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Updated: Oct 9, 2026
Mouse Models Of Helicobacter Infection And Gastric Pathologies
Published on: October 18, 2018
Infection with cagA- and vacA-positive and -negative strains of Helicobacter pylori in a mouse model
E Sturegård1, H Sjunnesson, H Nilsson
1Department of Infectious Diseases and Medical Microbiology, Lund University, Sölvegatan 23, S-22362, Lund, Sweden.
Abstract:
To study the role of cytotoxin-associated protein (cagA) and vacuolating cytotoxin (vacA) in Helicobacter pylori infection in an experimental murine model, mice were infected with seven strains with different cagA and vacA status. Groups of 10 NMRI mice were challenged and were killed 5 weeks later. In a second study, 20 mice were challenged with a mixture of the same seven strains and killed 1, 3, 15 and 17 weeks post-inoculation. All seven strains were found to colonize the mice for the 5-week experimental period. Animals infected with vacA-positive strains, regardless of cagA status, showed an elevation of antibody titers. Two cagA-negative and vacA-positive strains and one cagA- and vacA-positive strain were found to 'take over' in the mixed infection as analyzed by the randomly amplified polymorphic DNA-polymerase chain reaction technique and in one mouse stomach we found coexistence of two of the strains. We found no evidence of the different strains colonizing different parts of the stomach.
Insights
Helicobacter pylori strains expressing vacuolating cytotoxin (vacA) induced higher antibody titers in mice. Certain vacA-positive strains, with or without cytotoxin-associated protein (cagA), dominated mixed infections.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Helicobacter pylori is a significant human pathogen.
- The roles of cytotoxin-associated protein (cagA) and vacuolating cytotoxin (vacA) in H. pylori pathogenesis are critical.
- Understanding strain dynamics in vivo is essential for comprehending infection outcomes.
Purpose of the Study:
- To investigate the impact of cagA and vacA on H. pylori colonization and host immune response in a murine model.
- To analyze the competitive dynamics of different H. pylori strains during mixed infections.
Main Methods:
- Experimental infection of NMRI mice with seven H. pylori strains varying in cagA and vacA status.
- Analysis of colonization, antibody titers, and strain dominance using randomly amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR).
- Infection monitored at multiple time points post-inoculation.
Main Results:
- All seven H. pylori strains successfully colonized mice over a 5-week period.
- Mice infected with vacA-positive strains exhibited elevated antibody titers, irrespective of cagA status.
- In mixed infections, specific vacA-positive strains (both cagA-positive and cagA-negative) demonstrated competitive advantages, leading to dominance.
- Coexistence of multiple strains was observed in some cases, but distinct compartmentalization was not found.
Conclusions:
- Vacuolating cytotoxin (vacA) plays a significant role in eliciting host antibody responses during H. pylori infection.
- The vacA genotype influences the competitive fitness of H. pylori strains during mixed infections in a murine model.
- CagA status appears less critical than vacA status in determining strain dominance in this experimental setting.
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