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Organelle Membrane Proteomics Reveals Differential Influence of Mycobacterial Lipoglycans on Macrophage Phagosome Maturation and Autophagosome Accumulation

[Image: see text] The mycobacterial cell wall component lipoarabinomannan (LAM) has been described as one of the key virulence factors of Mycobacterium tuberculosis. Modification of the terminal arabinan residues of this lipoglycan with mannose caps in M. tuberculosis or with phosphoinositol caps in...

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Autores principales: Shui, Wenqing, Petzold, Christopher J., Redding, Alyssa, Liu, Jun, Pitcher, Austin, Sheu, Leslie, Hsieh, Tsung-yen, Keasling, Jay D., Bertozzi, Carolyn R.
Formato: Texto
Lenguaje:English
Publicado: American Chemical Society 2010
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018347/
https://www.ncbi.nlm.nih.gov/pubmed/21105745
http://dx.doi.org/10.1021/pr100688h
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author Shui, Wenqing
Petzold, Christopher J.
Redding, Alyssa
Liu, Jun
Pitcher, Austin
Sheu, Leslie
Hsieh, Tsung-yen
Keasling, Jay D.
Bertozzi, Carolyn R.
author_facet Shui, Wenqing
Petzold, Christopher J.
Redding, Alyssa
Liu, Jun
Pitcher, Austin
Sheu, Leslie
Hsieh, Tsung-yen
Keasling, Jay D.
Bertozzi, Carolyn R.
author_sort Shui, Wenqing
collection PubMed
description [Image: see text] The mycobacterial cell wall component lipoarabinomannan (LAM) has been described as one of the key virulence factors of Mycobacterium tuberculosis. Modification of the terminal arabinan residues of this lipoglycan with mannose caps in M. tuberculosis or with phosphoinositol caps in Mycobacterium smegmatis results in distinct host immune responses. Given that M. tuberculosis typically persists in the phagosomal vacuole after being phagocytosed by macrophages, we performed a proteomic analysis of that organelle after treatment of macrophages with LAMs purified from the two mycobacterial species. The quantitative changes in phagosomal proteins suggested a distinct role for mannose-capped LAM in modulating protein trafficking pathways that contribute to the arrest of phagosome maturation. Enlightened by our proteomic data, we performed further experiments to show that only the LAM from M. tuberculosis inhibits accumulation of autophagic vacuoles in the macrophage, suggesting a new function for this virulence-associated lipid.
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spelling pubmed-30183472011-01-11 Organelle Membrane Proteomics Reveals Differential Influence of Mycobacterial Lipoglycans on Macrophage Phagosome Maturation and Autophagosome Accumulation Shui, Wenqing Petzold, Christopher J. Redding, Alyssa Liu, Jun Pitcher, Austin Sheu, Leslie Hsieh, Tsung-yen Keasling, Jay D. Bertozzi, Carolyn R. J Proteome Res [Image: see text] The mycobacterial cell wall component lipoarabinomannan (LAM) has been described as one of the key virulence factors of Mycobacterium tuberculosis. Modification of the terminal arabinan residues of this lipoglycan with mannose caps in M. tuberculosis or with phosphoinositol caps in Mycobacterium smegmatis results in distinct host immune responses. Given that M. tuberculosis typically persists in the phagosomal vacuole after being phagocytosed by macrophages, we performed a proteomic analysis of that organelle after treatment of macrophages with LAMs purified from the two mycobacterial species. The quantitative changes in phagosomal proteins suggested a distinct role for mannose-capped LAM in modulating protein trafficking pathways that contribute to the arrest of phagosome maturation. Enlightened by our proteomic data, we performed further experiments to show that only the LAM from M. tuberculosis inhibits accumulation of autophagic vacuoles in the macrophage, suggesting a new function for this virulence-associated lipid. American Chemical Society 2010-11-24 2011-01-07 /pmc/articles/PMC3018347/ /pubmed/21105745 http://dx.doi.org/10.1021/pr100688h Text en Copyright © 2010 American Chemical Society http://pubs.acs.orgThis is an open-access article distributed under the ACS AuthorChoice Terms & Conditions. Any use of this article, must conform to the terms of that license which are available at http://pubs.acs.org.
spellingShingle Shui, Wenqing
Petzold, Christopher J.
Redding, Alyssa
Liu, Jun
Pitcher, Austin
Sheu, Leslie
Hsieh, Tsung-yen
Keasling, Jay D.
Bertozzi, Carolyn R.
Organelle Membrane Proteomics Reveals Differential Influence of Mycobacterial Lipoglycans on Macrophage Phagosome Maturation and Autophagosome Accumulation
title Organelle Membrane Proteomics Reveals Differential Influence of Mycobacterial Lipoglycans on Macrophage Phagosome Maturation and Autophagosome Accumulation
title_full Organelle Membrane Proteomics Reveals Differential Influence of Mycobacterial Lipoglycans on Macrophage Phagosome Maturation and Autophagosome Accumulation
title_fullStr Organelle Membrane Proteomics Reveals Differential Influence of Mycobacterial Lipoglycans on Macrophage Phagosome Maturation and Autophagosome Accumulation
title_full_unstemmed Organelle Membrane Proteomics Reveals Differential Influence of Mycobacterial Lipoglycans on Macrophage Phagosome Maturation and Autophagosome Accumulation
title_short Organelle Membrane Proteomics Reveals Differential Influence of Mycobacterial Lipoglycans on Macrophage Phagosome Maturation and Autophagosome Accumulation
title_sort organelle membrane proteomics reveals differential influence of mycobacterial lipoglycans on macrophage phagosome maturation and autophagosome accumulation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018347/
https://www.ncbi.nlm.nih.gov/pubmed/21105745
http://dx.doi.org/10.1021/pr100688h
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