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Infection and Immunity, September 2005, p. 5395-5401, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.5395-5401.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Cell Surface Heparan Sulfate Promotes Replication of Toxoplasma gondii

Joseph R. Bishop, Brett E. Crawford, and Jeffrey D. Esko*

Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093-0687

Received 15 February 2005/ Returned for modification 31 March 2005/ Accepted 15 April 2005

Previous work suggests that cell surface heparan sulfate acts as a receptor for the Apicomplexan parasite Toxoplasma gondii. Using Chinese hamster ovary cell mutants defective in heparan sulfate biosynthesis, we show that heparan sulfate is necessary and sufficient for infectivity. Further, we demonstrate that the parasite requires N sulfation of heparan sulfate initiated by N-deacetylase/N-sulfotransferase-1, but 2-O sulfation and 6-O sulfation appear to be dispensable. In order to study the role of heparan sulfate in other cell types, we created a conditional allele for N-deacetylase/N-sulfotransferase-1 by using Cre-loxP technology. Mammary tumor cells lacking N-deacetylase/N-sulfotransferase-1 exhibited reduced toxoplasma infectivity like Chinese hamster ovary cell mutants. Surprisingly, heparin, chemically modified heparinoids, and monoclonal antibodies to heparan sulfate had no effect on toxoplasma infection. T. gondii attachment and invasion were unchanged in N-deacetylase/N-sulfotransferase-1-inactivated cells as well, but replication was reduced. Thus, heparan sulfate does not appear to function as a receptor for T. gondii but instead facilitates parasite replication postinvasion.


* Corresponding author. Mailing address: 9500 Gilman Dr., CMM-East, Rm. 1055, La Jolla, CA 92093-0687. Phone: (858) 822-1100. Fax: (858) 534-5611. E-mail: jesko{at}ucsd.edu.

Editor: J. B. Bliska


Infection and Immunity, September 2005, p. 5395-5401, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.5395-5401.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.