Toxoplasma gondii uses sulfated proteoglycans for substrate and host cell attachment

Toxoplasma gondii is an obligate intracellular parasite that actively invad es a wide variety of vertebrate cells, although the basis of this pervasive cell recognition is not understood. We demonstrate here that binding to th e substratum and to host cells is partially mediated by interaction with su lfated glycosaminoglycans (GAGs), Addition of excess soluble GAGs blocked p arasite attachment to serum coated glass, thereby preventing gliding motili ty of extracellular parasites. Similarly, excess soluble GAGs decreased the attachment of parasites to human host cells from a variety of lineages, in cluding monocytic, fibroblast, endothelial, epithelial, and macrophage cell s. The inhibition of parasite attachment by GAGs was observed with heparin and heparan sulfate and also with chondroitin sulfates, indicating that the ligands for attachment are capable of recognizing a broad range of GAGs. T he importance of sulfated proteoglycan recognition was further supported by the demonstration that GAG-deficient mutant host cells, and wild-type cell s treated enzymatically to remove GAGs, were partially resistant to parasit e invasion. Collectively, these studies reveal that sulfated proteoglycans are one determinant used for substrate and cell recognition by Toxoplasma, The widespread distribution of these receptors may contribute to the broad host and tissue ranges of this highly successful intracellular parasite.