Authors

A ALQAISI¹; P Denny¹;  ¹ Durham university

Discussion

The phylum Apicomplexa includes many parasites that cause serious human and animal disease, for example Plasmodium (malaria), Eimeria (coccidiosis) and Toxoplasma (toxoplasmosis). Treatments against these parasites are limited and novel solutions are urgently required. Recently, research has focused on parasite specific features of lipid biosynthesis as potential drug targets. In particular the biosynthesis of sphingolipids, which have essential roles in many processes, has been highlighted as a potential target.

Using the model apicomplexan Toxoplasma gondii we are studying the role of parasite and host sphingolipid biosynthesis in invasion and proliferation. To do this we are functionally characterizing the Toxoplasma sphingolipid biosynthetic pathway. In parallel, the response of the host sphingolipid biosynthetic pathway to parasite infection is being investigated. Results so far demonstrate that host cell SPT is up-regulated on T. gondii infection, indicating that sphingolipid biosynthesis is increased. However, metabolic labelling shows that several distinct complex sphingolipids, including inositol phosphorylceramide (IPC), are synthesized independently by the parasite. The fungal IPC synthase inhibitor aureobasidin A (AbA) has been reported to target Toxoplasma IPC synthesis. Our results show that AbA and an orthologue are active against the parasite, however their effect on Toxoplasma de novo sphingolipid biosynthesis is unclear.