- Helicobacter pylori strain PMSS1 is a well-characterized, virulent clinical isolate that has become a widely used model for studying H. pylori pathogenesis in murine (mouse) models.
- It was originally isolated from a patient in the United States with duodenal ulcer disease and belongs to the hpEurope population.
- What distinguishes PMSS1 from other mouse-adapted H. pylori strains, such as SS1, is that PMSS1 retains a fully functional cag pathogenicity island (cagPAI), enabling it to deliver CagA into host cells through a functional type IV secretion system (T4SS). This feature makes PMSS1 particularly valuable for in vivo studies of CagA-mediated host signaling, inflammation, and early carcinogenic changes, which cannot be adequately modeled using cagPAI-deficient strains.
- PMSS1 is cagA-positive and carries Western-type CagA, which contains EPIYA-A, -B, and -C phosphorylation motifs. Upon translocation into gastric epithelial cells, CagA undergoes tyrosine phosphorylation and interacts with host proteins such as SHP-2 and PAR1b, altering cell polarity, inducing pro-inflammatory signaling (e.g., IL-8 production), and promoting epithelial cell elongation (hummingbird phenotype). In mouse models, these CagA-dependent effects contribute to gastric epithelial hyperplasia, immune cell infiltration, and in some cases, precancerous lesions such as atrophic gastritis and metaplasia when infection is prolonged. This makes PMSS1 a powerful strain for modeling the early stages of gastric carcinogenesis, particularly when combined with transgenic or immune-compromised mouse strains.
- Another key virulence factor of PMSS1 is Vacuolating cytotoxin A (VacA). PMSS1 harbors the s1/m1 vacA alleles, which encode a highly active VacA protein. This toxin disrupts host cell endosomal trafficking, induces vacuole formation, and modulates immune cell function—suppressing T-cell activation and promoting persistence of infection. Together, CagA and VacA contribute to chronic inflammation, tissue damage, and the immune evasion strategies that allow H. pylori to persist in the gastric niche for years or even decades. PMSS1 also expresses other key outer membrane proteins (OMPs) such as BabA, SabA, and HopQ, which enhance adherence to host epithelial cells and facilitate interaction with host cell receptors, including CEACAMs, which are crucial for CagA translocation.
- A major advantage of PMSS1 is its robust colonization capacity in mice, making it suitable for long-term infection experiments. Unlike the widely used Sydney strain 1 (SS1), which has mutations in the cagPAI rendering it non-functional, PMSS1 enables researchers to study both inflammation and virulence factor-dependent pathology in a physiologically relevant context. This has opened up new avenues for exploring H. pylori-driven disease mechanisms, including studies of host immune responses, epithelial transformation, and microbial persistence. PMSS1 is also amenable to genetic manipulation, and isogenic mutants (e.g., ΔcagA, ΔvacA, ΔcagE) have been developed to dissect the individual contributions of each virulence factor.
- In summary, H. pylori strain PMSS1 is a crucial model for translational research, bridging in vitro molecular studies with in vivo disease modeling. Its ability to colonize mice while maintaining a fully active T4SS and potent virulence factor expression makes it an indispensable tool for studying the pathogenesis of H. pylori–associated diseases such as gastritis, ulcers, and gastric cancer. It also plays an essential role in preclinical testing of novel therapeutics and vaccines targeting H. pylori infection and inflammation.
