ArticleThe Biochemical journal2005
Characterization of the inositol phosphorylceramide synthase activity from Trypanosoma cruzi.
Article in The Biochemical journal, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- Mechanisms of aureobasidin A inhibition and drug resistance in a fungal IPC synthase complex.Nature communications · 2025Article
- Article
- Innovations in Antifungal Drug Discovery among Cell Envelope Synthesis Enzymes through Structural Insights.Journal of fungi (Basel, Switzerland) · 2024Review
- Disruption of the inositol phosphorylceramide synthase gene affects Trypanosoma cruzi differentiation and infection capacity.PLoS neglected tropical diseases · 2023Article
- Biological and Molecular Effects ofFrontiers in cellular and infection microbiology · 2021Article
- The identification of small molecule inhibitors of the plant inositol phosphorylceramide synthase which demonstrate herbicidal activity.Scientific reports · 2019Article
- Tamoxifen inhibits the biosynthesis of inositolphosphorylceramide in Leishmania.International journal for parasitology. Drugs and drug resistance · 2018Article
- The antifungal Aureobasidin A and an analogue are active against the protozoan parasite Toxoplasma gondii but do not inhibit sphingolipid biosynthesis.Parasitology · 2018Article
- Comparative sphingolipidomics of disease-causing trypanosomatids reveal unique lifecycle- and taxonomy-specific lipid chemistries.Scientific reports · 2017Article
- Lipid synthesis in protozoan parasites: a comparison between kinetoplastids and apicomplexans.Progress in lipid research · 2013Review
- Identification and functional analysis of Trypanosoma cruzi genes that encode proteins of the glycosylphosphatidylinositol biosynthetic pathway.PLoS neglected tropical diseases · 2013Article
- Sphingolipid synthesis and scavenging in the intracellular apicomplexan parasite, Toxoplasma gondii.Molecular and biochemical parasitology · 2013Article
- Sphingolipid and ceramide homeostasis: potential therapeutic targets.Biochemistry research international · 2012Article
- The Sphingolipid Biosynthetic Pathway Is a Potential Target for Chemotherapy against Chagas Disease.Enzyme research · 2011Article
- Single-cell analysis of phosphoinositide 3-kinase and phosphatase and tensin homolog activation.Faraday discussions · 2011Article
- Cell-free synthesis and functional characterization of sphingolipid synthases from parasitic trypanosomatid protozoa.The Journal of biological chemistry · 2010Article
- Phospholipid and sphingolipid metabolism in Leishmania.Molecular and biochemical parasitology · 2010Review
- Sphingolipids in parasitic protozoa.Advances in experimental medicine and biology · 2010Review
- Inhibition of inositol phosphorylceramide synthase by the cyclic peptide aureobasidin A.Antimicrobial agents and chemotherapy · 2009Article
- An inositolphosphorylceramide synthase is involved in regulation of plant programmed cell death associated with defense in Arabidopsis.The Plant cell · 2008Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
IPC (inositol phosphorylceramide) synthase is an enzyme essential for fungal viability, and it is the target of potent antifungal compounds such as rustmicin and aureobasidin A. Similar to fungi and some other lower eukaryotes, the protozoan parasite Trypanosoma cruzi is capable of synthesizing free or protein-linked glycoinositolphospholipids containing IPC. As a first step towards understanding the importance and mechanism of IPC synthesis in T. cruzi, we investigated the effects of rustmicin and aureobasidin A on the proliferation of different life-cycle stages of the parasite. The compounds did not interfere with the axenic growth of epimastigotes, but aureobasidin A decreased the release of trypomastigotes from infected murine peritoneal macrophages and the number of intracellular amastigotes in a dose-dependent manner. We have demonstrated for the first time that all forms of T. cruzi express an IPC synthase activity that is capable of transferring inositol phosphate from phosphatidylinositol to the C-1 hydroxy group of C6-NBD-cer {6-[N-(7-nitro-2,1,3-benzoxadiazol-4-yl)-amino]hexanoylceramide} to form inositol phosphoryl-C6-NBD-cer, which was purified and characterized by its chromatographic behaviour on TLC and HPLC, sensitivity to phosphatidylinositol-specific phospholipase C and resistance to mild alkaline hydrolysis. Unlike the Saccharomyces cerevisiae IPC synthase, the T. cruzi enzyme is stimulated by Triton X-100 but not by bivalent cations, CHAPS or fatty-acid-free BSA, and it is not inhibited by rustmicin or aureobasidin A, or the two in combination. Further studies showed that aureobasidin A has effects on macrophages independent of the infecting T. cruzi cells. These results suggest that T. cruzi synthesizes its own IPC, but by a mechanism that is not affected by rustmicin and aureobasidin A.
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