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Sphingolipid synthesis and scavenging in the intracellular apicomplexan parasite, Toxoplasma gondii

Pratt, S.; Wansadhipathi-Kannangara, N.K.; Bruce, C.R.; Mina, J.G.; Shams-Eldin, H.; Casas, J.; Hanada, K.; Schwarz, R.T.; Sonda, S.; Denny, P.W.

Sphingolipid synthesis and scavenging in the intracellular apicomplexan parasite, Toxoplasma gondii Thumbnail


Authors

S. Pratt

N.K. Wansadhipathi-Kannangara

C.R. Bruce

H. Shams-Eldin

J. Casas

K. Hanada

R.T. Schwarz

S. Sonda



Abstract

Sphingolipids are essential components of eukaryotic cell membranes, particularly the plasma membrane, and are involved in a diverse array of signal transduction pathways. Mammals produce sphingomyelin (SM) as the primary complex sphingolipid via the well characterised SM synthase. In contrast yeast, plants and some protozoa utilise an evolutionarily related inositol phosphorylceramide (IPC) synthase to synthesize IPC. This activity has no mammalian equivalent and IPC synthase has been proposed as a target for anti-fungals and anti-protozoals. However, detailed knowledge of the sphingolipid biosynthetic pathway of the apicomplexan protozoan parasites was lacking. In this study bioinformatic analyses indicated a single copy orthologue of the putative SM synthase from the apicomplexan Plasmodium falciparum (the causative agent of malaria) was a bona fide sphingolipid synthase in the related model parasite, Toxoplasma gondii (TgSLS). Subsequently, TgSLS was indicated, by complementation of a mutant cell line, to be a functional orthologue of the yeast IPC synthase (AUR1p), demonstrating resistance to the well characterised AUR1p inhibitor aureobasidin A. In vitro, recombinant TgSLS exhibited IPC synthase activity and, for the first time, the presence of IPC was demonstrated in T. gondii lipid extracts by mass spectrometry. Furthermore, host sphingolipid biosynthesis was indicated to influence, but be non-essential for, T. gondii proliferation, suggesting that whilst scavenging does take place de novo sphingolipid synthesis may be important for parasitism.

Citation

Pratt, S., Wansadhipathi-Kannangara, N., Bruce, C., Mina, J., Shams-Eldin, H., Casas, J., …Denny, P. (2013). Sphingolipid synthesis and scavenging in the intracellular apicomplexan parasite, Toxoplasma gondii. Molecular and Biochemical Parasitology, 87(1), 43-51. https://doi.org/10.1016/j.molbiopara.2012.11.007

Journal Article Type Article
Publication Date Jan 1, 2013
Deposit Date Nov 29, 2012
Publicly Available Date Mar 29, 2024
Journal Molecular and Biochemical Parasitology
Print ISSN 0166-6851
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 87
Issue 1
Pages 43-51
DOI https://doi.org/10.1016/j.molbiopara.2012.11.007
Keywords Toxoplasma, Sphingolipid, Inositol phosphorylceramide synthase, Host–parasite interaction.

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Copyright Statement
© 2012 Elsevier B.V. Open access under CC BY license.






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