ArticleAntimicrobial agents and chemotherapy2008
A sphingolipid inhibitor induces a cytokinesis arrest and blocks stage differentiation in Giardia lamblia.
Article in Antimicrobial agents and chemotherapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Ultrastructural characterization of the putative defensive glands (warts) in the sessile, colonial rotiferZoologischer Anzeiger · 2023Article
- Lipid Polarization during Cytokinesis.Cells · 2022Review
- Lipid profile of Trichinella papuae muscle-stage larvae.Scientific reports · 2020Article
- Who Needs a Contractile Actomyosin Ring? The Plethora of Alternative Ways to Divide a Protozoan Parasite.Frontiers in cellular and infection microbiology · 2019Review
- Transcriptomic Profiling of High-DensityFrontiers in cellular and infection microbiology · 2017Article
- An Interactome-Centered Protein Discovery Approach Reveals Novel Components Involved in Mitosome Function and Homeostasis in Giardia lamblia.PLoS pathogens · 2016Article
- Sphingolipids, Lipid Rafts, and Giardial Encystation: The Show Must Go On.Current tropical medicine reports · 2015Article
- Giardia intestinalis incorporates heme into cytosolic cytochrome b₅.Eukaryotic cell · 2014Article
- Glucosylceramide transferase activity is critical for encystation and viable cyst production by an intestinal protozoan, Giardia lamblia.The Journal of biological chemistry · 2013Article
- Inhibition of glycosphingolipid biosynthesis induces cytokinesis failure.Journal of the American Chemical Society · 2011Article
- Lipid metabolism in Giardia: a post-genomic perspective.Parasitology · 2011Review
- Glucosylceramide synthesis inhibition affects cell cycle progression, membrane trafficking, and stage differentiation in Giardia lamblia.Journal of lipid research · 2010Article
- Sphingolipids in parasitic protozoa.Advances in experimental medicine and biology · 2010Review
- Novel role of sphingolipid synthesis genes in regulating giardial encystation.Infection and immunity · 2008Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sphingolipid biosynthesis pathways have recently emerged as a promising target for therapeutic intervention against pathogens, including parasites. A key step in the synthesis of complex sphingolipids is the glucosylation of ceramide, mediated by glucosylceramide (GlcCer) synthase, whose activity can be inhibited by PPMP (1-phenyl-2-palmitoylamino-3-morpholino-1-propanol). In this study, we investigated whether PPMP inhibits the proliferation and differentiation of the pathogenic parasite Giardia lamblia, the major cause of parasite-induced diarrhea worldwide. PPMP was found to block in vitro parasite replication in a dose-dependent manner, with a 50% inhibitory concentration of 3.5 muM. The inhibition of parasite replication was irreversible at 10 muM PPMP, a concentration that did not affect mammalian cell metabolism. Importantly, PPMP inhibited the completion of cell division at a specific stage in late cytokinesis. Microscopic analysis of cells incubated with PPMP revealed the aberrant accumulation of cellular membranes belonging to the endoplasmic reticulum network in the caudal area of the parasites. Finally, PPMP induced a 90% reduction in G. lamblia differentiation into cysts, the parasite stage responsible for the transmission of the disease. These results show that PPMP is a powerful inhibitor of G. lamblia in vitro and that as-yet-uncharacterized sphingolipid biosynthetic pathways are potential targets for the development of anti-G. lamblia agents.
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