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2005 | 54 | 4 | 307-319
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Helicobacter pylori - patogen roku 2005

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Helicobacter pylori - Nobel Prize 2005
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The Nobel Prize in Physiology or Medicine for 2005 has been awarded jointly to Barry J. Marshall and J. Robin Warren for their discovery of 'the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease'. This year's Nobel Winners made the remarkable and unexpected discovery that inflammation in the stomach (gastritis) as well as ulceration of the stomach or duodenum (peptic ulcer disease) is the result of an infection of the stomach caused by the bacterium Helicobacter pylori. Thanks to the pioneering discovery by Marshall and Warren, peptic ulcer disease are no longer a chronic, frequently disabling condition, but a disease that can be cured by a short regimen of antibiotics and acid secretion inhibitors. The discovery of Helicobacter pylori has also led to increased understanding of the connection between chronic infection, inflammation and cancer. Helicobacter pylori, a gramnegative spiral-shaped bacterium, member of ε-Proteobacteria, colonizes the gastric mucosa of humans. it is now recognized that H. pylori infects about half of the world's population (87% of Polish population). Infection is typically contracted in early childhood, frequently by transmission from mother to child, and the bacteria may remain in the stomach for the rest of the person's life. H. pylori has been identified as the causative agent of chronic inflammation, chronic gastritis and peptic ulceration and is believed to be a risk factor for the development of mucosa-associated lymphoid tissue lymphoma and adenocarcinoma of the stomach. The World Health organization has assigned H. pylori as class i carcinogens. Although more than 50% of the human population is infected with H. pylori only a subset develops the disease. The nature and severity of the disease depend on host characteristics, bacterial genotype and environmental factors. The focus of this minireview is on three major virulence factors of Helicobacter pylori: vacuolating cytotoxin VacA, CagA - an effector molecule of the type four secretion system and urease. VacA and CagA have also immunomodulatory activities that enable H. pylori to establish a chronic infection. The molecular basis by which H. pylori triggers cell signaling cascades and promotes inflammation and epithelial cell proliferation is described as well. This minireview also highlights recent developments in the field of H. pylori diagnosis and vaccine construction.
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  • Uniwerytet Warszawski Instytut Mikrobiologii Zakład Genetyki Bakterii, Miecznikowa 1, 02-096 Warszawa, Polska
  • Uniwerytet Warszawski Instytut Mikrobiologii Zakład Genetyki Bakterii, Miecznikowa 1, 02-096 Warszawa, Polska
  • Uniwerytet Warszawski Instytut Mikrobiologii Zakład Genetyki Bakterii, Miecznikowa 1, 02-096 Warszawa, Polska
  • Amieva M R., Vogelmann R., Covacci A., Tompkins L. S., Nelson W. J., Falkow S., 2003. Disruption of the epithelial apical-junctional complex by Helicobacter pylori cagA. Science 300, 1430-1434.
  • 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, 820-827.
  • Bjorkholm B., Salama N. R., 2003. Genomics of Helicobacter. Helicobacter 8, 1-7.
  • Blaser M. J., Atherton J. C., 2004. Helicobacter pylori persistence: Biology and disease. J. Clin. Invest. 113, 321-333.
  • Bourzac K. M., Guillemin K., 2005. Helicobacter pylorihost cell interactions mediated by type iv secretion. Cell Microbiol. 7, 911-919.
  • Churin Y., Kardalinou E., Meyer T. F., Naumann M., 2001. Pathogenicity island-dependent activation of rho gtpases rac1 and cdc42 in Helicobacter pylori infection. Mol. Microbiol. 40, 815-823.
  • Del Giudice G., Covacci A., Telford J. L., Montecucco C., Rappuoli R., 2001. The design of vaccines against Helicobacter pylori and their development. Ann. Rev. Immunol. 19, 523-563.
  • Dzieniszewski J., Jarosz M., Grupa Robocza PTG, 2004. Postępowanie w zakażeniu Helicobacter pylori (rok 2004). Wytyczne opracowane przez grupę roboczą Polskiego Towarzystwa Genetycznego. Gastroenterol. Pol. 11, 41-48.
  • Dzwonek A., Mikula M., Woszczynski M., Hennig E., Ostrowski J., 2004. Protective effect of vaccination with DNA of the H. pylori genomic library in experimentally infected Mice. Cell Mol. Biol. Lett. 9, 483-495.
  • Elomar E., Carrington M., Chow W., Mccoll K., Bream J., Young H., Herrera J., Lissowska J., Yuan C., Rothman N., Lanyon G., Martin M., Fraumeni J. J., Rabkin C., 2000. Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 404, 398-402.
  • Fischer W., Puls J., Buhrdorf R., Gebert B., Odenbreit S., Haas R., 2001. Systematic mutagenesis of the Helicobacter pylori cag pathogenicity island: Essential genes for cagA translocation in host cells and induction if interleukin-8. Mol. Microbiol. 42, 1337-1348.
  • Forsyth M. H., Atherton J. C., Blaser M. J., Cover T. L., 1998. Heterogeneity in levels of vacuolating cytotoxin gene (vacA) transcription among Helicobacter pylori strains. Infect. Immun. 66, 3088-3094.
  • Galmiche A., Rassow J., Doye A., Cagnol S., Chambard J. C., Contamin S., De Thillot V., Just I. R. V., Solcia E., Van Obberghen E., Boquet P., 2000. The N-terminal 34 kda fragment of Helicobacter pylori vacuolating cytotoxin targets mitochondria and induces cytochrome c Release. Embo J. 19, 6361-6370.
  • Gisbert J. P., Pajares J. M., 2005. Helicobacter pylori 'rescue' therapy after failure of two eradication treatments. Helicobacter 10, 363-372.
  • Haas G., Karaali G., Ebermayer K., Metzger W. G., Lamer S., Zimnyarndt U., Diescher S., Goebel U. B., Vogt K., Roznowski A. B., Wiedenmann B. J., Meyer T. F., Aebischer T., Jungblut P. R., 2002. Immunoproteomics of Helicobacter pylori infection and relation to gastric disease. Proteomics 2, 313-324.
  • Hardin F. J., Wright R. A., 2002. Helicobacter pylori: Review and update. Hospital Physician May, 23-31.
  • 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. Usa 99, 14428-14433.
  • Kavermann H., Burns B. P., Angermuller K., Odenbreit S., Fischer W., Melchers K., Haas R., 2003. Dentification and characterization of Helicobacter pylori genes essential for gastric colonization. J. Exp. Med. 197, 813-822
  • Kidd M., Modlin I. M., 1998. A century of Helicobacter pylori: Paradigms lost-paradigms regained. Digestion 59, 1-15
  • Kuck D., Kolmerer B., Iking Konert C., Krammer P. H., Stremmel W., Rudi J., 2001. Vacuolating cytotoxin of Helicobacter pylori induces apoptosis in the human gastric epithelial cell line AGS. Infect. Immun. 69, 5080-5087.
  • Lanzavecchia S., Bellon P. L., Lupetti P., Dallai R., Rappuoli R., Telford J. L., 1998. Three-dimensional reconstruction of metal replicas of the Helicobacter pylori vacuolating cytotoxin. J. Struct. Biol. 121, 9-18.
  • Lax A. J., Thomas W., 2002. How bacteria could cause cancer: One step at a time. Trends Microbiol. 10, 293-299
  • Liu X. F., Hu J. L., Quan Q. Z., Sun Z. Q., Wang Y. J., 2005. Systemic immune responses to oral administration of recombinant attenuated Salmonella typhimurium expressing Helicobacter pylori urease in mice. World J. Gastroenterol. 11, 2154-2156.
  • Mai U. E., Perez Perez G. I., Allen J. B., Wahl S. M., Blaser M. J., Smith P. D., 1992. Surface proteins from Helicobacter pylori exhibit chemotactic activity for human leukocytes and are present in gastric mucosa. J. Exp. Med. 175, 517-525.
  • Michetti P., Svennerholm A. M., 2003. Helicobacter pylori - inflammation, immunity and vaccines. Helicobacter 8, 31-35.
  • Mikuła M., Dzwonek A., Jagusztyn-Krynicka E. K., Ostrowski J., 2003. Quantitative detection for low levels of Helicobacter pylori infection in experimentally infected mice by real-time PCR. J. Microbiol. Methods. 55, 351-359.
  • Mimuro H., Suzuki T., Tanaka J., Asahi M., Haas R., Sasakawa C., 2002. Grb2 is a key mediator of Helicobacter pylori cagA protein activities. Mol. Cell 10, 745-755.
  • Naumann M., 2005. Pathogenicity island-dependent effects of Helicobacter pylori on intracellular signal transduction in epithelial cells. Int. J. Med. Microbiol. 295, 335-341.
  • Naumann M., Crabtree J. E., 2004. Helicobacter pylori-induced epithelial cell signalling in gastric carcinogenesis. Trends Microbiol.12, 29-36.
  • Prinz C., Hafsi N., 2003. Helicobacter pylori virulence factors and the host immune response: Implications for therapeutic vaccination. Trends Microbiol. 11, 134-138
  • Radosz-Komoniewska H., Bek T., Jozwiak J., Martirosian G., 2005. Pathogenicity of Helicobacter pylori infection. Clin. Microbiol. Infect. 11, 602-610
  • Rautelin H. L. P., Megraud F., 2003. Diagnosis of Helicobacter pylori infection. Helicobacter 8, 13-20.
  • Reyrat J. M., Pelicic V., Papini E., Montecucco C., Rappuoli R., Telford J. L., 1999. Towards deciphering the Helicobacter pylori cytotoxin. Mol. Microbiol. 34, 197-204.
  • Ricci V., Galmiche A., Doye A., Necchi V., Solcia E., Boquet P., 2000. High cell sensitivity to Helicobacter pylori VacA toxin depends on a gpi-anchored protein and is not blocked by inhibition of the clathrin-mediated pathway of endocytosis. Mol. Biol. Cell. 11, 3897-3909.
  • Rieder G., Fischer W., Haas R., 2005. Interaction of Helicobacter pylori with host cells: function of secreted and translocated molecules. Curr. Opin. Microbiol. 8, 67-73.
  • Ruggiero P., Peppoloni S., Rappuoli R., 2003. The quest for a vaccine against Helicobacter pylori: How to move from mouse to man? Microbes Infect. 5, 749-756
  • Schraw W., Li Y., Mcclain M. S., Van Der Goot F. G., Cover T. L., 2002. Association of Helicobacter pylori vacuolating toxin (VacA) with lipid rafts. J. Biol. Chem. 277, 34642-34650
  • Selbach M., Moese S., Hurwitz R., Hauck C. R., Meyer T. F., 2003. The Helicobacter pylori cagA protein induces cortactin dephosphorylation and actin rearrangement By C-Src Inactivation. Embo J. 22, 515-528
  • Shibayama K., Doi Y., Shibata N., Yagi T., Nada T., Iinuma Y., Arakawa Y., 2001. Apoptotic signaling pathway activated by Helicobacter pylori infection and increase of apoptosis-inducing activity under serum-starved conditions. Infect. Immun. 69, 3181-3189.
  • Smoot D. T., Mobley H. L. T., Chippendale G. R., Lewison J. F., Resau J. H., 1990. Helicobacter pylori urease activity is toxic to human gastric epithelial cells. Infect. Immun. 58, 1992-1994.
  • Suzuki M., Miura S., Suematsu M., Suzuki H., Fukumura D., Kurose I., Suzuki H., Kai A., Kudoh Y., Ohashi M., Tsuchiya M., 1992. Helicobacter pylori - associated ammonia production enhances neutrophil-dependent gastric mucosal cell injury. Am. J. Physiol. 263, G719-G725.
  • Todoroki I., Watanabe K., Miyashita M., Seno K., Nomura T., Yokoyama Y., Tochikubo K., Itoh M., 2000. Suppressive effects of DNA vaccines encoding heat shock protein on Helicobacter pylori -induced gastritis in mice. Biochem. Biophys. Res. Commun. 277, 159-163.
  • Torres V. J., Ivie S. E., Mcclain M. S., 2005. Functional properties of the P33 and P55 domains of the Helicobacter pylori vacuolating cytotoxin. J. Biol. Chem. 280, 21107-21114.
  • Tsutsumi R., Higashi H., Higuchi M., Okada M., 2003. Attenuation of Helicobacter pylori cagA x shp-2 signaling by interaction between cagA and c-terminal src kinase. J. Biol. Chem. 278, 3664-3670.
  • Utt M., Nilsson I., Ljungh A., Wadstrom T., 2002. Identification of novel immunogenic proteins of Helicobacter pylori by proteome technology. J. Immunol. Meth. 259, 1-10.
  • Viala J., Chaput C., Boneca I. G., Cardona A., Girardin S. E., Moran A. P., Athman R., Memet S., Huerre M. R., Coyle A. J., Distefano P. S., Sansonetti P. J., Labigne A., Bertin J., Philpott D. J., 2004. Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island. Nat. Immunol. 5, 1166-1174.
  • Walduck A., Schmitt A., Lucas B., Aebischer T., 2004. Transcription profiling analysis of the mechanisms of vaccine-induced protection against H. Pylori. Faseb J. 18, 1955-1957.
  • Wallasch C., Crabtree J. E., Bevec D., Robinson P. A., Wagner H., Ullrich A., 2002. Helicobacter pylori-stimulated egf receptor transactivation requires metalloprotease cleavage of HB-EGF. Biochem. Biophys. Res. Commun. 295, 695-701.
  • Xuc., Li Z. S., Du Y. Q., Tu Z. X., Gong Y. F., Jin J., Wu H. Y., 2005. Construction of a recombinant attenuated Salmonella typhimurium DNA vaccine carrying Helicobacter pylori hpaA. World J. Gastroenterol. 11, 114-117.
  • Yahiro K., Niidome T., Hatakeyama T., Aoyagi H., Kurazono H., Padilla P. I., Wada A., Hirayama T., 1997. Helicobacter pylori vacuolating cytotoxin binds to the 140-kda protein in human gastric cancer cell lines, AZ-521 and AGS. Biochem. Biophys. Res. Commun. 238, 629-632.
  • Yahiro K., Niidome T., Kimura M., Hatakeyama T., Aoyagi H., Kurazono H., Imagawa K., Wada A., Moss J., Hirayama T., 1999. Activation of Helicobacter pylori vaca toxin by alkaline or acid conditions increases its binding to a 250-kda receptor protein-tyrosine phosphatase beta. J. Biol. Chem. 274, 36693-36699.
  • Yamaoka Y., Kodama T., Kita M., Imanishi J., Kashima K., Graham D., 1998. Relationship of vaca genotypes of Helicobacter pylori to caga status, cytotoxin production, and clinical outcome. Helicobacter 3, 241-253.
  • Zhang H., Fang D. C., Wang R. Q., Yang S. M., Liu H. F., 2004. Effect of Helicobacter pylori infection on expression of bcl-2 family members in gastric adenocarcinoma. World J. Gastroenterol. 10, 227-230.
  • Zhang H., Zhang X., Liu M., Zhang J., Li Y., 2005. Expression and characterization of Helicobacter pylori HspA protein in transgenic tobacco plants. Biotechnol. Appl. Biochem. Sep 1.
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