Metabolic modulation: Pneumocystis phosphoglucomutase is a target influencing host recognition

Herein, this manuscript explores the significance of the phosphoglucomutase (PGM) enzyme in Pneumocystis spp., focusing on its role in fungal surface mannoprotein formation. Through expression of the Pneumocystis murina Pmpgm2 in a Saccharomyces cerevisiae pgm2Δ strain, we demonstrate restoration of...

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Main Authors: Theodore J. Kottom, Eva M. Carmona, Bernd Lepenies, Andrew H. Limper
Format: Article
Language:English
Published: Elsevier 2024-06-01
Series:The Cell Surface
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2468233024000057
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author Theodore J. Kottom
Eva M. Carmona
Bernd Lepenies
Andrew H. Limper
author_facet Theodore J. Kottom
Eva M. Carmona
Bernd Lepenies
Andrew H. Limper
author_sort Theodore J. Kottom
collection DOAJ
description Herein, this manuscript explores the significance of the phosphoglucomutase (PGM) enzyme in Pneumocystis spp., focusing on its role in fungal surface mannoprotein formation. Through expression of the Pneumocystis murina Pmpgm2 in a Saccharomyces cerevisiae pgm2Δ strain, we demonstrate restoration of binding to the mannose receptor (MR) and macrophages to wildtype yeast levels in this complemented strain. Gas Chromatography-Mass Spectroscopy (GC-MS) confirmed reduced mannose content in the pgm2Δ yeast strain compared to the wild-type and complemented Pmpgm2 cDNA-expressing strains. This study underscores fungal PGM function in dolichol glucosyl phosphate biosynthesis, crucial for proper cell wall mannoprotein formation. Furthermore, highlighting the conservation of targetable cysteine residues across fungal pathogens, PGM inhibition maybe a potential therapeutic strategy against a broad spectrum of fungal infections.
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spelling doaj.art-3ec2e587d8c64200bd5b5835f69758212024-03-28T06:38:32ZengElsevierThe Cell Surface2468-23302024-06-0111100123Metabolic modulation: Pneumocystis phosphoglucomutase is a target influencing host recognitionTheodore J. Kottom0Eva M. Carmona1Bernd Lepenies2Andrew H. Limper3Thoracic Diseases Research Unit, Departments of Medicine and Biochemistry, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Corresponding author.Thoracic Diseases Research Unit, Departments of Medicine and Biochemistry, Mayo Clinic College of Medicine, Rochester, MN 55905, USAResearch Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, Hannover, Germany; Institute for Immunology, University of Veterinary Medicine Hannover, Hannover, GermanyThoracic Diseases Research Unit, Departments of Medicine and Biochemistry, Mayo Clinic College of Medicine, Rochester, MN 55905, USAHerein, this manuscript explores the significance of the phosphoglucomutase (PGM) enzyme in Pneumocystis spp., focusing on its role in fungal surface mannoprotein formation. Through expression of the Pneumocystis murina Pmpgm2 in a Saccharomyces cerevisiae pgm2Δ strain, we demonstrate restoration of binding to the mannose receptor (MR) and macrophages to wildtype yeast levels in this complemented strain. Gas Chromatography-Mass Spectroscopy (GC-MS) confirmed reduced mannose content in the pgm2Δ yeast strain compared to the wild-type and complemented Pmpgm2 cDNA-expressing strains. This study underscores fungal PGM function in dolichol glucosyl phosphate biosynthesis, crucial for proper cell wall mannoprotein formation. Furthermore, highlighting the conservation of targetable cysteine residues across fungal pathogens, PGM inhibition maybe a potential therapeutic strategy against a broad spectrum of fungal infections.http://www.sciencedirect.com/science/article/pii/S2468233024000057PneumocystisPhosphoglucomutaseMannoproteinC-type lectin receptors (CLRs)
spellingShingle Theodore J. Kottom
Eva M. Carmona
Bernd Lepenies
Andrew H. Limper
Metabolic modulation: Pneumocystis phosphoglucomutase is a target influencing host recognition
The Cell Surface
Pneumocystis
Phosphoglucomutase
Mannoprotein
C-type lectin receptors (CLRs)
title Metabolic modulation: Pneumocystis phosphoglucomutase is a target influencing host recognition
title_full Metabolic modulation: Pneumocystis phosphoglucomutase is a target influencing host recognition
title_fullStr Metabolic modulation: Pneumocystis phosphoglucomutase is a target influencing host recognition
title_full_unstemmed Metabolic modulation: Pneumocystis phosphoglucomutase is a target influencing host recognition
title_short Metabolic modulation: Pneumocystis phosphoglucomutase is a target influencing host recognition
title_sort metabolic modulation pneumocystis phosphoglucomutase is a target influencing host recognition
topic Pneumocystis
Phosphoglucomutase
Mannoprotein
C-type lectin receptors (CLRs)
url http://www.sciencedirect.com/science/article/pii/S2468233024000057
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