Dataset Information

Host Determinants of Expression of the Helicobacter pylori BabA Adhesin.

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. 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-/-, TLR2-/- and TLR4-/- mice that are defective in toll like receptor signaling. The presence of other bacteria had no effect on BabA expression as shown by infection of germ free mice. Moreover, loss of BabA expression was not dependent on Le^b expression or the capacity of BabA to bind Le^b. 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 not driven by adaptive immunity or toll-like receptor signaling, and that BabA may have other, unrecognized functions in addition to serving as an adhesin that binds Le^b.

SUBMITTER: Kable ME

PROVIDER: S-EPMC5394467 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Host Determinants of Expression of the Helicobacter pylori BabA Adhesin.

Kable Mary E ME Hansen Lori M LM Styer Cathy M CM Deck Samuel L SL Rakhimova Olena O Shevtsova Anna A Eaton Kathryn A KA Martin Miriam E ME Gideonsson Pär P Borén Thomas T Solnick Jay V JV

Scientific reports 20170418

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. 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-/-, TLR2-/- and TLR4-/- mice that are defective ...[more]

PMID: 28418004

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Project description:UNLABELLED:Helicobacter pylori undergoes rapid microevolution during chronic infection, but very little is known about how this affects host interaction factors. The best-studied adhesin of H. pylori is BabA, which mediates binding to the blood group antigen Lewis b [Le(b)]. To study the dynamics of Le(b) adherence during human infection, we analyzed paired H. pylori isolates obtained sequentially from chronically infected individuals. A complete loss or significant reduction of Le(b) binding was observed in strains from 5 out of 23 individuals, indicating that the Le(b) binding phenotype is quite stable during chronic human infection. Sequence comparisons of babA identified differences due to mutation and/or recombination in 12 out of 16 strain pairs analyzed. Most amino acid changes were found in the putative N-terminal extracellular adhesion domain. One strain pair that had changed from a Le(b) binding to a nonbinding phenotype was used to study the role of distinct sequence changes in Le(b) binding. By transformations of the nonbinding strain with a babA gene amplified from the binding strain, H. pylori strains with mosaic babA genes were generated. Recombinants were enriched for a gain of Le(b) binding by biopanning or for BabA expression on the bacterial surface by pulldown assay. With this approach, we identified several amino acid residues affecting the strength of Le(b) binding. Additionally, the data showed that the C terminus of BabA, which is predicted to encode an outer membrane ?-barrel domain, plays an essential role in the biogenesis of this protein. IMPORTANCE:Helicobacter pylori causes a chronic infection of the human stomach that can lead to ulcers and cancer. The bacterium can bind to gastric epithelial cells with specialized outer membrane proteins. The best-studied protein is the BabA adhesin which binds to the Lewis b blood group antigen. Since H. pylori is a bacterium with very high genetic variability, we asked whether babA evolves during chronic infection and how mutations or recombination in babA affect binding. We found that BabA-mediated adherence was stable in most individuals but observed a complete loss of binding or reduced binding in 22% of individuals. One strain pair in which binding was lost was used to generate babA sequences that were mosaics of a functional allele and a nonfunctional allele, and the mosaic sequences were used to identify amino acids critically involved in binding of BabA to Lewis b.

Dataset Information

Host Determinants of Expression of the Helicobacter pylori BabA Adhesin.

Publications

Host Determinants of Expression of the Helicobacter pylori BabA Adhesin.

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