Helicobacter pylori: an up-to-date overview on the virulence and pathogenesis mechanisms

Abstract

Helicobacter pylori is an organism associated with ulcer disease and gastric cancer. The latter is one of the most prevalent malignancies and currently the fourth major cause of cancer-related deaths globally. The pathogen infects about 50% of the world population, and currently, no treatment ensures its total elimination. There has been an increase in our understanding of the pathophysiology and pathogenesis mechanisms of H. pylori over the years. H. pylori can induce several genetic alterations, express numerous virulence factors, and trigger diverse adaptive mechanisms during its adherence and colonization. For successful colonization and infection establishment, several effector proteins/toxins are released by the organism. Evidence is also available reporting spiral to coccoid transition as a unique tactic H. pylori uses to survive in the host's gastrointestinal tract (GIT). Thus, the virulence and pathogenicity of H. pylori are under the control of complex interplay between the virulence factors, host, and environmental factors. Expounding the role of the various virulence factors in H. pylori pathogenesis and clinical outcomes is crucial for vaccine development and in providing and developing a more effective therapeutic intervention. Here we critically reflect on H. pylori infection and delineate what is currently known about the virulence and pathogenesis mechanisms of H. pylori.

Keywords: Gastric cancer; Helicobacter pylori; OMPs; Peptic ulcer; Virulence; cagA; dupA; vacA.

Fig. 1

Virulence and pathogenesis mechanisms of H. pylori. Colonization and establishment of diseases and infection by H. pylori depend on four major stages: (1) adaptation to the acidic environment of the gastric mucosa, (2) the movement towards the epithelial cells using the flagella, (3) penetration of the epithelial cell barrier and attachment to specific receptors, and (4) tissue damage and other detrimental health effects. Therefore, to successfully colonize the host and establish infection, H. pylori must be able to survive the acidic stomach, attach to the host cells (using several adhesins), and release toxins that damage host tissues. The VacA helps in the disruption of the epithelial barrier. Also, the macrophages can be induced by the urease. The induction brings about alterations in gastric physiology. Several other effector proteins play a crucial role in the pathogenesis of H. pylori