When more sugar is better—a GPI side chain modification results in a less virulent phenotype during a protozoan infection

ABSTRACT The assembly and function of side chain modifications of glycosylphosphatidylinositol (GPI) units (anchors or free forms) are poorly defined. In a recent study, two enzymes, PIGJ and PIGE, of the protozoan parasite Toxoplasma gondii were identified and shown to be involved in the assembly o...

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Main Author: Frank Seeber
Format: Article
Language:English
Published: American Society for Microbiology 2024-12-01
Series:mBio
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Online Access:https://journals.asm.org/doi/10.1128/mbio.02740-24
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author Frank Seeber
author_facet Frank Seeber
author_sort Frank Seeber
collection DOAJ
description ABSTRACT The assembly and function of side chain modifications of glycosylphosphatidylinositol (GPI) units (anchors or free forms) are poorly defined. In a recent study, two enzymes, PIGJ and PIGE, of the protozoan parasite Toxoplasma gondii were identified and shown to be involved in the assembly of such GPI side chains (J. A. Alvarez, E. Gas-Pascual, S. Malhi, J. C. Sánchez-Arcila, et al., mBio 15:e00527–24, 2024, https://doi.org/10.1128/mbio.00527-24). PIGJ adds N-acetylgalactosamine to the GPI core structure, while PIGE subsequently adds a terminal glucose. Deletion of PIGJ resulted in the loss of the side chain and, strikingly, increased mortality in infected mice, in contrast to PIGE knockouts. Absence of the side chain led to increased binding of the scavenger receptor CD36 to mutant parasites. In galectin-3 knockout mice, the virulent phenotype of side-chain-deficient parasites was largely lost. While the exact mechanisms remain to be elucidated by more experiments, these findings provide the first evidence for the importance of GPI side chains in parasite-host interactions in vivo.
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spelling doaj-art-74efec6c58e8487798a19bb643c3e38c2024-12-11T14:02:30ZengAmerican Society for MicrobiologymBio2150-75112024-12-01151210.1128/mbio.02740-24When more sugar is better—a GPI side chain modification results in a less virulent phenotype during a protozoan infectionFrank Seeber0FG 16: Mycotic and Parasitic Agents and Mycobacteria, Robert Koch-Institut, Berlin, GermanyABSTRACT The assembly and function of side chain modifications of glycosylphosphatidylinositol (GPI) units (anchors or free forms) are poorly defined. In a recent study, two enzymes, PIGJ and PIGE, of the protozoan parasite Toxoplasma gondii were identified and shown to be involved in the assembly of such GPI side chains (J. A. Alvarez, E. Gas-Pascual, S. Malhi, J. C. Sánchez-Arcila, et al., mBio 15:e00527–24, 2024, https://doi.org/10.1128/mbio.00527-24). PIGJ adds N-acetylgalactosamine to the GPI core structure, while PIGE subsequently adds a terminal glucose. Deletion of PIGJ resulted in the loss of the side chain and, strikingly, increased mortality in infected mice, in contrast to PIGE knockouts. Absence of the side chain led to increased binding of the scavenger receptor CD36 to mutant parasites. In galectin-3 knockout mice, the virulent phenotype of side-chain-deficient parasites was largely lost. While the exact mechanisms remain to be elucidated by more experiments, these findings provide the first evidence for the importance of GPI side chains in parasite-host interactions in vivo.https://journals.asm.org/doi/10.1128/mbio.02740-24parasitologyToxoplasma gondiiglycobiology
spellingShingle Frank Seeber
When more sugar is better—a GPI side chain modification results in a less virulent phenotype during a protozoan infection
mBio
parasitology
Toxoplasma gondii
glycobiology
title When more sugar is better—a GPI side chain modification results in a less virulent phenotype during a protozoan infection
title_full When more sugar is better—a GPI side chain modification results in a less virulent phenotype during a protozoan infection
title_fullStr When more sugar is better—a GPI side chain modification results in a less virulent phenotype during a protozoan infection
title_full_unstemmed When more sugar is better—a GPI side chain modification results in a less virulent phenotype during a protozoan infection
title_short When more sugar is better—a GPI side chain modification results in a less virulent phenotype during a protozoan infection
title_sort when more sugar is better a gpi side chain modification results in a less virulent phenotype during a protozoan infection
topic parasitology
Toxoplasma gondii
glycobiology
url https://journals.asm.org/doi/10.1128/mbio.02740-24
work_keys_str_mv AT frankseeber whenmoresugarisbetteragpisidechainmodificationresultsinalessvirulentphenotypeduringaprotozoaninfection