Helicobacter pylori r-Glutamyl Transpeptidase Plays a Role in Detoxification of Epigallocatechin Gallate

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Patsayawan Jennuwat
Jarunee Kaulpiboon
Sasichai Kangsadalampai


The emergence of antibiotic resistance in Helicobacter pylori, a major cause of dyspepsia and a carcinogenic agent of gastric cancer, has led to the search for new natural antibacterial compounds. It has been reported that epigallocatechin gallate (EGCG), the most potent catechin found in green tea (Camellia sinensis L.), exhibits antibacterial activity against several bacteria, including H. pylori. Recently, the inhibition of the human liver cell gif.latex?\gamma-glutamyl transpeptidase (GGT) by EGCG has been demonstrated. However, there have been no reports on the effect of EGCG on H. pylori GGT, which is one of the bacterial virulence factors. Based on the evidence of human GGT inhibition, it is assumed that the EGCG can also inhibit H. pylori GGT through mechanisms that may include a reduction in the bacterial ggt gene expression. To extend our knowledge, the effect of EGCG on the H. pylori ggt mRNA level was examined. The minimal inhibitory concentration (MIC) of EGCG against H. pylori was determined and found to be 250 µg/ml. Subsequently, the ggt gene expression level of the H. pylori grown on a media containing EGCG at sub-MIC (125 µg/ml) and no EGCG was studied using the quantitative RT-PCR with SYBR green fluorescein method. The result showed that the ggt gene expression of H. pylori exposed to EGCG was up-regulated by over 12 fold (p < 0.01). This finding contradicts the expected reduction in gene expression. The observed increase in transcriptional level of the bacterial ggt gene in this study indicates that, besides its role in bacterial colonization, the H. pylori GGT is produced as a respond to EGCG exposure, possibly due to the fact that the enzyme involves the detoxification of toxic substances.


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Warren, J.R. and Marshall, B., 1983, Unidentified curved bacilli on gastric epithelium in active chronic gastritis, Lancet. 1: 1273-1275.

Marshall, B. and Warren, J.R., 1984, Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration, The lancet. 323: 1311-1315.

Owen, R.J., 1998, Helicobacter--species classification and identification, Br. Med. Bull. 54: 17-30.

Cover, T.L., 2016, Helicobacter pylori diversity and gastric cancer risk, MBio. 7: e01869-15.

Hooi, J.K.Y., Lai, W.Y., Ng, W.K., Suen, M.M.Y., Underwood, F.E., Tanyingoh, D., et al., 2017, Global prevalence of Helicobacter pylori infection: Systematic review and meta-analysis. Gastroenterology. 153: 420-429.

Gatta, L., Vakil, N., Vaura, D. and Scapignato, C., 2013, Global eradication rates for Helicobacter pylori infection: systematic review and meta-analysis of sequential therapy, BMJ. 347: f4587.

Mégraud, F., 2004, H. pylori antibiotic resistance: prevalence, importance, and advances in testing, Gut. 53: 1374–1384.

Alba, C., Blanco, A. and Alarcon T., 2017, Antibiotic resistance in Helicobacter pylori, Curr. Opin. Infect. Dis. 30: 489–497.

Abreu, A.C., McBain, A.J. and Simões M., 2012, Plants as sources of new antimicrobials and resistance-modifying agents, Nat. Prod. Rep. 29: 1007.

Pezeshki, A., Safi, S., Feizi, A., Askari, G. and Karami, F., 2016, The effect of green tea extract supplementation on liver enzymes in patients with nonalcoholic fatty liver disease, Int. J. Prev. Med. 7: 28

Chen C.N., Liang, C.M., Lai, J.R., Tsai, Y.J., Tsay, J.S. and Lin, J.K., 2003, Capillary electrophoretic determination of theanine, caffeine, and catechins in fresh tea leaves and oolong tea and their effects on rat neurosphere adhesion and migration, J. Agric. Food Chem.. 51: 7495–7503.

Cabrera, C., Giménez, R. and López M.C., 2003, Determination of tea components with antioxidant activity, J. Agric. Food. Chem. 51: 4427-4435.

Ogunleye, A.A., Xue, F. and Michels, K.B., 2010, Green tea consumption and breast cancer risk or recurrence: a meta-analysis, Breast Cancer Res Treat. 119: 477-484.

Kurahashi, N., Sasazuki, S., Iwasaki, M., Inoue, M. and Tsugane, S., 2008, Green tea consumption and prostate cancer risk in Japanese men: a prospective study, JPHC Study Group, Am J Epidemiol. 167: 71-77.

Yuan, J.M., Sun, C. and Butler, L,M., 2011, Tea and cancer prevention: epidemiological studies, Pharmacol. Res. 64: 123-135.

Hirano, R., Momiyama, Y., Takahashi, R., Taniguchi, H., Kondo, K., Nakamura, H. and Ohsuzu, F., 2002, Comparison of green tea intake in Japanese patients with and without angiographic coronary artery disease, Am. J. Cardiol. 90: 1150-1153.

Kao, Y.H., Chang, H.H., Lee, M.J. and Chen, C.L., 2006, Tea, obesity, and diabetes, Mol. Nutr Food Res. 50: 188-210.

Li, S., Hattori, T. and Kodama, E.N., 2011, Epigallocatechin gallate inhibits the HIV reverse transcription step, Antivir. Chem. Chemother. 21: 239-243.

Yanagawa, Y., Yamamoto, Y., Hara, Y. and Shimamura, T., 2003, A combination effect of epigallocatechin gallate, a major compound of green tea catechins, with antibiotics on Helicobacter pylori growth in vitro, Curr. Microbiol. 47: 244-249.

Taylor, P.W., Hamilton-Miller, J.M. and Stapleton, P.D., 2005, Antimicrobial properties of green tea catechins, Food Sci Technol Bull. 2: 71-81.

Okubo, S., Toda, M., Hara, Y. and Shimamura, T., 1991, Antifungal and fungicidal activities of tea extract and catechin against Trichophyton, Nihon Saikingaku Zasshi. 46: 509-514.

Vance, S.H., Tucci, M. and Benghuzzi, H., 2011, Evaluation of the antimicrobial efficacy of green tea extract (egcg) against streptococcus pyogenes in vitro-biomed 2011, Biomed Sci Instrum. 47: 177-182.

Hassani, A.R., Ordouzadeh, N., Ghaemi, A., Amirmozafari, N., Hamdi, K. and Nazari, R., 2009, In vitro inhibition of Helicobacter pylori urease with non and semi fermented Camellia sinensis, Indian J. Med. Microbiol. 27: 30-34.

Mabe, K., Yamada, M., Oguni, I and Takahashi, T., 1999, In vitro and in vivo activities of tea catechins against Helicobacter pylori, Antimicrob. Agents Chemother. 43: 1788–1791.

Stoicov, C., Saffari, R. and Houghton, J., 2009, Green tea inhibits Helicobacter growth in vivo and in vitro, Int. J. Antimicrob. Agents. 33: 473-478.

Lee, S.I., Kim, H.J. and Boo, Y.C., 2008, Effect of green tea and (-)-epigallocatechin gallate on ethanol-induced toxicity in HepG2 cells, Phytother. Res. 22: 669-674.

Leduc, D., Gallaud, J., Stingl, K. and de Reuse, H., 2010, Coupled amino acid deamidase transport systems essential for Helicobacter pylori colonization, Infect. Immun. 78: 2782-2792.

Shibayama, K., Wachino, J., Arakawa, Y., Saidijam, M., Rutherford, N.G. and Henderson, P.J., 2007, Metabolism of glutamine and glutathione via gamma-glutamyltranspeptidase and glutamate transport in Helicobacter pylori: Possible significance in the pathophysiology of the organism, Mol. Microbiol. 64: 396-406.

Stark, R.M., Suleiman, M.S., Hassan, I.J., Greenman, J. and Millar, M.R., 1997, Amino acid utilization and deamination of glutamine and asparagine by Helicobacter pylori, J. Med. Microbiol. 46: 793-800.

Chevalier, C., Thiberge, J., Ferrero, R.L. and Labigne, A., 1999, Essential role of Helicobacter pylori γ-glutamyl trans-peptidase for the colonization of the gastric mucosa of mice, Mol. Microbiol. 31: 1359- 1372.

Gong, M. and Ho, B., 2004, Prominent role of γ-glutamyl-transpeptidase on the growth of Helicobacter pylori, World J Gastroenterol. 10: 2994-2996.

Ritdet, N., Rojpibulstit, P. and Kangsadalampai, S., 2021, Expression of Helicobacter pylori virulence genes under atmospheric condition, Sci. Tech. Asia. 26: 210-219.

Chomczynski, P. and Sacchi, N., 1987, Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction, Anal. Biochem. 162: 156-159.

Shao, C., Sun, Y., Wang, N., Yu, H., Zhou, Y., Chen, C. and Jia, J., 2013, Change of proteome components of Helicobacter pylori biofilms induced by serum starvation, Mol. Med. Rep. 8: 1761-1766.

Pfaffl, M.W., 2001, A new mathematical model for relative quantification in real-time RT-PCR, Nucl. Acids Res. 29: e45.

Ki, MR., Yun, N.R. and Hwang, S.Y., 2013, Glutamine-induced production and secretion of Helicobacter pylori gamma-glutamyltranspeptidase at low pH and its putative role in glutathione transport, J. Microbiol. Biotechnol. 23:467-472.

Paolicchi, A., Sotiropuolou, M., Perego, P., Daubeuf, S., Visvikis, A., Lorenzini, E., Franzini, M., Romiti, N., Chieli, E., Leone, R., Apostoli, P., Colangelo, D., Zunino, F., Pompella, A., 2003, -Glutamyl transpeptidase catalyses the extracellular detoxification of cisplatin in a human cell line derived from the proximal convoluted tubule of the kidney, Eur. J. Cancer. 39: 996–1003.

Keillor, J.W., Castonguay, R. and Lherbet, C., 2005, Gamma-glutamyl transpeptidase substrate specificity and catalytic mechanism, Methods Enzymol, 401: 449-467.

Zhang, H. and Forman, H.J., 2009, Redox regulation of -glutamyl transpeptidase, Am. J. Respir. Cell Mol. Biol. 41: 509–515.

Ubiyvovk, V.M., Blazhenko, O.V., Gigot, D., Penninckx, M., Sibirny, A.A., 2006, Role of γ-glutamyltranspeptidase in detoxification of xenobiotics in the yeasts Hansenula polymorpha and Saccharomyces cerevisiae, Cell Biol. Int. 30: 665-671.