Evidence map›Paper›PMID 15720561›Full record

ArticleMolecular microbiology2005

Leishmania salvage and remodelling of host sphingolipids in amastigote survival and acidocalcisome biogenesis.

Kai Zhang, Fong-Fu Hsu, David A Scott, Roberto Docampo, John Turk, Stephen M Beverley

Open access · bronzeAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
8.1field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

66 citing papers in PubMed, 111 citations in OpenAlex.

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  13. Fatty Acid Profiles ofPathogens (Basel, Switzerland) · 2022
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  14. Review
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  17. Frontiers in cellular and infection microbiology · 2021
    Article
  18. Review
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6 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Kai ZhangDepartment of Molecular Microbiology, Box 8230, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
Fong-Fu Hsu
David A Scott
Roberto Docampo
John Turk
Stephen M Beverley
Washington University in St. Louis · US

Funding

Washington University Nutrition Obesity Research CenterP30DK056341 · NIDDK · WASHINGTON UNIVERSITY · PI Brian N Finck · 1999 to 2026
$30.2M
TRANSGENICS COREP60DK020579 · NIDDK · WASHINGTON UNIVERSITY · PI SCHAFFER, JEAN E. · 1986 to 2012
$25.2M
YOGA LIFESTYLE INTERVENTION REDUCES BLOOD PRESSURE IN HIV-INFECTED ADULTSP41RR000954 · NCRR · WASHINGTON UNIVERSITY · PI GROSS, MICHAEL L · 1985 to 2011
$16.0M
MECHANISM OF GENE AMPLIFICATION IN LEISHMANIAR01AI021903 · NIAID · WASHINGTON UNIVERSITY · PI BEVERLEY, STEPHEN M · 1985 to 2010
$2.6M
MODE OF ACTION TRYPANOCIDAL DRUGS--INVOLVEMENT OF CA++R01AI023259 · NIAID · UNIVERSITY OF ILLINOIS URBANA-CHAMPAIGN · PI DOCAMPO, ROBERTO · 1987 to 2002
$1.1M
DRUG RESISTANCE AND GENE AMPLIFICATION IN LEISHMANIAR37AI021903 · NIAID · WASHINGTON UNIVERSITY · PI BEVERLEY, STEPHEN M · 1993 to 2002
$960k
Acidocalcisomes in Trypanosoma cruziR21AI023259 · NIAID · UNIVERSITY OF ILLINOIS URBANA-CHAMPAIGN · PI DOCAMPO, ROBERTO · 2003 to 2003
$383k
NCRR NIH HHS P41 RR000954NCRR NIH HHS P41-RR-00954NIAID NIH HHS AI21903NIAID NIH HHS AI23259NIAID NIH HHS R01 AI021903NIAID NIH HHS R01 AI023259NIAID NIH HHS R21 AI023259NIAID NIH HHS R37 AI021903NIDDK NIH HHS P30 DK056341NIDDK NIH HHS P30-DK-56341NIDDK NIH HHS P60 DK020579NIDDK NIH HHS P60-DK-20579
6 · The paper itself

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.

Indexed as

AnimalsCell CycleCytoplasmic GranulesLeishmaniaMiceMice, Inbred BALB CSphingolipidsSphingolipids

Identifiers

PMID15720561
PMCPMC3803142
OpenAlexW2142634854

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.