ArticleMolecular microbiology2005
Leishmania salvage and remodelling of host sphingolipids in amastigote survival and acidocalcisome biogenesis.
Article in Molecular microbiology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 111 citations in OpenAlex.
- Article
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- VAPA mediates lipid exchange between Leishmania amazonensis and host macrophages.PLoS pathogens · 2025Article
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- Integration of hepatic lipidomics and transcriptomics reveals dysregulation of lipid metabolism in a golden hamster model of visceral leishmaniasis.Frontiers in immunology · 2025Article
- 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
- Evaluation of theACS infectious diseases · 2024Article
- Advances in the cellular biology, biochemistry, and molecular biology of acidocalcisomes.Microbiology and molecular biology reviews : MMBR · 2024Review
- The intersection of hostMicrobiology and molecular biology reviews : MMBR · 2024Review
- Ethanolaminephosphate cytidylyltransferase is essential for survival, lipid homeostasis and stress tolerance in Leishmania major.PLoS pathogens · 2023Article
- Ethanolaminephosphate cytidyltransferase is essential for survival, lipid homeostasis and stress tolerance inbioRxiv : the preprint server for biology · 2023Article
- Fatty Acid Profiles ofPathogens (Basel, Switzerland) · 2022Article
- Balancing de novo synthesis and salvage of lipids by Leishmania amastigotes.Current opinion in microbiology · 2021Review
- Antileishmanial Chemotherapy through Clemastine Fumarate Mediated Inhibition of theACS infectious diseases · 2021Article
- Albumin-based nanoparticles as contrast medium for MRI: vascular imaging, tissue and cell interactions, and pharmacokinetics of second-generation nanoparticles.Histochemistry and cell biology · 2021Article
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- Sterol 14-α-demethylase is vital for mitochondrial functions and stress tolerance in Leishmania major.PLoS pathogens · 2020Article
- Farnesyl pyrophosphate synthase is essential for the promastigote and amastigote stages in Leishmania major.Molecular and biochemical parasitology · 2019Article
6 more citing papers are in PubMed but not listed here.
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6 authors at 1 institution in 1 country.
Funding
Abstract
Sphingolipids (SLs) play essential roles in most eukaryotes, but in the trypanosomatid protozoan Leishmania major their functions differ significantly. Previously we showed that null mutants defective in de novo sphingoid base synthesis (spt2-) lacked SLs but grew well and retained lipid rafts while replicating as promastigotes in vitro. However, they experienced catastrophic defects in membrane trafficking on entry into stationary phase, and failed to differentiate to the infective metacyclic form. Here we showed this mutant retained the ability to enter macrophages silently and inhibit activation, although as expected most parasites were destroyed. However, in mouse infections, after a delay rapidly progressive lesions appeared, and purified amastigotes were fully virulent to macrophages and mice. Mass spectrometry of spt2- amastigote lipids revealed the presence of high levels of parasite-specific inositol phosphorylceramides (IPCs) not synthesized by the mammalian hosts. Inhibitor studies showed that salvage occurs at the level of complex SLs, suggesting that parasites carry out 'headgroup' remodelling. Additionally, we describe a new defect of the spt2- promastigotes involving 'empty' acidocalcisomes (ACs), which may point to the origin of this organelle from the lysosome-related organelle/multivesicular body biogenesis pathway. However, ACs in spt2- amastigotes appeared quantitatively and morphologically normal. Thus salvage of SLs and other molecules by intracellular amastigotes play key roles in AC biogenesis and parasite survival in the host.
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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.