Epithelial attachment alters the outcome of Helicobacter pylori infection

Abstract

Genetically defined in vivo models are needed to assess the importance of target cell attachment in bacterial pathogenesis. Gastric colonization by Helicobacter pylori in human populations is common and persistent, and has various outcomes including peptic ulcers and cancer. The impact of attachment on the course of infection was examined in transgenic mice expressing a human receptor for H. pylori in their gastric epithelium. Persistent infection by a clinical isolate occurred at comparable microbial densities in transgenic and nontransgenic littermates. However, microbial attachment in transgenic mice resulted in production of autoantibodies to Lewis x carbohydrate epitopes shared by bacteria and acid-secreting parietal cells, chronic gastritis, and parietal cell loss. This model should help identify bacterial and host genes that produce attachment-related pathology.

Impaired mucus-bicarbonate barrier inHelicobacter pylori-infected mice

“…Thus the presence of Le b in the host and BabA in the bacteria mediates adherence to the gastric epithelial lining and implies a supposedly more severe infection. Indeed, the ␣-1,3/4FT mice developed more severe gastritis when infected than their nontransgenic littermates and also develop autoantibodies against parietal cells (14). Gastric permeability was also increased in the infected mice, in conformity with findings in H. pylori-infected patients (11) and animals (34).…”

“…␣-1,3/4FT mice use human ␣-1,3/4FT to express Le b epitopes in their pit region and surface mucus cells (14). Le b is a blood group antigen that is recognized by an H. pylori adhesin, blood group antigen-binding adhesin (BabA) (19).…”

“…The strain has been shown to infect this line of mice under normal conditions (14). Isolates of Hp1 were cultured on Columbia II agar plates (BBL, Becton-Dickinson; Cockeysville, MD) with 10% horse serum and 8.5% denatured horse blood (chocolate agar) under microaerophilic conditions at 37°C.…”

Production of anti-Helicobacter pylori urease-specific immunoglobulin in egg yolk using an antigenic epitope of H. pylori urease

“…Development of a vaccine is the basic approach to H. pylori treatment, but efficacy data are still lacking in humans (Kusters, 2001). H. pylori is able to bind to several receptors at the surface of gastric epithelial cells (Guruge et al, 1998;Taylor et al, 1998); thus prevention of H. pylori binding to gastric epithelial cells could represent a potential target for H. pylori treatment. We previously reported that egg-yolk-derived immunoglobulin (IgY) obtained from hens that were immunized with H. pylori whole-cell lysate may provide a novel alternative approach to the treatment of H. pylori infection (Shin et al, 2002).…”

Glycosaminoglycan-binding microbial proteins in tissue adhesion and invasion: key events in microbial pathogenicity

“…These early observations, as well as the observation that GAG-like molecules and, possibly sulphated glycolipids bind to organisms grown in brain heart infusion broth encouraged a comparison of the influence of various media and culture conditions on expression of GAG binding. GAG-binding proteins of H. pylori were expressed optimally in GabCamp broth, unlike production of sialic acid-specific and other H. pylori HAS and Lewis-binding proteins which were expressed optimally on solid media such as GabCamp agar [50,51]. The opacity factor or Opa adhesin of N. gonorrhoeae was expressed when the bacteria were grown in polysaccharide-free medium [52].…”