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Published on: December 17, 2011
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
Background & Aims:
Mouse models of Helicobacter pylori infection have yielded variable results with respect to colonization and inflammation. We examined whether outer membrane proteins (OMPs) or the cag pathogenicity island (PAI) was responsible for some of this variability.
Methods:
C57BL/6 mice received clinical H. pylori isolates with different genotypes for the cag PAI and OMP gene switch status, as well as isogenic gene knockout mutants for cagE, oipA, babA2, hopZ, cagE/oipA, or oipA/hopZ. Bacterial density, histology, and mucosal cytokine/chemokine levels were measured after 4 and 12 weeks.
Results:
oipA, hopZ, hopO, and hopP switch status influenced both H. pylori density and colonization ability in mice. When 2 or more of the genes were "off," colonization rates were markedly reduced compared with those for strains with all genes "on" (from 58% to 0% after 12 weeks). oipA knockout mutants caused reduced inflammation and decreased mucosal interleukin 6 messenger RNA and KC messenger RNA and protein levels. H. pylori density and colonization ability were reduced if hopO or hopP switch status was changed from "on" to "off." There was a close relationship (r > 0.7) between the H. pylori density of the gastric mucosa of humans and mice when using the same H. pylori strains.
Conclusions:
Many of the differences reported with mouse models may reflect subtle unrecognized differences (e.g., switch status of an OMP gene), emphasizing the necessity of characterizing isolates before and after experiments. The mouse model may be suitable for investigating factors related to colonization ability, H. pylori density, and gastric mucosal inflammation.
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.
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