H. pylori is a Gram-negative, crimp and motile bacterium that colonizes the hostile microniche of the human stomach roughly one half of the human population. Then persists for the host’s entire life, but only causes overt gastric disease in a subset of infected hosts. To the reasons contributing to the development of diseases, usually include: concomitant infections of the gastrointestinal tract, improper sterilization of medical instruments, usually endoscopes, nonobservance of personal hygiene rules, prolonged contact with infected or carriers, including family members and a number of other factors. Clinically, H. pylori plays a causative role in the development of a wide spectrum of diseases including chronic active gastritis, peptic and duodenal ulceration, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Due to the global distribution of H. pylori, we are able to conclude that smart strategies are contributing to adaptation of the bacterium in an aggressive environment of a stomach and lifelong permanent circulation in its host. Thirty-four years after the discovery of this bacterium, there are still many unanswered questions. For example, which strategies help the bacterium to survive in this inhospitable conditions? Understanding the mechanisms governing H. pylori persistence will improve identification of the increased risk of different gastric diseases in persons infected with this bacterium. A well-defined and long-term equilibrium between the human host and H. pylori allows bacterial persistence in the gastric microniche; although this coexistence leads to a high risk of severe diseases the diseases which are listed above. In this review, we discuss the pathogenesis of this bacterium and the mechanisms it uses to promote persistent colonization of the gastric mucosa, with a focus on recent insights into the role of some virulence factors like urease, LPS, outer membrane proteins, cytotoxins, factors, promoting invasion. Information on the mechanisms related to H. pylori persistence can also provide the direction for future research concerning effective therapy and management of gastroduodenal disorders. The topics presented in the current review are important for elucidating the strategies used by H. pylori to help the bacterium persist in relation to the many unfavorable features of living in the gastric microniche.

Gastric and duodenal recurrent inflammatory diseases have a high prevalence, but the role played by microbes in its development remained unclear. However, the data published in 1983 by Marshall and Warren about isolatingHelicobacter pylorifrom the stomach mucosa of the patient with gastritis and proposing relevant cultivation methods was the turning point in investigating etiology of the upper digestive tract inflammatory disorders. Moreover, it was shown that the majority ofH. pylorispp. are found within the gastric lumen upon colonization, whereas around 20% of them are attached to the epithelial cells in the stomach. In addition, effects of interacting H. pylori with gastric epithelium and activation of some defense mechanisms due to bacterial colonization and spreading were analyzed. It was found that along with triggering pro-inflammatory response induced by proteins VacA as well as phosphorylated/unphosphorylated CagA, wherein the latter is able to induce a set of protective reactionsH. pyloridisrupts intercellular contacts, affects epithelial cell polarity and proliferation, and activates SHP-2 phosphatase resulting in emerging diverse types of cellular responses. The activation mechanisms for the mitogen-activated protein kinase (MAPK) pathway were discussed. The ability ofH. pylorito regulate apoptosis, particularly via its suppression, by expressing ERK kinase and protein MCL1 facilitating bacterial survival in the gastric mucosa as well as beneficial effects related to bacterial circulation on gastric epithelial cell survival elicited by anti-apoptotic factors were also examined. Of note, persistence of H. pylori are mainly determined by activating transcriptional factors including NF-κB, NFAT, SRF, T-cell lymphoid enhancing factor (TCF/LEF), regulating activity of MCL1 protein, in turn, being one of the main anti-apoptotic factors, as well as induced production of the migration inhibitory factor (MIF). The role of VacA cytotoxin in triggering epithelial cell apoptosis via caspase-mediated pathways was also considered. Infection withH. pyloriis accompanied by release of proinflammatory cytokine cocktail detected bothin vitroandin vivo. In particular, bacterial urease activating transcriptional factor NF-κB was shown to play a crucial role in inducing cytokine production. Moreover, such signaling pathways may be activated afterH. pyloriis attached to the cognate receptor in the gastric epithelial surface by interacting with CD74 and MHC class II molecules. Finally, a role for various CD4+T cell subsets, particularly type 17 T helper cells (Th17) in inducing immune response against H. pylori antigens in gastric mucosa was revealed were also discussed.

Helicobacter pylori is one of the most common commensal microorganisms in the human body, colonizing up to 60% of the inhabitants on all continents. Some H. pylori strains have acquired virulent properties and their presence can significantly complicate the course of type B atrophic gastritis, gastric ulcer and duodenal ulcer, as well as gastric malignant diseases. In such situations, eradication therapy seems to be pathogenetically justified. In 1996, there were proposed the International Recommendations for standard first-line 7–10-day course triple eradication therapy, including a proton pump inhibitor (PPI), amoxicillin and clarithromycin. Until the beginning of the XXIth century, the International Recommendations has been actively and highly efficiently (up to 90%) used everywhere, but later reports started to emerge regarding a catastrophic decrease in therapeutic outcome (up to 60%). Later, it turned out that the effectiveness of the three-component (triple) therapy directly correlates with the resistance to clarithromycin substantially increased in recent decades, which necessitated generation of new schemes for H. pylori elimination. The results of various schemes for H. pylori eradication were analyzed, including variants of modified triple therapy associated with the inclusion of new drugs or prolonged duration of the therapeutic protocol. In particular, it was proposed to replace amoxicillin with metronidazole. However, further studies have shown that the combination of clarithromycin with amoxicillin seems to be preferable due to the high level of H. pylori resistance to metronidazole recorded in many countries. Attempts to use probiotics in parallel, particularly cultures of various Lactobacillus species, were analyzed, which increases the level of eradication during standard triple therapy from 61.5% to 81.6%, and significantly reduces the severity of side effects. It has been shown that a promising approach to increase the effectiveness of 7-day first-line therapy schemes with clarithromycin is to use modern effective PPIs (for example, esomeprazole or rabeprazole). The scheme of modified sequential therapy with the replacement of clarithromycin with tetracycline or levofloxacin, which has shown high efficiency has been considered. A variant of standard triple therapy modified into quadrotherapy by adding metronidazole or tinidazole was analyzed. It has been shown that the sequential therapy scheme is ineffective for eradication of multidrug-resistant strains. Ideally, the treatment of bacterial infections should be based on endoscopic sampling of gastric mucosa biopsies, followed by microbiological determination of in vitro antibacterial drug sensitivity in bacterial isolates.