Skip to main content
SpringerLink
Log in

Helicobacter pylori and Related Virulence Factors for Gastrointestinal Diseases

  • Chapter
  • First Online:
Gastric Cancer

Abstract

Helicobacter pylori—a worldwide spread bacterium—is still infecting more than half of humans. This bacterium is closely associated with serious human diseases such as gastric cancer. As only few infected humans develop the most severe clinical outcomes, there have been important efforts for identifying and understanding factors predicting bacterial virulence. Here, we discuss main features of virulence factors that have emerged from decades of intensive researches in the world. From tens of candidate virulent factors found out by epidemiological studies and explored by laboratory experiments, the cag pathogenicity island, the VacA, and several outer membrane proteins such as BabA are so far the most studied. Many other candidate virulent factors such as the serine protease HtrA and H. pylori-related prophages have been identified recently and would be attracting an increasing interest. Topics regarding the virulence of H. pylori species have accounted for the most dynamic among related researches, especially as access to genome sequences is increasing. Therefore, we will attempt to highlight the most recent findings in direct line with each discussed H. pylori virulence factor.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet. 1984;1(8390):1311–5. Epub 1984/06/16.

    Article  CAS  PubMed  Google Scholar 

  2. Yamaoka Y. Mechanisms of disease: helicobacter pylori virulence factors. Nat Rev Gastroenterol Hepatol. 2010;7(11):629–41. Epub 2010/10/13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med. 2001;345(11):784–9. Epub 2001/09/15.

    Article  CAS  PubMed  Google Scholar 

  4. Talley NJ, Zinsmeister AR, Weaver A, DiMagno EP, Carpenter HA, Perez-Perez GI, et al. Gastric adenocarcinoma and Helicobacter pylori infection. J Nat Cancer Inst. 1991;83(23):1734–9. Epub 1991/12/04.

    Article  CAS  PubMed  Google Scholar 

  5. Parsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH, Orentreich N, et al. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med. 1991;325(16):1127–31. Epub 1991/10/17.

    Article  CAS  PubMed  Google Scholar 

  6. Group IW. Schistosomes, liver flukes and Helicobacter pylori. IARC working group on the evaluation of carcinogenic risks to humans. Lyon, 7-14 June 1994. IARC Monogr Eval Carcinog Risks Hum. 1994;61:1–241.

    Google Scholar 

  7. Censini S, Lange C, Xiang Z, Crabtree JE, Ghiara P, Borodovsky M, et al. cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors. Proc Natl Acad Sci U S A. 1996;93(25):14648–53. Epub 1996/12/10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Tegtmeyer N, Neddermann M, Asche CI, Backert S. Subversion of host kinases: a key network in cellular signaling hijacked by Helicobacter pylori CagA. Mol Microbiol. 2017;105(3):358–72. Epub 2017/05/17.

    Article  CAS  PubMed  Google Scholar 

  9. Blaser MJ, Perez-Perez GI, Kleanthous H, Cover TL, Peek RM, Chyou P, et al. Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach. Cancer Res. 1995;55(10):2111–5.

    CAS  PubMed  Google Scholar 

  10. Parsonnet J, Friedman G, Orentreich N, Vogelman H. Risk for gastric cancer in people with CagA positive or CagA negative Helicobacter pylori infection. Gut. 1997;40(3):297–301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Wirth H-P, Beins MH, Yang M, Tham KT, Blaser MJ. Experimental infection of Mongolian gerbils with wild-type and mutant Helicobacter pylori strains. Infect Immun. 1998;66(10):4856–66.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Yamaoka Y, Kita M, Kodama T, Sawai N, Kashima K, Imanishi J. Induction of various cytokines and development of severe mucosal inflammation by cagA gene positive Helicobacter pylori strains. Gut. 1997;41(4):442–51. Epub 1997/12/10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Yamaoka Y, Kodama T, Gutierrez O, Kim JG, Kashima K, Graham DY. Relationship between Helicobacter pylori iceA, cagA, and vacA status and clinical outcome: studies in four different countries. J Clin Microbiol. 1999;37(7):2274–9. Epub 1999/06/12.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Yamaoka Y, El-Zimaity HM, Gutierrez O, Figura N, Kim JG, Kodama T, et al. Relationship between the cagA 3′ repeat region of Helicobacter pylori, gastric histology, and susceptibility to low pH. Gastroenterology. 1999;117(2):342–9. Epub 1999/07/27.

    Article  CAS  PubMed  Google Scholar 

  15. 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(8):2258–63. Epub 1998/07/17.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 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 U S A. 1993;90(12):5791–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Xia Y, Yamaoka Y, Zhu Q, Matha I, Gao X. A comprehensive sequence and disease correlation analyses for the C-terminal region of CagA protein of Helicobacter pylori. PLoS One. 2009;4(11):e7736. Epub 2009/11/07.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. 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(5555):683–6. Epub 2001/12/18.

    Article  CAS  PubMed  Google Scholar 

  19. Hatakeyama M. Helicobacter pylori and gastric carcinogenesis. J Gastroenterol. 2009;44(4):239–48. Epub 2009/03/10.

    Article  CAS  PubMed  Google Scholar 

  20. Hayashi T, Senda M, Suzuki N, Nishikawa H, Ben C, Tang C, et al. Differential mechanisms for SHP2 binding and activation are exploited by geographically distinct Helicobacter pylori CagA oncoproteins. Cell Rep. 2017;20(12):2876–90.

    Article  CAS  PubMed  Google Scholar 

  21. Nagase L, Hayashi T, Senda T, Hatakeyama M. Dramatic increase in SHP2 binding activity of Helicobacter pylori Western CagA by EPIYA-C duplication: its implications in gastric carcinogenesis. Sci Rep. 2015;5:15749. Epub 2015/10/29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Matsuo Y, Shiota S, Matsunari O, Suzuki R, Watada M, Binh TT, et al. Helicobacter pylori cagA 12-bp insertion can be a marker for duodenal ulcer in Okinawa, Japan. J Gastroenterol Hepatol. 2013;28(2):291–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Hayashi T, Senda M, Morohashi H, Higashi H, Horio M, Kashiba Y, et al. Tertiary structure-function analysis reveals the pathogenic signaling potentiation mechanism of Helicobacter pylori oncogenic effector CagA. Cell Host Microbe. 2012;12(1):20–33. Epub 2012/07/24.

    Article  CAS  PubMed  Google Scholar 

  24. Kaplan-Turkoz B, Jimenez-Soto LF, Dian C, Ertl C, Remaut H, Louche A, et al. Structural insights into Helicobacter pylori oncoprotein CagA interaction with beta1 integrin. Proc Natl Acad Sci U S A. 2012;109(36):14640–5. Epub 2012/08/22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Schindele F, Weiss E, Haas R, Fischer W. Quantitative analysis of CagA type IV secretion by Helicobacter pylori reveals substrate recognition and translocation requirements. Mol Microbiol. 2016;100(1):188–203.

    Article  CAS  PubMed  Google Scholar 

  26. Loh JT, Shaffer CL, Piazuelo MB, Bravo LE, McClain MS, Correa P, et al. Analysis of cagA in Helicobacter pylori strains from Colombian populations with contrasting gastric cancer risk reveals a biomarker for disease severity. Cancer Epidemiol Biomark Prev. 2011;20(10):2237–49. Epub 2011/08/24.

    Article  CAS  Google Scholar 

  27. Ferreira RM, Pinto-Ribeiro I, Wen X, Marcos-Pinto R, Dinis-Ribeiro M, Carneiro F, et al. Helicobacter pylori cagA promoter region sequences influence CagA expression and interleukin 8 secretion. J Infect Dis. 2016;213(4):669–73. Epub 2015/09/25.

    Article  CAS  PubMed  Google Scholar 

  28. Jang S, Su H, Blum FC, Bae S, Choi YH, Kim A, et al. Dynamic expansion and contraction of cagA copy number in Helicobacter pylori impact development of gastric disease. MBio. 2017;8(1):e01779–16. Epub 2017/02/23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Draper JL, Hansen LM, Bernick DL, Abedrabbo S, Underwood JG, Kong N, et al. Fallacy of the unique genome: sequence diversity within single Helicobacter pylori strains. MBio. 2017;8(1):e02321–16. Epub 2017/02/23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Leunk RD, Johnson PT, David BC, Kraft WG, Morgan DR. Cytotoxic activity in broth-culture filtrates of Campylobacter pylori. J Med Microbiol. 1988;26(2):93–9. Epub 1988/06/01.

    Article  CAS  PubMed  Google Scholar 

  31. Yahiro K, Hirayama T, Moss J, Noda M. Helicobacter pylori VacA toxin causes cell death by inducing accumulation of cytoplasmic connexin 43. Cell Death Dis. 2015;6:e1971.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Thi Huyen Trang T, Thanh Binh T, Yamaoka Y. Relationship between vacA types and development of gastroduodenal diseases. Toxins. 2016;8(6):182.

    Article  PubMed Central  CAS  Google Scholar 

  33. Bakhti SZ, Latifi-Navid S, Mohammadi S, Zahri S, Bakhti FS, Feizi F, et al. Relevance of Helicobacter pylori vacA 3′-end region polymorphism to gastric cancer. Helicobacter. 2016;21(4):305–16.

    Article  CAS  PubMed  Google Scholar 

  34. Ogiwara H, Sugimoto M, Ohno T, Vilaichone RK, Mahachai V, Graham DY, et al. Role of deletion located between the intermediate and middle regions of the Helicobacter pylori vacA gene in cases of gastroduodenal diseases. J Clin Microbiol. 2009;47(11):3493–500. Epub 2009/09/04.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Foegeding NJ, Caston RR, McClain MS, Ohi MD, Cover TL. An overview of Helicobacter pylori VacA toxin biology. Toxins. 2016;8(6):173. Epub 2016/06/09.

    Article  PubMed Central  CAS  Google Scholar 

  36. Amilon KR, Letley DP, Winter JA, Robinson K, Atherton JC. Expression of the Helicobacter pylori virulence factor vacuolating cytotoxin A (vacA) is influenced by a potential stem-loop structure in the 5′ untranslated region of the transcript. Mol Microbiol. 2015;98(5):831–46. Epub 2015/08/12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Nakashima S, Kakugawa T, Yura H, Tomonaga M, Harada T, Hara A, et al. Identification of Helicobacter pylori VacA in human lung and its effects on lung cells. Biochem Biophys Res Commun. 2015;460(3):721–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Chang H, Chen D, Ni B, Zuo Q, Wang C, Han R, et al. Cortactin mediates apoptosis of gastric epithelial cells induced by VacA protein of Helicobacter pylori. Dig Dis Sci. 2016;61(1):80–90.

    Article  CAS  PubMed  Google Scholar 

  39. Alm RA, Bina J, Andrews BM, Doig P, Hancock RE, Trust TJ. Comparative genomics of Helicobacter pylori: analysis of the outer membrane protein families. Infect Immun. 2000;68(7):4155–68. Epub 2000/06/17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kennemann L, Didelot X, Aebischer T, Kuhn S, Drescher B, Droege M, et al. Helicobacter pylori genome evolution during human infection. Proc Natl Acad Sci U S A. 2011;108(12):5033–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Didelot X, Nell S, Yang I, Woltemate S, van der Merwe S, Suerbaum S. Genomic evolution and transmission of Helicobacter pylori in two South African families. Proc Natl Acad Sci U S A. 2013;110(34):13880–5. Epub 2013/07/31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Morelli G, Didelot X, Kusecek B, Schwarz S, Bahlawane C, Falush D, et al. Microevolution of Helicobacter pylori during prolonged infection of single hosts and within families. PLoS Genet. 2010;6(7):e1001036. Epub 2010/07/28.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Yamaoka Y, Kwon DH, Graham DY. A M(r) 34,000 proinflammatory outer membrane protein (oipA) of Helicobacter pylori. Proc Natl Acad Sci U S A. 2000;97(13):7533–8. Epub 2000/06/15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Bjornham O, Fallman E, Axner O, Ohlsson J, Nilsson UJ, Boren T, et al. Measurements of the binding force between the Helicobacter pylori adhesin BabA and the Lewis b blood group antigen using optical tweezers. J Biomed Opt. 2005;10(4):44024. Epub 2005/09/24.

    Article  PubMed  CAS  Google Scholar 

  45. Aspholm M, Olfat FO, Norden J, Sonden B, Lundberg C, Sjostrom R, et al. SabA is the H. pylori hemagglutinin and is polymorphic in binding to sialylated glycans. PLoS Pathog. 2006;2(10):e110. Epub 2006/11/24.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Senkovich OA, Yin J, Ekshyyan V, Conant C, Traylor J, Adegboyega P, et al. Helicobacter pylori AlpA and AlpB bind host laminin and influence gastric inflammation in gerbils. Infect Immun. 2011;79(8):3106–16. Epub 2011/05/18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Javaheri A, Kruse T, Moonens K, Mejias-Luque R, Debraekeleer A, Asche CI, et al. Helicobacter pylori adhesin HopQ engages in a virulence-enhancing interaction with human CEACAMs. Nat Microbiol. 2016;2:16189. Epub 2016/10/18.

    Article  CAS  PubMed  Google Scholar 

  48. Koniger V, Holsten L, Harrison U, Busch B, Loell E, Zhao Q, et al. Helicobacter pylori exploits human CEACAMs via HopQ for adherence and translocation of CagA. Nat Microbiol. 2016;2:16188. Epub 2016/10/18.

    Article  PubMed  CAS  Google Scholar 

  49. Marcos NT, Magalhaes A, Ferreira B, Oliveira MJ, Carvalho AS, Mendes N, et al. Helicobacter pylori induces beta3GnT5 in human gastric cell lines, modulating expression of the SabA ligand sialyl-Lewis x. J Clin Investig. 2008;118(6):2325–36. Epub 2008/05/17.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Ansari S, Yamaoka Y. Helicobacter pylori BabA in adaptation for gastric colonization. World J Gastroenterol. 2017;23(23):4158–69. Epub 2017/07/12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Ilver D, Arnqvist A, Ogren J, Frick IM, Kersulyte D, Incecik ET, et al. Helicobacter pylori adhesin binding fucosylated histo-blood group antigens revealed by retagging. Science. 1998;279(5349):373–7. Epub 1998/02/07.

    Article  CAS  PubMed  Google Scholar 

  52. Matteo MJ, Armitano RI, Romeo M, Wonaga A, Olmos M, Catalano M. Helicobacter pylori bab genes during chronic colonization. Int J Mol Epidemiol Genet. 2011;2(3):286–91. Epub 2011/09/15.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Hennig EE, Allen JM, Cover TL. Multiple chromosomal loci for the babA gene in hHelicobacter pylori. Infect Immun. 2006;74(5):3046–51. Epub 2006/04/20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Ansari S, Kabamba ET, Shrestha PK, Aftab H, Myint T, Tshering L, et al. Helicobacter pylori bab characterization in clinical isolates from Bhutan, Myanmar, Nepal and Bangladesh. PLoS One. 2017;12(11):e0187225. Epub 2017/11/07.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Ishijima N, Suzuki M, Ashida H, Ichikawa Y, Kanegae Y, Saito I, et al. BabA-mediated adherence is a potentiator of the Helicobacter pylori type IV secretion system activity. J Biol Chem. 2011;286(28):25256–64. Epub 2011/05/21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Su YL, Huang HL, Huang BS, Chen PC, Chen CS, Wang HL, et al. Combination of OipA, BabA, and SabA as candidate biomarkers for predicting Helicobacter pylori-related gastric cancer. Sci Rep. 2016;6:36442. Epub 2016/11/08.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Kable ME, Hansen LM, Styer CM, Deck SL, Rakhimova O, Shevtsova A, et al. Host determinants of expression of the Helicobacter pylori BabA adhesin. Sci Rep. 2017;7:46499. Epub 2017/04/19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Hansen LM, Gideonsson P, Canfield DR, Boren T, Solnick JV. Dynamic expression of the BabA adhesin and its BabB paralog during helicobacter pylori infection in rhesus macaques. Infect Immun. 2017;85(6):e00094–17. Epub 2017/04/12.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Sweeney EG, Guillemin K. H. pylori’s BabA embraces change. Cell Host Microbe. 2016;19(1):5–7. Epub 2016/01/15.

    Article  CAS  PubMed  Google Scholar 

  60. Bugaytsova JA, Bjornham O, Chernov YA, Gideonsson P, Henriksson S, Mendez M, et al. Helicobacter pylori adapts to chronic infection and gastric disease via pH-responsive BabA-mediated adherence. Cell Host Microbe. 2017;21(3):376–89. Epub 2017/03/11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Subedi S, Moonens K, Romao E, Lo A, Vandenbussche G, Bugaytsova J, et al. Expression, purification and X-ray crystallographic analysis of the Helicobacter pylori blood group antigen-binding adhesin BabA. Acta Crystallogr F Struct Biol Commun. 2014;70(Pt 12):1631–5. Epub 2014/12/09.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Moonens K, Remaut H. Evolution and structural dynamics of bacterial glycan binding adhesins. Curr Opin Struct Biol. 2017;44:48–58. Epub 2017/01/04.

    Article  CAS  PubMed  Google Scholar 

  63. Bäckström A, Lundberg C, Kersulyte D, Berg DE, Borén T, Arnqvist A. Metastability of Helicobacter pylori bab adhesin genes and dynamics in Lewis b antigen binding. Proc Natl Acad Sci U S A. 2004;101(48):16923–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Loh JT, Torres VJ, Algood HM, McClain MS, Cover TL. Helicobacter pylori HopQ outer membrane protein attenuates bacterial adherence to gastric epithelial cells. FEMS Microbiol Lett. 2008;289(1):53–8. Epub 2008/12/10.

    Article  CAS  PubMed  Google Scholar 

  65. Cao P, Lee KJ, Blaser MJ, Cover TL. Analysis of hopQ alleles in East Asian and Western strains of Helicobacter pylori. FEMS Microbiol Lett. 2005;251(1):37–43. Epub 2005/08/17.

    Article  CAS  PubMed  Google Scholar 

  66. Ohno T, Sugimoto M, Nagashima A, Ogiwara H, Vilaichone RK, Mahachai V, et al. Relationship between Helicobacter pylori hopQ genotype and clinical outcome in Asian and Western populations. J Gastroenterol Hepatol. 2009;24(3):462–8. Epub 2009/02/20.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Belogolova E, Bauer B, Pompaiah M, Asakura H, Brinkman V, Ertl C, et al. Helicobacter pylori outer membrane protein HopQ identified as a novel T4SS-associated virulence factor. Cell Microbiol. 2013;15(11):1896–912. Epub 2013/06/21.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Jiménez-Soto LF, Clausen S, Sprenger A, Ertl C, Haas R. Dynamics of the Cag-type IV secretion system of Helicobacter pylori as studied by bacterial co-infections. Cell Microbiol. 2013;15(11):1924–37.

    PubMed  Google Scholar 

  69. Yamaoka Y, Kwon DH, Graham DY. A Mr 34,000 proinflammatory outer membrane protein (oipA) of Helicobacter pylori. Proc Natl Acad Sci U S A. 2000;97(13):7533–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Yamaoka Y, Kita M, Kodama T, Imamura S, Ohno T, Sawai N, et al. Helicobacter pylori infection in mice: role of outer membrane proteins in colonization and inflammation. Gastroenterology. 2002;123(6):1992–2004. Epub 2002/11/28.

    Article  CAS  PubMed  Google Scholar 

  71. Kudo T, Nurgalieva ZZ, Conner ME, Crawford S, Odenbreit S, Haas R, et al. Correlation between Helicobacter pylori OipA protein expression and oipA gene switch status. J Clin Microbiol. 2004;42(5):2279–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Ando T, Peek RM, Pride D, Levine SM, Takata T, Lee YC, et al. Polymorphisms of Helicobacter pylori HP0638 reflect geographic origin and correlate with cagA status. J Clin Microbiol. 2002;40(1):239–46. Epub 2002/01/05.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Markovska R, Boyanova L, Yordanov D, Gergova G, Mitov I. 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. 2011;71(4):335–40. Epub 2011/09/23.

    Article  CAS  PubMed  Google Scholar 

  74. Backert S, Naumann M. What a disorder: proinflammatory signaling pathways induced by Helicobacter pylori. Trends Microbiol. 2010;18(11):479–86.

    Article  CAS  PubMed  Google Scholar 

  75. Dossumbekova A, Prinz C, Mages J, Lang R, Kusters JG, Van Vliet AH, et al. Helicobacter pylori HopH (OipA) and bacterial pathogenicity: genetic and functional genomic analysis of hopH gene polymorphisms. J Infect Dis. 2006;194(10):1346–55.

    Article  CAS  PubMed  Google Scholar 

  76. Odenbreit S, Swoboda K, Barwig I, Ruhl S, Borén T, Koletzko S, et al. Outer membrane protein expression profile in Helicobacter pylori clinical isolates. Infect Immun. 2009;77(9):3782–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Matsuo Y, Kido Y, Yamaoka Y. Helicobacter pylori outer membrane protein-related pathogenesis. Toxins. 2017;9(3):E101. Epub 2017/03/14.

    Article  PubMed  CAS  Google Scholar 

  78. Tabassam FH, Graham DY, Yamaoka Y. Helicobacter pylori-associated regulation of forkhead transcription factors FoxO1/3a in human gastric cells. Helicobacter. 2012;17(3):193–202. Epub 2012/04/21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Tabassam FH, Graham DY, Yamaoka Y. OipA plays a role in Helicobacter pylori-induced focal adhesion kinase activation and cytoskeletal re-organization. Cell Microbiol. 2008;10(4):1008–20. Epub 2007/12/11.

    Article  CAS  PubMed  Google Scholar 

  80. Teymournejad O, Mobarez AM, Hassan ZM, Talebi Bezmin Abadi A. Binding of the Helicobacter pylori OipA causes apoptosis of host cells via modulation of Bax/Bcl-2 levels. Sci Rep. 2017;7(1):8036. Epub 2017/08/16.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Al-Maleki AR, Loke MF, Lui SY, Ramli NSK, Khosravi Y, Ng CG, et al. Helicobacter pylori outer inflammatory protein A (OipA) suppresses apoptosis of AGS gastric cells in vitro. Cell Microbiol. 2017;19(12). Epub 2017/08/05. https://onlinelibrary.wiley.com/action/showCitFormats?doi=10.1111%2Fcmi.12771.

  82. Mahboubi M, Falsafi T, Sadeghizadeh M, Mahjoub F. The role of outer inflammatory protein A (OipA) in vaccination of theC57BL/6 mouse model infected by Helicobacter pylori. Turkish J Med Sci. 2017;47(1):326–33. Epub 2017/03/07.

    Article  CAS  Google Scholar 

  83. Lu H, Hsu PI, Graham DY, Yamaoka Y. Duodenal ulcer promoting gene of Helicobacter pylori. Gastroenterology. 2005;128(4):833–48. Epub 2005/04/13.

    Article  CAS  PubMed  Google Scholar 

  84. Covacci A, Telford JL, Del Giudice G, Parsonnet J, Rappuoli R. Helicobacter pylori virulence and genetic geography. Science. 1999;284(5418):1328–33. Epub 1999/05/21.

    Article  CAS  PubMed  Google Scholar 

  85. Santos A, Queiroz DM, Menard A, Marais A, Rocha GA, Oliveira CA, et al. New pathogenicity marker found in the plasticity region of the Helicobacter pylori genome. J Clin Microbiol. 2003;41(4):1651–5. Epub 2003/04/19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Occhialini A, Marais A, Alm R, Garcia F, Sierra R, Megraud F. Distribution of open reading frames of plasticity region of strain J99 in Helicobacter pylori strains isolated from gastric carcinoma and gastritis patients in Costa Rica. Infect Immun. 2000;68(11):6240–9. Epub 2000/10/18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Schmidt HM, Andres S, Kaakoush NO, Engstrand L, Eriksson L, Goh KL, 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(1):5. Epub 2009/04/03.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Arachchi HS, Kalra V, Lal B, Bhatia V, Baba CS, Chakravarthy S, et al. Prevalence of duodenal ulcer-promoting gene (dupA) of Helicobacter pylori in patients with duodenal ulcer in North Indian population. Helicobacter. 2007;12(6):591–7. Epub 2007/11/16.

    Article  CAS  PubMed  Google Scholar 

  89. Argent RH, Burette A, Miendje Deyi VY, Atherton JC. The presence of dupA in Helicobacter pylori is not significantly associated with duodenal ulceration in Belgium, South Africa, China, or North America. Clin Infect Dis. 2007;45(9):1204–6. Epub 2007/10/06.

    Article  CAS  PubMed  Google Scholar 

  90. Zhang L, Wang P, Wei SL, Liu CJ. Advances in relationship between gastric disease and polymorphisms in both Helicobacter pylori virulence factors and host genetics. Yi chuan = Hereditas. 2011;33(6):558–66. Epub 2011/06/21.

    Article  PubMed  CAS  Google Scholar 

  91. Paredes-Osses E, Saez K, Sanhueza E, Hebel S, Gonzalez C, Briceno C, et al. Association between cagA, vacAi, and dupA genes of Helicobacter pylori and gastroduodenal pathologies in Chilean patients. Folia Microbiol. 2017;62(5):437–44. Epub 2017/03/12.

    Article  CAS  Google Scholar 

  92. Shiota S, Matsunari O, Watada M, Hanada K, Yamaoka Y. Systematic review and meta-analysis: the relationship between the Helicobacter pylori dupA gene and clinical outcomes. Gut Pathog. 2010;2(1):13. Epub 2010/11/03.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Gressmann H, Linz B, Ghai R, Pleissner KP, Schlapbach R, Yamaoka Y, et al. Gain and loss of multiple genes during the evolution of Helicobacter pylori. PLoS Genet. 2005;1(4):e43. Epub 2005/10/12.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Talebi Bezmin Abadi A, Perez-Perez G. Role of dupA in virulence of Helicobacter pylori. World J Gastroenterol. 2016;22(46):10118–23. Epub 2016/12/29.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Jung SW, Sugimoto M, Shiota S, Graham DY, Yamaoka Y. The intact dupA cluster is a more reliable Helicobacter pylori virulence marker than dupA alone. Infect Immun. 2012;80(1):381–7. Epub 2011/11/01.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Queiroz DM, Rocha GA, Rocha AM, Moura SB, Saraiva IE, Gomes LI, et al. dupA polymorphisms and risk of Helicobacter pylori-associated diseases. Int J Med Microbiol. 2011;301(3):225–8. Epub 2010/11/06.

    Article  CAS  PubMed  Google Scholar 

  97. Talebi Bezmin Abadi A. The Helicobacter pylori dupA: a novel biomarker for digestive diseases. Front Med. 2014;1:13. Epub 2014/01/01.

    Google Scholar 

  98. Takahashi A, Shiota S, Matsunari O, Watada M, Suzuki R, Nakachi S, et al. Intact long-type dupA as a marker for gastroduodenal diseases in Okinawan subpopulation, Japan. Helicobacter. 2013;18(1):66–72. Epub 2012/10/17.

    Article  CAS  PubMed  Google Scholar 

  99. Silva B, Nunes A, Vale FF, Rocha R, Gomes JP, Dias R, et al. The expression of Helicobacter pylori tfs plasticity zone cluster is regulated by pH and adherence, and its composition is associated with differential gastric IL-8 secretion. Helicobacter. 2017;22(4):e12390. Epub 2017/04/25.

    Article  CAS  Google Scholar 

  100. Peek RM Jr, Thompson SA, Donahue JP, Tham KT, Atherton JC, Blaser MJ, et al. Adherence to gastric epithelial cells induces expression of a Helicobacter pylori gene, iceA, that is associated with clinical outcome. Proc Assoc Am Physicians. 1998;110(6):531–44. Epub 1998/11/21.

    CAS  PubMed  Google Scholar 

  101. Xu Q, Morgan RD, Roberts RJ, Xu SY, van Doorn LJ, Donahue JP, et al. Functional analysis of iceA1, a CATG-recognizing restriction endonuclease gene in Helicobacter pylori. Nucleic Acids Res. 2002;30(17):3839–47. Epub 2002/08/31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Ito Y, Azuma T, Ito S, Suto H, Miyaji H, Yamazaki Y, et al. Sequence analysis and clinical significance of the iceA gene from Helicobacter pylori strains in Japan. J Clin Microbiol. 2000;38(2):483–8. Epub 2000/02/03.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Nishiya D, Shimoyama T, Fukuda S, Yoshimura T, Tanaka M, Munakata A. Evaluation of the clinical relevance of the iceA1 gene in patients with Helicobacter pylori infection in Japan. Scand J Gastroenterol. 2000;35(1):36–9. Epub 2000/02/15.

    Article  CAS  PubMed  Google Scholar 

  104. Maeda S, Amarsanaa J, Mitsuno Y, Hirata Y, Akanuma M, Ikenoue T, et al. Relationship between nuclear factor-kappaB activation and virulence factors of Helicobacter pylori in Japanese clinical isolates. J Gastroenterol Hepatol. 2002;17(5):556–62. Epub 2002/06/27.

    Article  CAS  PubMed  Google Scholar 

  105. van Doorn LJ, Figueiredo C, Sanna R, Plaisier A, Schneeberger P, de Boer W, et al. Clinical relevance of the cagA, vacA, and iceA status of Helicobacter pylori. Gastroenterology. 1998;115(1):58–66. Epub 1998/07/03.

    Article  PubMed  Google Scholar 

  106. Shiota S, Watada M, Matsunari O, Iwatani S, Suzuki R, Yamaoka Y. Helicobacter pylori iceA, clinical outcomes, and correlation with cagA: a meta-analysis. PLoS One. 2012;7(1):e30354. Epub 2012/01/27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Yakoob J, Abbas Z, Khan R, Salim SA, Abrar A, Awan S, et al. Helicobacter pylori: correlation of the virulence marker iceA allele with clinical outcome in a high prevalence area. Br J Biomed Sci. 2015;72(2):67–73. Epub 2015/07/02.

    Article  CAS  PubMed  Google Scholar 

  108. Zhang SH, Xie Y, Li BM, Liu DS, Wan SH, Luo LJ, et al. Prevalence of Helicobacter pylori cagA, vacA, and iceA genotypes in children with gastroduodenal diseases. Zhongguo dang dai er ke za zhi = Chinese J Contemp Pediatr. 2016;18(7):618–24. Epub 2016/07/15.

    Google Scholar 

  109. Dabiri H, Jafari F, Baghaei K, Shokrzadeh L, Abdi S, Pourhoseingholi MA, et al. Prevalence of Helicobacter pylori vacA, cagA, cagE, oipA, iceA, babA2 and babB genotypes in Iranian dyspeptic patients. Microb Pathog. 2017;105:226–30. Epub 2017/02/22.

    Article  CAS  PubMed  Google Scholar 

  110. Sharma RP, Miftahussurur M, Shrestha PK, Subsomwong P, Uchida T, Yamaoka Y. Nepalese Helicobacter pylori genotypes reflects a geographical diversity than a true virulence factor. Asian Pac J Cancer Prev. 2017;18(10):2637–41. Epub 2017/10/27.

    PubMed  PubMed Central  Google Scholar 

  111. Gharibi S, Falsafi T, Alebouyeh M, Farzi N, Vaziri F, Zali MR. Relationship between histopathological status of the Helicobacter pylori infected patients and proteases of H. pylori in isolates carrying diverse virulence genotypes. Microb Pathog. 2017;110:100–6. Epub 2017/06/21.

    Article  CAS  PubMed  Google Scholar 

  112. Canchaya C, Proux C, Fournous G, Bruttin A, Brussow H. Prophage genomics. Microbiol Mol Biol Rev. 2003;67(2):238–76, table of contents. Epub 2003/06/10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Rodriguez-Valera F, Martin-Cuadrado AB, Rodriguez-Brito B, Pasic L, Thingstad TF, Rohwer F, et al. Explaining microbial population genomics through phage predation. Nat Rev Microbiol. 2009;7(11):828–36. Epub 2009/10/17.

    Article  CAS  PubMed  Google Scholar 

  114. Marshall BJ, Armstrong JA, Francis GJ, Nokes NT, Wee SH. Antibacterial action of bismuth in relation to Campylobacter pyloridis colonization and gastritis. Digestion. 1987;37(Suppl 2):16–30. Epub 1987/01/01.

    Article  PubMed  Google Scholar 

  115. Heintschel von Heinegg E, Nalik HP, Schmid EN. Characterisation of a Helicobacter pylori phage (HP1). J Med Microbiol. 1993;38(4):245–9. Epub 1993/04/01.

    Article  CAS  PubMed  Google Scholar 

  116. Schmid EN, von Recklinghausen G, Ansorg R. Bacteriophages in Helicobacter (Campylobacter) pylori. J Med Microbiol. 1990;32(2):101–4. Epub 1990/06/01.

    Article  CAS  PubMed  Google Scholar 

  117. Vale FF, Matos AP, Carvalho P, Vítor JM. Helicobacter pylori phage screening. Microsc Microanal. 2008;14(S3):150–1.

    Article  CAS  Google Scholar 

  118. Eppinger M, Baar C, Linz B, Raddatz G, Lanz C, Keller H, et al. Who ate whom? Adaptive Helicobacter genomic changes that accompanied a host jump from early humans to large felines. PLoS Genet. 2006;2(7):e120.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  119. Arnold IC, Zigova Z, Holden M, Lawley TD, Rad R, Dougan G, et al. Comparative whole genome sequence analysis of the carcinogenic bacterial model pathogen Helicobacter felis. Genome Biol Evol. 2011;3:302–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Lehours P, Vale FF, Bjursell MK, Melefors O, Advani R, Glavas S, et al. Genome sequencing reveals a phage in Helicobacter pylori. MBio. 2011;2(6):e00239–11. Epub 2011/11/17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Vale FF, Nunes A, Oleastro M, Gomes JP, Sampaio DA, Rocha R, et al. Genomic structure and insertion sites of Helicobacter pylori prophages from various geographical origins. Sci Rep. 2017;7:42471. Epub 2017/02/17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Uchiyama J, Takemura-Uchiyama I, Kato S, Takeuchi H, Sakaguchi Y, Ujihara T, et al. Screening of KHP30-like prophages among Japanese Helicobacter pylori strains, and genetic analysis of a defective KHP30-like prophage sequence integrated in the genome of the H. pylori strain NY40. FEMS Microbiol Lett. 2016;363(16):fnw157. Epub 2016/07/09.

    Article  PubMed  CAS  Google Scholar 

  123. Secka O, Vale FF, Buissonniere A, Thomas JE, Megraud F, Lehours P. Phylogeographic agreement between prophage and bacterial housekeeping genes in Helicobacter pylori strains from the Gambia. Helicobacter. 2017;22(5):e12394. Epub 2017/05/26.

    Article  Google Scholar 

  124. Kyrillos A, Arora G, Murray B, Rosenwald AG. The presence of phage orthologous genes in Helicobacter pylori correlates with the presence of the virulence factors CagA and VacA. Helicobacter. 2016;21(3):226–33. Epub 2015/11/28.

    Article  CAS  PubMed  Google Scholar 

  125. Mucito-Varela E, Castillo-Rojas G, Cevallos MA, Lozano L, Merino E, Lopez-Leal G, et al. Complete genome sequence of Helicobacter pylori strain 29CaP isolated from a mexican patient with gastric cancer. Genome Announc. 2016;4(1):e01512–5. Epub 2016/01/16.

    PubMed  PubMed Central  Google Scholar 

  126. Qumar S, Majid M, Kumar N, Tiwari SK, Semmler T, Devi S, et al. Genome dynamics and molecular infection epidemiology of multidrug-resistant Helicobacter pullorum isolates obtained from broiler and free-range chickens in India. Appl Environ Microbiol. 2017;83(1):e02305–16. Epub 2016/11/07.

    CAS  PubMed  Google Scholar 

  127. Hoy B, Lower M, Weydig C, Carra G, Tegtmeyer N, Geppert T, et al. Helicobacter pylori HtrA is a new secreted virulence factor that cleaves E-cadherin to disrupt intercellular adhesion. EMBO Rep. 2010;11(10):798–804. Epub 2010/09/04.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Hoy B, Geppert T, Boehm M, Reisen F, Plattner P, Gadermaier G, et al. Distinct roles of secreted HtrA proteases from gram-negative pathogens in cleaving the junctional protein and tumor suppressor E-cadherin. J Biol Chem. 2012;287(13):10115–20. Epub 2012/02/18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Schmidt TP, Goetz C, Huemer M, Schneider G, Wessler S. Calcium binding protects E-cadherin from cleavage by Helicobacter pylori HtrA. Gut Pathog. 2016;8:29. Epub 2016/06/09.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  130. Schmidt TP, Perna AM, Fugmann T, Bohm M, Jan H, Haller S, et al. Identification of E-cadherin signature motifs functioning as cleavage sites for Helicobacter pylori HtrA. Sci Rep. 2016;6:23264. Epub 2016/03/18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Tegtmeyer N, Moodley Y, Yamaoka Y, Pernitzsch SR, Schmidt V, Traverso FR, et al. Characterisation of worldwide Helicobacter pylori strains reveals genetic conservation and essentiality of serine protease HtrA. Mol Microbiol. 2016;99(5):925–44. Epub 2015/11/17.

    Article  CAS  PubMed  Google Scholar 

  132. Harrer A, Boehm M, Backert S, Tegtmeyer N. Overexpression of serine protease HtrA enhances disruption of adherens junctions, paracellular transmigration and type IV secretion of CagA by Helicobacter pylori. Gut Pathog. 2017;9:40. Epub 2017/08/05.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  133. Noto JM, Peek RM Jr. Helicobacter pylori makes a molecular incision to gain epithelial entry. Cell Host Microbe. 2017;22(4):434–6. Epub 2017/10/13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu-City, Oita, Japan

    Evariste Tshibangu Kabamba & Yoshio Yamaoka

  2. Department of Medicine-Gastroenterology, Baylor College of Medicine and Michael E. Debakey Veterans Affairs Medical Center, Houston, TX, USA

    Yoshio Yamaoka

Authors
  1. Evariste Tshibangu Kabamba
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoshio Yamaoka
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yoshio Yamaoka .

Editor information

Editors and Affiliations

  1. Department of Internal Medicine, Kawasaki Medical School Kurashiki, Okayama, Japan

    Akiko Shiotani

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Kabamba, E.T., Yamaoka, Y. (2019). Helicobacter pylori and Related Virulence Factors for Gastrointestinal Diseases. In: Shiotani, A. (eds) Gastric Cancer. Springer, Singapore. https://doi.org/10.1007/978-981-13-1120-8_3

Download citation

  • DOI: https://doi.org/10.1007/978-981-13-1120-8_3

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-13-1119-2

  • Online ISBN: 978-981-13-1120-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation