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 Elliott, S. P.
Right arrow Articles by Haslam, D. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Elliott, S. P.
Right arrow Articles by Haslam, D. B.

 Previous Article  |  Next Article 

Infection and Immunity, November 2003, p. 6543-6552, Vol. 71, No. 11
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.11.6543-6552.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Forssman Synthetase Expression Results in Diminished Shiga Toxin Susceptibility

a Role for Glycolipids in Determining Host-Microbe Interactions

Sean P. Elliott,{dagger} Min Yu, Huaijin Xu, and David B. Haslam*

Departments of Pediatrics and Molecular Microbiology, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, Missouri 63110

Received 12 May 2003/ Returned for modification 7 July 2003/ Accepted 27 July 2003

Forssman glycolipid (FG), the product of Forssman synthetase (FS), is widely expressed among nonprimate mammalian species. Here, we describe a molecular and genetic relationship between FG expression and Shiga toxin (Stx) susceptibility. We have isolated the FS cDNA from human, canine, and murine cells. Whereas the murine and canine FS genes express a functional enzyme, the human FS cDNA was found to express a protein that lacks FS activity, despite a high degree of sequence identity with the enzymatically active murine and canine FS genes. In order to examine the relationship between FG expression and Stx susceptibility, Vero cells were transfected with the three FS orthologues or a vector control. Complementation with the human FS cDNA had no effect on Stx susceptibility, whereas stable expression of the canine and murine FS resulted in markedly decreased susceptibility to toxin. Among individual cells, an inverse correlation between FG expression and Stx binding was demonstrated. Moreover, only strongly FG-reactive cells were capable of growing in the presence of Stx. These cells were found to have high levels of FG expression and a correspondingly diminished GbO3 content. We conclude that expression of a functionally active FS modifies Stx receptor glycolipids to FG and results in markedly decreased susceptibility to toxin. We speculate that inactivation of the FS gene during primate evolution may account, at least in part, for the marked susceptibility of human cells to Stx.

* Corresponding author. Mailing address: Washington University School of Medicine, Box 8116, One Children's Place, St. Louis, MO 63110. Phone: (314) 286-2888. Fax: (314) 286-2895. E-mail: haslam{at}kids.wustl.edu.

Editor: A. D. O'Brien

{dagger} Present address: Department of Pediatrics, University of Arizona, Tucson, Ariz.

Infection and Immunity, November 2003, p. 6543-6552, Vol. 71, No. 11
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.11.6543-6552.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Casals, F., Ferrer-Admetlla, A., Sikora, M., Ramirez-Soriano, A., Marques-Bonet, T., Despiau, S., Roubinet, F., Calafell, F., Bertranpetit, J., Blancher, A. (2009). Human pseudogenes of the ABO family show a complex evolutionary dynamics and loss of function. Glycobiology 19: 583-591 [Abstract] [Full Text]  
  • Houliston, R S., Bernatchez, S., Karwaski, M.-F., Mandrell, R. E, Jarrell, H. C, Wakarchuk, W. W, Gilbert, M. (2009). Complete chemoenzymatic synthesis of the Forssman antigen using novel glycosyltransferases identified in Campylobacter jejuni and Pasteurella multocida. Glycobiology 19: 153-159 [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]  
  • Zhao, L., Haslam, D. B (2005). A quantitative and highly sensitive luciferase-based assay for bacterial toxins that inhibit protein synthesis. J Med Microbiol 54: 1023-1030 [Abstract] [Full Text]  
  • Yu, M., Haslam, D. B. (2005). Shiga Toxin Is Transported from the Endoplasmic Reticulum following Interaction with the Luminal Chaperone HEDJ/ERdj3. Infect. Immun. 73: 2524-2532 [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»