Protein O-mannosylation deficiency increases LprG-associated lipoarabinomannan release by Mycobacterium tuberculosis and enhances the TLR2-associated inflammatory response

Abstract Protein O-mannosylation is crucial for the biology of Mycobacterium tuberculosis but the key mannosylated protein(s) involved and its(their) underlying function(s) remain unknown. Here, we demonstrated that the M. tuberculosis mutant (Δpmt) deficient for protein O-mannosylation exhibits enh...

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Autores principales:	Henar Alonso, Julien Parra, Wladimir Malaga, Delphine Payros, Chia-Fang Liu, Céline Berrone, Camille Robert, Etienne Meunier, Odile Burlet-Schiltz, Michel Rivière, Christophe Guilhot
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f3789c592a2c43ffbed294cffb4cbee9
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spelling	oai:doaj.org-article:f3789c592a2c43ffbed294cffb4cbee92021-12-02T16:06:56ZProtein O-mannosylation deficiency increases LprG-associated lipoarabinomannan release by Mycobacterium tuberculosis and enhances the TLR2-associated inflammatory response10.1038/s41598-017-08489-72045-2322https://doaj.org/article/f3789c592a2c43ffbed294cffb4cbee92017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08489-7https://doaj.org/toc/2045-2322Abstract Protein O-mannosylation is crucial for the biology of Mycobacterium tuberculosis but the key mannosylated protein(s) involved and its(their) underlying function(s) remain unknown. Here, we demonstrated that the M. tuberculosis mutant (Δpmt) deficient for protein O-mannosylation exhibits enhanced release of lipoarabinomannan (LAM) in a complex with LprG, a lipoprotein required for LAM translocation to the cell surface. We determined that LprG is O-mannosylated at a unique threonine position by mass spectrometry analyses of the purified protein. However, although replacement of this amino acid by an alanine residue completely abolished LprG O-mannosylation, the increased release of the LAM/LprG complex was preserved. We found that the increased secretion of this complex is due to enhanced LAM production in the Δpmt M. tuberculosis and M. smegmatis mutants relative to their wild-type counterparts. This abnormal release of LAM/LprG has functional consequences on the induction of inflammatory responses and provides a possible explanation for the reduced virulence of the M. tuberculosis Δpmt mutant.Henar AlonsoJulien ParraWladimir MalagaDelphine PayrosChia-Fang LiuCéline BerroneCamille RobertEtienne MeunierOdile Burlet-SchiltzMichel RivièreChristophe GuilhotNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Henar Alonso Julien Parra Wladimir Malaga Delphine Payros Chia-Fang Liu Céline Berrone Camille Robert Etienne Meunier Odile Burlet-Schiltz Michel Rivière Christophe Guilhot Protein O-mannosylation deficiency increases LprG-associated lipoarabinomannan release by Mycobacterium tuberculosis and enhances the TLR2-associated inflammatory response
description	Abstract Protein O-mannosylation is crucial for the biology of Mycobacterium tuberculosis but the key mannosylated protein(s) involved and its(their) underlying function(s) remain unknown. Here, we demonstrated that the M. tuberculosis mutant (Δpmt) deficient for protein O-mannosylation exhibits enhanced release of lipoarabinomannan (LAM) in a complex with LprG, a lipoprotein required for LAM translocation to the cell surface. We determined that LprG is O-mannosylated at a unique threonine position by mass spectrometry analyses of the purified protein. However, although replacement of this amino acid by an alanine residue completely abolished LprG O-mannosylation, the increased release of the LAM/LprG complex was preserved. We found that the increased secretion of this complex is due to enhanced LAM production in the Δpmt M. tuberculosis and M. smegmatis mutants relative to their wild-type counterparts. This abnormal release of LAM/LprG has functional consequences on the induction of inflammatory responses and provides a possible explanation for the reduced virulence of the M. tuberculosis Δpmt mutant.
format	article
author	Henar Alonso Julien Parra Wladimir Malaga Delphine Payros Chia-Fang Liu Céline Berrone Camille Robert Etienne Meunier Odile Burlet-Schiltz Michel Rivière Christophe Guilhot
author_facet	Henar Alonso Julien Parra Wladimir Malaga Delphine Payros Chia-Fang Liu Céline Berrone Camille Robert Etienne Meunier Odile Burlet-Schiltz Michel Rivière Christophe Guilhot
author_sort	Henar Alonso
title	Protein O-mannosylation deficiency increases LprG-associated lipoarabinomannan release by Mycobacterium tuberculosis and enhances the TLR2-associated inflammatory response
title_short	Protein O-mannosylation deficiency increases LprG-associated lipoarabinomannan release by Mycobacterium tuberculosis and enhances the TLR2-associated inflammatory response
title_full	Protein O-mannosylation deficiency increases LprG-associated lipoarabinomannan release by Mycobacterium tuberculosis and enhances the TLR2-associated inflammatory response
title_fullStr	Protein O-mannosylation deficiency increases LprG-associated lipoarabinomannan release by Mycobacterium tuberculosis and enhances the TLR2-associated inflammatory response
title_full_unstemmed	Protein O-mannosylation deficiency increases LprG-associated lipoarabinomannan release by Mycobacterium tuberculosis and enhances the TLR2-associated inflammatory response
title_sort	protein o-mannosylation deficiency increases lprg-associated lipoarabinomannan release by mycobacterium tuberculosis and enhances the tlr2-associated inflammatory response
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f3789c592a2c43ffbed294cffb4cbee9
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Protein O-mannosylation deficiency increases LprG-associated lipoarabinomannan release by Mycobacterium tuberculosis and enhances the TLR2-associated inflammatory response

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