Sphingolipid synthesis and scavenging in the intracellular apicomplexan parasite, Toxoplasma gondii
2013
Sphingolipidsare 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
sphingolipidvia 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
sphingolipidbiosynthetic 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
sphingolipidsynthase in the
related modelparasite, 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,
recombinantTgSLS 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
sphingolipidbiosynthesis was indicated to influence, but be
non-essentialfor, T. gondii proliferation, suggesting that whilst scavenging does take place de novo
sphingolipidsynthesis may be important for parasitism.
Keywords:
-
Correction
-
Source
-
Cite
-
Save
46
References
21
Citations
NaN
KQI