Essential role of urease in pathogenesis of gastritis induced by Helicobacter pylori in gnotobiotic piglets

Abstract

A mutant strain of Helicobacter pyloni with weak urease activity was created by using N-methyl-N'-nitro-N-nitrosoguanidine. The urease activity of the mutant (0.036 0.009 nmol of urea per ,ug of bacterial protein per min) was 0.4% of that of the parental strain (8.20 ± 2.30 nmol of urea per ,ug of bacterial protein per min). The mutant was otherwise indistinguishable from the parental strain. Both demonstrated prominent catalase and oxidase activities, and both produced vacuolating cytotoxin. Restriction endonuclease and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) patterns and ultrastructure were identical for the two strains. The mutant was fully motile, as evaluated by spreading in soft agar and by direct microscopic examination. Growth rate and colony size and morphology were identical for the mutant and parental strains. Seventeen gnotobiotic piglets were challenged with either the mutant or the parental strain and sacrificed 3 or 21 days after challenge. Gastric tissue was examined histologically and cultured for H. pyloni. Of seven piglets challenged with the parental strain, all became infected. H. pylori was not recovered from any of 10 piglets challenged with the urease-negative strain. Lymphofollicular gastritis was present in all seven piglets challenged with the parental strain but in none of the piglets challenged with the urease-negative strain. These results suggest that prominent urease activity is essential for colonization by H. pylori.

Toll‐like Receptor 2‐Mediated Gene Expression in Epithelial Cells During Helicobacter pylori Infection

“…The H. pylori strain 26695 (CagA + and VacA +), obtained from Dr Kathryn Eaton [17], was grown for 2 days on sheep blood agar plates (Remel, Lenexa, KS) in a humidified incubator with 10% CO 2 at 37 °C. One plate of bacteria was harvested with a sterile cotton swab and resuspended in phosphate-buffered saline (PBS) solution.…”

Characteristics of a Clinical Isolate of Urease‐Negative Helicobacter pylori and its Ability to Induce Gastric Ulcers in Mongolian Gerbils

“…Facts suggest that the enzyme plays a major role in the ability of the organism to colonize the acidic environment of the stomach by providing an alkaline microenvironment, subsequently damaging the gastric mucosa [5]. Furthermore, urease-negative mutant strains of H. pylori failed to colonize in gnotobiotic piglets [6], suggesting that the enzyme plays a role in permitting survival of the organism in the gastric mucosa.…”

Gastric Epithelial Expression of Macrophage Migration Inhibitory Factor is not Altered by Helicobacter pylori Infection in Humans

“…Infection with H. pylori represents a major cofactor in the pathogenesis of gastritis and gastric ulcer disease in humans. The bacterium survives the acidic condition of the gastric mucus by producing ammonia and thereby potentially counteracting the host protection mechanism by its neutralizing properties [33].…”