Medical Microbiology and Immunology

, Volume 182, Issue 5, pp 233–242 | Cite as

Ultrastructural localization of urease ofHelicobacter pylori

  • G. Bode
  • P. Malfertheiner
  • G. Lehnhardt
  • M. Nilius
  • H. Ditschuneit
Original Investigations


Helicobacter pylori urease was characterized by means of an enzyme histochemical electron microscopic technique. Ultrastructural analysis revealed no urease activity in one strain; in sevenH. pylori strains (43.75%), urease activity was associated with the cell membrane. Eight strains (50.0%) showed reaction product located within the cytoplasm. Urease activity showed no correlation with localization of activity. Our results demonstrate thatH. pylori urease is not uniform in allH. pylori strains, and differences in activity and localization of urease activity may account for different virulence activities.


Cell Membrane Microscopic Technique Urease Activity Ultrastructural Analysis Pylorus Strain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Austin JW, Doig P, Stewart M, Trust TJ (1991) Macromolecular structure and aggregation states ofHelicobacter pylori urease. J Bacteriol 173:5663–5667Google Scholar
  2. 2.
    Bode G, Malfertheiner P, Ditschuneit H (1988) Pathogenetic implications of ultrastructural findings inCampylobacter pylori-related gastroduodenal disease. Scand J Gastroenterol 23 [Suppl 142]: 25–39Google Scholar
  3. 3.
    Bode G, Malfertheiner P, Nilius M, Lehnhardt G, Ditschuneit H (1989) Ultrastructural localization of urease in outer membrane and periplasm ofCampylobacter pylori. J Clin Pathol 42:778–779Google Scholar
  4. 4.
    Borriello SP, Tarar M, Reed PY, Abimiku A, Adams P (1989) Substrate specificity and isomeric forms of Campylobacter urease. J Med Microbiol 28:XViiGoogle Scholar
  5. 5.
    Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254Google Scholar
  6. 6.
    Catrenich CE, Makin KM (1991) Characterization of the morphologic conversion of Helicobacter pylori from bacillary to coccoid forms. Scand J Gastroenterol 26 [Suppl 181]:58–64Google Scholar
  7. 7.
    Chen XG, Correa P, Offerhaus J, Rodriguez E, Jamrey F, Hoffmann E, Fox J, Hunter F, Diavolitsis S (1986) Ultrastructure of the gastric mucosa harboring Campylobacter-like organisms. Am J Clin Pathol 86:575–582Google Scholar
  8. 8.
    Costas M, Owen RJ, Morgan DD, Goodwin CS (1991) Loss of urease activity inHelicobacter mustelae. Lett Appl Microbiol 14:260–264Google Scholar
  9. 9.
    Cover TL, Paryear W, Perez-Perez GI, Blaser MJ (1991) Effect of urease on HeLa cell vacuolization induced byHelicobacter pylori cytotoxin. Infect Immun 59:1264–1270Google Scholar
  10. 10.
    Dunn BE, Campbell GP, Perez-Perez GI, Blaser MY (1990) Purification and characterization of urease fromHelicobacter pylori. J Biol Chem 265:9464–9469Google Scholar
  11. 11.
    Dunn BE, Sung C-C, Taylor NS, Fox JG (1991) Purification and characterization ofHelicobacter mustelae urease. Infect Immun 59:3343–3345Google Scholar
  12. 12.
    Eaton KA, Brooks CL, Morgan DR, Krakowka S (1991) Essential role of urease in pathogenesis of gastritis induced byHelicobacter pylori in gnotobiotic piglets. Infect immun 59:2470–2475Google Scholar
  13. 13.
    Evans DJ, Evans DG, Kirkpatrick SS, Graham DY (1991) Characterization of theHelicobacter pylori urease and purification of its subunits. Microb Pathog 10:15–26Google Scholar
  14. 14.
    Ferrero RL, Lee A (1991) The importance of urease in acid protection for the gastriccolonizing bacteriaHelicobacter pylori andHelicobacter felis, new species. Microb Ecol Health Dis 4:121–134Google Scholar
  15. 15.
    Ferrero RL, Hazell SL, Lee A (1988) The urease enzymes ofCampylobacter pylori and a related bacterium. J Med Microbiol 27:33–40Google Scholar
  16. 16.
    Goldie J, Velhuyzen van Zanten SJO, Jalali S, Richardson H, Hunt RH (1991) Inhibition of urease activity but not growth ofHelicobacter pylori by acetohydroxamic acid. J Clin Pathol 44:695–697Google Scholar
  17. 17.
    Hawtin PR, Stacey AR, Newell DG (1990) Investigation of the structure and localization of the urease ofHelicobacter pylori using monoclonal antibodies. J Gen Microbiol 136:1995–2000Google Scholar
  18. 18.
    Hu L-T, Mobley HL (1990) Purification and N-terminal analysis of urease fromHelicobacter pylori. Infect Immun 58:992–998Google Scholar
  19. 19.
    Kaltwasser H, Schlegel HG (1966) NADH-dependent coupled enzyme assay for urease and other ammonia-producing systems. Anal Biochem 16:132–138Google Scholar
  20. 20.
    Kasper G, Dickgiesser N (1985) Isolation from gastric epithelium of Campylobacter-like bacteria that are distinct from “Campylobacter pyloridis”. Lancet I:111–112Google Scholar
  21. 21.
    Langenberg ML, Tytgat GN, Schipper MEI, Rietra PYGM, Zanen HC (1984). Campylobacter-like organisms in the stomach of patients and healthy individuals. Lancet 1:1384Google Scholar
  22. 22.
    Majewski SIH, Goodwin CS (1988) Restriction endonuclease analysis of the genome ofCampylobacter pylori with a rapid extraction method: evidence for considerable genomic variation. J Infect Dis 157:465–471Google Scholar
  23. 23.
    Marshall BJ, Langton SR (1986) Urea hydrolysis in patients withCampylobacter pyloridis infection. Lancet I:965–966Google Scholar
  24. 24.
    Marshall BJ, Barrett LJ, Prakash C, McCallum RW, Guerrant RL (1990) Urea protectsHelicobacter (Campylobacter) pylori from the bactericidal effect of acid. Gastroenterology 99:697–702Google Scholar
  25. 25.
    McDermott WV (1958) Role of ammonia intoxication in hepatic coma. Bull NY Acad Med 34:359–365Google Scholar
  26. 26.
    McLean RJ, Cheng KY, Gould WD, Costerton JW (1985) Cytochemical localization of urease in a rumenStaphylococcus sp. by electron microscopy. Appl Environ Microbiol 49:253–255Google Scholar
  27. 27.
    McLean RJ, Cheng KY, Gould WD, Nickel JC, Costerton JW (1986) Histochemical and biochemical urease localization in the periplasma and outer membrane of two Proteus mirabilis strains. Can J Microbiol 32:772–778Google Scholar
  28. 28.
    McNulty CAM, Dent JC, Uff JS, Gear MWL, Wilkinson SP (1989) Detection of Campylobacter pylori by the biopsy urease test: an assessment in 1445 patients. Gut 30:1058–1062Google Scholar
  29. 29.
    Mobley HLT, Hausinger RP (1989) Microbial ureases: singnificance regulation, and molecular characterization. Microbiol Rev 53:85–108Google Scholar
  30. 30.
    Mobley HLT, Cortesia MJ, Rosenthal LE, Jones BD (1988). Characterization of urease fromCampylobacter pylori. J Clin Microbiol 26:831–836Google Scholar
  31. 31.
    Mulrooney SB, Pankratz HS, Hausinger RP (1989) Regulation of gene expression and cellular localization of clonedKlebsiella aerogenes (K. pneunoniae) urease. J Gen Microbiol 135:1769–1776Google Scholar
  32. 32.
    Murakami M, Yoo JK, Inada M, Miyake T (1988) Effect of ammonia on the gastric mucosa in rats: pathophysiological importance of urease in gastric ulcer disease. Jpn J Pharmacol 47:330–332Google Scholar
  33. 33.
    Nilius M, Bode G, Lehnhardt G, Malfertheiner P (1991) In vitro inhibition ofHelicobacter pylori urease: biochemical and ultrastructural analysis. Eur J Clin Invest 21:551–557Google Scholar
  34. 34.
    Rosenstein IYM, Hamilton-Miller YMT (1984) Inhibitor of urease as chemotherapeutic agents. Crit Rev Microbiol 11:1–12Google Scholar
  35. 35.
    Senior BW, Bradford NC, Simpson DS (1980) The ureases ofProteus strains in relation to virulence for the urinary tract. J Med Microbiol 13:507–512Google Scholar
  36. 36.
    Smoot DT, Mobley HLT, Chippendale GR, Lewison JF, Resan JH (1990)Helicobacter pylori urease activity is toxic to human gastric epithelial cells. Infect Immun 58:1992–1994Google Scholar
  37. 37.
    Taylor M, Goodwin CS, Karim QN (1988) Two urease activities with different pH optima inCampylobacter pylori and similar organisms. FEMS Microbiol Lett 55:259–262Google Scholar
  38. 38.
    Thomson L, Tasman-Yones C, Morris A, Wiggens P, Lee S, Forlong C (1989) Ammonia produced byCampylobacter pylori neutralizes H+ moving through gastric mucus. Scand J Gastroenterol 24:761–768Google Scholar
  39. 39.
    Tompkins DS, West AP (1987)Campylobacter pylori, acid, and bile. J Clin Pathol 40:1387Google Scholar
  40. 40.
    Tompkins DS, Millar MR, West AP (1988) Isoelectric focusing of ureases fromCampylobacter pylori and related organisms. J Clin Microbiol 26:2678–2679Google Scholar
  41. 41.
    Vinthier O (1976) Localization of urease activity in ureaplasma urealyticum cells. Acta pathol microbiol Scand [B] 84:217–224Google Scholar
  42. 42.
    von Wulffen H (1987) Low degree of relatedness betweenCampylobacter pyloridis and enteropathogenicCampylobacter species as revealed by DNA-DNA blot hybridization and immunoblot studies. FEMS Microbiol Lett 42:129–133Google Scholar
  43. 43.
    Xu J-K, Goodwin CS, Cooper M, Robinson J (1990) Intracellular vacuolization caused by the urease ofHelicobacter pylori. J Infect Dis 161:1302–1304Google Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • G. Bode
    • 1
  • P. Malfertheiner
    • 1
  • G. Lehnhardt
    • 1
  • M. Nilius
    • 1
  • H. Ditschuneit
    • 1
  1. 1.Department of Internal Medicine IUniversity of UlmUlmGermany

Personalised recommendations