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 Kumar, P.
Right arrow Articles by Bhatnagar, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kumar, P.
Right arrow Articles by Bhatnagar, R.

 Previous Article  |  Next Article 

Infection and Immunity, September 2002, p. 4997-5007, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.4997-5007.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Anthrax Edema Toxin Requires Influx of Calcium for Inducing Cyclic AMP Toxicity in Target Cells

Praveen Kumar, Nidhi Ahuja, and Rakesh Bhatnagar*

Centre for Biotechnology, Jawaharlal Nehru University, New Delhi 110067, India

Received 9 April 2002/ Returned for modification 9 May 2002/ Accepted 27 May 2002

The anthrax edema toxin comprises two proteins: protective antigen and edema factor. Anthrax protective antigen binds to the receptors on the surface of target cells and facilitates the entry of edema factor into these target cells. Edema factor (EF) is an adenylate cyclase that catalyzes the synthesis of cyclic AMP (cAMP) in the cytosol of the host cells. In this study, we examined the requirement of extracellular calcium for anthrax edema toxin-induced toxicity in host cells. The cAMP response generated by edema toxin was analyzed in a variety of cells, including CHO, macrophage-like RAW264.7, human neutrophils, and human lymphocytes. Our investigations reveal that after EF reaches the cell cytosol, a rapid influx of calcium is triggered in the host cell that has a pivotal role in determining the cAMP response of the affected cells. Although the cAMP response generated by edema toxin in different cell types varied in intensity and in the time of initiation, the influx of calcium invariably preceded cAMP accumulation. Agents that blocked the uptake of calcium also inhibited edema toxin-induced accumulation of cAMP in the host cells. This is the first report that demonstrates that edema toxin induces accumulation of cAMP in lymphocytes. By accumulating cAMP, a potent inhibitor of immune cell function, edema toxin may actually be poisoning the immune system and thus facilitating the survival of the bacteria in the host.

* Corresponding author. Mailing address: Centre for Biotechnology, Jawaharlal Nehru University, New Delhi 110067, India. Phone: (91) 11-6179751. Fax: (91) 11-6198234/6865886. E-mail: rakbhat01{at}yahoo.com.

Editor: J. T. Barbieri

Infection and Immunity, September 2002, p. 4997-5007, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.4997-5007.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Yeager, L. A., Chopra, A. K., Peterson, J. W. (2009). Bacillus anthracis Edema Toxin Suppresses Human Macrophage Phagocytosis and Cytoskeletal Remodeling via the Protein Kinase A and Exchange Protein Activated by Cyclic AMP Pathways. Infect. Immun. 77: 2530-2543 [Abstract] [Full Text]  
  • Richter, J. F., Gitter, A. H., Gunzel, D., Weiss, S., Mohamed, W., Chakraborty, T., Fromm, M., Schulzke, J. D. (2009). Listeriolysin O affects barrier function and induces chloride secretion in HT-29/B6 colon epithelial cells. Am. J. Physiol. Gastrointest. Liver Physiol. 296: G1350-G1359 [Abstract] [Full Text]  
  • Bourdeau, R. W., Malito, E., Chenal, A., Bishop, B. L., Musch, M. W., Villereal, M. L., Chang, E. B., Mosser, E. M., Rest, R. F., Tang, W.-J. (2009). Cellular Functions and X-ray Structure of Anthrolysin O, a Cholesterol-dependent Cytolysin Secreted by Bacillus anthracis. J. Biol. Chem. 284: 14645-14656 [Abstract] [Full Text]  
  • Saenz, J. B., Doggett, T. A., Haslam, D. B. (2007). Identification and Characterization of Small Molecules That Inhibit Intracellular Toxin Transport. Infect. Immun. 75: 4552-4561 [Abstract] [Full Text]  
  • Tait, A. S., Dalton, M., Geny, B., D'Agnillo, F., Popoff, M. R., Sternberg, E. M. (2007). The Large Clostridial Toxins from Clostridium sordellii and C. difficile Repress Glucocorticoid Receptor Activity. Infect. Immun. 75: 3935-3940 [Abstract] [Full Text]  
  • Fiser, R., Masin, J., Basler, M., Krusek, J., Spulakova, V., Konopasek, I., Sebo, P. (2007). Third Activity of Bordetella Adenylate Cyclase (AC) Toxin-Hemolysin: MEMBRANE TRANSLOCATION OF AC DOMAIN POLYPEPTIDE PROMOTES CALCIUM INFLUX INTO CD11b+ MONOCYTES INDEPENDENTLY OF THE CATALYTIC AND HEMOLYTIC ACTIVITIES. J. Biol. Chem. 282: 2808-2820 [Abstract] [Full Text]  
  • Crawford, M. A., Aylott, C. V., Bourdeau, R. W., Bokoch, G. M. (2006). Bacillus anthracis Toxins Inhibit Human Neutrophil NADPH Oxidase Activity.. J. Immunol. 176: 7557-7565 [Abstract] [Full Text]  
  • Hanson, J. F., Taft, S. C., Weiss, A. A. (2006). Neutralizing Antibodies and Persistence of Immunity following Anthrax Vaccination. CVI 13: 208-213 [Abstract] [Full Text]  
  • Duverger, A., Jackson, R. J., van Ginkel, F. W., Fischer, R., Tafaro, A., Leppla, S. H., Fujihashi, K., Kiyono, H., McGhee, J. R., Boyaka, P. N. (2006). Bacillus anthracis Edema Toxin Acts as an Adjuvant for Mucosal Immune Responses to Nasally Administered Vaccine Antigens. J. Immunol. 176: 1776-1783 [Abstract] [Full Text]  
  • Cote, C. K., Van Rooijen, N., Welkos, S. L. (2006). Roles of Macrophages and Neutrophils in the Early Host Response to Bacillus anthracis Spores in a Mouse Model of Infection. Infect. Immun. 74: 469-480 [Abstract] [Full Text]  
  • Krakauer, T., Little, S. F., Stiles, B. G. (2005). Bacillus anthracis Edema Toxin Inhibits Staphylococcus aureus Enterotoxin B Effects In Vitro: a Potential Protein Therapeutic?. Infect. Immun. 73: 7069-7073 [Abstract] [Full Text]  
  • Barth, H., Aktories, K., Popoff, M. R., Stiles, B. G. (2004). Binary Bacterial Toxins: Biochemistry, Biology, and Applications of Common Clostridium and Bacillus Proteins. Microbiol. Mol. Biol. Rev. 68: 373-402 [Abstract] [Full Text]  
  • Ulmer, T. S., Soelaiman, S., Li, S., Klee, C. B., Tang, W.-J., Bax, A. (2003). Calcium Dependence of the Interaction between Calmodulin and Anthrax Edema Factor. J. Biol. Chem. 278: 29261-29266 [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»