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A protein with a molecular weight of 70,000 to 150,000 which was extracted from merozoites of Toxoplasma gondii enhanced the host cell penetration of the merozoites. The optimal pH and temperature for penetration of merozoites coincided with those favoring the action of the penetration-enhancing protein. In addition, a dependence on Ca and Mg existed for penetration of merozoites, either in the presence or absence of this protein. No evidence was found that indicated that the enhancing effect on penetration elicited by the protein was due to increased phagocytic capacity of host cells (HeLa) or improved motility of the merozoites. Electron microscopy demonstrated that the protein, in high concentration, caused disruption of cytoplasmic membranes. In a 100-fold-lower concentration, which still caused a marked enhancement of penetration, no such effect was observed. However, the vacuoles surrounding the penetrated parasites seemed smaller than for merozoites penetrating in cultures to which no penetration-enhancing factor was given, and the membranes limiting the vacuoles demonstrated discontinuities more often. The penetration-enchancing effect of some known enzymes was studies. However, none of these enzymes seemed to correspond to the penetration-enhancing protein of toxoplasma. The mode of entry of toxoplasma merozoites into host cells is discussed. It is concluded that phagocytosis must play a less important role and that merozoites actively penetrate the cytoplasmic membranes of the host cells. The penetration is proposed to be a result of combined mechanical and chemical actions. It is suggested that an enzymatic function of the penetration-enhancing factor released by the merozoites is of importance. The membrane limiting the vacuole of a penetrated merozoite seems to be newly formed in the cell after penetration is completed.

Interactions between Toxoplasma gondii and its host cells: function of the penetration-enhancing factor of toxoplasma