A report in Science presents evidence that the functional adaptation of a bacterial adhesin in response to changes in the predominant blood groups in the local human population contributes to the success of Helicobacter pylori as a gastric pathogen.

H. pylori persistently colonizes the gastric mucosa, and is present in more than 50% of the global population. H. pylori infection is a risk factor for the development of gastritis, peptic ulcers and gastric adenocarcinoma. Several H. pylori adhesins have been identified that help the bacterium stick to the surface of gastric epithelial cells. Now, researchers from the United States and Sweden have undertaken a large-scale study of the variations in binding of one particular adhesin, BabA.

In humans, a combination of cell-surface protein, glycoprotein and glycolipid antigens determines an individual's blood type, with two of the most common systems being the ABO and Lewis antigens, which are highly expressed in the gastric epithelium. Previously, H. pylori BabA had been shown to bind to the H antigen and its associated Lewis antigen, Lewis b (Leb), which correspond to blood group O.

Initially, Aspholm-Hurtig et al. studied variation in Lewis antigen binding capacity in a small group of H. pylori strains and found that the strains tested fell into two distinct categories — generalists, which bind blood group A, B and O Lewis antigens, and specialists, which only bind Leb, the blood group O Lewis antigen. When the analysis was extended to 377 different H. pylori isolates from a variety of geographical locations the authors noticed that geography seemed to influence binding: 95% of isolates from Sweden, Germany, Spain, Japan and Alaska were generalists, whereas 40% of Amerindian isolates examined (from Peru, Venezuela and Columbia) were specialists. The preponderance of specialists in the South American isolates examined is in line with the fact that, unusually, the Amerindian populations in this region are almost all blood group O.

The affinity of BabA for Leb is higher than it is for the other Lewis antigens, and the authors speculate this could increase the strength of binding of H. pylori to the gastric epithelium in individuals who are blood group O. There is no further differentiation in affinity for Leb between specialists and generalists however, indicating that for generalists, the key to successful long-term survival within a host population is a flexible binding capacity.

Evolutionary analysis revealed that BabA has been subject to heterogeneous selection pressure, as well as evidence for diversifying selection for amino acid changes. The authors conclude this study by proposing that the binding specificity of BabA can evolve rapidly during cycles of selection for adherence during infection and transmission, and this rapid adaptation of BabA has contributed to the success of H. pylori as a pathogen.