Host cell P-glycoprotein is essential for cholesterol uptake and replication of Toxoplasma gondii

Bottova, I. and Hehl, A. B. and Stefanic, S. and Fabrias, G. and Casas, J. and Schraner, E. and Pieters, J. and Sonda, S.. (2009) Host cell P-glycoprotein is essential for cholesterol uptake and replication of Toxoplasma gondii. Journal of biological chemistry, 284 (26). pp. 17438-17448.

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Official URL: http://edoc.unibas.ch/dok/A5259381

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P-glycoprotein (P-gp) is a membrane-bound efflux pump that actively exports a wide range of compounds from the cell and is associated with the phenomenon of multidrug resistance. However, the role of P-gp in normal physiological processes remains elusive. Using P-gp-deficient fibroblasts, we showed that P-gp was critical for the replication of the intracellular parasite Toxoplasma gondii but was not involved in invasion of host cells by the parasite. Importantly, we found that the protein participated in the transport of host-derived cholesterol to the intracellular parasite. T. gondii replication in P-gp-deficient host cells not only resulted in reduced cholesterol content in the parasite but also altered its sphingolipid metabolism. In addition, we found that different levels of P-gp expression modified the cholesterol metabolism in uninfected fibroblasts. Collectively our findings reveal a key and previously undocumented role of P-gp in host-parasite interaction and suggest a physiological role for P-gp in cholesterol trafficking in mammalian cells.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology > Biochemistry (Pieters)
UniBasel Contributors:Pieters, Jean
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Society of Biological Chemists
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:27 Sep 2017 09:50
Deposited On:22 Mar 2012 13:22

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