- Helicobacter pylori strain B128 is a mouse-colonizing clinical isolate that has been pivotal in bridging the gap between laboratory studies and animal models of infection. Originally isolated from a human patient with gastritis, B128 belongs to the hpEurope population and displays moderate to high virulence.
- It carries both of H. pylori’s major virulence factors: the cag pathogenicity island (cagPAI) and the vacA gene with alleles associated with strong cytotoxic activity. Importantly, a mouse-adapted derivative of this strain—B128 7.13—has become a widely used model for studying gastric carcinogenesis in rodents, especially in Mongolian gerbils and transgenic mouse models.
- B128 harbors a functional type IV secretion system (T4SS) encoded by the cagPAI, enabling it to translocate the CagA oncoprotein into gastric epithelial cells. The CagA protein in B128 is a Western-type, carrying multiple EPIYA-C motifs, which upon phosphorylation, interact with host signaling proteins such as SHP-2 and PAR1b. These interactions lead to cytoskeletal disruption, cell elongation, increased pro-inflammatory cytokine production (e.g., IL-8), and disruption of cell junctions. B128 has been shown to induce these canonical CagA-associated responses in cultured epithelial cells, confirming the integrity and activity of its secretion system.
- The VacA toxin produced by B128 is of the s1/m1 genotype, corresponding to a highly active cytotoxin capable of inducing large intracellular vacuoles, mitochondrial dysfunction, and immune modulation. VacA also plays an important role in subverting host T-cell responses, contributing to immune evasion and chronic persistence of the bacteria in the gastric mucosa. In combination, CagA and VacA from B128 contribute to a strong inflammatory profile, which makes this strain particularly useful for studying host-pathogen interactions, mucosal immune responses, and precancerous changes in the gastric epithelium.
- What makes B128 especially significant in the context of gastric cancer research is its derivative strain B128 7.13, which has been used to induce gastric adenocarcinoma in animal models, particularly in INS-GAS mice (gastrin-overexpressing mice predisposed to gastric neoplasia). Infection with B128 7.13 in these mice leads to progressive inflammation, atrophic gastritis, intestinal metaplasia, dysplasia, and ultimately gastric carcinoma, thereby providing a valuable model for studying the entire continuum of H. pylori-induced gastric carcinogenesis. This model has been essential for unraveling the contributions of bacterial virulence, host genetics, and environmental factors in the development of gastric cancer.
- B128 also expresses a complement of outer membrane proteins (OMPs) such as BabA and SabA, which mediate adhesion to gastric epithelial cells through binding to fucosylated and sialylated host glycans. These adhesins facilitate close contact with host cells, enhancing CagA translocation and persistent colonization. Moreover, B128 exhibits genetic stability in laboratory culture and is genetically tractable, although not as naturally competent as G27. Nevertheless, researchers have used B128 and its derivatives for gene knockout and functional analysis of key virulence genes, particularly in the context of in vivo infections.
- In summary, H. pylori strain B128 is a highly relevant clinical isolate with both functional CagA and VacA, and has been foundational for in vivo studies of inflammation and cancer. Its ability to colonize mice and induce gastric pathology makes it a cornerstone strain in experimental models of gastric disease. Through its mouse-adapted variant B128 7.13, it continues to play a central role in understanding how H. pylori infection leads to chronic inflammation and progression to gastric cancer.
