Host cell P-glycoprotein is essential for cholesterol uptake and replication of Toxoplasma gondii.
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.
Bottova
Iveta
I
Institute of Parasitology, University of Zurich, Zurich, Switzerland.
Hehl
Adrian B
AB
Stefanić
Sasa
S
Fabriàs
Gemma
G
Casas
Josefina
J
Schraner
Elisabeth
E
Pieters
Jean
J
Sonda
Sabrina
S
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000502:physiology*; D000818:Animals; D001692:Biological Transport; D015153:Blotting, Western; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D002853:Chromatography, Liquid; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006790:Host-Parasite Interactions; D008055:Lipids / Q000032:analysis; D013058:Mass Spectrometry; D051379:Mice; D018345:Mice, Knockout; D041681:NIH 3T3 Cells / Q000469:parasitology; D018688:Neospora / Q000378:metabolism; D014122:Toxoplasma / Q000254:growth & development* / Q000378:metabolism*
D018435:ATP Binding Cassette Transporter, Subfamily B; D008055:Lipids; D002784:Cholesterol