The Helicobacter pylori cag pathogenicity island as a determinant of gastric cancer risk

Abstract

Helicobacter pylori strains can be broadly classified into two groups based on whether they contain or lack a chromosomal region known as the cag pathogenicity island ( cag PAI). Colonization of the human stomach with cag PAI-positive strains is associated with an increased risk of gastric cancer and peptic ulcer disease, compared to colonization with cag PAI-negative strains. The cag PAI encodes a secreted effector protein (CagA) and components of a type IV secretion system (Cag T4SS) that delivers CagA and non-protein substrates into host cells. Animal model experiments indicate that CagA and the Cag T4SS stimulate a gastric mucosal inflammatory response and contribute to the development of gastric cancer. In this review, we discuss recent studies defining structural and functional features of CagA and the Cag T4SS and mechanisms by which H. pylori strains containing the cag PAI promote the development of gastric cancer and peptic ulcer disease.

Subdomains of theHelicobacter pyloriCag T4SS outer membrane core complex exhibit structural independence

“…H. pylori colonization of the stomach results in gastric inflammation (gastritis) and an increased risk for the development of gastric cancer, peptic ulcer disease, and mucosa-associated lymphoid tissue lymphoma ( Atherton, 2006 ; Kusters et al, 2006 ; Malfertheiner et al, 2023 ). H. pylori strains harboring the cag pathogenicity island ( cag PAI), a 40-kb chromosomal region that encodes a type IV secretion system (T4SS) and the secreted effector protein CagA, are more frequently associated with gastric cancer and peptic ulcer disease, compared with cag PAI–negative strains ( Blaser et al, 1995 ; Parsonnet et al, 1997 ; Nomura et al, 2002 ; Plummer et al, 2007 ; Cover, 2016 ; Tran et al, 2024 ).…”

A prominent role of LncRNA H19 in H. pylori CagA induced DNA damage response and cell malignancy

“…It is thought that cagA-positive strains are associated with more severe inflammation, higher levels of atrophy and a greater likelihood of progression to gastric adenocarcinoma than cagA-negative strains 31 . To date, there has been relatively little progress in determining the pathogenesis of GC by H. pylori CagA 32 .…”

Bioactive peptides as alternative treatment for Helicobacter pylori infection

“…This colonization process is synchronized with the secretion of a variety of enzymes by the pathogen, which induce pH changes, alter mucus composition, and release effector proteins to facilitate adhesion and invasion of host cells, resulting in damage and successful colonization (Figure 1) [21,35] effector proteins [36][37][38]. The progression of the infection has also been associated with the presence of the cag Pathogenicity Island (CagPAI), a set of 27 genes that are unique to the strains that are positive for the cytotoxin-associated gene A (cagA-positive), from which 17 genes are related to the activity of the Type IV Secretion System (T4SS) that allows the translocation of effector proteins inside the targeted cell inducing morphological changes and affecting cell proliferation [34,[39][40][41][42]. The gene cagA encodes an effector protein that is also known as an oncoprotein, therefore patients infected with cagA-positive strains are more prone to the development of peptic ulcers and to the progression to gastric cancer [21,43,44].…”