Helicobacter pylori γ-glutamyl transpeptidase: a formidable virulence factor

Abstract

Helicobacter pylori (H. pylori) produce an enzyme known as γ-glutamyl transpeptidase (HpGGT) that is highly conserved and common to all strains. HpGGT has been gaining increasing attention as an important virulence factor of the bacterium, having been demonstrated to be an important colonization factor in several animal models and has also recently been strongly associated with the development of peptic ulcer disease. From the results of various independent researcher groups, it is clear that HpGGT acts through several pathways to damage gastric epithelial cells including the induction of apoptosis and cell cycle arrest, production of reactive oxygen species leading to DNA damage, promotion of inflammation by increasing cyclooxygenase-2 and interleukin-8 expression, and upregulation of heparin-binding epidermal growth factor-like growth factor resulting in cell survival and proliferation. In addition, the potential role of HpGGT in promoting gastric carcinogenesis will also be discussed in this review. Apart from affecting the gastric epithelium, HpGGT also has immunomodulatory actions on host immune cells where it displays an antiproliferative effect on T cells by inducing cell cycle arrest and also works with other H. pylori virulence factors to skew dendritic cells towards a tolerogenic phenotype, possibly contributing to the persistence of the pathogen in the gastric mucosa.

Keywords: Carcinogenesis; Gamma-glutamyl transpeptidase; Helicobacter pylori; Immunomodulation; Pathogenesis.

Figure 1

Schematic diagram highlighting important effects of Helicobacter pylori γ-glutamyl transpeptidase on both gastric epithelial and immune cells and their implications on carcinogenesis and persistence of Helicobacter pylori in the gastric mucosa. COX-2: Cyclooxygenase-2; HpGGT: Helicobacter pylori (H. pylori) γ-glutamyl transpeptidase; GSH: Glutathione; HB-EGF: Heparin-binding epidermal growth factor-like growth factor; IL-8: Interleukin-8; LPS: Lipopolysaccharide; miR-155: microRNA-155; NF-κB: Nuclear factor-kappa B; ROS: Reactive oxygen species; VacA: Vacuolating cytotoxin. Red arrows indicate upregulation of the respective molecules.