ArticlePLoS pathogens2009
Degradation of host sphingomyelin is essential for Leishmania virulence.
Article in PLoS pathogens, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 76 citations in OpenAlex.
- Article
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- Unraveling Leishmania major Metacyclogenesis: A Comprehensive Analysis of Transcriptomic and Metabolomic ProfilesIranian biomedical journal · 2025Article
- Leishmania protein KMP-11 modulates cholesterol transport and membrane fluidity to facilitate host cell invasion.EMBO reports · 2024Article
- Evolutionary divergent clusters of transcribed extinct truncated retroposons drive low mRNA expression and developmental regulation in the protozoan Leishmania.BMC biology · 2024Article
- Molecular Characterization of Sterol C4-Methyl Oxidase inInternational journal of molecular sciences · 2024Article
- Alarming situation of emerging H5 and H7 avian influenza and effective control strategies.Emerging microbes & infections · 2023Review
- Data Independent Acquisition Reveals In-Depth Serum Proteome Changes in Canine Leishmaniosis.Metabolites · 2023Article
- The lipidome ofFrontiers in cellular and infection microbiology · 2022Article
- Balancing de novo synthesis and salvage of lipids by Leishmania amastigotes.Current opinion in microbiology · 2021Review
- Nonspecific phospholipase C4 hydrolyzes phosphosphingolipids and sustains plant root growth during phosphate deficiency.The Plant cell · 2021Article
- Antileishmanial Chemotherapy through Clemastine Fumarate Mediated Inhibition of theACS infectious diseases · 2021Article
- Comparative mitochondrial proteomics of Leishmania tropica clinical isolates resistant and sensitive to meglumine antimoniate.Parasitology research · 2020Article
- Phosphatidylcholine synthesis through cholinephosphate cytidylyltransferase is dispensable in Leishmania major.Scientific reports · 2019Article
- Article
- A Targeted Mass Spectrometric Analysis Reveals the Presence of a Reduced but Dynamic Sphingolipid Metabolic Pathway in an Ancient Protozoan,Frontiers in cellular and infection microbiology · 2019Article
- DNA prime-protein boost vaccine encoding HLA-A2, HLA-A24 and HLA-DR1 restricted epitopes of CaNA2 against visceral leishmaniasis.Immunology · 2019Article
- Complex Interplay between Sphingolipid and Sterol Metabolism Revealed by Perturbations to the Leishmania Metabolome Caused by Miltefosine.Antimicrobial agents and chemotherapy · 2018Article
- The glycosomal alkyl-dihydroxyacetonephosphate synthase TbADS is essential for the synthesis of ether glycerophospholipids in procyclic trypanosomes.Experimental parasitology · 2018Article
- Lipidomics and anti-trypanosomatid chemotherapy.Clinical and translational medicine · 2017Review
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
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-virulent procyclics to highly virulent metacyclics. To further probe SL metabolism, we identified a gene encoding a putative neutral sphingomyelinase (SMase) and/or IPC hydrolase (IPCase), designated ISCL (Inositol phosphoSphingolipid phospholipase C-Like). Despite the lack of sphingomyelin synthesis, L. major promastigotes exhibited a potent SMase activity which was abolished upon deletion of ISCL, and increased following over-expression by episomal complementation. ISCL-dependent activity with sphingomyelin was about 20 fold greater than that seen with IPC. Null mutants of ISCL (iscl(-)) showed modest accumulation of IPC, but grew and differentiated normally in vitro. Interestingly, iscl(-) mutants did not induce lesion pathology in the susceptible BALB/c mice, yet persisted indefinitely at low levels at the site of infection. Notably, the acute virulence of iscl(-) was completely restored by the expression of ISCL or heterologous mammalian or fungal SMases, but not by fungal proteins exhibiting only IPCase activity. Together, these findings strongly suggest that degradation of host-derived sphingomyelin plays a pivotal role in the proliferation of Leishmania in mammalian hosts and the manifestation of acute disease pathology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.