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Inhibitory Effect of Aureobasidin A on Toxoplasma gondii

Department of Biochemistry, Biozentrum, University of Basel, Basel,¹ Institute of Parasitology, University of Zurich, Zurich,² Institute of Parasitology, University of Berne, Berne, Switzerland,⁴ Laboratory of Biochemistry and Molecular Biology, San Paolo University Hospital, School of Medicine, University of Milan, Milan, Italy³

Received 8 July 2004/ Returned for modification 20 August 2004/ Accepted 18 January 2005

The apicomplexan parasite Toxoplasma gondii is a leading opportunistic pathogen associated with AIDS and congenital birth defects. Due to the need for identifying new parasite-specific treatments, the possibility of targeting sphingolipid biosynthesis in the parasite was investigated. Aureobasidin A, an inhibitor of the enzyme synthesizing the sphingolipid inositol phosphorylceramide, which is present in fungi, plants, and some protozoa but absent in mammalian cells, was found to block in vitro T. gondii replication without affecting host cell metabolism. Aureobasidin A treatment did not induce tachyzoite to bradyzoite stage conversion in T. gondii but resulted in a loss of intracellular structures and vacuolization within the parasite. In addition, aureobasidin A inhibited sphingolipid synthesis in T. gondii. Sphingolipid biosynthetic pathways may therefore be considered targets for the development of anti-T. gondii agents.

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