2009
DOI: 10.1371/journal.ppat.1000692
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Degradation of Host Sphingomyelin Is Essential for Leishmania Virulence

Abstract: In eukaryotes, sphingolipids (SLs) are important membrane components and powerful signaling molecules. In Leishmania, the major group of SLs is inositol phosphorylceramide (IPC), which is common in yeast and Trypanosomatids but absent in mammals. In contrast, sphingomyelin is not synthesized by Leishmania but is abundant in mammals. In the promastigote stage in vitro, Leishmania use SL metabolism as a major pathway to produce ethanolamine (EtN), a metabolite essential for survival and differentiation from non-… Show more

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Cited by 67 publications
(114 citation statements)
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“…IPC synthase activity is evident in both the insect and mammalian stages of the L. major lifecycle, however in the intra-macrophage form the parasite is predicted to scavenge host cell ceramide for use as substrate by LmjIPCS (Zhang, et al 2005;Zhang, et al 2009). …”
Section: Introductionmentioning
confidence: 99%
“…IPC synthase activity is evident in both the insect and mammalian stages of the L. major lifecycle, however in the intra-macrophage form the parasite is predicted to scavenge host cell ceramide for use as substrate by LmjIPCS (Zhang, et al 2005;Zhang, et al 2009). …”
Section: Introductionmentioning
confidence: 99%
“…Enzymes involved in sphingolipid biosynthesis and degradation pathways, such as inositol-phosphoryl ceramide synthase 1 (Ipc1) (35) and inositol phosphosphingolipid-phospholipase C1 (Isc1) (53), have been found to promote pathogenicity in C. neoformans. The importance of sphingolipids for pathogenicity has also been recognized in some parasitic pathogens, including Leishmania and Trypanosoma species, and related enzymes have been proposed as potential drug targets (36,37,45,60,67). The diacyglycerol (DAG)-protein kinase C1 (Pkc1) signaling pathway is critical for virulence factor production and pathogenicity in C. neoformans (18,19,24,25).…”
mentioning
confidence: 99%
“…Despite their lack of sphingomyelin synthesis, Leishmania parasites possess a potent neutral sphingomyelinase (SMase) called inositol phosphosphingolipid phospholipase C-like (ISCL), which is responsible for the degradation of both host-derived sphingomyelin and parasite-derived IPC (35). ISCL null mutants (iscl Ϫ mutants, generated from wild-type [WT] L. major) had only minor defects during the promastigote stage in culture but completely failed to multiply or cause disease in susceptible BALB/c mice (35). Importantly, this deficiency can be corrected only by other SMases and not IPC hydrolases (IPCases), suggesting that the degradation of host-derived sphingomyelin (not parasite-synthesized IPC) is essential for Leishmania growth in mammals (35).…”
mentioning
confidence: 99%
“…ISCL null mutants (iscl Ϫ mutants, generated from wild-type [WT] L. major) had only minor defects during the promastigote stage in culture but completely failed to multiply or cause disease in susceptible BALB/c mice (35). Importantly, this deficiency can be corrected only by other SMases and not IPC hydrolases (IPCases), suggesting that the degradation of host-derived sphingomyelin (not parasite-synthesized IPC) is essential for Leishmania growth in mammals (35).…”
mentioning
confidence: 99%
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