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Infection and Immunity, May 2004, p. 2915-2921, Vol. 72, No. 5
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.5.2915-2921.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Toxopain-1 Is Critical for Infection in a Novel Chicken Embryo Model of Congenital Toxoplasmosis

Xuchu Que,1 Annette Wunderlich,1 Keith A. Joiner,2 and Sharon L. Reed1*

Departments of Pathology and Medicine, University of California, San Diego, California 92103-8416,1 Department of Medicine, Yale University Medical School, New Haven, Connecticut 065292

Received 25 September 2003/ Returned for modification 16 November 2003/ Accepted 31 December 2003

We tested the hypothesis that cathepsins and specifically toxopain-1, a cathepsin B, play a critical role in the pathogenesis of toxoplasmosis. We found that inhibiting the expression of toxopain-1-specific mRNA and protein by >60% significantly decreased the capacity of the parasites to multiply and invade in vitro. To relate these in vitro results to the role of toxopain-1 in pathogenesis in vivo, we developed a novel chicken embryo model of congenital toxoplasmosis. Inhibiting either toxopain-1 expression or specific cysteine proteinase activity significantly reduced congenital infection of chicken embryos, as determined by histopathology and by the number of parasites quantified by real-time PCR. Our new model provides key in vivo validation for the hypothesis that toxopain-1 is a potential drug target in Toxoplasma gondii and also provides a new animal model for rapid, inexpensive screening of antiparasitic compounds.

* Corresponding author. Mailing address: Division of Infectious Diseases, University of California, San Diego Medical Center, 200 W. Arbor Dr., San Diego, CA 92103-8416. Phone: (619) 543-6146. Fax: (619) 543-6614. E-mail: slreed{at}ucsd.edu. {dagger} Present address: College of Medicine, University of Arizona, Tucson, AZ 85724.

Editor: W. A. Petri, Jr.

Infection and Immunity, May 2004, p. 2915-2921, Vol. 72, No. 5
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.5.2915-2921.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Huynh, M.-H., Carruthers, V. B. (2009). Tagging of Endogenous Genes in a Toxoplasma gondii Strain Lacking Ku80. Eukaryot Cell 8: 530-539 [Abstract] [Full Text]  
  • Melendez-Lopez, S. G., Herdman, S., Hirata, K., Choi, M.-H., Choe, Y., Craik, C., Caffrey, C. R., Hansell, E., Chavez-Munguia, B., Chen, Y. T., Roush, W. R., McKerrow, J., Eckmann, L., Guo, J., Stanley, S. L. Jr., Reed, S. L. (2007). Use of Recombinant Entamoeba histolytica Cysteine Proteinase 1 To Identify a Potent Inhibitor of Amebic Invasion in a Human Colonic Model. Eukaryot Cell 6: 1130-1136 [Abstract] [Full Text]  
  • Que, X., Engel, J. C., Ferguson, D., Wunderlich, A., Tomavo, S., Reed, S. L. (2007). Cathepsin Cs Are Key for the Intracellular Survival of the Protozoan Parasite, Toxoplasma gondii. J. Biol. Chem. 282: 4994-5003 [Abstract] [Full Text]  


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