Helicobacter pylori VacA, a distinct toxin exerts diverse functionalities in numerous cells: An overview

Abstract

Background Helicobacter pylori, gastric cancer‐causing bacteria, survive in their gastric environment of more than 50% of the world population. The presence of H. pylori in the gastric vicinity promotes the development of various diseases including peptic ulcer and gastric carcinoma. H. pylori produce and secret Vacuolating cytotoxin A (VacA), a major toxin facilitating the bacteria against the host defense system. The toxin causes multiple effects in epithelial cells and immune cells, especially T cells, B cells, and Macrophages. Methods This review describes the diverse functionalities of protein toxin VacA. The specific objective of this review is to address the overall structure, mechanism, and functions of VacA in various cell types. The recent advancements are summarized and discussed and thus conclusion is drawn based on the overall reported evidences. Results The searched articles on H. pylori VacA were evaluated and limited up to 66 articles for this review. The articles were divided into four major categories including articles on vacA gene, VacA toxin, distinct effects of VacA toxin, and their effects on various cells. Based on these studies, the review article was prepared. Conclusions This review describes an overview of how VacA is secreted by H. pylori and contributes to colonization and virulence in multiple ways by affecting epithelial cells, T cells, Dendritic cells, B cells, and Macrophages. The reported evidence suggests that the comprehensive outlook need to be developed for understanding distinctive functionalities of VacA.

Molecular Mechanism of Helicobacter pylori-Induced Gastric Cancer

“…VacA channels are formed in the cytoplasmic membrane and then enter the membrane of the endosomes and mitochondria through endocytotic vesicles [75]. VacA protein can separate the tight junction of the epithelial cells in gastric mucosa, As a result, VacA crosses through epithelial cells [76]. VacA has various effects on the host cell including cell vacuolization, alteration in mitochondrial membrane permeability, inhibition of T-lymphocyte activation and proliferation, and activation cell signaling [76].…”

“…VacA protein can separate the tight junction of the epithelial cells in gastric mucosa, As a result, VacA crosses through epithelial cells [ 76 ]. VacA has various effects on the host cell including cell vacuolization, alteration in mitochondrial membrane permeability, inhibition of T-lymphocyte activation and proliferation, and activation cell signaling [ 76 ]. The membranes of VacA-induced vacuoles carry markers of late endosomes and lysosomes; therefore, VacA-induced vacuoles are derived from the endosome-lysosome pathway.…”

Cortactin: A Major Cellular Target of the Gastric Carcinogen Helicobacter pylori

“…Once inside the cell, CagA initiates various signaling cascades by disrupting cell signaling networks that can lead to cytoskeletal rearrangements, altered cell polarity, and localized disruption of the epithelial barrier [11,78]. The VacA toxin (a pore-forming toxin) affects both epithelial cells and immune cells, including T cells, B cells, and macrophages [79]. This virulence factor dampens apoptosis and autophagy, while it promotes immune tolerance and as such enables persistent infection [73].…”

Characterization and genetic diversity of Helicobacter pylori type IV secretion system components CagI and CagN and their association with clinical outcomes among Iranian patients

“…In our study, the vacA s1 genotype was found to be more prevalent among PUD patients, however, there was no signi cant association between the presence of other virulence genes and clinical disease outcomes. The mosaic combination of s-and m-region allelic genotypes also has been established to be associated with the pathogenicity of H. pylori [42,43]. Accordingly, type s1m1 H. pylori strains express large amounts of VacA toxin and are strongly associated with a higher level of in ammation and mucosal ulceration, while vacA s1m2-harboring strains produce moderate amount of toxin and vacA s2m2 strains are virtually non-toxic and rarely associated to clinical outcome [44].…”