Cargando…

LprG-Mediated Surface Expression of Lipoarabinomannan Is Essential for Virulence of Mycobacterium tuberculosis

Mycobacterium tuberculosis employs various virulence strategies to subvert host immune responses in order to persist and cause disease. Interaction of M. tuberculosis with mannose receptor on macrophages via surface-exposed lipoarabinomannan (LAM) is believed to be critical for cell entry, inhibitio...

Descripción completa

Detalles Bibliográficos
Autores principales: Gaur, Rajiv L., Ren, Kangning, Blumenthal, Antje, Bhamidi, Suresh, Gibbs, Sara, Jackson, Mary, Zare, Richard N., Ehrt, Sabine, Ernst, Joel D., Banaei, Niaz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4169494/
https://www.ncbi.nlm.nih.gov/pubmed/25232742
http://dx.doi.org/10.1371/journal.ppat.1004376
_version_ 1782335709929013248
author Gaur, Rajiv L.
Ren, Kangning
Blumenthal, Antje
Bhamidi, Suresh
Gibbs, Sara
Jackson, Mary
Zare, Richard N.
Ehrt, Sabine
Ernst, Joel D.
Banaei, Niaz
author_facet Gaur, Rajiv L.
Ren, Kangning
Blumenthal, Antje
Bhamidi, Suresh
Gibbs, Sara
Jackson, Mary
Zare, Richard N.
Ehrt, Sabine
Ernst, Joel D.
Banaei, Niaz
author_sort Gaur, Rajiv L.
collection PubMed
description Mycobacterium tuberculosis employs various virulence strategies to subvert host immune responses in order to persist and cause disease. Interaction of M. tuberculosis with mannose receptor on macrophages via surface-exposed lipoarabinomannan (LAM) is believed to be critical for cell entry, inhibition of phagosome-lysosome fusion, and intracellular survival, but in vivo evidence is lacking. LprG, a cell envelope lipoprotein that is essential for virulence of M. tuberculosis, has been shown to bind to the acyl groups of lipoglycans but the role of LprG in LAM biosynthesis and localization remains unknown. Using an M. tuberculosis lprG mutant, we show that LprG is essential for normal surface expression of LAM and virulence of M. tuberculosis attributed to LAM. The lprG mutant had a normal quantity of LAM in the cell envelope, but its surface was altered and showed reduced expression of surface-exposed LAM. Functionally, the lprG mutant was defective for macrophage entry and inhibition of phagosome-lysosome fusion, was attenuated in macrophages, and was killed in the mouse lung with the onset of adaptive immunity. This study identifies the role of LprG in surface-exposed LAM expression and provides in vivo evidence for the essential role surface LAM plays in M. tuberculosis virulence. Findings have translational implications for therapy and vaccine development.
format Online
Article
Text
id pubmed-4169494
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-41694942014-09-22 LprG-Mediated Surface Expression of Lipoarabinomannan Is Essential for Virulence of Mycobacterium tuberculosis Gaur, Rajiv L. Ren, Kangning Blumenthal, Antje Bhamidi, Suresh Gibbs, Sara Jackson, Mary Zare, Richard N. Ehrt, Sabine Ernst, Joel D. Banaei, Niaz PLoS Pathog Research Article Mycobacterium tuberculosis employs various virulence strategies to subvert host immune responses in order to persist and cause disease. Interaction of M. tuberculosis with mannose receptor on macrophages via surface-exposed lipoarabinomannan (LAM) is believed to be critical for cell entry, inhibition of phagosome-lysosome fusion, and intracellular survival, but in vivo evidence is lacking. LprG, a cell envelope lipoprotein that is essential for virulence of M. tuberculosis, has been shown to bind to the acyl groups of lipoglycans but the role of LprG in LAM biosynthesis and localization remains unknown. Using an M. tuberculosis lprG mutant, we show that LprG is essential for normal surface expression of LAM and virulence of M. tuberculosis attributed to LAM. The lprG mutant had a normal quantity of LAM in the cell envelope, but its surface was altered and showed reduced expression of surface-exposed LAM. Functionally, the lprG mutant was defective for macrophage entry and inhibition of phagosome-lysosome fusion, was attenuated in macrophages, and was killed in the mouse lung with the onset of adaptive immunity. This study identifies the role of LprG in surface-exposed LAM expression and provides in vivo evidence for the essential role surface LAM plays in M. tuberculosis virulence. Findings have translational implications for therapy and vaccine development. Public Library of Science 2014-09-18 /pmc/articles/PMC4169494/ /pubmed/25232742 http://dx.doi.org/10.1371/journal.ppat.1004376 Text en © 2014 Gaur et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Gaur, Rajiv L.
Ren, Kangning
Blumenthal, Antje
Bhamidi, Suresh
Gibbs, Sara
Jackson, Mary
Zare, Richard N.
Ehrt, Sabine
Ernst, Joel D.
Banaei, Niaz
LprG-Mediated Surface Expression of Lipoarabinomannan Is Essential for Virulence of Mycobacterium tuberculosis
title LprG-Mediated Surface Expression of Lipoarabinomannan Is Essential for Virulence of Mycobacterium tuberculosis
title_full LprG-Mediated Surface Expression of Lipoarabinomannan Is Essential for Virulence of Mycobacterium tuberculosis
title_fullStr LprG-Mediated Surface Expression of Lipoarabinomannan Is Essential for Virulence of Mycobacterium tuberculosis
title_full_unstemmed LprG-Mediated Surface Expression of Lipoarabinomannan Is Essential for Virulence of Mycobacterium tuberculosis
title_short LprG-Mediated Surface Expression of Lipoarabinomannan Is Essential for Virulence of Mycobacterium tuberculosis
title_sort lprg-mediated surface expression of lipoarabinomannan is essential for virulence of mycobacterium tuberculosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4169494/
https://www.ncbi.nlm.nih.gov/pubmed/25232742
http://dx.doi.org/10.1371/journal.ppat.1004376
work_keys_str_mv AT gaurrajivl lprgmediatedsurfaceexpressionoflipoarabinomannanisessentialforvirulenceofmycobacteriumtuberculosis
AT renkangning lprgmediatedsurfaceexpressionoflipoarabinomannanisessentialforvirulenceofmycobacteriumtuberculosis
AT blumenthalantje lprgmediatedsurfaceexpressionoflipoarabinomannanisessentialforvirulenceofmycobacteriumtuberculosis
AT bhamidisuresh lprgmediatedsurfaceexpressionoflipoarabinomannanisessentialforvirulenceofmycobacteriumtuberculosis
AT gibbssara lprgmediatedsurfaceexpressionoflipoarabinomannanisessentialforvirulenceofmycobacteriumtuberculosis
AT jacksonmary lprgmediatedsurfaceexpressionoflipoarabinomannanisessentialforvirulenceofmycobacteriumtuberculosis
AT zarerichardn lprgmediatedsurfaceexpressionoflipoarabinomannanisessentialforvirulenceofmycobacteriumtuberculosis
AT ehrtsabine lprgmediatedsurfaceexpressionoflipoarabinomannanisessentialforvirulenceofmycobacteriumtuberculosis
AT ernstjoeld lprgmediatedsurfaceexpressionoflipoarabinomannanisessentialforvirulenceofmycobacteriumtuberculosis
AT banaeiniaz lprgmediatedsurfaceexpressionoflipoarabinomannanisessentialforvirulenceofmycobacteriumtuberculosis