Replication of Coxiella burnetii is inhibited in CHO K-1 cells treated with inhibitors of cholesterol metabolism.
Coxiella burnetii directs the synthesis of a large parasitophorous vacuole (PV) that is required for its replication. While some lysosomal characteristics of the PV have been described, the origin and composition of the PV membrane remain largely undefined. Cholesterol is an essential component of mammalian membranes where it lends mechanical stability and serves as a platform for signaling proteins. Using infected Chinese hamster ovary cells as a model, we examined whether cholesterol is trafficked to the C. burnetii PV membrane and the effects of inhibitors of cholesterol metabolism on C. burnetii replication. When infected cells were stained with filipin, a fluorescent polyene antifungal agent that binds cholesterol, obvious staining of PV was observed indicating the PV membrane is cholesterol-rich. Furthermore, replication of C. burnetii was significantly inhibited in cells treated with the cholesterol metabolism inhibitors lovastatin, ketoconazole, imipramine, progesterone, and U18666A. These data suggest that cholesterol is an important component of the C. burnetii PV membrane and that normal cellular cholesterol metabolism is required for optimal C. burnetii replication.
Coxiella Pathogenesis Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840, USA.
Dale
D
Howe
Robert A
RA
Heinzen
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D016466:CHO Cells; D002455:Cell Division / Q000187:drug effects*; D002784:Cholesterol / Q000378:metabolism*; D016997:Coxiella burnetii / Q000187:drug effects* / Q000254:growth & development*; D006224:Cricetinae; D003412:Cricetulus; D006131:Growth Inhibitors / Q000494:pharmacology*; D014617:Vacuoles / Q000187:drug effects
D000900:Anti-Bacterial Agents; D000924:Anticholesteremic Agents; D006131:Growth Inhibitors; D002784:Cholesterol