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World J Gastroenterol. Dec 7, 2013; 19(45): 8203-8210
Published online Dec 7, 2013. doi: 10.3748/wjg.v19.i45.8203
Helicobacter pyloriγ-glutamyl transpeptidase: A formidable virulence factor
Samantha Shi Min Ling, Khay Guan Yeoh, Bow Ho
Samantha Shi Min Ling, Bow Ho, Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
Khay Guan Yeoh, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
Author contributions: Ling SSM performed the literature review and wrote the article; Yeoh KG was involved in editing and reviewing the article; Ho B was responsible for critically reviewing and revising the article for important intellectual content; all authors have read and approved the final version to be published.
Supported by Singapore National Medical Research Council, No. R182000180213
Correspondence to: Bow Ho, Professor, Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117597, Singapore. bow_ho@nuhs.edu.sg
Telephone: +65-65163672 Fax: +65-67766872
Received: October 1, 2013
Revised: November 7, 2013
Accepted: November 18, 2013
Published online: December 7, 2013
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: Helicobacter pylori, Gamma-glutamyl transpeptidase, Pathogenesis, Immunomodulation, Carcinogenesis

Core tip:Helicobacter pylori produce γ-glutamyl transpeptidase (HpGGT), an important virulence factor associated with the development of peptic ulcer disease. HpGGT acts through several pathways to damage gastric epithelial cells including induction of apoptosis and cell cycle arrest, production of reactive oxygen species, promotion of inflammation and upregulation of heparin-binding epidermal growth factor-like growth factor which may then lead to carcinogenesis. HpGGT also has immunomodulatory actions on immune cells where it displays an antiproliferative effect on T cells and skews dendritic cells towards a tolerogenic phenotype, possibly contributing to the persistence of the pathogen in the gastric mucosa.