Helicobacter pylori infection in mice: Role of outer membrane proteins in colonization and inflammation

Yoshio Yamaoka1, Masakazu Kita, Tadashi Kodama

  • 1Department of Medicine, Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas 77030, USA. yyamaoka@bcm.tmc.edu

Gastroenterology
|November 28, 2002
PubMed
Abstract

Insights

Outer membrane protein (OMP) gene status significantly impacts Helicobacter pylori colonization and density in mouse models. Characterizing these genetic variations is crucial for reliable experimental outcomes in H. pylori research.

Area of Science:

  • Microbiology
  • Immunology
  • Gastroenterology

Background:

  • Mouse models of Helicobacter pylori infection exhibit inconsistent colonization and inflammation results.
  • Variability may stem from differences in outer membrane proteins (OMPs) or the cag pathogenicity island (PAI).

Purpose of the Study:

  • To investigate the role of OMP gene switch status and the cag PAI in H. pylori colonization and inflammation variability in mouse models.
  • To determine if specific OMP genes influence bacterial density and host immune response.

Main Methods:

  • C57BL/6 mice were infected with clinical H. pylori isolates and isogenic mutants with varying cag PAI and OMP genotypes.
  • Bacterial density, histology, and mucosal cytokine/chemokine levels were assessed at 4 and 12 weeks post-infection.

Main Results:

  • Switch status of oipA, hopZ, hopO, and hopP genes significantly affected H. pylori density and colonization.
  • Reduced colonization rates (0% vs. 58%) were observed when two or more OMP genes were inactive.
  • oipA knockout mutants led to decreased inflammation and lower levels of IL-6 and KC.
  • A strong correlation (r > 0.7) was found between H. pylori density in human and mouse gastric mucosa.

Conclusions:

  • Subtle genetic variations, such as OMP gene switch status, contribute to variability in H. pylori mouse models.
  • Thorough characterization of H. pylori isolates is essential before and after experimental use.
  • The mouse model is suitable for studying H. pylori colonization, density, and gastric inflammation.

Related Concept Videos

Pathophysiology of Peptic Ulcer Disease: Injurious Factors01:22

Pathophysiology of Peptic Ulcer Disease: Injurious Factors

Peptic ulcers are sores on the stomach's inner lining and the upper small intestine, which are the result of disruptions in the mucosal layer that houses parietal cells which produce gastric acid, and chief cells which secrete pepsinogen.
In the antrum region, G cells secrete the gastrin hormone that binds to gastrin-cholecystokinin-B (CCK2) receptors on parietal and enterochromaffin-like (ECL) cells in the fundic glands. Simultaneously, the vagus nerve releases acetylcholine, which binds to M3...
Pathophysiology of Peptic Ulcer Disease: Mucosal Defense Factors01:24

Pathophysiology of Peptic Ulcer Disease: Mucosal Defense Factors

Peptic ulcer disease, commonly called PUD, represents a multifaceted condition characterized by disruptions in the lining of the gastrointestinal (GI)  tract. Central to the protection of the gastrointestinal lining is the mucosal-bicarbonate barrier. This physiological defense mechanism is a formidable shield against the corrosive effects of gastric acid and pepsin secretion in the stomach. Its role is pivotal in maintaining the structural integrity of the stomach's inner lining. Bicarbonate,...
Colonisation of Pathogens01:25

Colonisation of Pathogens

Pathogen colonization of host tissues is a critical step in the development of infectious diseases. Various pathogenic microorganisms, including bacteria, fungi, viruses, and protozoa, have evolved complex strategies to attach to, invade, and persist within host environments. These mechanisms enable pathogens to establish infections, evade immune responses, and resist antimicrobial treatments.Attachment to Host CellsIn bacteria, colonization typically begins with adherence to host epithelial...
Peptic Ulcer01:27

Peptic Ulcer

Peptic ulcers are erosive lesions of the gastric or duodenal lining, most commonly caused by Helicobacter pylori infection. This Gram-negative, helical bacterium has adapted to survive the stomach’s acidic environment by producing urease, which converts urea into ammonia and carbon dioxide. The ammonia neutralizes gastric acid in the bacterium’s immediate environment, allowing colonization of the gastric mucosa. H. pylori attaches to mucus-secreting epithelial cells, penetrates the mucus...
Gastritis II: Pathophysiology01:26

Gastritis II: Pathophysiology

The pathophysiology of gastritis begins with the colonization of the stomach lining by Helicobacter pylori (H. pylori). This bacterium spreads mainly via the oral-oral route through saliva or shared utensils, and can also be transmitted in overcrowded or unhygienic environments through contaminated water, despite its brief survival outside the body.ColonizationOnce ingested, H. pylori enters the stomach and begins colonization by navigating through the mucus layer lining the stomach wall. It...
Peptic Ulcer Disease II: Pathophysiology01:24

Peptic Ulcer Disease II: Pathophysiology

Peptic ulcer disease develops when protective mechanisms of the gastrointestinal mucosa are overwhelmed by harmful factors, leading to localized erosions in the stomach or proximal duodenum. The main causes are Helicobacter pylori infection and chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs).Helicobacter pylori–Induced InjuryBacterial Adaptation and Colonization:H. pylori is a spiral, Gram-negative bacterium adapted to the acidic stomach. and transmitted through oral-oral or...