Location: Immunity and Disease Prevention ResearchTitle: Host determinants of expression of the helicobacter pylori BabA adhesin
|HANSEN, LORI - University Of California|
|STYER, CATHY - University Of California|
|GIDEONSSON, PAR - University Of Umea|
|DECK, SAMUEL - University Of California|
|SHEVTSOVA, ANNA - University Of Umea|
|RAKHIMOVA, OLENA - University Of Umea|
|EATON, KATHRYN - University Of Michigan Medical School|
|MARTIN, MIRIAM - University Of California|
|BOREN, THOMAS - University Of Umea|
|SOLNICK, JAY - University Of California|
Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/17/2017
Publication Date: 4/18/2017
Citation: Kable, M.E., Hansen, L.M., Styer, C.M., Gideonsson, P., Deck, S.L., Shevtsova, A., Rakhimova, O., Eaton, K.A., Martin, M.E., Boren, T., Solnick, J.V. 2017. Host determinants of expression of the helicobacter pylori BabA adhesin. Scientific Reports. 7:46499.
Interpretive Summary: Helicobacter pylori infects about half of the world’s population and is known to cause peptic ulcer and gastric cancer. However, only about 10% of individuals who are infected develop disease. Individual diet, genetics and expression of certain bacterial proteins (virulence factors) have all been implicated in tipping the scales toward disease for certain people. The BabA protein is one of several bacterial proteins that is found more commonly in H. pylori strains associated with disease. This protein is expressed on the outer membrane of the bacteria and facilitates attachment to the Lewis B glycan within the mucosal lining of the stomach. Because of the correlational relationship between BabA and disease, we examined how BabA expression might be impacted by various host responses to infection. We found that the aspects of the host stomach environment that are most typically expected to influence bacterial infection had no impact on selecting against expression of BabA. These included elements of the host innate (TLR) and adaptive (B and T lymphocyte) immune responses and the presence of other bacteria in the stomach. Instead host gender had the greatest impact on expression of BabA. Male mice were colonized with higher numbers of H. pylori bacteria in general and significantly more BabA expressing H. pylori than female mice. Interestingly, BabA did not need to be functional for bacterial loss of BabA expression to take place. These results are surprising and highly relevant for individuals interested in the control, treatment and infection dynamics of mucosal pathogens.
Technical Abstract: Expression of the Helicobacter pylori blood group antigen binding adhesin A (BabA) is more common in strains isolated from patients with peptic ulcer disease or gastric cancer, rather than asymptomatic colonization. BabA is highly polymorphic genetically and functionally among different clinical isolates. In animal models, expression of BabA is often lost by gene conversion or phase variation early during experimental infection. Here we used mouse models to examine host determinants that affect H. pylori BabA expression. BabA expression was lost by phase variation as frequently in WT mice as in RAG2-/- mice that do not have functional B or T cells, and in MyD88-/- mice that are defective in toll like receptor signaling. Moreover, loss of BabA expression was not dependent on Leb expression or the capacity of BabA to bind Leb. Surprisingly, gender was the host determinant most associated with loss of BabA expression, which was maintained to a greater extent in male mice and was associated with greater bacterial load. These results suggest the possibility that loss of BabA expression is unrelated to the host immune response, and that BabA may have other, unrecognized functions in addition to serving as an adhesin that binds Leb.