Host Cell P-glycoprotein Is Essential for Cholesterol Uptake and Replication of Toxoplasma gondii |
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| Authors: | Iveta Bottova Adrian B Hehl Sa?a ?tefani? Gemma Fabriàs Josefina Casas Elisabeth Schraner Jean Pieters Sabrina Sonda |
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| Institution: | From the Institutes of ‡Parasitology and ;¶Veterinary Anatomy, University of Zurich, 8057 Zurich, Switzerland, ;the §Institut de Química Avançada de Catalunya, Consejo Superior de Investigaciones Científicas, 08034 Barcelona, Spain, and ;‖Biozentrum, University of Basel, 4056 Basel, Switzerland |
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| Abstract: | 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. |
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