Journal Article

Toxoplasma gondii secretory proteins bind to sulfated heparin structures

Nahid Azzouz, Faustin Kamena, Paola Laurino, Raghavendra Kikkeri, Corinne Mercier, Marie-France Cesbron-Delauw, Jean-François Dubremetz, Luisa De Cola and Peter H Seeberger

in Glycobiology

Published on behalf of Society for Glycobiology

Volume 23, issue 1, pages 106-120
Published in print January 2013 | ISSN: 0959-6658
Published online September 2012 | e-ISSN: 1460-2423 | DOI: https://dx.doi.org/10.1093/glycob/cws134

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Toxoplasma gondii is the causative agent of toxoplasmosis, one of the most widespread infections in humans and animals, and is a major opportunistic pathogen in immunocompromised patients. Toxoplasma gondii is unique as it can invade virtually any nucleated cell, although the mechanisms are not completely understood. Parasite attachment to the host cell is a prerequisite for reorientation and penetration and likely requires the recognition of molecules at the host cell surface. It has been reported that the affinity of tachyzoites, the invasive form of T. gondii, for host cells can be inhibited by a variety of soluble-sulfated glycosaminoglycans (GAGs), such as heparan sulfate. Using heparin-functionalized zeolites in the absence of host cells, we visualized heparin-binding sites on the surface of tachyzoites by confocal and atomic force microscopy. Furthermore, we report that protein components of the parasite rhoptry, dense granule and surface bind GAGs. In particular, the proteins ROP2 and ROP4 from the rhoptry, GRA2 from the dense granules and the surface protein SAG1 were found to bind heparin. The binding specificities and affinities of individual parasite proteins for natural heparin and heparin oligosaccharides were determined by a combination of heparin oligosaccharide microarrays and surface plasmon resonance. Our results suggest that interactions between sulfated GAGs and parasite surface antigens contribute to T. gondii attachment to host cell surfaces as well as initiating the invasion process, while rhoptries and dense granule organelles may play an important role during the establishment of the infection and during the life of the parasite inside the parasitophorous vacuole.

Keywords: cell invasion; glycosaminoglycans; heparin-binding proteins; Toxoplasma gondii

Journal Article.  9247 words.  Illustrated.

Subjects: Carbohydrates