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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Format: | Article |
Language: | English |
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Elsevier
2024-06-01
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Series: | The Cell Surface |
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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. |
first_indexed | 2024-04-24T17:27:59Z |
format | Article |
id | doaj.art-3ec2e587d8c64200bd5b5835f6975821 |
institution | Directory Open Access Journal |
issn | 2468-2330 |
language | English |
last_indexed | 2024-04-24T17:27:59Z |
publishDate | 2024-06-01 |
publisher | Elsevier |
record_format | Article |
series | The Cell Surface |
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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