to tumorigenesis, but this interaction is not well understood. Ironically, according to Thomas Borén and colleagues, this antibacterial inflammatory response promotes gastric-cell synthesis of sialylated glycoconjugates, which the bacteria exploit for adherence to the surface epithelium.
In Science, Borén's group reported that epithelial cells of inflamed gastric mucosa have sialylated glycosphingolipids (GSLs) on their surface, and they isolated a repetitive sialyl-di-Lewis x GSL (sLex/a) from human adenocarcinoma cells. The authors showed that H. pylori expresses an adhesin protein called sialic-acid-binding adhesin (SabA), which binds to sLex/a antigens and allows the bacteria to cling to the surface of the gastric cell. Interestingly, sLex/a was previously identified as a tumour antigen and a marker of gastric dysplasia. Boren's group showed that H. pylori infection causes formation of sLex/a antigens on the surface of human and monkey gastric epithelial cells.
SabA is not the only binding molecule that H. pylori possesses. Borén and colleagues previously showed that another bacterial adhesin protein, BabA, promotes attachment to the Lewis B (Leb) molecule on the gastric-cell surface. But bacteria could still adhere to these cells after the babA gene was deleted, so the sLex–SabA interaction is likely to be an important component of tumorigenesis.
So, what are the advantages of these adhesin proteins? They allow H. pylori strains to bind to gastric epithelial cells and they also protect the bacteria from being shed into the gastric lumen. The ability of these bacteria to cling tightly to gastric mucosal cells also ensures their access to the nourishing exudate from gastric epithelium that is damaged by the infection. Their persistence in the gastric mucosa causes the host inflammatory response to be maintained.
This study not only sheds new light on the mechanism that allows H. pylori to take advantage of the host inflammatory response, but also opens the possibility of more effective treatment for H. pylori infection. These bacteria have developed increasing resistance to antibiotics, so the BabA and SabA proteins might be useful components of a gastric cancer vaccine.
Kristine Novak
References
Mahdavi, J. et al. Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation. Science297, 573–578 (2002) | PubMed |
Peek, R. M. & Blaser, M. Helicobacter pylori and gastrointestinal tract adenocarcinomas. Nature Rev. Cancer2, 28–37 (2002) | Article | PubMed |
