- Helicobacter pylori strain SS1 (Sydney Strain 1) is one of the most widely used laboratory strains for in vivo infection studies, particularly in mouse models.
- It was originally derived from a clinical isolate and subsequently adapted for colonization in mice through serial passages in the murine stomach. The need for a murine-adapted strain arose because most wild-type H. pylori strains, including well-characterized clinical isolates like 26695 or J99, do not colonize mice efficiently. SS1 overcame this limitation and became the standard strain for establishing H. pylori infection in commonly used mouse strains, including C57BL/6 and BALB/c.
- One of the defining features of SS1 is that, during the adaptation process, it acquired mutations in the cag pathogenicity island (cagPAI), which rendered the type IV secretion system (T4SS) non-functional. As a result, although SS1 is cagA-positive, it cannot translocate CagA into host epithelial cells. This makes SS1 non-inflammatory compared to strains like PMSS1, which retain an active T4SS. While this is a limitation for studies focused on CagA-mediated pathogenesis or epithelial transformation, SS1 remains a valuable model for investigating other aspects of H. pylori biology, including chronic colonization, gastric inflammation, immune response, and vaccine development.
- SS1 does, however, express a functional Vacuolating cytotoxin A (VacA), although with moderate activity. The VacA allelic type in SS1 is typically s2/m2, which produces a less active form of the toxin compared to the s1/m1 variants found in more virulent strains like 26695 or PMSS1. As such, SS1 induces relatively mild vacuolation and cellular damage. Nonetheless, it can still modulate immune responses and contribute to persistent infection in mice. Additionally, SS1 expresses various outer membrane proteins (OMPs) such as HopZ, SabA, and OipA, although some of these adhesins show variable expression due to phase variation, which is common in H. pylori.
- The importance of SS1 in research cannot be overstated. It has been used extensively to study host-pathogen interactions, gastric mucosal immunity, cytokine responses, and the role of innate and adaptive immune components in infection. Its use has led to the development of mouse models of chronic gastritis, helping researchers uncover pathways involved in mucosal inflammation, epithelial remodeling, and even progression toward atrophy or metaplasia under prolonged infection. Although SS1 cannot induce the full spectrum of H. pylori-induced pathology due to the absence of functional CagA delivery, it remains an indispensable strain for long-term infection studies, immunological assays, and preclinical trials of vaccines or antimicrobial strategies.
- In summary, while H. pylori SS1 lacks a functional T4SS and exhibits moderate virulence compared to strains like PMSS1 or 26695, its ability to reliably colonize the murine stomach makes it an essential model organism in H. pylori research. It has significantly advanced our understanding of bacterial persistence, immune evasion, and host responses to infection in vivo. For studies requiring cagA activity, researchers often pair SS1 with complementary models like PMSS1; however, for foundational work in murine systems, SS1 remains a cornerstone of H. pylori pathogenesis research.
