Helicobacter Pylori + Virulence Factors
Helicobacter pylori (H. pylori) and its virulence genes, cagA (cytotoxin-associated protein A) and vacA (vacuolating toxin) are included on the GI-MAP. Helicobacter pylori has been evolving with human beings for well over 50,000 years, since they migrated out of Africa. H. pylori colonization has been implicated in a variety of gastroduodenal diseases including gastritis, gastric cancer, and duodenal and peptic ulcer. H. pylori has also been detected by stool PCR in cases of dyspepsia, abdominal pain, and chronic gastrointestinal symptoms. It is infamous for its causal link to ulcers and gastric cancer, which resulted in a Nobel prize awarded to Robin Warren and Barry Marshall in 2005. However, some sources are suggesting its role, at least in part, as a commensal organism. H. pylori may protect its host from certain atopic disorders, as well as other diseases such as eosophageal cancer reflux, and obesity.
Population data shows that H. pylori virulence varies geographically. It is associated with high rates of cancer in certain regions, but not in others. The difference may lie in H. pylori’s genetics. Host immune status and acid secretion seem to be other important factors contributing to H. pylori’s colonization and pathogenesis. The H. pylori virulence factors that are most well recognized are vacA and cagA.
The presence of cagA-positive H.pylori strains has been significantly associated with gastric cancer and peptic ulcer. The gene codes for a type IV secretion system which allows the bacterium to inject the cagA protein into the host cell. Once inside the host’s gastric epithelial cells, cagA can disrupt cell signaling, leading to abnormal proliferation, motility, and changes in the cytoskeleton.73 These changes to normal cell signaling can initiate cancer.
The presence of vacA has been associated with gastric cancer, peptic ulcer, and duodenal ulcer. The vacA gene is present in all strains of H.pylori but is polymorphic, which leads to different levels of vacuolating toxin. VacA toxins interact with certain receptors on host cells, setting off a chain of events including mitochondrial damage, inhibition of T-lymphocytes, and interference of antigen presentation.