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...

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Autores principales:	Rajiv L Gaur, Kangning Ren, Antje Blumenthal, Suresh Bhamidi, Fernando D González-Nilo, Mary Jackson, Richard N Zare, Sabine Ehrt, Joel D Ernst, Niaz Banaei
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/f9fc24d18cab44e6b9f1cabe82293ef1
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spelling	oai:doaj.org-article:f9fc24d18cab44e6b9f1cabe82293ef12021-11-25T05:46:02ZLprG-mediated surface expression of lipoarabinomannan is essential for virulence of Mycobacterium tuberculosis.1553-73661553-737410.1371/journal.ppat.1004376https://doaj.org/article/f9fc24d18cab44e6b9f1cabe82293ef12014-09-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1004376https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Mycobacterium 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.Rajiv L GaurKangning RenAntje BlumenthalSuresh BhamidiFernando D González-NiloMary JacksonRichard N ZareSabine EhrtJoel D ErnstNiaz BanaeiPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 9, p e1004376 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Rajiv L Gaur Kangning Ren Antje Blumenthal Suresh Bhamidi Fernando D González-Nilo Mary Jackson Richard N Zare Sabine Ehrt Joel D Ernst Niaz Banaei LprG-mediated surface expression of lipoarabinomannan is essential for virulence of Mycobacterium tuberculosis.
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	article
author	Rajiv L Gaur Kangning Ren Antje Blumenthal Suresh Bhamidi Fernando D González-Nilo Mary Jackson Richard N Zare Sabine Ehrt Joel D Ernst Niaz Banaei
author_facet	Rajiv L Gaur Kangning Ren Antje Blumenthal Suresh Bhamidi Fernando D González-Nilo Mary Jackson Richard N Zare Sabine Ehrt Joel D Ernst Niaz Banaei
author_sort	Rajiv L Gaur
title	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_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_sort	lprg-mediated surface expression of lipoarabinomannan is essential for virulence of mycobacterium tuberculosis.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/f9fc24d18cab44e6b9f1cabe82293ef1
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LprG-mediated surface expression of lipoarabinomannan is essential for virulence of Mycobacterium tuberculosis.

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