A Toxoplasma lectin-like activity specific for sulfated polysaccharides isinvolved in host cell infection

Toxoplasma gondii is one of the most widespread parasites of humans and ani mals. The parasite has a remarkable ability to invade a broad range of cell s within its mammalian hosts by mechanisms that are poorly understood at th e molecular level. This broad host cell specificity suggests that adhesion should involve the recognition of ubiquitous surface-exposed host molecules or, alternatively, the presence of various parasite attachment molecules a ble to recognize different host cell receptors. We have discovered a sugar- binding activity (lectin) in tachyzoites of T. gondii that plays a role in vitro in erythrocyte agglutination and infection of human fibroblasts and e pithelial cells. The ability to agglutinate erythrocytes can be reversed by a variety of soluble glycoconjugates, of which heparin, fucoidan, and dext ran sulfate were the most effective. Interestingly, infectivity of tachyzoi tes for human foreskin fibroblasts, cells that are commonly used to grow T. gondii in vitro, was increased by low concentrations of the sulfated glyco conjugates that inhibited hemagglutination activity (i.e. dextran sulfate a nd fucoidan) whereas high concentrations inhibited parasite infection. Furt hermore, inhibition of glycosaminoglycan biosynthesis and sulfation on the host cells reduced Toxoplasma infectivity. Finally, Toxoplasma tachyzoites showed a reduced ability to infect epithelial cell mutants deficient in the biosynthesis of surface proteoglycans The probable identity of the hemaggl utinin(s) was investigated by 1) direct binding of red blood cells to filte r blots of Toxoplasma proteins separated by polyacrylamide gel electrophore sis, and 2) binding of metabolically labeled parasite proteins to fixed mam malian cells. Three parasite bands were thus identified as candidate adhesi ns. These results suggest that attachment of T. gondii to its target cell i s mediated by parasite lectins and that sulfated sugars on the surface of h ost cells may function as a key parasite receptor.