- Helicobacter pylori is a highly diverse gastric pathogen that colonizes roughly half of the world’s population. Its infection is typically acquired in early childhood and persists for decades, often asymptomatically, but in some individuals, it leads to serious diseases such as peptic ulcers, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma.
- The clinical outcome of H. pylori infection is strongly influenced by bacterial strain variability. Over the years, researchers have identified numerous strains, each exhibiting unique genetic and phenotypic traits that affect their pathogenic potential. Understanding the diversity among H. pylori strains is crucial not only for studying disease mechanisms but also for developing region-specific therapeutic and preventive strategies.
- A defining characteristic of H. pylori is its exceptional genetic diversity and population structure, which reflect its long co-evolution with human hosts. The species displays one of the highest levels of intraspecies genetic variability among bacteria, largely due to frequent homologous recombination and horizontal gene transfer.
- Phylogenetic analyses have revealed distinct H. pylori populations that mirror ancient human migrations. These include hpEurope, hpEastAsia, hpAfrica1, hpAfrica2, hpAsia2, hpNEAfrica, and hpSahul, each adapted to specific human populations. For instance, the hpEastAsia strains, prevalent in East Asia, carry more oncogenic variants of the CagA protein and are strongly associated with the region’s high gastric cancer incidence. In contrast, hpAfrica1 and hpAfrica2 strains, common in sub-Saharan Africa, are associated with lower gastric cancer risk, despite high infection rates—a phenomenon referred to as the “African enigma.”
- Strain classification is often based on the presence and allelic variation of key virulence factors, most notably cagA and vacA.
- The cag pathogenicity island (cagPAI) encodes a type IV secretion system that injects the CagA effector protein into gastric epithelial cells. CagA disrupts host signaling by becoming tyrosine-phosphorylated and interacting with molecules such as SHP-2, leading to changes in cell morphology, proliferation, and inflammatory responses. Strains that express East Asian-type CagA (EPIYA-D motifs) are more potent in triggering oncogenic signaling than those with Western-type CagA (EPIYA-C motifs).
- Additionally, the vacA gene encodes a secreted cytotoxin that causes vacuolation in epithelial cells and modulates immune responses. Its activity is determined by polymorphisms in the signal (s), mid (m), and intermediate (i) regions, with s1/m1/i1 combinations being the most cytotoxic.
- Other virulence factors such as BabA, OipA, SabA, and HopQ further influence the strain’s ability to adhere to host tissues and provoke inflammation.
- In research, specific H. pylori strains have become indispensable tools for modeling infection and host responses.
- Strain 26695, isolated from a UK patient with gastritis, was the first H. pylori strain to be fully sequenced and is widely used in genetic and functional studies.
- Strain J99, from a duodenal ulcer patient, belongs to the hpAfrica1 lineage and offers insights into genomic variation among strains.
- Both 26695 and J99 are CagA-positive and carry active VacA (s1/m1), making them suitable for studying canonical virulence pathways.
- Strain G27, genetically close to 26695, is preferred for transformation studies due to its natural competence.
- Strain P12, a cagA- and vacA-positive isolate from a gastric cancer patient, is extensively used in in vitro infection models involving gastric epithelial cell lines like AGS. Its fully sequenced genome and availability of isogenic deletion mutants (e.g., ΔcagA, ΔvacA, ΔcagE) make it ideal for dissecting the role of individual virulence genes in epithelial responses.
- For in vivo studies, mouse-adapted strains such as Sydney Strain 1 (SS1) and PMSS1 are commonly employed. SS1, despite its inactivation of cagPAI, is capable of long-term colonization in mice and is widely used to model chronic infection and immune responses.
- PMSS1, derived from the clinical strain KUSPM06B and adapted to mice, retains a functional type IV secretion system, allowing researchers to study CagA translocation and inflammation in vivo. These strains are essential for understanding H. pylori persistence, immune modulation, and the development of gastritis and neoplasia under controlled conditions.
- Clinically, the identification and typing of H. pylori strains are important for risk stratification and treatment planning. The presence of cagA and certain vacA genotypes correlates with increased risk of severe disease, guiding decisions on eradication therapy in asymptomatic carriers.
- Furthermore, antibiotic resistance varies geographically and among strain types, reinforcing the need for local surveillance.
- In East Asia, the predominance of highly virulent, CagA-positive strains with active VacA underscores the importance of early detection and intervention, while in Africa, strain typing helps explain the paradox of high infection but low cancer incidence. Understanding strain variation also informs vaccine development, where antigens must account for global strain heterogeneity.
