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 derived 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:cholesterol acyltransferase (ACAT), a key enzyme for maintaining the intracellular homeostasis of cholesterol through the formation of cholesterol esters. In this study, we demonstrate that ACAT and cholesterol esters play a crucial role in the optimal replication of T. gondii. Moreover, we identified ACAT activity in T. gondii that can be modulated by pharmacological ACAT inhibitors with a consequent detrimental effect on parasite replication.
Sonda
S
S
Department of Medicine, Division of Infectious Diseases, University of California, San Francisco, California 94143-0868, USA.
Ting
L M
LM
Novak
S
S
Kim
K
K
Maher
J J
JJ
Farese
R V
RV
Ernst
J D
JD
D000813:Anilides / Q000494:pharmacology; D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D051379:Mice; D011973:Receptors, LDL / Q000032:analysis; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors / Q000502:physiology*; D014122:Toxoplasma / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development*
D000813:Anilides; D002788:Cholesterol Esters; D004791:Enzyme Inhibitors; D011973:Receptors, LDL; C069304:PD 128042; D002784:Cholesterol; D002785:Sterol O-Acyltransferase