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Role of succinyl substituents in the mannose-capping of lipoarabinomannan and control of inflammation in Mycobacterium tuberculosis infection
The covalent modification of bacterial (lipo)polysaccharides with discrete substituents may impact their biosynthesis, export and/or biological activity. Whether mycobacteria use a similar strategy to control the biogenesis of its cell envelope polysaccharides and modulate their interaction with the...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10503756/ https://www.ncbi.nlm.nih.gov/pubmed/37669276 http://dx.doi.org/10.1371/journal.ppat.1011636 |
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author | Palčeková, Zuzana Obregón-Henao, Andrés De, Kavita Walz, Amanda Lam, Ha Philp, Jamie Angala, Shiva Kumar Patterson, Johnathan Pearce, Camron Zuberogoitia, Sophie Avanzi, Charlotte Nigou, Jérôme McNeil, Michael Muñoz Gutiérrez, Juan F. Gilleron, Martine Wheat, William H. Gonzalez-Juarrero, Mercedes Jackson, Mary |
author_facet | Palčeková, Zuzana Obregón-Henao, Andrés De, Kavita Walz, Amanda Lam, Ha Philp, Jamie Angala, Shiva Kumar Patterson, Johnathan Pearce, Camron Zuberogoitia, Sophie Avanzi, Charlotte Nigou, Jérôme McNeil, Michael Muñoz Gutiérrez, Juan F. Gilleron, Martine Wheat, William H. Gonzalez-Juarrero, Mercedes Jackson, Mary |
author_sort | Palčeková, Zuzana |
collection | PubMed |
description | The covalent modification of bacterial (lipo)polysaccharides with discrete substituents may impact their biosynthesis, export and/or biological activity. Whether mycobacteria use a similar strategy to control the biogenesis of its cell envelope polysaccharides and modulate their interaction with the host during infection is unknown despite the report of a number of tailoring substituents modifying the structure of these glycans. Here, we show that discrete succinyl substituents strategically positioned on Mycobacterium tuberculosis (Mtb) lipoarabinomannan govern the mannose-capping of this lipoglycan and, thus, much of the biological activity of the entire molecule. We further show that the absence of succinyl substituents on the two main cell envelope glycans of Mtb, arabinogalactan and lipoarabinomannan, leads to a significant increase of pro-inflammatory cytokines and chemokines in infected murine and human macrophages. Collectively, our results validate polysaccharide succinylation as a critical mechanism by which Mtb controls inflammation. |
format | Online Article Text |
id | pubmed-10503756 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-105037562023-09-16 Role of succinyl substituents in the mannose-capping of lipoarabinomannan and control of inflammation in Mycobacterium tuberculosis infection Palčeková, Zuzana Obregón-Henao, Andrés De, Kavita Walz, Amanda Lam, Ha Philp, Jamie Angala, Shiva Kumar Patterson, Johnathan Pearce, Camron Zuberogoitia, Sophie Avanzi, Charlotte Nigou, Jérôme McNeil, Michael Muñoz Gutiérrez, Juan F. Gilleron, Martine Wheat, William H. Gonzalez-Juarrero, Mercedes Jackson, Mary PLoS Pathog Research Article The covalent modification of bacterial (lipo)polysaccharides with discrete substituents may impact their biosynthesis, export and/or biological activity. Whether mycobacteria use a similar strategy to control the biogenesis of its cell envelope polysaccharides and modulate their interaction with the host during infection is unknown despite the report of a number of tailoring substituents modifying the structure of these glycans. Here, we show that discrete succinyl substituents strategically positioned on Mycobacterium tuberculosis (Mtb) lipoarabinomannan govern the mannose-capping of this lipoglycan and, thus, much of the biological activity of the entire molecule. We further show that the absence of succinyl substituents on the two main cell envelope glycans of Mtb, arabinogalactan and lipoarabinomannan, leads to a significant increase of pro-inflammatory cytokines and chemokines in infected murine and human macrophages. Collectively, our results validate polysaccharide succinylation as a critical mechanism by which Mtb controls inflammation. Public Library of Science 2023-09-05 /pmc/articles/PMC10503756/ /pubmed/37669276 http://dx.doi.org/10.1371/journal.ppat.1011636 Text en © 2023 Palčeková et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Palčeková, Zuzana Obregón-Henao, Andrés De, Kavita Walz, Amanda Lam, Ha Philp, Jamie Angala, Shiva Kumar Patterson, Johnathan Pearce, Camron Zuberogoitia, Sophie Avanzi, Charlotte Nigou, Jérôme McNeil, Michael Muñoz Gutiérrez, Juan F. Gilleron, Martine Wheat, William H. Gonzalez-Juarrero, Mercedes Jackson, Mary Role of succinyl substituents in the mannose-capping of lipoarabinomannan and control of inflammation in Mycobacterium tuberculosis infection |
title | Role of succinyl substituents in the mannose-capping of lipoarabinomannan and control of inflammation in Mycobacterium tuberculosis infection |
title_full | Role of succinyl substituents in the mannose-capping of lipoarabinomannan and control of inflammation in Mycobacterium tuberculosis infection |
title_fullStr | Role of succinyl substituents in the mannose-capping of lipoarabinomannan and control of inflammation in Mycobacterium tuberculosis infection |
title_full_unstemmed | Role of succinyl substituents in the mannose-capping of lipoarabinomannan and control of inflammation in Mycobacterium tuberculosis infection |
title_short | Role of succinyl substituents in the mannose-capping of lipoarabinomannan and control of inflammation in Mycobacterium tuberculosis infection |
title_sort | role of succinyl substituents in the mannose-capping of lipoarabinomannan and control of inflammation in mycobacterium tuberculosis infection |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10503756/ https://www.ncbi.nlm.nih.gov/pubmed/37669276 http://dx.doi.org/10.1371/journal.ppat.1011636 |
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