Steven Pratt, Nilu Wansadhipathi-Kannangara, Catherine Bruce, John Mina, Hosam Shams-Eldin, Josefina Casas, Kentaro Hanada, Ralph T. Schwarz, Sabrina Sonda and Paul Denny 2012. Sphingolipid synthesis and scavenging in the intracellular apicomplexan parasite, Toxoplasma gondii. Molecular and Biochemical Parasitology. 187 (1), pp. 43-51. https://doi.org/10.1016/j.molbiopara.2012.11.007
| Title | Sphingolipid synthesis and scavenging in the intracellular apicomplexan parasite, Toxoplasma gondii |
|---|---|
| Type | Journal article |
| Authors | Steven Pratt, Nilu Wansadhipathi-Kannangara, Catherine Bruce, John Mina, Hosam Shams-Eldin, Josefina Casas, Kentaro Hanada, Ralph T. Schwarz, Sabrina Sonda and Paul Denny |
| 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 synthesise 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. |
| Keywords | Sphingolipids |
| Toxoplasma gondii | |
| Toxoplasmosis | |
| Sphingomyelin | |
| Inositol phosphoryl ceramide | |
| Journal | Molecular and Biochemical Parasitology |
| Journal citation | 187 (1), pp. 43-51 |
| ISSN | 1872-9428 |
| 0166-6851 | |
| Year | 2012 |
| Publisher | Elsevier |
| Accepted author manuscript | File Access Level Open (open metadata and files) |
| Publisher's version | License CC BY 3.0 File Access Level Open (open metadata and files) |
| Digital Object Identifier (DOI) | https://doi.org/10.1016/j.molbiopara.2012.11.007 |
| PubMed ID | 3629565 |
| Web address (URL) | https://www.sciencedirect.com/science/article/pii/S0166685112002836?via%3Dihub |
| Publication dates | |
| Published | Jan 2013 |
| Supplemental file | File Access Level Open (open metadata and files) |