Evidence map›Paper›PMID 26529232›Full record

ArticlePLoS neglected tropical diseases2015

Depletion of UDP-Glucose and UDP-Galactose Using a Degron System Leads to Growth Cessation of Leishmania major.

Sebastian Damerow, Carolin Hoppe, Giulia Bandini, Patricia Zarnovican, Falk F R Buettner, Falk R Buettner, Carsten G K Lüder, Michael A J Ferguson, Françoise H Routier

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PLoS neglected tropical diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

17 citing papers in PubMed, 30 citations in OpenAlex.

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  7. Consumption of Galactose byPathogens (Basel, Switzerland) · 2022
    Article
  8. Article
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  13. Identification ofMolecules (Basel, Switzerland) · 2019
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  14. Article
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  17. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

Sebastian DamerowDepartment of Cellular Chemistry, Hannover Medical School, Hannover, Germany.
Carolin HoppeDepartment of Cellular Chemistry, Hannover Medical School, Hannover, Germany.
Giulia BandiniDivision of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee, United Kingdom.
Patricia ZarnovicanDepartment of Cellular Chemistry, Hannover Medical School, Hannover, Germany.
Falk F R Buettner
Falk R BuettnerDepartment of Cellular Chemistry, Hannover Medical School, Hannover, Germany.
Carsten G K LüderInstitute for Medical Microbiology, Georg-August University, Goettingen, Germany.
Michael A J FergusonDivision of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee, United Kingdom.
Françoise H RoutierDepartment of Cellular Chemistry, Hannover Medical School, Hannover, Germany.
Medizinische Hochschule Hannover · DEUniversity of Dundee · GBUniversity of Göttingen · DE

Funding

Wellcome Trust 101842
6 · The paper itself

Abstract

Interconversion of UDP-glucose (UDP-Glc) and UDP-galactose (UDP-Gal) by the UDP-Glc 4´-epimerase intimately connects the biosynthesis of these two nucleotide sugars. Their de novo biosynthesis involves transformation of glucose-6-phosphate into glucose-1-phosphate by the phosphoglucomutase and subsequent activation into UDP-Glc by the specific UDP-Glc pyrophosphorylase (UGP). Besides UGP, Leishmania parasites express an uncommon UDP-sugar pyrophosphorylase (USP) able to activate both galactose-1-phosphate and glucose-1-phosphate in vitro. Targeted gene deletion of UGP alone was previously shown to principally affect expression of lipophosphoglycan, resulting in a reduced virulence. Since our attempts to delete both UGP and USP failed, deletion of UGP was combined with conditional destabilisation of USP to control the biosynthesis of UDP-Glc and UDP-Gal. Stabilisation of the enzyme produced by a single USP allele was sufficient to maintain the steady-state pools of these two nucleotide sugars and preserve almost normal glycoinositolphospholipids galactosylation, but at the apparent expense of lipophosphoglycan biosynthesis. However, under destabilising conditions, the absence of both UGP and USP resulted in depletion of UDP-Glc and UDP-Gal and led to growth cessation and cell death, suggesting that either or both of these metabolites is/are essential.

Indexed as

Gene DeletionGene Expression RegulationLeishmania majorUridine Diphosphate GalactoseUridine Diphosphate GlucoseUTP-Glucose-1-Phosphate UridylyltransferaseUTP-Hexose-1-Phosphate UridylyltransferaseUridine Diphosphate GalactoseUridine Diphosphate GlucoseUTP-Glucose-1-Phosphate UridylyltransferaseUTP-Hexose-1-Phosphate Uridylyltransferase

Identifiers

PMID26529232
PMCPMC4631452
OpenAlexW1906884173

What OpenQuestion holds

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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.