Strategies used byhelicobacter pylorito establish persistent infection

Abstract

Helicobacter pylori (H. pylori) is a Gram-negative and motile bacterium that colonizes the hostile microniche of the human stomach, then persists for the host’s entire life, if not effectively treated. Clinically, H. pylori plays a causative role in the development of a wide spectrum of diseases including chronic active gastritis, peptic ulceration, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Due to the global distribution of H. pylori, it is no exaggeration to conclude that smart strategies are contributing to adaptation of the bacterium to its permanent 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 microniche? This question is slightly easier to answer if we presume the same clinical concept for both persistent infection and disease. Understanding the mechanisms governing H. pylori persistence will improve identification of the increased risk of diseases such as gastric cancer in patients 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 such as gastric cancer. To escape the bactericidal activity of stomach acid, H. pylori secretes large amounts of surface-associated and cytosolic urease. The potential to avoid acidic conditions and immune evasion are discussed in order to explain the persistence of H. pylori colonization in the gastric mucosa, and data on bacterial genetic diversity are included. 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 immune system and the many unfavorable features of living in the gastric microniche.

Unraveling the factors and mechanism involved in persistence: Host‐pathogen interactions in Helicobacter pylori

“…H. pylori persistence in the gut is highly favored by secreting surface‐associated and cytosolic urease enzyme, which is converted into ammonia, carbon dioxide, and ammonium carbonate, which ultimately increases the pH of the stomach and makes its own microneutralized niche (Figure ) . Interestingly, H. pylori can modulate the expression of ammonium ion synthesis associated genes (urease, arginase, and formamidase) on exposure to acidic environment of the human gut …”

“…The less expression of BabA may promote less translocation of CagA and thereby increase the long‐term persistence of H. pylori. Overall, the differential expression of adhesion molecule in different H. pylori strains may induce by phase variation of the involved gene . Further, a detailed study is needed to reveal the association between differential expression of adhesion molecule and the complex process of H. pylori persistence.…”

“…These cells activated under the preinfection stage. Penetration of H. pylori immediately activates the innate immune system by phagocytic cells and their chemical responses like (a) reactive oxygen species (ROS) and (b) nitric oxide (NO) …”

“…Stockpiling of H. pylori can stimulate the production of megasomes. Delayed phagocytosis by producing megasomes could be one of the reasons to extend the survival duration of H. pylori for better response against immune system . H. pylori penetration into the epithelial mucus layer induces inflammation and produces phagocytic‐rich environment in which H. pylori manages to survive.…”

“…It acts as an immunosuppressant leading to the death of macrophages and check T‐cell development . H. pylori uses this toxin for the persistence under virulence stage by the following ways: (a) binding of VacA on T‐cell surface: secreted VacA toxin binds to the surface of T‐cells with the help of uncharacterized ligand, which leads to the inhibition of T‐cell proliferation, (b) VacA‐mediated apoptosis: VacA binds to epithelial cells through “receptor protein‐tyrosine phosphatase α” (RPTP α) and “low‐density lipoprotein receptor‐related protein 1” (LRP1) and induces cell death by modulating gap junction protein α‐1 (Cx43) . (c) VacA‐mediated mitochondrial apoptosis: VacA‐intoxicated cell induces the activation of the dynamin‐related protein 1 (Drp1) following the activation of proapoptotic protein (Bax), which leads to permeabilization of mitochondrial outer membrane and finally cell death.…”