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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-4856

Sonda, S; Stefanic, S; Hehl, A B (2008). A sphingolipid inhibitor induces a cytokinesis arrest and blocks stage differentiation in Giardia lamblia. Antimicrobial Agents and Chemotherapy, 52(2):563-569.


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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 parasiteinduced diarrhea worldwide. PPMP was found to block in vitro parasite replication in a dose-dependent manner, with a 50% inhibitory concentration of 3.5 M. The inhibition of parasite replication was irreversible at 10 MPPMP, 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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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Parasitology
04 Faculty of Medicine > Institute of Parasitology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
600 Technology
Date:February 2008
Deposited On:18 Nov 2008 15:42
Last Modified:27 Nov 2013 22:37
Publisher:American Society for Microbiology
Additional Information:Copyright: American Society for Microbiology
Publisher DOI:10.1128/AAC.01105-07
PubMed ID:18086854

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