Inhibitory effect of aureobasidin A on Toxoplasma gondii.
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.
Sonda
Sabrina
S
Department of Biochemistry, Biozentrum, University of Basel, Switzerland. sabrina.sonda@vetparas.unizh.ch
Sala
Giusy
G
Ghidoni
Riccardo
R
Hemphill
Andrew
A
Pieters
Jean
J
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002855:Chromatography, Thin Layer; D047630:Depsipeptides / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D007202:Indicators and Reagents; D050356:Lipid Metabolism; D046529:Microscopy, Electron, Transmission; D013107:Sphingolipids / Q000378:metabolism; D014122:Toxoplasma / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism
D000935:Antifungal Agents; D047630:Depsipeptides; D007202:Indicators and Reagents; D013107:Sphingolipids; C071398:aureobasidin A