Evidence map›Paper›PMID 27324409›Full record

ArticleCellular microbiology2017

Characterization of the Plasmodium falciparum and P. berghei glycerol 3-phosphate acyltransferase involved in FASII fatty acid utilization in the malaria parasite apicoplast.

Melanie J Shears, James I MacRae, Vanessa Mollard, Christopher D Goodman, Angelika Sturm, Lindsey M Orchard, Manuel Llinás, Malcolm J McConville, Cyrille Y Botté, Geoffrey I McFadden

Open access · hybridAbstract read
In one paragraph

Article in Cellular microbiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
4.2field-weighted citation impact, top 6% 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

18 citing papers in PubMed, 35 citations in OpenAlex.

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  12. Journal of lipid research · 2018
    Article
  13. Article
  14. Lipid analysis ofCell discovery · 2018
    Article
  15. Lipid response patterns in acute phase paediatricMetabolomics : Official journal of the Metabolomic Society · 2017
    Article
  16. Article
  17. Review
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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

10 authors at 5 institutions in 4 countries.

Melanie J ShearsSchool of BioSciences, University of Melbourne, VIC 3010, Australia.
James I MacRaeThe Francis Crick Institute, Metabolomics, The Ridgeway, Mill Hill, London, NW7 1AA, United Kingdom.
Vanessa MollardSchool of BioSciences, University of Melbourne, VIC 3010, Australia.
Christopher D GoodmanSchool of BioSciences, University of Melbourne, VIC 3010, Australia.
Angelika SturmSchool of BioSciences, University of Melbourne, VIC 3010, Australia.
Lindsey M OrchardDepartment of Biochemistry and Molecular Biology, Department of Chemistry and Center for Malaria Research, Pennsylvania State University, State College, University Park, PA, 16802, United States.
Manuel LlinásDepartment of Biochemistry and Molecular Biology, Department of Chemistry and Center for Malaria Research, Pennsylvania State University, State College, University Park, PA, 16802, United States.
Malcolm J McConvilleDepartment of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, VIC 3010, Australia.
Cyrille Y BottéApicolipid team, Institute for Advanced Biosciences UMR CNRS5309 INSMERM U1209, Université Grenoble Alpes, Grenoble, France.
Geoffrey I McFaddenSchool of BioSciences, University of Melbourne, VIC 3010, Australia.
University of Melbourne · AUPennsylvania State University · USAgriBio · AUCentre National de la Recherche Scientifique · FRThe Francis Crick Institute · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Malaria parasites can synthesize fatty acids via a type II fatty acid synthesis (FASII) pathway located in their apicoplast. The FASII pathway has been pursued as an anti-malarial drug target, but surprisingly little is known about its role in lipid metabolism. Here we characterize the apicoplast glycerol 3-phosphate acyltransferase that acts immediately downstream of FASII in human (Plasmodium falciparum) and rodent (Plasmodium berghei) malaria parasites and investigate how this enzyme contributes to incorporating FASII fatty acids into precursors for membrane lipid synthesis. Apicoplast targeting of the P. falciparum and P. berghei enzymes are confirmed by fusion of the N-terminal targeting sequence to GFP and 3' tagging of the full length protein. Activity of the P. falciparum enzyme is demonstrated by complementation in mutant bacteria, and critical residues in the putative active site identified by site-directed mutagenesis. Genetic disruption of the P. falciparum enzyme demonstrates it is dispensable in blood stage parasites, even in conditions known to induce FASII activity. Disruption of the P. berghei enzyme demonstrates it is dispensable in blood and mosquito stage parasites, and only essential for development in the late liver stage, consistent with the requirement for FASII in rodent malaria models. However, the P. berghei mutant liver stage phenotype is found to only partially phenocopy loss of FASII, suggesting newly made fatty acids can take multiple pathways out of the apicoplast and so giving new insight into the role of FASII and apicoplast glycerol 3-phosphate acyltransferase in malaria parasites.

Indexed as

ApicoplastsBacteriaDNA Mutational AnalysisFatty AcidsGene Knockout TechniquesGenetic Complementation TestGlycerol-3-Phosphate O-AcyltransferasePlasmodium bergheiPlasmodium falciparumProtein TransportFatty AcidsGlycerol-3-Phosphate O-Acyltransferase

Identifiers

PMID27324409
PMCPMC5213128
OpenAlexW2464931701

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.