Evidence map›Paper›PMID 40608817›Full record

ArticlePLoS pathogens2025

Hexosamine biosynthesis disruption impairs GPI production and arrests Plasmodium falciparum growth at schizont stages.

María Pía Alberione, Yunuen Avalos-Padilla, Gabriel W Rangel, Miriam Ramírez, Tais Romero-Uruñuela, Àngel Fenollar, Jonathan Ortega-Barrionuevo, Marcell Crispim, Terry K Smith, Manuel Llinás and 1 more

Abstract read
In one paragraph

Article in PLoS pathogens, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Free GPIs and Comparison of GPI Structures Among Species.International journal of molecular sciences · 2025
    Review
  2. Review
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

11 authors.

María Pía AlberioneISGlobal, Barcelona, Spain.
Yunuen Avalos-PadillaISGlobal, Barcelona, Spain.
Gabriel W RangelDepartment of Biochemistry and Molecular Biology and Huck Center for Malaria Research, Pennsylvania State University, University Park, Pennsylvania, United States of America.
Miriam RamírezISGlobal, Barcelona, Spain.
Tais Romero-UruñuelaISGlobal, Barcelona, Spain.
Àngel FenollarISGlobal, Barcelona, Spain.
Jonathan Ortega-BarrionuevoISGlobal, Barcelona, Spain.
Marcell CrispimISGlobal, Barcelona, Spain.
Terry K SmithBiomedical Sciences Research Complex (BSRC), School of Biology, University of St Andrews, St Andrews, United Kingdom.
Manuel LlinásDepartment of Biochemistry and Molecular Biology and Huck Center for Malaria Research, Pennsylvania State University, University Park, Pennsylvania, United States of America.
Luis IzquierdoISGlobal, Barcelona, Spain.ORCID 0000-0002-3704-9874

Funding

Discovering resistance-resistant antimalarial drug targetR21AI174085 · NIAID · PENNSYLVANIA STATE UNIVERSITY, THE · PI LLINAS, MANUEL · 2023 to 2024
$441k
NIAID NIH HHS R21 AI174085
6 · The paper itself

Abstract

UDP-N-acetylglucosamine (UDP-GlcNAc) is a crucial sugar nucleotide for glycan synthesis in eukaryotes. In the malaria parasite Plasmodium falciparum, UDP-GlcNAc is synthesized via the hexosamine biosynthetic pathway (HBP) and is essential for glycosylphosphatidylinositol (GPI) anchor production, the most prominent form of protein glycosylation in the parasite. In this study, we explore a conditional knockout of glucosamine-6-phosphate N-acetyltransferase (PfGNA1), a key HBP enzyme. PfGNA1 depletion led to significant disruptions in HBP metabolites, impairing GPI biosynthesis and causing mislocalization of the merozoite surface protein 1 (MSP1), the most abundant GPI-anchored protein in the parasite. Furthermore, parasites were arrested at the schizont stage, exhibiting severe segmentation defects and an incomplete rupture of the parasitophorous vacuole membrane (PVM), preventing egress from host red blood cells. Our findings demonstrate the critical role of HBP and GPI biosynthesis in P. falciparum asexual blood stage development and underscore the potential of targeting these pathways as a therapeutic strategy against malaria.

Indexed as

Glucosamine 6-Phosphate N-AcetyltransferaseGlycosylphosphatidylinositolsHexosaminesMalaria, FalciparumPlasmodium falciparumSchizontsAnimalsErythrocytesHumansProtozoan ProteinsGlucosamine 6-Phosphate N-AcetyltransferaseGlycosylphosphatidylinositolsHexosaminesProtozoan Proteins

Identifiers

PMID40608817
PMCPMC12251206

What OpenQuestion holds

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Registered trials

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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.