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


Bottova, I; Hehl, A B; Stefanic, S; Fabriàs, G; Casas, J; Schraner, E; Pieters, J; Sonda, S (2009). Host cell P-glycoprotein is essential for cholesterol uptake and replication of toxoplasma gondii. Journal of Biological Chemistry, 284(26):17438-17448.

Abstract

P-glycoprotein (P-gp) is a membrane-bound efflux pump which 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 of P-gp in cholesterol trafficking in mammalian cells.

P-glycoprotein (P-gp) is a membrane-bound efflux pump which 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 of P-gp in cholesterol trafficking in mammalian cells.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Veterinary Anatomy
05 Vetsuisse Faculty > Institute of Parasitology
04 Faculty of Medicine > Institute of Parasitology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
600 Technology
Language:English
Date:26 June 2009
Deposited On:11 Aug 2009 09:11
Last Modified:26 Aug 2016 07:32
Publisher:American Society for Biochemistry and Molecular Biology
ISSN:0021-9258
Additional Information: This research was originally published Bottova, I; Hehl, A B; Stefanic, S; Fabriàs, G; Casas, J; Schraner, E; Pieters, J; Sonda, S (2009). Host cell P-glycoprotein is essential for cholesterol uptake and replication of toxoplasma gondii. Journal of Biological Chemistry, 284(26):17438-17448. © the American Society for Biochemistry and Molecular Biology.
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:10.1074/jbc.M809420200
PubMed ID:19389707
Permanent URL: http://doi.org/10.5167/uzh-19284

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