Replication of Coxiella burnetii is inhibited in CHO K-1 cells treated with inhibitors of cholesterol metabolism - PubMed (original) (raw)

Replication of Coxiella burnetii is inhibited in CHO K-1 cells treated with inhibitors of cholesterol metabolism

Dale Howe et al. Ann N Y Acad Sci. 2005 Dec.

Abstract

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.

PubMed Disclaimer

Publication types

MeSH terms

Substances

LinkOut - more resources