Helicobacter Pylori Gamma-glutamyl Transpeptidase and Its Pathogenic Role

Overview

Journal World J Gastroenterol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2014 Feb 28

PMID 24574736

Citations 49

Authors

Vittorio Ricci

Maria Giannouli

Marco Romano

Raffaele Zarrilli

Affiliations

Soon will be listed here.

Abstract

Helicobacter pylori (H. pylori) gamma-glutamyl transpeptidase (GGT) is a bacterial virulence factor that converts glutamine into glutamate and ammonia, and converts glutathione into glutamate and cysteinylglycine. H. pylori GGT causes glutamine and glutathione consumption in the host cells, ammonia production and reactive oxygen species generation. These products induce cell-cycle arrest, apoptosis, and necrosis in gastric epithelial cells. H. pylori GGT may also inhibit apoptosis and induce gastric epithelial cell proliferation through the induction of cyclooxygenase-2, epidermal growth factor-related peptides, inducible nitric oxide synthase and interleukin-8. H. pylori GGT induces immune tolerance through the inhibition of T cell-mediated immunity and dendritic cell differentiation. The effect of GGT on H. pylori colonization and gastric persistence are also discussed.

Citing Articles

Pivotal role of virulence genes in pathogenicity and vaccine development.

Elbehiry A, Marzouk E, Abalkhail A, Sindi W, Alzahrani Y, Alhifani S Front Med (Lausanne). 2025; 11():1523991.

PMID: 39850097 PMC: 11756510. DOI: 10.3389/fmed.2024.1523991.

outer membrane vesicles and infected cell exosomes: new players in host immune modulation and pathogenesis.

Wang X, Wang J, Mao L, Yao Y Front Immunol. 2024; 15:1512935.

PMID: 39726601 PMC: 11670821. DOI: 10.3389/fimmu.2024.1512935.

Measuring the rate of NADPH consumption by glutathione reductase in the cytosol and mitochondria.

Ting K, Floro E, Dow R, Jongstra-Bilen J, Cybulsky M, Rocheleau J PLoS One. 2024; 19(12):e0309886.

PMID: 39637235 PMC: 11620681. DOI: 10.1371/journal.pone.0309886.

Optimized therapeutic potential of Sijunzi-similar formulae for chronic atrophic gastritis via Bayesian network meta-analysis.

Huang M, Luo S, Yang J, Xiong H, Lu X, Ma X EXCLI J. 2024; 23:1185-1207.

PMID: 39421026 PMC: 11484511. DOI: 10.17179/excli2024-7618.

Programmed cell death in infection and related gastric cancer.

Lin Y, Liu K, Lu F, Zhai C, Cheng F Front Cell Infect Microbiol. 2024; 14:1416819.

PMID: 39145306 PMC: 11322058. DOI: 10.3389/fcimb.2024.1416819.

References

Rossi M, Bolz C, Revez J, Javed S, El-Najjar N, Anderl F . Evidence for conserved function of γ-glutamyltranspeptidase in Helicobacter genus. PLoS One. 2012; 7(2):e30543. PMC: 3279353. DOI: 10.1371/journal.pone.0030543. View

Flahou B, Haesebrouck F, Chiers K, Van Deun K, Smet L, Devreese B . Gastric epithelial cell death caused by Helicobacter suis and Helicobacter pylori γ-glutamyl transpeptidase is mainly glutathione degradation-dependent. Cell Microbiol. 2011; 13(12):1933-55. DOI: 10.1111/j.1462-5822.2011.01682.x. View

Necchi V, Manca R, Ricci V, Solcia E . Evidence for transepithelial dendritic cells in human H. pylori active gastritis. Helicobacter. 2009; 14(3):208-22. DOI: 10.1111/j.1523-5378.2009.00679.x. View

Chiozzi V, Mazzini G, Oldani A, Sciullo A, Ventura U, Romano M . Relationship between Vac A toxin and ammonia in Helicobacter pylori-induced apoptosis in human gastric epithelial cells. J Physiol Pharmacol. 2009; 60(3):23-30. View

Williams K, Cullati S, Sand A, Biterova E, Barycki J . Crystal structure of acivicin-inhibited gamma-glutamyltranspeptidase reveals critical roles for its C-terminus in autoprocessing and catalysis. Biochemistry. 2009; 48(11):2459-67. PMC: 2668148. DOI: 10.1021/bi8014955. View

Amieva M, Vogelmann R, Covacci A, Tompkins L, Nelson W, Falkow S . Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA. Science. 2003; 300(5624):1430-4. PMC: 3369828. DOI: 10.1126/science.1081919. View

Gerhard M, Schmees C, Voland P, Endres N, Sander M, Reindl W . A secreted low-molecular-weight protein from Helicobacter pylori induces cell-cycle arrest of T cells. Gastroenterology. 2005; 128(5):1327-39. DOI: 10.1053/j.gastro.2005.03.018. View

Ricci V, Romano M, Boquet P . Molecular cross-talk between Helicobacter pylori and human gastric mucosa. World J Gastroenterol. 2011; 17(11):1383-99. PMC: 3070011. DOI: 10.3748/wjg.v17.i11.1383. View

Ito T, Kobayashi D, Uchida K, Takemura T, Nagaoka S, Kobayashi I . Helicobacter pylori invades the gastric mucosa and translocates to the gastric lymph nodes. Lab Invest. 2008; 88(6):664-81. DOI: 10.1038/labinvest.2008.33. View

10.

Xia H, Talley N . Apoptosis in gastric epithelium induced by Helicobacter pylori infection: implications in gastric carcinogenesis. Am J Gastroenterol. 2001; 96(1):16-26. DOI: 10.1111/j.1572-0241.2001.03447.x. View

11.

Sewald X, Gebert-Vogl B, Prassl S, Barwig I, Weiss E, Fabbri M . Integrin subunit CD18 Is the T-lymphocyte receptor for the Helicobacter pylori vacuolating cytotoxin. Cell Host Microbe. 2008; 3(1):20-9. DOI: 10.1016/j.chom.2007.11.003. View

12.

Valenzuela M, Bravo D, Canales J, Sanhueza C, Diaz N, Almarza O . Helicobacter pylori-induced loss of survivin and gastric cell viability is attributable to secreted bacterial gamma-glutamyl transpeptidase activity. J Infect Dis. 2013; 208(7):1131-41. DOI: 10.1093/infdis/jit286. View

13.

Radin J, Gonzalez-Rivera C, Ivie S, McClain M, Cover T . Helicobacter pylori VacA induces programmed necrosis in gastric epithelial cells. Infect Immun. 2011; 79(7):2535-43. PMC: 3191986. DOI: 10.1128/IAI.01370-10. View

14.

Beigier-Bompadre M, Moos V, Belogolova E, Allers K, Schneider T, Churin Y . Modulation of the CD4+ T-cell response by Helicobacter pylori depends on known virulence factors and bacterial cholesterol and cholesterol α-glucoside content. J Infect Dis. 2011; 204(9):1339-48. DOI: 10.1093/infdis/jir547. View

15.

Shibayama K, Wachino J, Arakawa Y, Saidijam M, Rutherford N, Henderson P . Metabolism of glutamine and glutathione via gamma-glutamyltranspeptidase and glutamate transport in Helicobacter pylori: possible significance in the pathophysiology of the organism. Mol Microbiol. 2007; 64(2):396-406. DOI: 10.1111/j.1365-2958.2007.05661.x. View

16.

Torres V, Vancompernolle S, Sundrud M, Unutmaz D, Cover T . Helicobacter pylori vacuolating cytotoxin inhibits activation-induced proliferation of human T and B lymphocyte subsets. J Immunol. 2007; 179(8):5433-40. DOI: 10.4049/jimmunol.179.8.5433. View

17.

Gebert B, Fischer W, Weiss E, Hoffmann R, Haas R . Helicobacter pylori vacuolating cytotoxin inhibits T lymphocyte activation. Science. 2003; 301(5636):1099-102. DOI: 10.1126/science.1086871. View

18.

Gong M, Ling S, Lui S, Yeoh K, Ho B . Helicobacter pylori gamma-glutamyl transpeptidase is a pathogenic factor in the development of peptic ulcer disease. Gastroenterology. 2010; 139(2):564-73. DOI: 10.1053/j.gastro.2010.03.050. View

19.

Meyer F, Ramanujam K, Gobert A, James S, Wilson K . Cutting edge: cyclooxygenase-2 activation suppresses Th1 polarization in response to Helicobacter pylori. J Immunol. 2003; 171(8):3913-7. DOI: 10.4049/jimmunol.171.8.3913. View

20.

Sundrud M, Torres V, Unutmaz D, Cover T . Inhibition of primary human T cell proliferation by Helicobacter pylori vacuolating toxin (VacA) is independent of VacA effects on IL-2 secretion. Proc Natl Acad Sci U S A. 2004; 101(20):7727-32. PMC: 419674. DOI: 10.1073/pnas.0401528101. View