EPIYA motif patterns among Cuban Helicobacter pylori CagA positive strains
Abstract
Introduction. It is known that polymorphisms in C-terminal region of CagA influence gastric disease development on Helicobacter pylori infection. Additionally, the geographic distribution of these polymorphisms has been associated with the appearance of more severe gastroduodenal pathologies.
Objective. To determine the CagA phosphorylation motifs pattern (EPIYA pattern) in Cuban H. pylori isolates, and to study its association with patient’s pathologies.
Materials and methods. DNAs from 95 H. pylori cagA-positive strains were used to amplify the 3’ variable region of cagA gene by PCR using two different strategies. Additionally, new primers were designed to identify either Western or Eastern CagA EPIYA motif type by PCR. To confirm the PCR results, PCR products from 14 representative isolates were purified and sequenced
Results. The distribution of the EPIYA motif found was: 2 AB (2.1 %), 1 AC (1.1 %), 1 BC (1.1 %), 70 ABC (73.6 %), 19 ABCC (20 %), and 2 ABCCC (2.1 %). Sequencing analysis confirmed the PCR classification in the 14 studied strains and showed three strains with unusual nucleotide sequences, not reported before. Distribution of the EPIYA-ABC pattern was equivalent in all pathologies (78.9 % in gastric ulcer, 72.5 % in duodenal ulcer and 72.2 % in non-ulcer dyspepsia).
Conclusion. The PCR results using the new primers confirmed that all studied strains carried the Western CagA type. No specific EPIYA motif was associated with peptic ulcer. This is the first report that shows EPIYA motif distribution in H. pylori isolates from the Caribbean region.
Downloads
References
Hatakeyama M, Higashi H. Helicobacter pylori CagA: A new paradigm for bacterial carcinogenesis. Cancer Sci. 2005;96:835-43.
Wu AH, Crabtree JE, Bernstein L, Hawtin P, Cockburn M, Tseng CC, et al. Role of Helicobacter pylori CagA+ strains and risk of adenocarcinoma of the stomach and esophagus. Int J Cancer. 2003;103:815-21.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69-90.
Backert S, Selbach M. Role of type IV secretion in Helicobacter pylori pathogenesis. Cell Microbiol. 2008;10:1573-81.
Covacci A, Censini S, Bugnoli M, Petracca R, Burroni D, Macchia G, et al. Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer. Proc Natl Acad Sci USA. 1993;90:5791-5.
Stein M, Bagnoli F, Halenbeck R, Rappuoli R, Fantl WJ, Covacci A. c-Src/Lyn kinases activate Helicobacter pylori CagA through tyrosine phosphorylation of the EPIYA motifs. Mol Microbiol. 2002;43:971-80.
Higashi H, Tsutsumi R, Fujita A, Yamazaki S, Asaka M, Azuma T, et al. Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites. Proc Natl Acad Sci USA. 2002;99:14428-33.
Segal ED, Cha J, Lo J, Falkow S, Tompkins LS. Altered states: Involvement of phosphorylated CagA in the induction of host cellular growth changes by Helicobacter pylori. Proc Natl Acad Sci USA. 1999;96:14559-64.
Smith M, Hold L, Tahara E, El-Omar E. Cellular and molecular aspects of gastric cancer. World J Gastroenterol. 2006;21:2979-90.
Kurashima Y, Murata-Kamiya N, Kikuchi K, Higashi H, Azuma T, Kondo S, et al. Deregulation of beta-catenin signal by Helicobacter pylori CagA requires the CagAmultimerization sequence. Int J Cancer. 2008;122:823-31.
Yokoyama K, Higashi H, Ishikawa S, Fujii Y, Kondo S, Kato H, et al. Functional antagonism between Helicobacter pylori CagA and vacuolating toxin VacA in control of the NFAT signaling pathway in gastric epithelial cells. Proc Natl Acad Sci USA. 2005;102:9661-6.
Brandt S, Kwok T, Hartig R, Konig W, Backert S. NF-κB activation and potentiation of proinflammatory responses by the Helicobacter pylori CagA protein. Proc Natl Acad Sci USA. 2005;102:9300-5.
Murata-Kamiya N, Kurashima Y, Teishikata Y, Yamahashi Y, Saito Y, Higashi H, et al. Helicobacter pylori CagA interacts with E-cadherin and deregulates the b-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells. Oncogene. 2007;26:4617-26.
Higashi H, Tsutsumi R, Muto S, Sugiyama T, Azuma T, Asaka M, et al. SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. Science. 2002;295:683-6.
Yamaoka Y, Kodama T, Kashima K, Graham DY, Sepulveda AR. Variants of the 3’ region of the cagA gene in Helicobacter pylori isolates from patients with different H. pylori-associated diseases. J Clin Microbiol. 1998;36:2258-63.
Azuma T, Yamakawa A, Yamazaki S, Fukuta K, Ohtani M, Ito Y, et al. Correlation between variation of the 3’ region of the cagA gene in Helicobacter pylori and disease outcome in Japan. J Infect Dis. 2002;186:1621-30.
Argent RH, Kidd M, Owen RJ, Thomas RJ, Limb MC, Atherton JC. Determinants and consequences of different levels of CagA phosphorylation for clinical isolates of Helicobacter pylori. Gastroenterology. 2004;127:514-23.
Basso D, Zambon CF, Letley DP, Stranges A, Marchet A, Rhead JL, et al. Clinical relevance of Helicobacter pylori cagA and vacA gene polymorphisms. Gastroenterology. 2008;135:91-9.
Ohnishi N, Yuasa H, Tanaka S, Sawa H, Miura M, Matsui A, et al. Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse. Proc Natl Acad Sci USA. 2008;22:1003-8.
Miura M, Ohnishi N, Tanaka S, Yanagiya K, Hatakeyama M. Differential oncogenic potential of geographically distinct Helicobacter pylori CagA isoforms in mice. Int J Cancer. 2009;125:2497-504.
Phillips AA, Jacobson JS, Magai C, Consedine N, Horowicz-Mehler NC, Neugut AI. Cancer incidence and mortality in the Caribbean. Cancer Invest. 2007;25:476-83.
Torres LE, Melian K, Moreno A, Alonso J, Sabatier CA, Hernández M, et al. Prevalence of vacA, cagA and babA2 genes in Cuban Helicobacter pylori isolates. World J Gastroenterol. 2009;15:204-10.
Xu C, Li ZS, Tu ZX, Xu GM, Gong YF, Man XH. Distribution of cagG gene in Helicobacter pylori isolates from Chinese patients with different gastroduodenal diseases and its clinical and pathological significance. World J Gastroenterol. 2003;9:2258-60.
Rudi J, Kolb C, Maiwald M, Kuck D, Sieg A, Galle PR, et al. Diversity of Helicobacter pylori vacA and cagA genes and relationship to VacA and CagA protein expression, cytotoxin production, and associated diseases. J Clin Microbiol. 1998;36:944-8.
Argent RH, Zhang Y, Atherton JC. Simple method for determination of the number of Helicobacter pylori CagA variable-region EPIYA tyrosine phosphorylation motifs by PCR. J Clin Microbiol. 2005;43:791-5.
Valmaseda T, Gisbert JP, Paniagua M, Pajares JM. Helicobacter pylori CagA antibodies in various gastroduodenal diseases from 2 different populations. Med Clin (Barc). 2002;118:90-3.
Panayotopoulou EG, Sgouras DN, Papadakos K, Kalliaropoulos A, Papatheodoridis G, Mentis AF, et al. Strategy to characterize the number and type of repeating EPIYA phosphorylation motifs in the carboxyl terminus of CagA protein in Helicobacter pylori clinical isolates. J Clin Microbiol. 2007;45:488-95.
Devi SM, Ahmed I, Khan AA, Rahman SA, Alvi A, Sechi LA, et al. Genomes of Helicobacter pylori from native Peruvians suggest admixture of ancestral and modern lineages and reveal a western type cag-pathogenicity island. BMC Genomics. 2006;7:191.
Argent RH, Hale JL, El Oma EM, Atherton JC. Differences in Helicobacter pylori CagA tyrosine phosphorylation motif patterns between Western and East Asian strains, and influences on interleukin-8 secretion. J Med Microbiol.2008;5:1062-7.
Occhialini A, Marais A, Urdaci M, Sierra R, Muñoz N, Covacci A, et al. Composition and gene expression of the cag pathogenicity island in Helicobacter pylori strains isolated from gastric carcinoma and gastritis patients in Costa Rica. Infect Immun. 2001;69:1902-8.
Reyes-León A, Atherton JC, Argent RH, Puente JL, Torres J. Heterogeneity in the activity of Mexican Helicobacter pylori strains in gastric epithelial cells and its association with diversity in the cagA gene. Infect Immun. 2007;75:3445-54.
.Yamaoka Y, El-Zimaity H, Gutiérrez O, Figura N, Kim J, Kodama T, et al. Relationship between the cagA 3’ repeat region of Helicobacter pylori, gastric histology, and susceptibility to low pH. Gastroenterology. 1999;117:342-9.
Schneider N, Krishna U, Romero-Gallo J, Israel DA, Piazuelo MB, Camargo MC, et al. Role of Helicobacter pylori
CagA molecular variations in induction of host pPhenotypes with carcinogenic potential. J Infect Dis. 2009;199:1218-21.
Sicinschi LA, Correa P, Peek RM, Camargo MC, Piazuelo MB, Romero-Gallo J, et al. CagA C-terminal variations in Helicobacter pylori strains from Colombian patients with gastric precancerous lesions. Clin Microbiol Infect. 2010;16:369-78.
An B, Lee G, Lim K, Moon BS, Kim JB. Identification of the repeated number of C and D regions of tyrosine phosphorylation motifs in Helicobacter pylori cagA using multiplex PCR. Microbiol Immunol. 2008;5:479-83.
Schmidt H, Andres S, Kaakoush N, Engstrand L, Eriksson L, Goh K, et al. The prevalence of the duodenal ulcer promoting gene (dupA) in Helicobacter pylori isolates varies by ethnic group and is not universally associated with disease development: A case-control study. Gut Pathog. 2009;1:5.
Yamaoka Y. Roles of the plasticity regions of Helicobacter pylori in gastroduodenal pathogenesis. J Med Microbiol. 2008;57:545-53.
Azuma T, Yamakawa A, Yamazaki S, Ohtani M, Ito Y, Muramatsu A, et al. Distinct diversity of the cag pathogenicity island among Helicobacter pylori strains in Japan. J Clin Microbiol. 2004;42:2508-17.
Vilaichone RK, Mahachai V, Tumwasorn S, Wu JY, Graham DY, Yamaoka Y. Molecular epidemiology and outcome of Helicobacter pylori infection in Thailand: A cultural cross roads. Helicobacter. 2004;9:453-9.
Zhu YL, Zheng S, Du Q, Qian KD, Fang PC. Characterization of CagA variable region of Helicobacter pylori isolates from Chinese patients. World J Gastroenterol. 2005;11:880-4.
Choi KD, Kim N, Lee DH, Kim JM, Kim JS, Jung HC, et al. Analysis of the 3´ variable region of the cagA gene of Helicobacter pylori isolated in Koreans. Dig Dis Sci. 2007;52:960-6.
Bosetti C , Malvezzi M, Chatenoud L, Negri E, Levi F, La Vecchia C. Trends in cancer mortality in the Americas, 1970-2000. Ann Oncol. 2005;16:489-511.
Some similar items:
- Oscar F. Herrán, María F. Ardila, Martha P. Rojas, Gustavo A. Hernández, Design of dietary questionnaires to study the relationships between diet and cancer prevalence in Colombia , Biomedica: Vol. 30 No. 1 (2010)
- Juan Carlos Cataño, Eaton-Lambert myasthenic syndrome , Biomedica: Vol. 30 No. 3 (2010)
- Juan Carlos Herrera, Luis Fernando Isaza, José Luis Ramírez, Gonzalo Vásquez, Carlos Mario Muñetón, Detection of chromosome 17 aneuplody and TP53 gene deletion in a broad variety of solid tumors by dual-color fluorescence in situ hybridization (FISH) , Biomedica: Vol. 30 No. 3 (2010)
- Yaliana Tafurt-Cardona, Leidy D. Jaramillo-Ruiz, Wilson Muñoz-Ordóñez, Sulma L. Muñoz-Benítez, Carlos H. Sierra-Torres, High frequency of chromosome aberrations observed in lymphocytes in postmenopausal obese women , Biomedica: Vol. 32 No. 3 (2012)
- Ricardo Cendales, Constanza Pardo, Claudia Uribe, Guillermo López, María Clara Yépez, Luis Eduardo Bravo, Data quality at population-based cancer registries in Colombia , Biomedica: Vol. 32 No. 4 (2012)
- Carolina Gallego, Jhon Carlos Castaño, Alejandra Giraldo, Daniel Ajzenberg, Marie-Laure Dardé, Jorge Enrique Gómez, Molecular and biological characterization of the CIBMUQ/HDC strain, a reference strain for Colombian Toxoplasma gondii. , Biomedica: Vol. 24 No. 3 (2004)
- Patricia Escandón, Elizabeth Quintero, Diana Granados, Sandra Huérfano, Alejandro Ruiz, Elizabeth Castañeda, Isolation of Cryptococcus gattii serotype B from detritus of Eucalyptus trees in Colombia. , Biomedica: Vol. 25 No. 3 (2005)
- Sonia Isabel Cuervo, Ricardo Sánchez, Julio César Gómez-Rincón, Cielo Almenares, Juan Pablo Osorio, María José Vargas, Behavior of carbapenemase-producing Klebsiella pneumoniae cases in cancer patients at a third level hospital in Bogotá, D.C. , Biomedica: Vol. 34 (2014): Abril, Suplemento 1, Resistencia bacteriana
- Piedad Agudelo-Flórez, Harold Durango, Diego Aranzazu, Juan David Rodas, Bruno Travi, Genotyping and evaluation of infection dynamics in a Colombian isolate of Leptospira santarosai in hamster as an experimental model , Biomedica: Vol. 34 No. 3 (2014)
- Dihadenys Lemus, Miguel Echemendía, Raúl Díaz, Alina Llop, María Josefa Llanes, Surveillance of antituberculosis-drug resistance in Cuba, 2010-2011 , Biomedica: Vol. 34 (2014): Abril, Suplemento 1, Resistencia bacteriana
Article metrics | |
---|---|
Abstract views | |
Galley vies | |
PDF Views | |
HTML views | |
Other views |