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Helicobacter pylori Genetic Polymorphisms in Gastric Disease Development

  • Jeannette M. Whitmire
  • D. Scott MerrellEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1149)

Abstract

Infecting half of the world’s population, Helicobacter pylori is a medically important bacterium that induces a variety of gastric diseases, including gastritis, peptic ulcer disease, and gastric cancer. Sequencing of almost 1000 H. pylori isolates has revealed a diverse genome that contains abundant polymorphic genetic elements; many of these lie in factors likely to be associated with virulence. To ascertain the effect of these varying genetic elements, numerous epidemiological studies have investigated the contribution of the various polymorphisms to gastric disease development; particular focus has been placed on polymorphisms in the outer membrane proteins (OMPs), an effector protein, and a toxin produced by H. pylori. These studies have revealed geographic variation in the prevalence of various polymorphisms as well as in the associations between particular polymorphisms and gastric disease development. Furthermore, researchers have identified polymorphisms in multiple genes that frequently occur in combination. Though no single polymorphic genetic factor alone can fully account for gastric disease development in a population, the evaluation of multiple polymorphisms in a colonizing H. pylori strain can aid in the assessment of the pathogenic potential of the strain. Here we review specific H. pylori genetic polymorphisms (Bab proteins, Hom proteins, HopQ, SabA, SabB, OipA, IceA, VacA and CagA) that have been linked to disease outcome and discuss how geographic location and virulence factor polymorphisms together contribute to H. pylori-induced disease.

Keywords

Genetic polymorphisms Virulence factors H. pylori Gastric disease Toxin 

References

  1. Abdi E, Latifi-Navid S, Zahri S, Yazdanbod A, Safaralizadeh R (2017) Helicobacter pylori genotypes determine risk of non-cardia gastric cancer and intestinal- or diffuse-type GC in Ardabil: a very high-risk area in northwestern Iran. Microb Pathog 107:287–292.  https://doi.org/10.1016/j.micpath.2017.04.007 CrossRefPubMedPubMedCentralGoogle Scholar
  2. Abdullah SM, Hussein NR, Salih AM, Merza MA, Goreal AA, Odeesh OY, Majed HS, Assafi MA, Hawrami K (2012) Infection with Helicobacter pylori strains carrying babA2 and cagA is associated with an increased risk of peptic ulcer disease development in Iraq. Arab J Gastroenterol 13(4):166–169.  https://doi.org/10.1016/j.ajg.2012.12.001 CrossRefPubMedPubMedCentralGoogle Scholar
  3. Acosta N, Quiroga A, Delgado P, Bravo MM, Jaramillo C (2010) Helicobacter pylori CagA protein polymorphisms and their lack of association with pathogenesis. World J Gastroenterol 16(31):3936–3943CrossRefPubMedPubMedCentralGoogle Scholar
  4. Alm RA, Bina J, Andrews BM, Doig P, Hancock RE, Trust TJ (2000) Comparative genomics of Helicobacter pylori: analysis of the outer membrane protein families. Infect Immun 68(7):4155–4168CrossRefPubMedPubMedCentralGoogle Scholar
  5. Ansari S, Yamaoka Y (2017) Helicobacter pylori BabA in adaptation for gastric colonization. World J Gastroenterol 23(23):4158–4169.  https://doi.org/10.3748/wjg.v23.i23.4158 CrossRefPubMedPubMedCentralGoogle Scholar
  6. Argent RH, Hale JL, El-Omar EM, Atherton JC (2008a) Differences in Helicobacter pylori CagA tyrosine phosphorylation motif patterns between western and East Asian strains, and influences on interleukin-8 secretion. J Med Microbiol 57(Pt 9):1062–1067.  https://doi.org/10.1099/jmm.0.2008/001818-0 CrossRefPubMedPubMedCentralGoogle Scholar
  7. Argent RH, Thomas RJ, Letley DP, Rittig MG, Hardie KR, Atherton JC (2008b) Functional association between the Helicobacter pylori virulence factors VacA and CagA. J Med Microbiol 57(Pt 2):145–150.  https://doi.org/10.1099/jmm.0.47465-0 CrossRefPubMedPubMedCentralGoogle Scholar
  8. Arnold IC, Hitzler I, Muller A (2012) The immunomodulatory properties of Helicobacter pylori confer protection against allergic and chronic inflammatory disorders. Front Cell Infect Microbiol 2:10.  https://doi.org/10.3389/fcimb.2012.00010 CrossRefPubMedPubMedCentralGoogle Scholar
  9. Asim M, Chikara SK, Ghosh A, Vudathala S, Romero-Gallo J, Krishna US, Wilson KT, Israel DA, Peek RM Jr, Chaturvedi R (2015) Draft genome sequence of gerbil-adapted carcinogenic Helicobacter pylori strain 7.13. Genome Announc 3(3).  https://doi.org/10.1128/genomeA.00641-15
  10. Atherton JC (2006) The pathogenesis of Helicobacter pylori-induced gastro-duodenal diseases. Annu Rev Pathol 1:63–96.  https://doi.org/10.1146/annurev.pathol.1.110304.100125 CrossRefPubMedPubMedCentralGoogle Scholar
  11. Atherton JC, Cao P, Peek RM Jr, Tummuru MK, Blaser MJ, Cover TL (1995) Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific vacA types with cytotoxin production and peptic ulceration. J Biol Chem 270(30):17771–17777CrossRefPubMedPubMedCentralGoogle Scholar
  12. Atherton JC, Peek RM Jr, Tham KT, Cover TL, Blaser MJ (1997) Clinical and pathological importance of heterogeneity in vacA, the vacuolating cytotoxin gene of Helicobacter pylori. Gastroenterology 112(1):92–99CrossRefPubMedPubMedCentralGoogle Scholar
  13. Azuma T, Yamazaki S, Yamakawa A, Ohtani M, Muramatsu A, Suto H, Ito Y, Dojo M, Yamazaki Y, Kuriyama M, Keida Y, Higashi H, Hatakeyama M (2004) Association between diversity in the Src homology 2 domain--containing tyrosine phosphatase binding site of Helicobacter pylori CagA protein and gastric atrophy and cancer. J Infect Dis 189(5):820–827.  https://doi.org/10.1086/381782 CrossRefPubMedPubMedCentralGoogle Scholar
  14. Backert S, Tegtmeyer N, Selbach M (2010) The versatility of Helicobacter pylori CagA effector protein functions: the master key hypothesis. Helicobacter 15(3):163–176.  https://doi.org/10.1111/j.1523-5378.2010.00759.x CrossRefPubMedPubMedCentralGoogle Scholar
  15. Bakhti SZ, Latifi-Navid S, Mohammadi S, Zahri S, Bakhti FS, Feizi F, Yazdanbod A, Siavoshi F (2016) Relevance of Helicobacter pylori vacA 3′-end region polymorphism to gastric cancer. Helicobacter 21(4):305–316.  https://doi.org/10.1111/hel.12284 CrossRefPubMedPubMedCentralGoogle Scholar
  16. Bakhti SZ, Latifi-Navid S, Zahri S, Bakhti FS, Hajavi N, Yazdanbod A (2017) Are Helicobacter pylori highly cytotoxic genotypes and cardia gastric adenocarcinoma linked? Lessons from Iran. Cancer Biomark 21(1):235–246.  https://doi.org/10.3233/cbm-170701 CrossRefPubMedPubMedCentralGoogle Scholar
  17. Basiri Z, Safaralizadeh R, Bonyadi MJ, Somi MH, Mahdavi M, Latifi-Navid S (2014) Helicobacter pylori vacA d1 genotype predicts risk of gastric adenocarcinoma and peptic ulcers in northwestern Iran. Asian Pac J Cancer Prev 15(4):1575–1579CrossRefPubMedPubMedCentralGoogle Scholar
  18. Basso D, Zambon CF, Letley DP, Stranges A, Marchet A, Rhead JL, Schiavon S, Guariso G, Ceroti M, Nitti D, Rugge M, Plebani M, Atherton JC (2008) Clinical relevance of Helicobacter pylori cagA and vacA gene polymorphisms. Gastroenterology 135(1):91–99.  https://doi.org/10.1053/j.gastro.2008.03.041 CrossRefPubMedPubMedCentralGoogle Scholar
  19. Batista SA, Rocha GA, Rocha AM, Saraiva IE, Cabral MM, Oliveira RC, Queiroz DM (2011) Higher number of Helicobacter pylori CagA EPIYA C phosphorylation sites increases the risk of gastric cancer, but not duodenal ulcer. BMC Microbiol 11:61.  https://doi.org/10.1186/1471-2180-11-61 CrossRefPubMedPubMedCentralGoogle Scholar
  20. Belogolova E, Bauer B, Pompaiah M, Asakura H, Brinkman V, Ertl C, Bartfeld S, Nechitaylo TY, Haas R, Machuy N, Salama N, Churin Y, Meyer TF (2013) Helicobacter pylori outer membrane protein HopQ identified as a novel T4SS-associated virulence factor. Cell Microbiol 15(11):1896–1912.  https://doi.org/10.1111/cmi.12158 CrossRefPubMedPubMedCentralGoogle Scholar
  21. Berthenet E, Yahara K, Thorell K, Pascoe B, Meric G, Mikhail JM, Engstrand L, Enroth H, Burette A, Megraud F, Varon C, Atherton JC, Smith S, Wilkinson TS, Hitchings MD, Falush D, Sheppard SK (2018) A GWAS on Helicobacter pylori strains points to genetic variants associated with gastric cancer risk. BMC Biol 16(1):84.  https://doi.org/10.1186/s12915-018-0550-3 CrossRefPubMedPubMedCentralGoogle Scholar
  22. Blaser MJ, Perez-Perez GI, Kleanthous H, Cover TL, Peek RM, Chyou PH, Stemmermann GN, Nomura A (1995) Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach. Cancer Res 55(10):2111–2115PubMedPubMedCentralGoogle Scholar
  23. Bridge DR, Merrell DS (2013) Polymorphism in the Helicobacter pylori CagA and VacA toxins and disease. Gut Microbes 4(2):101–117.  https://doi.org/10.4161/gmic.23797 CrossRefPubMedPubMedCentralGoogle Scholar
  24. Caner V, Yilmaz M, Yonetci N, Zencir S, Karagenc N, Kaleli I, Bagci H (2007) H. pylori iceA alleles are disease-specific virulence factors. World J Gastroenterol 13(18):2581–2585CrossRefPubMedPubMedCentralGoogle Scholar
  25. Cao P, Cover TL (2002) Two different families of hopQ alleles in Helicobacter pylori. J Clin Microbiol 40(12):4504–4511CrossRefPubMedPubMedCentralGoogle Scholar
  26. Cao P, Lee KJ, Blaser MJ, Cover TL (2005) Analysis of hopQ alleles in East Asian and Western strains of Helicobacter pylori. FEMS Microbiol Lett 251(1):37–43.  https://doi.org/10.1016/j.femsle.2005.07.023 CrossRefPubMedPubMedCentralGoogle Scholar
  27. Censini S, Lange C, Xiang Z, Crabtree JE, Ghiara P, Borodovsky M, Rappuoli R, Covacci A (1996) cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors. Proc Natl Acad Sci U S A 93(25):14648–14653CrossRefPubMedPubMedCentralGoogle Scholar
  28. Chen MY, He CY, Meng X, Yuan Y (2013) Association of Helicobacter pylori babA2 with peptic ulcer disease and gastric cancer. World J Gastroenterol 19(26):4242–4251.  https://doi.org/10.3748/wjg.v19.i26.4242 CrossRefPubMedPubMedCentralGoogle Scholar
  29. Chen YL, Mo XQ, Huang GR, Huang YQ, Xiao J, Zhao LJ, Wei HY, Liang Q (2016) Gene polymorphisms of pathogenic Helicobacter pylori in patients with different types of gastrointestinal diseases. World J Gastroenterol 22(44):9718–9726.  https://doi.org/10.3748/wjg.v22.i44.9718 CrossRefPubMedPubMedCentralGoogle Scholar
  30. Chiarini A, Cala C, Bonura C, Gullo A, Giuliana G, Peralta S, D’Arpa F, Giammanco A (2009) Prevalence of virulence-associated genotypes of Helicobacter pylori and correlation with severity of gastric pathology in patients from western Sicily, Italy. Eur J Clin Microbiol Infect Dis 28(5):437–446.  https://doi.org/10.1007/s10096-008-0644-x CrossRefPubMedGoogle Scholar
  31. Chiurillo MA, Moran Y, Canas M, Valderrama E, Alvarez A, Armanie E (2010) Combination of Helicobacter pylori-iceA2 and proinflammatory interleukin-1 polymorphisms is associated with the severity of histological changes in Venezuelan chronic gastritis patients. FEMS Immunol Med Microbiol 59(2):170–176.  https://doi.org/10.1111/j.1574-695X.2010.00675.x CrossRefPubMedPubMedCentralGoogle Scholar
  32. Chmiela M, Karwowska Z, Gonciarz W, Allushi B, Staczek P (2017) Host pathogen interactions in Helicobacter pylori related gastric cancer. World J Gastroenterol 23(9):1521–1540.  https://doi.org/10.3748/wjg.v23.i9.1521 CrossRefPubMedPubMedCentralGoogle Scholar
  33. Choi KD, Kim N, Lee DH, Kim JM, Kim JS, Jung HC, Song IS (2007) Analysis of the 3′ variable region of the cagA gene of Helicobacter pylori isolated in Koreans. Dig Dis Sci 52(4):960–966.  https://doi.org/10.1007/s10620-005-9030-z CrossRefPubMedPubMedCentralGoogle Scholar
  34. Chomvarin C, Namwat W, Chaicumpar K, Mairiang P, Sangchan A, Sripa B, Tor-Udom S, Vilaichone RK (2008) Prevalence of Helicobacter pylori vacA, cagA, cagE, iceA and babA2 genotypes in Thai dyspeptic patients. Int J Infect Dis 12(1):30–36.  https://doi.org/10.1016/j.ijid.2007.03.012 CrossRefPubMedPubMedCentralGoogle Scholar
  35. Colbeck JC, Hansen LM, Fong JM, Solnick JV (2006) Genotypic profile of the outer membrane proteins BabA and BabB in clinical isolates of Helicobacter pylori. Infect Immun 74(7):4375–4378.  https://doi.org/10.1128/iai.00485-06 CrossRefPubMedPubMedCentralGoogle Scholar
  36. Covacci A, Censini S, Bugnoli M, Petracca R, Burroni D, Macchia G, Massone A, Papini E, Xiang Z, Figura N (1993) Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer. Proc Natl Acad Sci U S A 90(12):5791–5795CrossRefPubMedPubMedCentralGoogle Scholar
  37. Cover TL, Blaser MJ (1992) Purification and characterization of the vacuolating toxin from Helicobacter pylori. J Biol Chem 267(15):10570–10575PubMedPubMedCentralGoogle Scholar
  38. Cover TL, Blaser MJ (2009) Helicobacter pylori in health and disease. Gastroenterology 136(6):1863–1873.  https://doi.org/10.1053/j.gastro.2009.01.073 CrossRefPubMedPubMedCentralGoogle Scholar
  39. Cover TL, Tummuru MK, Cao P, Thompson SA, Blaser MJ (1994) Divergence of genetic sequences for the vacuolating cytotoxin among Helicobacter pylori strains. J Biol Chem 269(14):10566–10573PubMedPubMedCentralGoogle Scholar
  40. Dadashzadeh K, Peppelenbosch MP, Adamu AI (2017) Helicobacter pylori pathogenicity factors related to gastric cancer. Can J Gastroenterol Hepatol 2017:7942489.  https://doi.org/10.1155/2017/7942489 CrossRefPubMedPubMedCentralGoogle Scholar
  41. de Bernard M, Burroni D, Papini E, Rappuoli R, Telford J, Montecucco C (1998) Identification of the Helicobacter pylori VacA toxin domain active in the cell cytosol. Infect Immun 66(12):6014–6016PubMedPubMedCentralGoogle Scholar
  42. de Jonge R, Pot RG, Loffeld RJ, van Vliet AH, Kuipers EJ, Kusters JG (2004) The functional status of the Helicobacter pylori sabB adhesin gene as a putative marker for disease outcome. Helicobacter 9(2):158–164.  https://doi.org/10.1111/j.1083-4389.2004.00213.x CrossRefPubMedPubMedCentralGoogle Scholar
  43. de Reuse H, Bereswill S (2007) Ten years after the first Helicobacter pylori genome: comparative and functional genomics provide new insights in the variability and adaptability of a persistent pathogen. FEMS Immunol Med Microbiol 50(2):165–176.  https://doi.org/10.1111/j.1574-695X.2007.00244.x CrossRefPubMedPubMedCentralGoogle Scholar
  44. Doenges JL (1938) Spirochetes in gastric glands of Macacus rhesus and humans without definite history of related disease. Proc Soc Exp Biol Med 38(4):536–538CrossRefGoogle Scholar
  45. Doenges JL (1939) Spirochetes in the gastric glands of Macacus rhesus and of man without related diseases. Arch Pathol 27:469–477Google Scholar
  46. Dossumbekova A, Prinz C, Mages J, Lang R, Kusters JG, Van Vliet AH, Reindl W, Backert S, Saur D, Schmid RM, Rad R (2006) Helicobacter pylori HopH (OipA) and bacterial pathogenicity: genetic and functional genomic analysis of hopH gene polymorphisms. J Infect Dis 194(10):1346–1355.  https://doi.org/10.1086/508426 CrossRefPubMedPubMedCentralGoogle Scholar
  47. Draper JL, Hansen LM, Bernick DL, Abedrabbo S, Underwood JG, Kong N, Huang BC, Weis AM, Weimer BC, van Vliet AH, Pourmand N, Solnick JV, Karplus K, Ottemann KM (2017) Fallacy of the unique genome: sequence diversity within single Helicobacter pylori strains. MBio 8(1).  https://doi.org/10.1128/mBio.02321-16
  48. Dunn BE, Cohen H, Blaser MJ (1997) Helicobacter pylori. Clin Microbiol Rev 10(4):720–741CrossRefPubMedPubMedCentralGoogle Scholar
  49. Eross B, Farkas N, Vincze A, Tinusz B, Szapary L, Garami A, Balasko M, Sarlos P, Czopf L, Alizadeh H, Rakonczay Z Jr, Habon T, Hegyi P (2018) Helicobacter pylori infection reduces the risk of Barrett’s esophagus: a meta-analysis and systematic review. Helicobacter 23(4):e12504.  https://doi.org/10.1111/hel.12504 CrossRefPubMedPubMedCentralGoogle Scholar
  50. Farzi N, Yadegar A, Aghdaei HA, Yamaoka Y, Zali MR (2018) Genetic diversity and functional analysis of oipA gene in association with other virulence factors among Helicobacter pylori isolates from Iranian patients with different gastric diseases. Infect Genet Evol 60:26–34.  https://doi.org/10.1016/j.meegid.2018.02.017 CrossRefPubMedPubMedCentralGoogle Scholar
  51. Ferreira RM, Machado JC, Leite M, Carneiro F, Figueiredo C (2012) The number of Helicobacter pylori CagA EPIYA C tyrosine phosphorylation motifs influences the pattern of gastritis and the development of gastric carcinoma. Histopathology 60(6):992–998.  https://doi.org/10.1111/j.1365-2559.2012.04190.x CrossRefPubMedPubMedCentralGoogle Scholar
  52. Figueiredo C, Quint WG, Sanna R, Sablon E, Donahue JP, Xu Q, Miller GG, Peek RM Jr, Blaser MJ, van Doorn LJ (2000) Genetic organization and heterogeneity of the iceA locus of Helicobacter pylori. Gene 246(1–2):59–68CrossRefPubMedPubMedCentralGoogle Scholar
  53. Figura N, Oderda G (1996) Reflections on the first description of the presence of Helicobacter species in the stomach of mammals. Helicobacter 1(1):4–5CrossRefPubMedPubMedCentralGoogle Scholar
  54. Figura N, Moretti E, Roviello F, Papini F, Marrelli D (2012) cagA structural types of Helicobacter pylori strains isolated from patients with gastric carcinoma and chronic gastritis only. Intern Emerg Med 7(Suppl 2):S103–S105.  https://doi.org/10.1007/s11739-012-0759-z CrossRefPubMedPubMedCentralGoogle Scholar
  55. Floch P, Megraud F, Lehours P (2017) Helicobacter pylori strains and gastric MALT lymphoma. Toxins (Basel) 9(4).  https://doi.org/10.3390/toxins9040132
  56. Foegeding NJ, Caston RR, McClain MS, Ohi MD, Cover TL (2016) An overview of Helicobacter pylori VacA toxin biology. Toxins (Basel) 8(6).  https://doi.org/10.3390/toxins8060173
  57. Forsyth MH, Atherton JC, Blaser MJ, Cover TL (1998) Heterogeneity in levels of vacuolating cytotoxin gene (vacA) transcription among Helicobacter pylori strains. Infect Immun 66(7):3088–3094PubMedPubMedCentralGoogle Scholar
  58. Franco AT, Israel DA, Washington MK, Krishna U, Fox JG, Rogers AB, Neish AS, Collier-Hyams L, Perez-Perez GI, Hatakeyama M, Whitehead R, Gaus K, O’Brien DP, Romero-Gallo J, Peek RM Jr (2005) Activation of beta-catenin by carcinogenic Helicobacter pylori. Proc Natl Acad Sci U S A 102(30):10646–10651.  https://doi.org/10.1073/pnas.0504927102 CrossRefPubMedPubMedCentralGoogle Scholar
  59. Freedberg A, Barron L (1940) The presence of spirochetes in human gastric mucosa. Am J Dig Dis 7(10):443–445.  https://doi.org/10.1007/bf02997393 CrossRefGoogle Scholar
  60. Fujimoto S, Olaniyi Ojo O, Arnqvist A, Wu JY, Odenbreit S, Haas R, Graham DY, Yamaoka Y (2007) Helicobacter pylori BabA expression, gastric mucosal injury, and clinical outcome. Clin Gastroenterol Hepatol 5(1):49–58.  https://doi.org/10.1016/j.cgh.2006.09.015 CrossRefPubMedPubMedCentralGoogle Scholar
  61. Furuta Y, Yahara K, Hatakeyama M, Kobayashi I (2011) Evolution of cagA oncogene of Helicobacter pylori through recombination. PLoS One 6(8):e23499.  https://doi.org/10.1371/journal.pone.0023499 CrossRefPubMedPubMedCentralGoogle Scholar
  62. Gerhard M, Lehn N, Neumayer N, Boren T, Rad R, Schepp W, Miehlke S, Classen M, Prinz C (1999) Clinical relevance of the Helicobacter pylori gene for blood-group antigen-binding adhesin. Proc Natl Acad Sci U S A 96(22):12778–12783CrossRefPubMedPubMedCentralGoogle Scholar
  63. Gunn MC, Stephens JC, Stewart JA, Rathbone BJ, West KP (1998) The significance of cagA and vacA subtypes of Helicobacter pylori in the pathogenesis of inflammation and peptic ulceration. J Clin Pathol 51(10):761–764CrossRefPubMedPubMedCentralGoogle Scholar
  64. Hansen LM, Gideonsson P, Canfield DR, Boren T, Solnick JV (2017) Dynamic expression of the BabA adhesin and its BabB paralog during Helicobacter pylori infection in rhesus macaques. Infect Immun 85(6).  https://doi.org/10.1128/iai.00094-17
  65. Hatakeyama M (2006) Helicobacter pylori CagA – a bacterial intruder conspiring gastric carcinogenesis. Int J Cancer 119(6):1217–1223.  https://doi.org/10.1002/ijc.21831 CrossRefPubMedPubMedCentralGoogle Scholar
  66. Higashi H, Tsutsumi R, Fujita A, Yamazaki S, Asaka M, Azuma T, Hatakeyama M (2002) Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites. Proc Natl Acad Sci U S A 99(22):14428–14433.  https://doi.org/10.1073/pnas.222375399 CrossRefPubMedPubMedCentralGoogle Scholar
  67. Homan M, Sterbenc A, Kocjan BJ, Luzar B, Zidar N, Orel R, Poljak M (2014) Prevalence of the Helicobacter pylori babA2 gene and correlation with the degree of gastritis in infected Slovenian children. Antonie Van Leeuwenhoek 106(4):637–645.  https://doi.org/10.1007/s10482-014-0234-0 CrossRefPubMedPubMedCentralGoogle Scholar
  68. Huang JY, Sweeney EG, Sigal M, Zhang HC, Remington SJ, Cantrell MA, Kuo CJ, Guillemin K, Amieva MR (2015) Chemodetection and destruction of host urea allows Helicobacter pylori to locate the epithelium. Cell Host Microbe 18(2):147–156.  https://doi.org/10.1016/j.chom.2015.07.002 CrossRefPubMedPubMedCentralGoogle Scholar
  69. Huang X, Deng Z, Zhang Q, Li W, Wang B, Li M (2016) Relationship between the iceA gene of Helicobacter pylori and clinical outcomes. Ther Clin Risk Manag 12:1085–1092.  https://doi.org/10.2147/tcrm.s107991 CrossRefPubMedPubMedCentralGoogle Scholar
  70. Hussein NR (2011) A study of Helicobacter pylori outer-membrane proteins (hom) A and B in Iraq and Turkey. J Infect Public Health 4(3):135–139.  https://doi.org/10.1016/j.jiph.2011.03.004 CrossRefPubMedPubMedCentralGoogle Scholar
  71. Hussein NR (2014) Helicobacter pylori vacA d1 genotype is associated with gastric cancer but not peptic ulcers in Kurdistan region, northern Iraq. Asian Pac J Cancer Prev 15(14):5965–5966CrossRefPubMedPubMedCentralGoogle Scholar
  72. Ilver D, Arnqvist A, Ogren J, Frick IM, Kersulyte D, Incecik ET, Berg DE, Covacci A, Engstrand L, Boren T (1998) Helicobacter pylori adhesin binding fucosylated histo-blood group antigens revealed by retagging. Science 279(5349):373–377CrossRefPubMedPubMedCentralGoogle Scholar
  73. International Agency for Research on Cancer (2012) Cancer fact sheets: Stomach Cancer. World Health Organization. http://gco.iarc.fr/today/fact-sheets-cancers?cancer=5&type=0&sex=0. Accessed 9-6-2018
  74. Ito S (1967) Anatomic structure of the gastric mucosa. In: Code CF (ed) Alimentary Canal, vol II. American Physiological Society, Washington, DC, pp 705–741Google Scholar
  75. Ito Y, Azuma T, Ito S, Suto H, Miyaji H, Yamazaki Y, Kato T, Kohli Y, Keida Y, Kuriyama M (2000) Sequence analysis and clinical significance of the iceA gene from Helicobacter pylori strains in Japan. J Clin Microbiol 38(2):483–488PubMedPubMedCentralGoogle Scholar
  76. Jang S, Jones KR, Olsen CH, Joo YM, Yoo YJ, Chung IS, Cha JH, Merrell DS (2010) Epidemiological link between gastric disease and polymorphisms in VacA and CagA. J Clin Microbiol 48(2):559–567.  https://doi.org/10.1128/jcm.01501-09 CrossRefPubMedPubMedCentralGoogle Scholar
  77. Javaheri A, Kruse T, Moonens K, Mejias-Luque R, Debraekeleer A, Asche CI, Tegtmeyer N, Kalali B, Bach NC, Sieber SA, Hill DJ, Koniger V, Hauck CR, Moskalenko R, Haas R, Busch DH, Klaile E, Slevogt H, Schmidt A, Backert S, Remaut H, Singer BB, Gerhard M (2016) Helicobacter pylori adhesin HopQ engages in a virulence-enhancing interaction with human CEACAMs. Nat Microbiol 2:16189.  https://doi.org/10.1038/nmicrobiol.2016.189 CrossRefPubMedPubMedCentralGoogle Scholar
  78. Jones KR, Joo YM, Jang S, Yoo YJ, Lee HS, Chung IS, Olsen CH, Whitmire JM, Merrell DS, Cha JH (2009) Polymorphism in the CagA EPIYA motif impacts development of gastric cancer. J Clin Microbiol 47(4):959–968.  https://doi.org/10.1128/jcm.02330-08 CrossRefPubMedPubMedCentralGoogle Scholar
  79. Jones KR, Whitmire JM, Merrell DS (2010) A tale of two toxins: Helicobacter pylori CagA and VacA modulate host pathways that impact disease. Front Microbiol 1:115.  https://doi.org/10.3389/fmicb.2010.00115 CrossRefPubMedPubMedCentralGoogle Scholar
  80. Jones KR, Jang S, Chang JY, Kim J, Chung IS, Olsen CH, Merrell DS, Cha JH (2011) Polymorphisms in the intermediate region of VacA impact Helicobacter pylori-induced disease development. J Clin Microbiol 49(1):101–110.  https://doi.org/10.1128/jcm.01782-10 CrossRefPubMedPubMedCentralGoogle Scholar
  81. Kang J, Jones KR, Jang S, Olsen CH, Yoo YJ, Merrell DS, Cha JH (2012) The geographic origin of Helicobacter pylori influences the association of the homB gene with gastric cancer. J Clin Microbiol 50(3):1082–1085.  https://doi.org/10.1128/jcm.06293-11 CrossRefPubMedPubMedCentralGoogle Scholar
  82. Kao CY, Sheu BS, Wu JJ (2016) Helicobacter pylori infection: an overview of bacterial virulence factors and pathogenesis. Biom J 39(1):14–23.  https://doi.org/10.1016/j.bj.2015.06.002 CrossRefGoogle Scholar
  83. Kasai K, Kobayashi R (1919) The stomach spirochete occurring in mammals. J Parasitol 6:1–10CrossRefGoogle Scholar
  84. Kidd M, Peek RM, Lastovica AJ, Israel DA, Kummer AF, Louw JA (2001) Analysis of iceA genotypes in south African Helicobacter pylori strains and relationship to clinically significant disease. Gut 49(5):629–635CrossRefPubMedPubMedCentralGoogle Scholar
  85. Kim A, Servetas SL, Kang J, Kim J, Jang S, Cha HJ, Lee WJ, Kim J, Romero-Gallo J, Peek RM Jr, Merrell DS, Cha JH (2015) Helicobacter pylori bab paralog distribution and association with cagA, vacA, and homA/B genotypes in American and South Korean clinical isolates. PLoS One 10(8):e0137078.  https://doi.org/10.1371/journal.pone.0137078 CrossRefPubMedPubMedCentralGoogle Scholar
  86. Koniger V, Holsten L, Harrison U, Busch B, Loell E, Zhao Q, Bonsor DA, Roth A, Kengmo-Tchoupa A, Smith SI, Mueller S, Sundberg EJ, Zimmermann W, Fischer W, Hauck CR, Haas R (2016) Helicobacter pylori exploits human CEACAMs via HopQ for adherence and translocation of CagA. Nat Microbiol 2:16188.  https://doi.org/10.1038/nmicrobiol.2016.188 CrossRefPubMedPubMedCentralGoogle Scholar
  87. Kusters JG, van Vliet AH, Kuipers EJ (2006) Pathogenesis of Helicobacter pylori infection. Clin Microbiol Rev 19(3):449–490.  https://doi.org/10.1128/cmr.00054-05 CrossRefPubMedPubMedCentralGoogle Scholar
  88. Kyburz A, Muller A (2017) Helicobacter pylori and extragastric diseases. Curr Top Microbiol Immunol 400:325–347.  https://doi.org/10.1007/978-3-319-50520-6_14 CrossRefPubMedPubMedCentralGoogle Scholar
  89. Latifi-Navid S, Mohammadi S, Maleki P, Zahri S, Yazdanbod A, Siavoshi F, Massarrat S (2013) Helicobacter pylori vacA d1/−i1 genotypes and geographic differentiation between high and low incidence areas of gastric cancer in Iran. Arch Iran Med 16(6):330–337.  https://doi.org/10.13166/aim.005 CrossRefPubMedPubMedCentralGoogle Scholar
  90. Leunk RD, Johnson PT, David BC, Kraft WG, Morgan DR (1988) Cytotoxic activity in broth-culture filtrates of Campylobacter pylori. J Med Microbiol 26(2):93–99.  https://doi.org/10.1099/00222615-26-2-93 CrossRefPubMedPubMedCentralGoogle Scholar
  91. Leylabadlo HE, Yekani M, Ghotaslou R (2016) Helicobacter pylori hopQ alleles (type I and II) in gastric cancer. Biomed Rep 4(5):601–604.  https://doi.org/10.3892/br.2016.634 CrossRefPubMedPubMedCentralGoogle Scholar
  92. Li Q, Liu J, Gong Y, Yuan Y (2017) Association of CagA EPIYA-D or EPIYA-C phosphorylation sites with peptic ulcer and gastric cancer risks: a meta-analysis. Medicine (Baltimore) 96(17):e6620.  https://doi.org/10.1097/md.0000000000006620 CrossRefGoogle Scholar
  93. Liu J, He C, Chen M, Wang Z, Xing C, Yuan Y (2013) Association of presence/absence and on/off patterns of Helicobacter pylori oipA gene with peptic ulcer disease and gastric cancer risks: a meta-analysis. BMC Infect Dis 13:555.  https://doi.org/10.1186/1471-2334-13-555 CrossRefPubMedPubMedCentralGoogle Scholar
  94. Liu H, Fero JB, Mendez M, Carpenter BM, Servetas SL, Rahman A, Goldman MD, Boren T, Salama NR, Merrell DS, Dubois A (2015) Analysis of a single Helicobacter pylori strain over a 10-year period in a primate model. Int J Med Microbiol 305(3):392–403.  https://doi.org/10.1016/j.ijmm.2015.03.002 CrossRefPubMedPubMedCentralGoogle Scholar
  95. Liu X, He B, Cho WC, Pan Y, Chen J, Ying H, Wang F, Lin K, Peng H, Wang S (2016) A systematic review on the association between the Helicobacter pylori vacA i genotype and gastric disease. FEBS Open Bio 6(5):409–417.  https://doi.org/10.1002/2211-5463.12046 CrossRefPubMedPubMedCentralGoogle Scholar
  96. Lockard VG, Boler RK (1970) Ultrastructure of a spiraled microorganism in the gastric mucosa of dogs. Am J Vet Res 31(8):1453–1462PubMedPubMedCentralGoogle Scholar
  97. Lopez-Vidal Y, Ponce-de-Leon S, Castillo-Rojas G, Barreto-Zuniga R, Torre-Delgadillo A (2008) High diversity of vacA and cagA Helicobacter pylori genotypes in patients with and without gastric cancer. PLoS One 3(12):e3849.  https://doi.org/10.1371/journal.pone.0003849 CrossRefPubMedPubMedCentralGoogle Scholar
  98. Mahdavi J, Sonden B, Hurtig M, Olfat FO, Forsberg L, Roche N, Angstrom J, Larsson T, Teneberg S, Karlsson KA, Altraja S, Wadstrom T, Kersulyte D, Berg DE, Dubois A, Petersson C, Magnusson KE, Norberg T, Lindh F, Lundskog BB, Arnqvist A, Hammarstrom L, Boren T (2002) Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation. Science 297(5581):573–578.  https://doi.org/10.1126/science.1069076 CrossRefPubMedPubMedCentralGoogle Scholar
  99. Markovska R, Boyanova L, Yordanov D, Gergova G, Mitov I (2011) Helicobacter pylori oipA genetic diversity and its associations with both disease and cagA, vacA s, m, and i alleles among Bulgarian patients. Diagn Microbiol Infect Dis 71(4):335–340.  https://doi.org/10.1016/j.diagmicrobio.2011.08.008 CrossRefPubMedPubMedCentralGoogle Scholar
  100. Marshall BJ (2001) One hundred years of discovery and rediscovery of Helicobacter pylori and its association with peptic ulcer disease. In: Mobley HLT, Mendz GL, Hazell SL (eds) Helicobacter pylori: physiology and genetics. ASM Press, Washington, DC, pp 19–24CrossRefGoogle Scholar
  101. Marshall BJ, Warren JR (1984) Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 323(8390):1311–1315CrossRefGoogle Scholar
  102. Marshall BJ, Royce H, Annear DI, Goodwin CS, Pearman JW, Warren JR, Armstrong JA (1984) Original isolation of Campylobacter pyloridis from human gastric mucosa. Microbios Lett 25:83–88Google Scholar
  103. Marshall BJ, Armstrong JA, McGechie DB, Glancy RJ (1985a) Attempt to fulfil Koch’s postulates for pyloric Campylobacter. Med J Aust 142(8):436–439CrossRefPubMedPubMedCentralGoogle Scholar
  104. Marshall BJ, McGechie DB, Rogers PA, Glancy RJ (1985b) Pyloric Campylobacter infection and gastroduodenal disease. Med J Aust 142(8):439–444CrossRefPubMedPubMedCentralGoogle Scholar
  105. Matos JI, de Sousa HA, Marcos-Pinto R, Dinis-Ribeiro M (2013) Helicobacter pylori CagA and VacA genotypes and gastric phenotype: a meta-analysis. Eur J Gastroenterol Hepatol 25(12):1431–1441.  https://doi.org/10.1097/MEG.0b013e328364b53e CrossRefPubMedPubMedCentralGoogle Scholar
  106. Matsuo Y, Kido Y, Yamaoka Y (2017) Helicobacter pylori outer membrane protein-related pathogenesis. Toxins (Basel) 9(3).  https://doi.org/10.3390/toxins9030101
  107. Matteo MJ, Armitano RI, Romeo M, Wonaga A, Olmos M, Catalano M (2011) Helicobacter pylori bab genes during chronic colonization. Int J Mol Epidemiol Genet 2(3):286–291PubMedPubMedCentralGoogle Scholar
  108. McClain MS, Cao P, Iwamoto H, Vinion-Dubiel AD, Szabo G, Shao Z, Cover TL (2001) A 12-amino-acid segment, present in type s2 but not type s1 Helicobacter pylori VacA proteins, abolishes cytotoxin activity and alters membrane channel formation. J Bacteriol 183(22):6499–6508.  https://doi.org/10.1128/jb.183.22.6499-6508.2001 CrossRefPubMedPubMedCentralGoogle Scholar
  109. McClain MS, Beckett AC, Cover TL (2017) Helicobacter pylori Vacuolating toxin and gastric Cancer. Toxins (Basel) 9(10).  https://doi.org/10.3390/toxins9100316
  110. Miehlke S, Kibler K, Kim JG, Figura N, Small SM, Graham DY, Go MF (1996) Allelic variation in the cagA gene of Helicobacter pylori obtained from Korea compared to the United States. Am J Gastroenterol 91(7):1322–1325PubMedPubMedCentralGoogle Scholar
  111. Miehlke S, Yu J, Schuppler M, Frings C, Kirsch C, Negraszus N, Morgner A, Stolte M, Ehninger G, Bayerdorffer E (2001) Helicobacter pylori vacA, iceA, and cagA status and pattern of gastritis in patients with malignant and benign gastroduodenal disease. Am J Gastroenterol 96(4):1008–1013.  https://doi.org/10.1111/j.1572-0241.2001.03685.x CrossRefPubMedPubMedCentralGoogle Scholar
  112. Miura M, Ohnishi N, Tanaka S, Yanagiya K, Hatakeyama M (2009) Differential oncogenic potential of geographically distinct Helicobacter pylori CagA isoforms in mice. Int J Cancer 125(11):2497–2504.  https://doi.org/10.1002/ijc.24740 CrossRefPubMedPubMedCentralGoogle Scholar
  113. Mizushima T, Sugiyama T, Komatsu Y, Ishizuka J, Kato M, Asaka M (2001) Clinical relevance of the babA2 genotype of Helicobacter pylori in Japanese clinical isolates. J Clin Microbiol 39(7):2463–2465.  https://doi.org/10.1128/jcm.39.7.2463-2465.2001 CrossRefPubMedPubMedCentralGoogle Scholar
  114. Moonens K, Hamway Y, Neddermann M, Reschke M, Tegtmeyer N, Kruse T, Kammerer R, Mejias-Luque R, Singer BB, Backert S, Gerhard M, Remaut H (2018) Helicobacter pylori adhesin HopQ disrupts trans dimerization in human CEACAMs. EMBO J 37(13).  https://doi.org/10.15252/embj.201798665
  115. Nishikawa H, Hatakeyama M (2017) Sequence polymorphism and intrinsic structural disorder as related to pathobiological performance of the Helicobacter pylori CagA oncoprotein. Toxins (Basel) 9(4).  https://doi.org/10.3390/toxins9040136
  116. Odenbreit S, Puls J, Sedlmaier B, Gerland E, Fischer W, Haas R (2000) Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion. Science 287(5457):1497–1500CrossRefPubMedPubMedCentralGoogle Scholar
  117. Ogiwara H, Sugimoto M, Ohno T, Vilaichone RK, Mahachai V, Graham DY, Yamaoka Y (2009) Role of deletion located between the intermediate and middle regions of the Helicobacter pylori vacA gene in cases of gastroduodenal diseases. J Clin Microbiol 47(11):3493–3500.  https://doi.org/10.1128/jcm.00887-09 CrossRefPubMedPubMedCentralGoogle Scholar
  118. Ogorodnik E, Raffaniello RD (2013) Analysis of the 3′-variable region of the cagA gene from Helicobacter pylori strains infecting patients at New York City hospitals. Microb Pathog 56:29–34.  https://doi.org/10.1016/j.micpath.2012.10.003 CrossRefPubMedPubMedCentralGoogle Scholar
  119. Ohnishi N, Yuasa H, Tanaka S, Sawa H, Miura M, Matsui A, Higashi H, Musashi M, Iwabuchi K, Suzuki M, Yamada G, Azuma T, Hatakeyama M (2008) Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse. Proc Natl Acad Sci U S A 105(3):1003–1008.  https://doi.org/10.1073/pnas.0711183105 CrossRefPubMedPubMedCentralGoogle Scholar
  120. Ohno T, Sugimoto M, Nagashima A, Ogiwara H, Vilaichone RK, Mahachai V, Graham DY, Yamaoka Y (2009) Relationship between Helicobacter pylori hopQ genotype and clinical outcome in Asian and Western populations. J Gastroenterol Hepatol 24(3):462–468.  https://doi.org/10.1111/j.1440-1746.2008.05762.x CrossRefPubMedPubMedCentralGoogle Scholar
  121. Ohno T, Vallstrom A, Rugge M, Ota H, Graham DY, Arnqvist A, Yamaoka Y (2011) Effects of blood group antigen-binding adhesin expression during Helicobacter pylori infection of Mongolian gerbils. J Infect Dis 203(5):726–735.  https://doi.org/10.1093/infdis/jiq090 CrossRefPubMedPubMedCentralGoogle Scholar
  122. Oleastro M, Menard A (2013) The role of Helicobacter pylori outer membrane proteins in adherence and pathogenesis. Biology (Basel) 2(3):1110–1134.  https://doi.org/10.3390/biology2031110 CrossRefGoogle Scholar
  123. Oleastro M, Cordeiro R, Ferrand J, Nunes B, Lehours P, Carvalho-Oliveira I, Mendes AI, Penque D, Monteiro L, Megraud F, Menard A (2008) Evaluation of the clinical significance of homB, a novel candidate marker of Helicobacter pylori strains associated with peptic ulcer disease. J Infect Dis 198(9):1379–1387.  https://doi.org/10.1086/592166 CrossRefPubMedPubMedCentralGoogle Scholar
  124. Oleastro M, Cordeiro R, Menard A, Yamaoka Y, Queiroz D, Megraud F, Monteiro L (2009a) Allelic diversity and phylogeny of homB, a novel co-virulence marker of Helicobacter pylori. BMC Microbiol 9:248.  https://doi.org/10.1186/1471-2180-9-248 CrossRefPubMedPubMedCentralGoogle Scholar
  125. Oleastro M, Cordeiro R, Yamaoka Y, Queiroz D, Megraud F, Monteiro L, Menard A (2009b) Disease association with two Helicobacter pylori duplicate outer membrane protein genes, homB and homA. Gut Pathog 1(1):12.  https://doi.org/10.1186/1757-4749-1-12 CrossRefPubMedPubMedCentralGoogle Scholar
  126. Oleastro M, Santos A, Cordeiro R, Nunes B, Megraud F, Menard A (2010) Clinical relevance and diversity of two homologous genes encoding glycosyltransferases in Helicobacter pylori. J Clin Microbiol 48(8):2885–2891.  https://doi.org/10.1128/jcm.00401-10 CrossRefPubMedPubMedCentralGoogle Scholar
  127. Olfat FO, Zheng Q, Oleastro M, Voland P, Boren T, Karttunen R, Engstrand L, Rad R, Prinz C, Gerhard M (2005) Correlation of the Helicobacter pylori adherence factor BabA with duodenal ulcer disease in four European countries. FEMS Immunol Med Microbiol 44(2):151–156.  https://doi.org/10.1016/j.femsim.2004.10.010 CrossRefPubMedPubMedCentralGoogle Scholar
  128. Pagliaccia C, de Bernard M, Lupetti P, Ji X, Burroni D, Cover TL, Papini E, Rappuoli R, Telford JL, Reyrat JM (1998) The m2 form of the Helicobacter pylori cytotoxin has cell type-specific vacuolating activity. Proc Natl Acad Sci U S A 95(17):10212–10217CrossRefPubMedPubMedCentralGoogle Scholar
  129. Parsonnet J, Friedman GD, Orentreich N, Vogelman H (1997) Risk for gastric cancer in people with CagA positive or CagA negative Helicobacter pylori infection. Gut 40(3):297–301CrossRefPubMedPubMedCentralGoogle Scholar
  130. Peek RM Jr, Thompson SA, Donahue JP, Tham KT, Atherton JC, Blaser MJ, Miller GG (1998) Adherence to gastric epithelial cells induces expression of a Helicobacter pylori gene, iceA, that is associated with clinical outcome. Proc Assoc Am Physicians 110(6):531–544PubMedPubMedCentralGoogle Scholar
  131. Pormohammad A, Ghotaslou R, Leylabadlo HE, Nasiri MJ, Dabiri H, Hashemi A (2018) Risk of gastric cancer in association with Helicobacter pylori different virulence factors: a systematic review and meta-analysis. Microb Pathog 118:214–219.  https://doi.org/10.1016/j.micpath.2018.03.004 CrossRefPubMedPubMedCentralGoogle Scholar
  132. Pride DT, Blaser MJ (2002) Concerted evolution between duplicated genetic elements in Helicobacter pylori. J Mol Biol 316(3):629–642.  https://doi.org/10.1006/jmbi.2001.5311 CrossRefPubMedPubMedCentralGoogle Scholar
  133. Ren S, Higashi H, Lu H, Azuma T, Hatakeyama M (2006) Structural basis and functional consequence of Helicobacter pylori CagA multimerization in cells. J Biol Chem 281(43):32344–32352.  https://doi.org/10.1074/jbc.M606172200 CrossRefPubMedPubMedCentralGoogle Scholar
  134. Rhead JL, Letley DP, Mohammadi M, Hussein N, Mohagheghi MA, Eshagh Hosseini M, Atherton JC (2007) A new Helicobacter pylori vacuolating cytotoxin determinant, the intermediate region, is associated with gastric cancer. Gastroenterology 133(3):926–936.  https://doi.org/10.1053/j.gastro.2007.06.056 CrossRefPubMedPubMedCentralGoogle Scholar
  135. Ribeiro ML, Godoy AP, Benvengo YH, Mendonca S, Pedrazzoli J Jr (2003) Clinical relevance of the cagA, vacA and iceA genotypes of Helicobacter pylori in Brazilian clinical isolates. FEMS Immunol Med Microbiol 36(3):181–185CrossRefPubMedPubMedCentralGoogle Scholar
  136. Rizzato C, Torres J, Plummer M, Munoz N, Franceschi S, Camorlinga-Ponce M, Fuentes-Panana EM, Canzian F, Kato I (2012) Variations in Helicobacter pylori cytotoxin-associated genes and their influence in progression to gastric cancer: implications for prevention. PLoS One 7(1):e29605.  https://doi.org/10.1371/journal.pone.0029605 CrossRefPubMedPubMedCentralGoogle Scholar
  137. Robinson K (2015) Helicobacter pylori-mediated protection against extra-gastric immune and inflammatory disorders: the evidence and controversies. Diseases 3(2):34–55.  https://doi.org/10.3390/diseases3020034 CrossRefPubMedPubMedCentralGoogle Scholar
  138. Saberi S, Schmidt A, Eybpoosh S, Esmaili M, Talebkhan Y, Mohajerani N, Oghalaie A, Eshagh Hosseini M, Mohagheghi MA, Bugaytova J, Boren T, Mohammadi M (2016) Helicobacter pylori strains from duodenal ulcer patients exhibit mixed babA/B genotypes with low levels of BabA adhesin and Lewis b binding. Dig Dis Sci 61(10):2868–2877.  https://doi.org/10.1007/s10620-016-4217-z CrossRefPubMedPubMedCentralGoogle Scholar
  139. Sahara S, Sugimoto M, Vilaichone RK, Mahachai V, Miyajima H, Furuta T, Yamaoka Y (2012) Role of Helicobacter pylori cagA EPIYA motif and vacA genotypes for the development of gastrointestinal diseases in southeast Asian countries: a meta-analysis. BMC Infect Dis 12:223.  https://doi.org/10.1186/1471-2334-12-223
  140. Salama N, Guillemin K, McDaniel TK, Sherlock G, Tompkins L, Falkow S (2000) A whole-genome microarray reveals genetic diversity among Helicobacter pylori strains. Proc Natl Acad Sci U S A 97(26):14668–14673.  https://doi.org/10.1073/pnas.97.26.14668 CrossRefPubMedPubMedCentralGoogle Scholar
  141. Salaun L, Linz B, Suerbaum S, Saunders NJ (2004) The diversity within an expanded and redefined repertoire of phase-variable genes in Helicobacter pylori. Microbiology 150(Pt 4):817–830.  https://doi.org/10.1099/mic.0.26993-0 CrossRefPubMedPubMedCentralGoogle Scholar
  142. Servetas SL, Kim A, Su H, Cha JH, Merrell DS (2018) Comparative analysis of the Hom family of outer membrane proteins in isolates from two geographically distinct regions: the United States and South Korea. Helicobacter 23(2):e12461.  https://doi.org/10.1111/hel.12461 CrossRefPubMedPubMedCentralGoogle Scholar
  143. Sheu BS, Odenbreit S, Hung KH, Liu CP, Sheu SM, Yang HB, Wu JJ (2006) Interaction between host gastric Sialyl-Lewis X and H. pylori SabA enhances H. pylori density in patients lacking gastric Lewis B antigen. Am J Gastroenterol 101(1):36–44.  https://doi.org/10.1111/j.1572-0241.2006.00358.x CrossRefPubMedPubMedCentralGoogle Scholar
  144. Sheu SM, Sheu BS, Chiang WC, Kao CY, Wu HM, Yang HB, Wu JJ (2012) H. pylori clinical isolates have diverse babAB genotype distributions over different topographic sites of stomach with correlation to clinical disease outcomes. BMC Microbiol 12:89.  https://doi.org/10.1186/1471-2180-12-89 CrossRefPubMedPubMedCentralGoogle Scholar
  145. Shokrzadeh L, Baghaei K, Yamaoka Y, Dabiri H, Jafari F, Sahebekhtiari N, Tahami A, Sugimoto M, Zojaji H, Zali MR (2010) Analysis of 3′-end variable region of the cagA gene in Helicobacter pylori isolated from Iranian population. J Gastroenterol Hepatol 25(1):172–177.  https://doi.org/10.1111/j.1440-1746.2009.05979.x CrossRefPubMedPubMedCentralGoogle Scholar
  146. Sicinschi LA, Correa P, Peek RM, Camargo MC, Piazuelo MB, Romero-Gallo J, Hobbs SS, Krishna U, Delgado A, Mera R, Bravo LE, Schneider BG (2010) CagA C-terminal variations in Helicobacter pylori strains from Colombian patients with gastric precancerous lesions. Clin Microbiol Infect 16(4):369–378.  https://doi.org/10.1111/j.1469-0691.2009.02811.x CrossRefPubMedPubMedCentralGoogle Scholar
  147. Solnick JV, Hansen LM, Salama NR, Boonjakuakul JK, Syvanen M (2004) Modification of Helicobacter pylori outer membrane protein expression during experimental infection of rhesus macaques. Proc Natl Acad Sci U S A 101(7):2106–2111.  https://doi.org/10.1073/pnas.0308573100 CrossRefPubMedPubMedCentralGoogle Scholar
  148. Stein M, Bagnoli F, Halenbeck R, Rappuoli R, Fantl WJ, Covacci A (2002) c-Src/Lyn kinases activate Helicobacter pylori CagA through tyrosine phosphorylation of the EPIYA motifs. Mol Microbiol 43(4):971–980CrossRefPubMedPubMedCentralGoogle Scholar
  149. Styer CM, Hansen LM, Cooke CL, Gundersen AM, Choi SS, Berg DE, Benghezal M, Marshall BJ, Peek RM Jr, Boren T, Solnick JV (2010) Expression of the BabA adhesin during experimental infection with Helicobacter pylori. Infect Immun 78(4):1593–1600.  https://doi.org/10.1128/iai.01297-09 CrossRefPubMedPubMedCentralGoogle Scholar
  150. Talarico S, Whitefield SE, Fero J, Haas R, Salama NR (2012) Regulation of Helicobacter pylori adherence by gene conversion. Mol Microbiol 84(6):1050–1061.  https://doi.org/10.1111/j.1365-2958.2012.08073.x CrossRefPubMedPubMedCentralGoogle Scholar
  151. Talebi Bezmin Abadi A, Mohabbati Mobarez A (2014) High prevalence of Helicobacter pylori hopQ II genotype isolated from Iranian patients with gastroduodenal disorders. J Pathog 2014:842469.  https://doi.org/10.1155/2014/842469 CrossRefPubMedPubMedCentralGoogle Scholar
  152. Talebi Bezmin Abadi A, Rafiei A, Ajami A, Hosseini V, Taghvaei T, Jones KR, Merrell DS (2011) Helicobacter pylori homB, but not cagA, is associated with gastric cancer in Iran. J Clin Microbiol 49(9):3191–3197.  https://doi.org/10.1128/jcm.00947-11 CrossRefPubMedPubMedCentralGoogle Scholar
  153. Tegtmeyer N, Zabler D, Schmidt D, Hartig R, Brandt S, Backert S (2009) Importance of EGF receptor, HER2/Neu and Erk1/2 kinase signalling for host cell elongation and scattering induced by the Helicobacter pylori CagA protein: antagonistic effects of the vacuolating cytotoxin VacA. Cell Microbiol 11(3):488–505.  https://doi.org/10.1111/j.1462-5822.2008.01269.x CrossRefPubMedPubMedCentralGoogle Scholar
  154. Tegtmeyer N, Harrer A, Schmitt V, Singer BB, Backert S (2019) Expression of CEACAM1 or CEACAM5 in AZ-521 cells restores the type IV secretion deficiency for translocation of CagA by Helicobacter pylori. Cell Microbiol 21:e12965.  https://doi.org/10.1111/cmi.12965 CrossRefPubMedPubMedCentralGoogle Scholar
  155. Thi Huyen Trang T, Thanh Binh T, Yamaoka Y (2016) Relationship between vacA types and development of gastroduodenal diseases. Toxins (Basel) 8(6).  https://doi.org/10.3390/toxins8060182
  156. Tomb JF, White O, Kerlavage AR, Clayton RA, Sutton GG, Fleischmann RD, Ketchum KA, Klenk HP, Gill S, Dougherty BA, Nelson K, Quackenbush J, Zhou L, Kirkness EF, Peterson S, Loftus B, Richardson D, Dodson R, Khalak HG, Glodek A, McKenney K, Fitzegerald LM, Lee N, Adams MD, Hickey EK, Berg DE, Gocayne JD, Utterback TR, Peterson JD, Kelley JM, Cotton MD, Weidman JM, Fujii C, Bowman C, Watthey L, Wallin E, Hayes WS, Borodovsky M, Karp PD, Smith HO, Fraser CM, Venter JC (1997) The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature 388(6642):539–547.  https://doi.org/10.1038/41483 CrossRefPubMedPubMedCentralGoogle Scholar
  157. Tombola F, Pagliaccia C, Campello S, Telford JL, Montecucco C, Papini E, Zoratti M (2001) How the loop and middle regions influence the properties of Helicobacter pylori VacA channels. Biophys J 81(6):3204–3215.  https://doi.org/10.1016/s0006-3495(01)75956-5 CrossRefPubMedPubMedCentralGoogle Scholar
  158. Torres LE, Melian K, Moreno A, Alonso J, Sabatier CA, Hernandez M, Bermudez L, Rodriguez BL (2009) Prevalence of vacA, cagA and babA2 genes in Cuban Helicobacter pylori isolates. World J Gastroenterol 15(2):204–210CrossRefPubMedPubMedCentralGoogle Scholar
  159. Torres K, Valderrama E, Sayegh M, Ramirez JL, Chiurillo MA (2014) Study of the oipA genetic diversity and EPIYA motif patterns in cagA-positive Helicobacter pylori strains from Venezuelan patients with chronic gastritis. Microb Pathog 76:26–32.  https://doi.org/10.1016/j.micpath.2014.09.006 CrossRefPubMedPubMedCentralGoogle Scholar
  160. van Doorn LJ, Figueiredo C, Sanna R, Plaisier A, Schneeberger P, de Boer W, Quint W (1998) Clinical relevance of the cagA, vacA, and iceA status of Helicobacter pylori. Gastroenterology 115(1):58–66CrossRefPubMedPubMedCentralGoogle Scholar
  161. Wang WC, Wang HJ, Kuo CH (2001) Two distinctive cell binding patterns by vacuolating toxin fused with glutathione S-transferase: one high-affinity m1-specific binding and the other lower-affinity binding for variant m forms. Biochemistry 40(39):11887–11896CrossRefPubMedPubMedCentralGoogle Scholar
  162. Warren JR, Marshall B (1983) Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet 1(8336):1273–1275PubMedGoogle Scholar
  163. Weel JF, van der Hulst RW, Gerrits Y, Roorda P, Feller M, Dankert J, Tytgat GN, van der Ende A (1996) The interrelationship between cytotoxin-associated gene A, vacuolating cytotoxin, and Helicobacter pylori-related diseases. J Infect Dis 173(5):1171–1175CrossRefPubMedPubMedCentralGoogle Scholar
  164. White JR, Winter JA, Robinson K (2015) Differential inflammatory response to Helicobacter pylori infection: etiology and clinical outcomes. J Inflamm Res 8:137–147.  https://doi.org/10.2147/jir.s64888 CrossRefPubMedPubMedCentralGoogle Scholar
  165. Wroblewski LE, Peek RM Jr, Wilson KT (2010) Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clin Microbiol Rev 23(4):713–739.  https://doi.org/10.1128/cmr.00011-10 CrossRefGoogle Scholar
  166. Yadegar A, Mobarez AM, Alebouyeh M, Mirzaei T, Kwok T, Zali MR (2014) Clinical relevance of cagL gene and virulence genotypes with disease outcomes in a Helicobacter pylori infected population from Iran. World J Microbiol Biotechnol 30(9):2481–2490.  https://doi.org/10.1007/s11274-014-1673-5 CrossRefPubMedPubMedCentralGoogle Scholar
  167. Yakoob J, Abbas Z, Khan R, Salim SA, Awan S, Abrar A, Jafri W (2016) Helicobacter pylori outer membrane protein Q allele distribution is associated with distinct pathologies in Pakistan. Infect Genet Evol 37:57–62.  https://doi.org/10.1016/j.meegid.2015.10.027 CrossRefPubMedPubMedCentralGoogle Scholar
  168. Yamaoka Y, El-Zimaity HM, Gutierrez O, Figura N, Kim JG, Kodama T, Kashima K, Graham DY (1999) Relationship between the cagA 3′ repeat region of Helicobacter pylori, gastric histology, and susceptibility to low pH. Gastroenterology 117(2):342–349CrossRefPubMedPubMedCentralGoogle Scholar
  169. Yamaoka Y, Kwon DH, Graham DY (2000) A M(r) 34,000 proinflammatory outer membrane protein (oipA) of Helicobacter pylori. Proc Natl Acad Sci U S A 97(13):7533–7538.  https://doi.org/10.1073/pnas.130079797 CrossRefPubMedPubMedCentralGoogle Scholar
  170. Yamaoka Y, Kikuchi S, el-Zimaity HM, Gutierrez O, Osato MS, Graham DY (2002) Importance of Helicobacter pylori oipA in clinical presentation, gastric inflammation, and mucosal interleukin 8 production. Gastroenterology 123(2):414–424CrossRefPubMedPubMedCentralGoogle Scholar
  171. Yamaoka Y, Ojo O, Fujimoto S, Odenbreit S, Haas R, Gutierrez O, El-Zimaity HM, Reddy R, Arnqvist A, Graham DY (2006) Helicobacter pylori outer membrane proteins and gastroduodenal disease. Gut 55(6):775–781.  https://doi.org/10.1136/gut.2005.083014 CrossRefPubMedPubMedCentralGoogle Scholar
  172. Yamaoka Y, Kato M, Asaka M (2008) Geographic differences in gastric cancer incidence can be explained by differences between Helicobacter pylori strains. Intern Med 47(12):1077–1083CrossRefPubMedPubMedCentralGoogle Scholar
  173. Yanai A, Maeda S, Hikiba Y, Shibata W, Ohmae T, Hirata Y, Ogura K, Yoshida H, Omata M (2007) Clinical relevance of Helicobacter pylori sabA genotype in Japanese clinical isolates. J Gastroenterol Hepatol 22(12):2228–2232.  https://doi.org/10.1111/j.1440-1746.2007.04831.x CrossRefPubMedPubMedCentralGoogle Scholar
  174. Ye D, Willhite DC, Blanke SR (1999) Identification of the minimal intracellular vacuolating domain of the Helicobacter pylori vacuolating toxin. J Biol Chem 274(14):9277–9282CrossRefPubMedPubMedCentralGoogle Scholar
  175. Yordanov D, Boyanova L, Markovska R, Gergova G, Mitov I (2012) Significance of Helicobacter pylori vacA intermediate region genotyping-a Bulgarian study. Diagn Microbiol Infect Dis 74(3):253–257.  https://doi.org/10.1016/j.diagmicrobio.2012.07.008 CrossRefPubMedPubMedCentralGoogle Scholar
  176. Yu J, Leung WK, Go MY, Chan MC, To KF, Ng EK, Chan FK, Ling TK, Chung SC, Sung JJ (2002) Relationship between Helicobacter pylori babA2 status with gastric epithelial cell turnover and premalignant gastric lesions. Gut 51(4):480–484CrossRefPubMedPubMedCentralGoogle Scholar
  177. Zambon CF, Navaglia F, Basso D, Rugge M, Plebani M (2003) Helicobacter pylori babA2, cagA, and s1 vacA genes work synergistically in causing intestinal metaplasia. J Clin Pathol 56(4):287–291CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Microbiology and ImmunologyUniformed Services University of the Health SciencesBethesdaUSA

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