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.

Inhibitory effect of aureobasidin A on toxoplasma gondii / Sabrina Sonda, Giusy Sala, Riccardo Ghidoni, Andrew Hemphill, Jean Pieters. - In: ANTIMICROBIAL AGENTS AND CHEMOTHERAPY. - ISSN 0066-4804. - 49:5(2005), pp. 1794-1801.

Inhibitory effect of aureobasidin A on toxoplasma gondii

Riccardo Ghidoni;
2005

Abstract

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.
Sphingolipids; Opportunist infection; Congenital defects; Pathogens; Acquired immune deficiency syndrome; Replication; Inositol; bradyzoites; Metabolism; Mammalian cells; tachyzoites; Antimicrobial agents; Toxoplasma gondii
Settore BIO/10 - Biochimica
2005
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/8653
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