Helicobacter pylori (H. pylori), discovered in 1982, is a microaerophilic, spiral-shaped gram-negative bacterium that is able to colonize the human stomach. Nearly half of the world's population is infected by this pathogen. Its ability to induce gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma has been confirmed. The susceptibility of an individual to these clinical outcomes is multifactorial and depends on H. pylori virulence, environmental factors, the genetic susceptibility of the host and the reactivity of the host immune system. Despite the host immune response, H. pylori infection can be difficult to eradicate. H. pylori is categorized as a group I carcinogen since this bacterium is responsible for the highest rate of cancer-related deaths worldwide. Early detection of cancer can be lifesaving. The 5-year survival rate for gastric cancer patients diagnosed in the early stages is nearly 90%. Gastric cancer is asymptomatic in the early stages but always progresses over time and begins to cause symptoms when untreated. In 97% of stomach cancer cases, cancer cells metastasize to other organs. H. pylori infection is responsible for nearly 60% of the intestinal-type gastric cancer cases but also influences the development of diffuse gastric cancer. The host genetic susceptibility depends on polymorphisms of genes involved in H. pylori-related inflammation and the cytokine response of gastric epithelial and immune cells. H. pylori strains differ in their ability to induce a deleterious inflammatory response. H. pylori-driven cytokines accelerate the inflammatory response and promote malignancy. Chronic H. pylori infection induces genetic instability in gastric epithelial cells and affects the DNA damage repair systems. Therefore, H. pylori infection should always be considered a pro-cancerous factor.

In this review, we shall focus on the last year progression understanding the pathogenesis of Helicobacter pylori infection in the light of recent data related to adaptation of H pylori to the harsh acidic environment in the stomach, colonization of gastric mucosa via interaction with mucin 5 (MUC5AC) and other host cell receptors, the ability to form biofilm, interference with the host metabolic pathways, and induction of neuroimmune cross‐talk as well as downregulation of gastric barrier homeostasis and its consequences for the disease development. The role of the membrane vesicles of these bacteria has been emphasized as an important source of virulence factors. Furthermore, we shall describe molecular and functional studies on new aspects of VacA and CagA virulence, including the role of urease in the upregulation of VacA toxicity, an epithelial‐mesenchymal transition mediated by CagA, and the role of interaction of HopQ adhesin with carcinoembryonic antigen‐related cell adhesion molecules (CEACAMs) in CagA translocation into the host cells by the type IV secretion system (T4SS). The role of molecular mimicry between a common sequence (ATVLA) of H pylori heat shock protein (Hsp) B and human Hsp60 in the induction of potentially autoreactive antibodies is discussed. All these new data illustrate further progress in understanding H pylori pathogenicity and facilitate the search for new therapeutic targets as well as development of immunoprophylaxis methods based on new chimeric UreB and HpA proteins.

Molecular mimicry in Helicobacter pylori infections

Helicobacter pylori - (H. pylori) play a role in the pathogenesis of gastritis, gastric and duodenal ulcers as well as gastric cancer. A possible involvement of outer membrane vesicles (OMVs) produced by H. pylori in the distribution of bacterial antigens through the gastric epithelial barrier and their role in the development of local and systemic host inflammatory and immune responses has been suggested. OMVs contain various biologically active compounds, which internalize into host cells affecting signaling pathways and promoting apoptosis of gastric epithelial and immunocompetent cells. OMVs-associated H. pylori virulence factors may strengthen or downregulate the immune responses leading to disease development. This review describes the biological importance of H. pylori OMVs and their role in the course of H. pylori infections, as well as H. pylori related local and systemic effects.

Helicobacter pylori colonizes the human gastric mucosa, causing chronic inflammation, peptic ulcers and gastric cancer. A cascade of harmful processes results from the interaction of these bacteria with the gastric epithelium. To investigate these processes in terms of upregulation of oxidative stress and cell apoptosis and downregulation of the pro-regenerative activity of cells. We employed an in vivo guinea pig model at 7 or 28 days postinoculation with H. pylori, corresponding to an acute or chronic stage of infection, respectively, and an in vitro model of guinea pig primary gastric epithelial cells and fibroblasts treated with bacterial components: glycine acid extract (GE), urease subunit A (UreA), cytotoxin-associated gene A protein (CagA) and lipopolysaccharide (LPS). Cells were evaluated for metabolic activity (MTT reduction), myeloperoxidase (MPO) and metalloproteinase (MMP-9) secretion, lipid peroxidation (4-hydroxynonenal (4HNE)), migration (wound healing), proliferation (Ki-67 antigen) and cell apoptosis (TUNEL assay; Bcl-xL, Bax, Bcl-2 expression; caspase 3 cleavage). Significant infiltration of the gastric mucosa by inflammatory cells in vivo in response to H. pylori was accompanied by oxidative stress and cell apoptosis, which were more intense 7 than 28 days after inoculation. The increase in cell proliferation was more intense in chronic than acute infection. H. pylori components GE, CagA, UreA, and LPS upregulated oxidative stress and apoptosis. Only H. pylori LPS inhibited cell migration and proliferation, which was accompanied by the upregulation of MMP-9. H. pylori infection induces cell apoptosis in conjunction with increased oxidative stress. Elevated apoptosis protects against deleterious inflammation and neoplasia; however, it reduces cell integrity. Upregulation of cell migration and proliferation in response to injury in the milieu of GE, CagA or UreA facilitates tissue regeneration but increases the risk of neoplasia. By comparison, downregulation of cell regeneration by H. pylori LPS may promote chronic inflammation.