Summary of project PR002252

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002252. The data can be accessed directly via it's Project DOI: 10.21228/M8J242 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

Project ID: PR002252
Project DOI:doi: 10.21228/M8J242
Project Title:Hexosamine Biosynthesis Disruption Impairs GPI Production and Arrests Plasmodium falciparum Growth at Schizont Stages
Project Summary:UDP-N-acetylglucosamine (UDP-GlcNAc) is a crucial sugar nucleotide for glycan synthesis in eukaryotes. In 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 this 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. As a result, 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 development and underscore the potential of targeting these pathways as a therapeutic strategy against malaria.
Institute:Pennsylvania State University
Department:Biochemistry and Molecular Biology
Laboratory:Manuel LlinĂ¡s
Last Name:Rangel
First Name:Gabriel
Address:491 Pollock Road, University Park, PA, 16802, USA
Email:grangel0955@gmail.com
Phone:8148673527

Summary of all studies in project PR002252

Study IDStudy TitleSpeciesInstituteAnalysis
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ST003642 Hexosamine Biosynthesis Disruption Impairs GPI Production and Arrests Plasmodium falciparum Growth at Schizont Stages Plasmodium falciparum Pennsylvania State University MS 2025-01-06 1 20 Uploaded data (769.1M)*
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