Cholesterol esterification by host and parasite is essential for optimal proliferation of Toxoplasma gondii

Upon host cell invasion the apicomplexan parasite Toxoplasma gondii resides in a specialized compartment termed the parasitophorous vacuole that is de rived from the host cell membrane but modified by the parasite. Despite the segregation of the parasitophorous vacuole from the host endocytic network , the intravacuolar parasite has been shown to acquire cholesterol from the host cell. In order to characterize further the role of sterol metabolism in T. gondii biology, we focused our studies on the activity of acyl-CoA:ch olesterol acyltransferase (ACAT), a key enzyme for maintaining the intracel lular homeostasis of cholesterol through the formation of cholesterol ester s. In this study, we demonstrate that ACAT and cholesterol esters play a cr ucial role in the optimal replication of T. gondii. Moreover, we identified ACAT activity in T. gondii that can be modulated by pharmacological ACAT i nhibitors with a consequent detrimental effect on parasite replication.