This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Salama, N. R.
Right arrow Articles by Falkow, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Salama, N. R.
Right arrow Articles by Falkow, S.

 Previous Article  |  Next Article 

Infection and Immunity, February 2001, p. 730-736, Vol. 69, No. 2
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.2.730-736.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Vacuolating Cytotoxin of Helicobacter pylori Plays a Role during Colonization in a Mouse Model of Infection

Nina R. Salama,1,* Glen Otto,2 Lucy Tompkins,1 and Stanley Falkow1

Department of Microbiology and Immunology1 and Department of Comparative Medicine,2 Stanford University School of Medicine, Stanford, California 94305

Received 23 August 2000/Returned for modification 18 October 2000/Accepted 8 November 2000

Helicobacter pylori, the causative agent of gastritis and ulcer disease in humans, secretes a toxin called VacA (vacuolating cytotoxin) into culture supernatants. VacA was initially characterized and purified on the basis of its ability to induce the formation of intracellular vacuoles in tissue culture cells. H. pylori strains possessing different alleles of vacA differ in their ability to express active toxin. Those strains expressing higher toxin levels are correlated with more severe gastric disease. However, the specific role(s) played by VacA during the course of infection and disease is not clear. We have used a mouse model of H. pylori infection to begin to address this role. A null mutation of vacA compromises H. pylori in its ability to initially establish infection. If an infection by a vacA mutant is established, the bacterial load and degree of inflammation are similar to those associated with an isogenic wild-type strain. Thus, in this infection model, vacA plays a role in the initial colonization of the host, suggesting that strains of H. pylori expressing active alleles of vacA may be better adapted for host-to-host transmission.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Sherman Fairchild Science Building, D031, 299 Campus Dr., Stanford, CA 94305-5124. Phone: (650)723-2671. Fax: (650)723-1837. E-mail: nsalama{at}leland.stanford.edu

Infection and Immunity, February 2001, p. 730-736, Vol. 69, No. 2
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.2.730-736.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Talarico, S., Gold, B. D., Fero, J., Thompson, D. T., Guarner, J., Czinn, S., Salama, N. R. (2009). Pediatric Helicobacter pylori Isolates Display Distinct Gene Coding Capacities and Virulence Gene Marker Profiles. J. Clin. Microbiol. 47: 1680-1688 [Abstract] [Full Text]  
  • Alamuri, P., Eaton, K. A., Himpsl, S. D., Smith, S. N., Mobley, H. L. T. (2009). Vaccination with Proteus Toxic Agglutinin, a Hemolysin-Independent Cytotoxin In Vivo, Protects against Proteus mirabilis Urinary Tract Infection. Infect. Immun. 77: 632-641 [Abstract] [Full Text]  
  • Castillo, A. R., Woodruff, A. J., Connolly, L. E., Sause, W. E., Ottemann, K. M. (2008). Recombination-Based In Vivo Expression Technology Identifies Helicobacter pylori Genes Important for Host Colonization. Infect. Immun. 76: 5632-5644 [Abstract] [Full Text]  
  • Peek, R. M. Jr (2008). Helicobacter pylori infection and disease: from humans to animal models. DMM 1: 50-55 [Abstract] [Full Text]  
  • Ivie, S. E., McClain, M. S., Torres, V. J., Algood, H. M. S., Lacy, D. B., Yang, R., Blanke, S. R., Cover, T. L. (2008). Helicobacter pylori VacA Subdomain Required for Intracellular Toxin Activity and Assembly of Functional Oligomeric Complexes. Infect. Immun. 76: 2843-2851 [Abstract] [Full Text]  
  • Ayala, G., Torres-Mena, J., Lopez-Carrillo, L. (2008). Association between Helicobacter pylori VacA antigens and gastric cancer depends on the detection method used: immunoblot versus neutralization of the vacuolating activity of VacA. J Med Microbiol 57: 9-14 [Abstract] [Full Text]  
  • Brumell, J. H., Scidmore, M. A. (2007). Manipulation of Rab GTPase Function by Intracellular Bacterial Pathogens. Microbiol. Mol. Biol. Rev. 71: 636-652 [Abstract] [Full Text]  
  • Carpenter, B. M., McDaniel, T. K., Whitmire, J. M., Gancz, H., Guidotti, S., Censini, S., Merrell, D. S. (2007). Expanding the Helicobacter pylori Genetic Toolbox: Modification of an Endogenous Plasmid for Use as a Transcriptional Reporter and Complementation Vector. Appl. Environ. Microbiol. 73: 7506-7514 [Abstract] [Full Text]  
  • Williams, S. M., Chen, Y.-T., Andermann, T. M., Carter, J. E., McGee, D. J., Ottemann, K. M. (2007). Helicobacter pylori Chemotaxis Modulates Inflammation and Bacterium-Gastric Epithelium Interactions in Infected Mice. Infect. Immun. 75: 3747-3757 [Abstract] [Full Text]  
  • Baldwin, D. N., Shepherd, B., Kraemer, P., Hall, M. K., Sycuro, L. K., Pinto-Santini, D. M., Salama, N. R. (2007). Identification of Helicobacter pylori Genes That Contribute to Stomach Colonization. Infect. Immun. 75: 1005-1016 [Abstract] [Full Text]  
  • Algood, H. M. S., Torres, V. J., Unutmaz, D., Cover, T. L. (2007). Resistance of Primary Murine CD4+ T Cells to Helicobacter pylori Vacuolating Cytotoxin. Infect. Immun. 75: 334-341 [Abstract] [Full Text]  
  • Kundu, P., Mukhopadhyay, A. K., Patra, R., Banerjee, A., Berg, D. E., Swarnakar, S. (2006). Cag Pathogenicity Island-independent Up-regulation of Matrix Metalloproteinases-9 and -2 Secretion and Expression in Mice by Helicobacter pylori Infection. J. Biol. Chem. 281: 34651-34662 [Abstract] [Full Text]  
  • McClain, M. S., Czajkowsky, D. M., Torres, V. J., Szabo, G., Shao, Z., Cover, T. L. (2006). Random Mutagenesis of Helicobacter pylori vacA To Identify Amino Acids Essential for Vacuolating Cytotoxic Activity. Infect. Immun. 74: 6188-6195 [Abstract] [Full Text]  
  • Osaki, T., Hanawa, T., Manzoku, T., Fukuda, M., Kawakami, H., Suzuki, H., Yamaguchi, H., Yan, X., Taguchi, H., Kurata, S., Kamiya, S. (2006). Mutation of luxS affects motility and infectivity of Helicobacter pylori in gastric mucosa of a Mongolian gerbil model.. J Med Microbiol 55: 1477-1485 [Abstract] [Full Text]  
  • Kusters, J. G., van Vliet, A. H. M., Kuipers, E. J. (2006). Pathogenesis of Helicobacter pylori Infection. Clin. Microbiol. Rev. 19: 449-490 [Abstract] [Full Text]  
  • Ruggiero, P., Tombola, F., Rossi, G., Pancotto, L., Lauretti, L., Del Giudice, G., Zoratti, M. (2006). Polyphenols Reduce Gastritis Induced by Helicobacter pylori Infection or VacA Toxin Administration in Mice.. Antimicrob. Agents Chemother. 50: 2550-2552 [Abstract] [Full Text]  
  • Genisset, C., Galeotti, C. L., Lupetti, P., Mercati, D., Skibinski, D. A. G., Barone, S., Battistutta, R., de Bernard, M., Telford, J. L. (2006). A Helicobacter pylori Vacuolating Toxin Mutant That Fails To Oligomerize Has a Dominant Negative Phenotype. Infect. Immun. 74: 1786-1794 [Abstract] [Full Text]  
  • Gancz, H., Censini, S., Merrell, D. S. (2006). Iron and pH Homeostasis Intersect at the Level of Fur Regulation in the Gastric Pathogen Helicobacter pylori. Infect. Immun. 74: 602-614 [Abstract] [Full Text]  
  • Gauthier, N. C., Monzo, P., Kaddai, V., Doye, A., Ricci, V., Boquet, P. (2005). Helicobacter pylori VacA Cytotoxin: A Probe for a Clathrin-independent and Cdc42-dependent Pinocytic Pathway Routed to Late Endosomes. Mol. Biol. Cell 16: 4852-4866 [Abstract] [Full Text]  
  • Pinto-Santini, D., Salama, N. R. (2005). The Biology of Helicobacter pylori Infection, a Major Risk Factor for Gastric Adenocarcinoma. Cancer Epidemiol. Biomarkers Prev. 14: 1853-1858 [Abstract] [Full Text]  
  • Fitchen, N., Letley, D. P, O'Shea, P., Atherton, J. C, Williams, P., Hardie, K. R (2005). All subtypes of the cytotoxin VacA adsorb to the surface of Helicobacter pylori post-secretion. J Med Microbiol 54: 621-630 [Abstract] [Full Text]  
  • Moore, J. M., Salama, N. R. (2005). Mutational Analysis of Metronidazole Resistance in Helicobacter pylori. Antimicrob. Agents Chemother. 49: 1236-1237 [Abstract] [Full Text]  
  • McGee, D. J., Langford, M. L., Watson, E. L., Carter, J. E., Chen, Y.-T., Ottemann, K. M. (2005). Colonization and Inflammation Deficiencies in Mongolian Gerbils Infected by Helicobacter pylori Chemotaxis Mutants. Infect. Immun. 73: 1820-1827 [Abstract] [Full Text]  
  • Terry, K., Williams, S. M., Connolly, L., Ottemann, K. M. (2005). Chemotaxis Plays Multiple Roles during Helicobacter pylori Animal Infection. Infect. Immun. 73: 803-811 [Abstract] [Full Text]  
  • Suto, H., Zhang, M., Berg, D. E. (2005). Age-Dependent Changes in Susceptibility of Suckling Mice to Individual Strains of Helicobacter pylori. Infect. Immun. 73: 1232-1234 [Abstract] [Full Text]  
  • Thompson, L. J., Danon, S. J., Wilson, J. E., O'Rourke, J. L., Salama, N. R., Falkow, S., Mitchell, H., Lee, A. (2004). Chronic Helicobacter pylori Infection with Sydney Strain 1 and a Newly Identified Mouse-Adapted Strain (Sydney Strain 2000) in C57BL/6 and BALB/c Mice. Infect. Immun. 72: 4668-4679 [Abstract] [Full Text]  
  • Sundrud, M. S., Torres, V. J., Unutmaz, D., Cover, T. L. (2004). Inhibition of primary human T cell proliferation by Helicobacter pylori vacuolating toxin (VacA) is independent of VacA effects on IL-2 secretion. Proc. Natl. Acad. Sci. USA 101: 7727-7732 [Abstract] [Full Text]  
  • Ladeira, M. S.P., Rodrigues, M. A.M., Salvadori, D. M.F., Queiroz, D. M.M., Freire-Maia, D. V. (2004). DNA Damage in Patients Infected by Helicobacter pylori. Cancer Epidemiol. Biomarkers Prev. 13: 631-637 [Abstract] [Full Text]  
  • Li, Y., Wandinger-Ness, A., Goldenring, J. R., Cover, T. L. (2004). Clustering and Redistribution of Late Endocytic Compartments in Response to Helicobacter pylori Vacuolating Toxin. Mol. Biol. Cell 15: 1946-1959 [Abstract] [Full Text]  
  • Gauthier, N. C., Ricci, V., Gounon, P., Doye, A., Tauc, M., Poujeol, P., Boquet, P. (2004). Glycosylphosphatidylinositol-anchored Proteins and Actin Cytoskeleton Modulate Chloride Transport by Channels Formed by the Helicobacter pylori Vacuolating Cytotoxin VacA in HeLa Cells. J. Biol. Chem. 279: 9481-9489 [Abstract] [Full Text]  
  • Dailidiene, D., Dailide, G., Ogura, K., Zhang, M., Mukhopadhyay, A. K., Eaton, K. A., Cattoli, G., Kusters, J. G., Berg, D. E. (2004). Helicobacter acinonychis: Genetic and Rodent Infection Studies of a Helicobacter pylori-Like Gastric Pathogen of Cheetahs and Other Big Cats. J. Bacteriol. 186: 356-365 [Abstract] [Full Text]  
  • Willhite, D. C., Cover, T. L., Blanke, S. R. (2003). Cellular Vacuolation and Mitochondrial Cytochrome c Release Are Independent Outcomes of Helicobacter pylori Vacuolating Cytotoxin Activity That Are Each Dependent on Membrane Channel Formation. J. Biol. Chem. 278: 48204-48209 [Abstract] [Full Text]  
  • Merrell, D. S., Thompson, L. J., Kim, C. C., Mitchell, H., Tompkins, L. S., Lee, A., Falkow, S. (2003). Growth Phase-Dependent Response of Helicobacter pylori to Iron Starvation. Infect. Immun. 71: 6510-6525 [Abstract] [Full Text]  
  • Bury-Mone, S., Skouloubris, S., Dauga, C., Thiberge, J.-M., Dailidiene, D., Berg, D. E., Labigne, A., De Reuse, H. (2003). Presence of Active Aliphatic Amidases in Helicobacter Species Able To Colonize the Stomach. Infect. Immun. 71: 5613-5622 [Abstract] [Full Text]  
  • Gebert, B., Fischer, W., Weiss, E., Hoffmann, R., Haas, R. (2003). Helicobacter pylori Vacuolating Cytotoxin Inhibits T Lymphocyte Activation. Science 301: 1099-1102 [Abstract] [Full Text]  
  • Merrell, D. S., Goodrich, M. L., Otto, G., Tompkins, L. S., Falkow, S. (2003). pH-Regulated Gene Expression of the Gastric Pathogen Helicobacter pylori. Infect. Immun. 71: 3529-3539 [Abstract] [Full Text]  
  • Ayraud, S., Janvier, B., Salaun, L., Fauchere, J.-L. (2003). Modification in the ppk Gene of Helicobacterpylori during Single and Multiple Experimental Murine Infections. Infect. Immun. 71: 1733-1739 [Abstract] [Full Text]  
  • Dattelbaum, J. D., Lockatell, C. V., Johnson, D. E., Mobley, H. L. T. (2003). UreR, the Transcriptional Activator of the Proteus mirabilis Urease Gene Cluster, Is Required for Urease Activity and Virulence in Experimental Urinary Tract Infections. Infect. Immun. 71: 1026-1030 [Abstract] [Full Text]  
  • Guillemin, K., Salama, N. R., Tompkins, L. S., Falkow, S. (2002). Cag pathogenicity island-specific responses of gastric epithelial cells to Helicobacter pylori infection. Proc. Natl. Acad. Sci. USA 99: 15136-15141 [Abstract] [Full Text]  
  • Suerbaum, S., Michetti, P. (2002). Helicobacter pylori Infection. NEJM 347: 1175-1186 [Full Text]  
  • Andermann, T. M., Chen, Y.-T., Ottemann, K. M. (2002). Two Predicted Chemoreceptors of Helicobacter pylori Promote Stomach Infection. Infect. Immun. 70: 5877-5881 [Abstract] [Full Text]  
  • 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 [Abstract] [Full Text]  
  • Ricci, V., Manzo, B. A., Tuccillo, C., Boquet, P., Ventura, U., Romano, M., Zarrilli, R. (2002). NSAIDs counteract H. pylori VacA toxin-induced cell vacuolation in MKN 28 gastric mucosal cells. Am. J. Physiol. Gastrointest. Liver Physiol. 283: G511-G520 [Abstract] [Full Text]  
  • Patel, H. K., Willhite, D. C., Patel, R. M., Ye, D., Williams, C. L., Torres, E. M., Marty, K. B., MacDonald, R. A., Blanke, S. R. (2002). Plasma Membrane Cholesterol Modulates Cellular Vacuolation Induced by the Helicobacter pylori Vacuolating Cytotoxin. Infect. Immun. 70: 4112-4123 [Abstract] [Full Text]  
  • Willhite, D. C., Ye, D., Blanke, S. R. (2002). Fluorescence Resonance Energy Transfer Microscopy of the Helicobacter pylori Vacuolating Cytotoxin within Mammalian Cells. Infect. Immun. 70: 3824-3832 [Abstract] [Full Text]  
  • Guo, B. P., Mekalanos, J. J. (2002). Rapid genetic analysis of Helicobacter pylori gastric mucosal colonization in suckling mice. Proc. Natl. Acad. Sci. USA 99: 8354-8359 [Abstract] [Full Text]  
  • Ottemann, K. M., Lowenthal, A. C. (2002). Helicobacter pylori Uses Motility for Initial Colonization and To Attain Robust Infection. Infect. Immun. 70: 1984-1990 [Abstract] [Full Text]  
  • Supajatura, V., Ushio, H., Wada, A., Yahiro, K., Okumura, K., Ogawa, H., Hirayama, T., Ra, C. (2002). Cutting Edge: VacA, a Vacuolating Cytotoxin of Helicobacter pylori, Directly Activates Mast Cells for Migration and Production of Proinflammatory Cytokines. J. Immunol. 168: 2603-2607 [Abstract] [Full Text]  
  • McClain, M. S., Cao, P., Iwamoto, H., Vinion-Dubiel, A. D., Szabo, G., Shao, Z., Cover, T. L. (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: 6499-6508 [Abstract] [Full Text]  
  • Fischer, W., Buhrdorf, R., Gerland, E., Haas, R. (2001). Outer Membrane Targeting of Passenger Proteins by the Vacuolating Cytotoxin Autotransporter of Helicobacter pylori. Infect. Immun. 69: 6769-6775 [Abstract] [Full Text]  
  • Solnick, J. V., Hansen, L. M., Canfield, D. R., Parsonnet, J. (2001). Determination of the Infectious Dose of Helicobacter pylori during Primary and Secondary Infection in Rhesus Monkeys (Macaca mulatta). Infect. Immun. 69: 6887-6892 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»