Toxoplasma gondii LCAT Primarily Contributes to Tachyzoite Egress

Abstract

Toxoplasma gondii is one of the most successful human pathogens, infecting an estimated 2.5 billion people across the globe. Pathogenesis seen during acute or reactivated toxoplasmosis has been closely tied to the parasite’s intracellular lytic life cycle, which culminates in an event called egress that results in the release of freshly replicated parasites from the infected host cell. Despite the highly destructive, cytolytic nature of this event and its downstream consequences, very little is known about how the parasite accomplishes this step. Previous work has suggested a role for a secreted phospholipase, LCAT, in Toxoplasma egress and roles in cell traversal and egress in the Plasmodium species orthologue. We confirm here that LCAT-deficient tachyzoites are unable to efficiently egress from infected monolayers, and we provide evidence that LCAT catalytic activity is required for its role in egress. Egress is a crucial phase of the Toxoplasma gondii intracellular lytic cycle. This is a process that drives inflammation and is strongly associated with the pathogenesis observed during toxoplasmosis. Despite the link between this process and virulence, little is known about egress on a mechanistic or descriptive level. Previously published work has suggested that a phospholipase, lecithin-cholesterol acyltransferase (LCAT), secreted from the parasite’s dense granules contributes to parasite growth, virulence, and egress. Here we present evidence from several independent mutant parasite lines confirming a role for LCAT in efficient egress, although no defects in growth or virulence were apparent. We also show via genetic complementation that the catalytic activity of LCAT is required for its role in parasite egress. This work solidifies the contribution of LCAT to egress of T. gondii tachyzoites. IMPORTANCE Toxoplasma gondii is one of the most successful human pathogens, infecting an estimated 2.5 billion people across the globe. Pathogenesis seen during acute or reactivated toxoplasmosis has been closely tied to the parasite’s intracellular lytic life cycle, which culminates in an event called egress that results in the release of freshly replicated parasites from the infected host cell. Despite the highly destructive, cytolytic nature of this event and its downstream consequences, very little is known about how the parasite accomplishes this step. Previous work has suggested a role for a secreted phospholipase, LCAT, in Toxoplasma egress and roles in cell traversal and egress in the Plasmodium species orthologue. We confirm here that LCAT-deficient tachyzoites are unable to efficiently egress from infected monolayers, and we provide evidence that LCAT catalytic activity is required for its role in egress.